446 Sentences With "respiratory depression"

"In adults, the respiratory depression, the part that slows the breathing and you stop breathing, is limited, and so there's a lot less respiratory depression in adults," Spiller said.

It can also cause respiratory depression and severe allergic reactions.

Possible side effects include extreme sleepiness, respiratory depression, coma and death.

Using them together can lead to extreme sleepiness, respiratory depression, coma and death.

"The biggest thing that hospitals get sued for is respiratory depression," Baral said.

In children, respiratory depression can be life-threatening and may require mechanical ventilation.

The cause of death from opioids is typically hypoventilation, also known as respiratory depression.

They can also trigger life-threatening side effects, including respiratory depression leading to death.

The side effects of severe constipation, somnolence and respiratory depression aren't even a consideration.

More than 20 cases of fatal respiratory depression have been documented in infants and children.

With the painkiller codeine, a rare genetic variation has led to respiratory depression and death.

"It doesn't cause respiratory depression because of where it sits on the receptor," he said.

Kratom has been linked to seizures and respiratory depression, but deaths related to it appear rare.

Mitchell Gomez: Feelings of euphoria and relaxation, sedation, drowsiness, dizziness, nausea, respiratory depression or arrest, and death.

The FDA warns combining Xanax with opiods can result in "profound sedation, respiratory depression, coma and death."

It also exhibits a "ceiling effect" on respiratory depression, reducing the risk of death due to overdose.

But more than half were for patients younger than 12, those at greatest risk of respiratory depression.

And the chemical isn't known to cause the same, sometimes deadly, side effects as opioids, such as respiratory depression.

But think twice before pouring your pet a pint, Petplan says, even a sip can cause fatal respiratory depression.

Majumdar and Váradi hope to continue refining the molecule in order to eliminate respiratory depression and other side effects altogether.

An overdose of fentanyl can result in severe respiratory depression or arrest, during which breathing is slowed or ceases altogether.

McDonnell wrote that "as little as" 2 to 3 milligrams of fentanyl can induce respiratory depression, respiratory arrest and possibly death.

"Injecting a patient with super-potent morphine could result in serious consequences including respiratory depression, coma, and death," the agency said.

Unfortunately, in very young children under 5, preschoolers, toddlers, infants ... that protection isn't there, and they do get this respiratory depression.

In comparison to the respiratory depression from the opioids like heroin or fentanyl, the risk from cannabis exposure is far smaller.

But they are also drugs with dangerous side effects, including respiratory depression, and they raise serious issues of abuse and addiction.

These distinctions mean the new opioids could decrease the risk of addiction and eliminate a leading cause of overdose death: respiratory depression.

Research has shown kratom's potential as an opioid substitute, offering pain relief seemingly without the life-threatening side effect of respiratory depression.

"The whole field is sort of opening up, and there's hope that there's molecules that at least don't cause respiratory depression," he said.

Some patients appear sluggish and have symptoms similar to an opioid overdose, including confusion, respiratory depression, vomiting, seizure, loss of consciousness or unresponsiveness.

But a potent side-effect of opioids has always been respiratory depression: At high doses you get so sedated that you stop breathing.

"Gabapentinoids are increasingly prescribed to patients with opioids and benzodiazapines, which increases the risk of respiratory depression and death," Seamans said by email.

The result can be kidney failure, fatal respiratory depression, gastrointestinal bleeding or a life-threatening heart arrhythmia, depending on the person and the drug.

Those drugs have a potentially lethal side effect: slowed breathing known as respiratory depression, even to the point that users stop breathing and die.

Other potential side effects, according to the National Institute for Drug Abuse, include drowsiness, respiratory depression and arrest, nausea, confusion, constipation, sedation, unconsciousness, and coma.

"It seems like it has huge, huge potential as tomorrow's pain reliever that can separate out addiction, abuse, respiratory depression and constipation from analgesia," he said.

Some, such as morphine, bind to the receptor and activate two signaling pathways: one mediating pain cessation and the other producing side effects like respiratory depression.

Kratom doesn't seem to share the dangerous side effect of respiratory depression that other opioids have—that's when someone's breathing slows down and could stop completely.

Studies have shown oliceridine relieves pain like morphine but doesn't cause respiratory depression or constipation, and patients are less likely to build up a tolerance to it.

At the same time, opioids may also results in a host of negative effects as well, often triggering nausea, vomiting, and respiratory depression, which can be fatal.

While she had heard mixing depressants was risky, she didn't realize just how intensely these substances, taken in combination, could magnify the respiratory depression each produced on its own.

A recent study on mice showed the analgesic effects of PZM21 last substantially longer than those of morphine, and resulted in less respiratory depression and constipation than conventional opioids.

Of note, none of the 44 deaths that involved Kratom were from respiratory failure and there has been no observation in the literature that Kratom users experienced respiratory depression.

Unlike methadone and all other opioids, patients on buprenorphine can tolerate increasing doses of the drug without causing respiratory depression, which is how individuals die from an opioid overdose.

This statement is still true if the mechanism causing death is respiratory depression and probably still largely true if the form of cannabis is lower THC content herbal cannabis.

The DEA says 2 to 3 milligrams of fentanyl is enough to cause respiratory depression, arrest and possible death -- a measurement equivalent to five to seven grains of table salt.

Because of its unknown contents, drug users might underestimate its strength, ingesting more opioid than they are normally known to tolerate, causing a respiratory depression that leads to fatal overdose.

Reports of over sedation and respiratory depression secondary to marijuana ingestion have been reported in young children who have consumed very large amounts of THC relative to their body size.

This is why Kratom consumption does not lead to classic opioid symptoms, such as the feared respiratory depression, which is often the cause of death for opioids like morphine and fentanyl.

These consequences can be deadly: Using gabapentin at the same time as opioids is associated with four times the risk of "respiratory depression," which is the main cause of death for overdoses.

Just 2 to 3 milligrams of fentanyl -- equivalent to five to seven grains of table salt -- is enough to cause respiratory depression, arrest and possible death, according to the Drug Enforcement Administration.

Half of kids stayed in the hospital less than 11 hours, and tended to have symptoms like drowsiness, agitation and vomiting, though four kids also experienced breathing difficulty known as respiratory depression.

But for people taking the drugs, maintaining a round-the-clock regimen is vital: Without it, patients' tolerance to them decreases, and they are at risk for accidental overdose, respiratory depression and death.

But initial results in mice suggest the new drug might be less addictive than morphine and other opiate painkillers and avoid a side effect known as respiratory depression that results in overdose deaths, scientists say.

" Boyer said kratom may have other risks, such as seizures, but he noted that it might be safer than most opioids because "there does not seem to be respiratory depression when kratom is used alone.

" More specifically, he said, "I think most people know that narcotics, in general, can cause respiratory depression and we are all familiar with cases where morphine, heroin or fentanyl overdoses can stop breathing and cause death.

Thus it would (a) eliminate, or at least appreciably minimize, the euphoria that the drug produces in users who relapse, and (b) end the risk of respiratory depression that accompanies an overdose, causing the addict to stop breathing.

Naloxone (also known by the brand name Narcan) works by attaching to the same brain receptors that receive heroin and other opioids, and blocking those compounds for 30 to 60 minutes to reverse the respiratory depression that can result from an opioid overdose.

Funded by the UW Alcohol and Drug Abuse Institute and the National Science Foundation, the app is a contactless system that converts a smartphone into a short-range active sonar, using frequency shifts to identify respiratory depression, apnea and gross motor movements associated with acute opioid toxicity.

In fact, the Food and Drug Administration began requiring "boxed warnings and patient-focused Medication Guides" on labels to inform consumers about the risks of combined use of opioids and benzodiazepines in 2016, and said that combined use could cause risks including respiratory depression, dizziness and death.

"Direct kratom overdoses from the life-threatening respiratory depression that usually occurs with opioid overdoses have not been reported," says Oliver Grundmann, clinical associate professor of medicinal chemistry at the University of Florida, who recently reviewed the research on kratom for the International Journal of Legal Medicine.

Consequently, using the two types of drugs together can lead to respiratory depression, coma and death, according to Nabarun Dasgupta, a senior epidemiologist at the Gillings School of Global Health at the University of North Carolina at Chapel Hill, who was not involved in the most recent study.

" While there have been no reported overdoses related to the medication, the Perrigo Company said side effects of an overdose can include "hyperexcitability, rapid eye movements, changes in muscle reflexes, ataxia, dystonia, hallucinations, stupor and coma," adding that other effects have included "nausea, vomiting, tachycardia, irregular heartbeat, seizures, respiratory depression and death.

"One of the problems is at higher doses, that dampening can be too much and it can lead to respiratory depression, so the signals that go out of the brain to the lungs, to your diaphragm muscles to say, 'breathe,' are basically turned off or turned off so much that individuals ... can die," said Arnot.

Respiratory depression is the leading cause of death from opioid use. Although evidence is sparse, the risk from respiratory depression caused by taking Mitragyna speciosa appears to be low, but the Food and Drug Administration listed respiratory depression as a concern.

Scopolamine induces respiratory depression at hallucinogenic doses. The combination of anesthesia (in the hospital) and Datura is usually fatal due to combined respiratory depression. Seizures as well as fevers as high as have been reported.

Respiratory stimulants such as nikethamide were traditionally used to counteract respiratory depression from CNS depressant overdose, but offered limited effectiveness. A new respiratory stimulant drug called BIMU8 is being investigated which seems to be significantly more effective and may be useful for counteracting the respiratory depression produced by opiates and similar drugs without offsetting their therapeutic effects. If the respiratory depression occurs from opioid overdose, usually an opioid antagonist, most likely naloxone, will be administered. This will rapidly reverse the respiratory depression unless complicated by other depressants.

Through the use of agents researchers were able to treat obtundation and respiratory depression.

Respiratory depression from severe impairment of skeletal muscle function is found in some people.

Symptoms of acute barbiturate poisoning include drowsiness, confusion, coma, respiratory depression, hypotension, and shock.

Side effects are similar to those of other opioids and include itching, nausea and respiratory depression.

Side effects can include itching, nausea and potentially serious respiratory depression which can be life-threatening. Respiratory depression can be a problem with alphaprodine even at normal therapeutic doses. Unlike pethidine, prodine does not produce toxic metabolites and is therefore more suitable for high-dose therapy.

Studies in primates showed it to have analgesic effects but without producing respiratory depression or reinforcing effects.

Side effects of dextromethorphan at normal therapeutic doses can include: A rare side effect is respiratory depression.

Benzoctamine is a drug that possesses sedative and anxiolytic properties. Marketed as Tacitin by Ciba-Geigy, it is different from most sedative drugs because in most clinical trials it does not produce respiratory depression, but actually stimulates the respiratory system. As a result, when compared to other sedative and anxiolytic drugs such as benzodiazepines like diazepam, it is a safer form of tranquilizing. However, when co-administered with other drugs that cause respiratory depression, like morphine, it can cause increased respiratory depression.

Sudden loss of consciousness, simultaneous respiratory and metabolic acidosis, fast heartbeat, increased blood pressure, pupil constriction, coma, respiratory depression and death may follow from an overdose. Somebody who has overdosed and suffers from respiratory depression may be kept alive by performing a tracheal intubation and then giving artificial respiration with pumps.

Tiagabine overdose can produce neurological symptoms such as lethargy, single or multiple seizures, status epilepticus, coma, confusion, agitation, tremors, dizziness, dystonias/abnormal posturing, and hallucinations, as well as respiratory depression, tachycardia, hypertension, and hypotension. Overdose may be fatal especially if the victim presents with severe respiratory depression and/or unresponsiveness.

Prolonged lack of oxygenation from respiratory depression can also lead to detrimental damage to the brain and spinal cord and can leave the person unable to walk or function normally, even if treatment with naloxone is given. Alcohol also causes respiratory depression and therefore when taken with opioids can increase the risk of respiratory depression and death. In young children, opioid overdose may not be apparent right away. This is due to absorption, distribution, and metabolism differences between young children and adults, and the higher amount of opioid ingestion per kilogram of body weight.

Cardiovascular effects include hypotension, bradycardia, arrhythmias, and/or cardiac arrest – some of which may be due to hypoxemia secondary to respiratory depression.

However, in the setting of acute pain management, buprenorphine appears to cause the same rate of respiratory depression as other opioids such as morphine.

Many dissociatives have general depressant effects and can produce sedation, respiratory depression, analgesia, anesthesia, and ataxia, as well as cognitive and memory impairment and amnesia.

The most severe side effect associated with buprenorphine is respiratory depression (insufficient breathing). It occurs more often in those who are also taking benzodiazepines, alcohol, or have underlying lung disease. The usual reversal agents for opioids, such as naloxone, may be only partially effective and additional efforts to support breathing may be required. Respiratory depression may be less than with other opioids, particularly with chronic use.

In healthy humans, 0.15 mg/kg of midazolam may cause respiratory depression, which is postulated to be a central nervous system (CNS) effect. When midazolam is administered in combination with fentanyl, the incidence of hypoxemia or apnea becomes more likely. Although the incidence of respiratory depression/arrest is low (0.1–0.5%) when midazolam is administered alone at normal doses, the concomitant use with CNS acting drugs, mainly analgesic opiates, may increase the possibility of hypotension, respiratory depression, respiratory arrest, and death, even at therapeutic doses. Potential drug interactions involving at least one CNS depressant were observed for 84% of midazolam users who were subsequently required to receive the benzodiazepine antagonist flumazenil.

In October 2010, further investigation showed repinotan able to counteract respiratory depression caused by morphine. Repinotan continues to be examined, but has not yet been commercially released.

Because sufentanil is very potent, practitioners must be prepared to reverse the effects of the drug should the patient exhibit symptoms of overdose such as respiratory depression or respiratory arrest. As for all other opioid-based medications, naloxone (trade name Narcan) is the definitive antidote for overdose. Depending on the amount administered, it can reverse the respiratory depression and, if enough is administered, completely reverse the effects of sufentanil.

Sameridine is a 4-phenylpiperidine derivative that is related to the opioid analgesic drug pethidine (meperidine). Sameridine has an unusual pharmacological profile, being both a local anaesthetic and a μ-opioid partial agonist. It is currently under development for use in surgical anasthesia, mainly administered by intrathecal infusion. It produces less respiratory depression than morphine, even at a high dose, and produces no respiratory depression at a low dose.

Severe overdosage may cause tachypnea or hyperpnea, hallucinations, hypertensive crisis, convulsions or delirium, but in some individuals there may be CNS depression with somnolence, stupor or respiratory depression.

In the immediate period after an overdose, monitoring for gastrointestinal symptoms, cardiac dysrhythmias, and respiratory depression is appropriate, and may require gastrointestinal decontamination with activated charcoal or gastric lavage.

Though benzoctamine does not potentiate the effects of alcohol, studies have shown it can potentiate the respiratory depression seen with morphine in rats, while also reducing morphine's analgesic effects.

Fatal opioid overdose typically occurs due to bradypnea, hypoxemia, and decreased cardiac output (hypotension occurs due to vasodilation, & bradycardia further contributes to decreased cardiac output). A potentiation effect occurs when opioids are combined with ethanol, benzodiazepines, or barbiturates, which results in an increased risk for overdose to occur. Substantial tolerance to respiratory depression develops quickly, and tolerant individuals can withstand larger doses. However, tolerance to respiratory depression is lost just as quickly during withdrawal.

A BAC from 0.25% to 0.40% causes stupor, unconsciousness, anterograde amnesia, vomiting (death may occur due to inhalation of vomit (pulmonary aspiration) while unconscious) and respiratory depression (potentially life-threatening). A BAC from 0.35% to 0.80% causes a coma (unconsciousness), life-threatening respiratory depression and possibly fatal alcohol poisoning. With all alcoholic beverages, drinking while driving, operating an aircraft or heavy machinery increases the risk of an accident; many countries have penalties for drunk driving.

It produces similar effects to other opioids, such as analgesia and sedation, along with side effects such as nausea, itching, vomiting and respiratory depression which may be harmful or fatal.

The risk of opioid-related adverse effects such as respiratory depression, falls, cognitive impairment and sedation is increased. Tramadol may interact with other medications and increase the risk for adverse events.

This toxicity with the combination of overdosed dextroproxyphene (with its CNS/respiratory depression/vomit with risk for aspiration pneumonia, as well as cardiotoxicity) and paracetamol-induced liver damage can result in death.

Presumably methylketobemidone produces similar effects to ketobemidone and other opioids, such as analgesia and sedation, along with side effects such as nausea, itching, vomiting and respiratory depression which may be harmful or fatal.

Presumably propylketobemidone produces similar effects to ketobemidone and other opioids, such as analgesia and sedation, along with side effects such as nausea, itching, vomiting and respiratory depression which may be harmful or fatal.

In the second case, because carbon dioxide is rapidly exiting the lungs, alveolar PCO2 would be very low. Note that these two situations, those of respiratory depression and hyperventilation, produce effects that are immediately analogous to the experiment described previously, in which the partial pressures of carbon dioxide were varied and the resulting changes in pH observed. As indicated by the Davenport diagram, respiratory depression, which results in a high PCO2, will lower blood pH. Hyperventilation will have the opposite effects.

Side effects of laudanum are generally the same as with morphine, and include euphoria, dysphoria, pruritus, sedation, constipation, reduced tidal volume, respiratory depression, as well as psychological dependence, physical dependence, miosis, and xerostomia. Overdose can result in severe respiratory depression or collapse and death. The ethanol component can also induce adverse effects at higher doses; the side effects are the same as with alcohol. Long-term use of laudanum in nonterminal diseases is discouraged due to the possibility of drug tolerance and addiction.

In December 2019, the U.S. Food and Drug Administration (FDA) warned about serious breathing issues for those taking gabapentin or pregabalin when used with CNS depressants or for those with lung problems. The FDA required new warnings about the risk of respiratory depression to be added to the prescribing information of the gabapentinoids. The FDA also required the drug manufacturers to conduct clinical trials to further evaluate their abuse potential, particularly in combination with opioids, because misuse and abuse of these products together is increasing, and co-use may increase the risk of respiratory depression. Among 49 case reports submitted to the FDA over the five-year period from 2012 to 2017, twelve people died from respiratory depression with gabapentinoids, all of whom had at least one risk factor.

Woman with myxedema, Bulgaria, 1930s. Myxedema can occur in the lower leg (pretibial myxedema) and behind the eyes (exophthalmos). Severe cases, requiring hospitalization can exhibit signs of hypothermia, hypoglycemia, hypotension, respiratory depression, and coma.

As a result, the elderly, the obese, and those with kidney or liver disease are more vulnerable to prolonged sedation with midazolam. Respiratory depression is also associated with midazolam when given in high doses.

Oral formulations were also available. Piminodine has similar effects to other opioids, and produces analgesia, sedation and euphoria. Side effects can include itching, nausea and potentially serious respiratory depression which can be life-threatening.

Brifentanil (A-3331) is an opioid analgesic that is an analogue of fentanyl and was developed in the early 1990s. Brifentanil is most similar to highly potent, short-acting fentanyl analogues such as alfentanil. The effects of brifentanil are very similar to those of alfentanil, with strong but short lasting analgesia and sedation, and particularly notable itching and respiratory depression. Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening.

Doxapram is an intravenous CNS and respiratory stimulant that is typically used to treat respiratory depression caused by anesthesia or chronic obstructive pulmonary disease. Doxapram can also be used as a treatment for neonatal apnea, but it can be dangerous, so caution must be taken. Doxapram has been used to treat respiratory depression in drug overdoses; however, there are many drugs for which this is not effective. The side effects of Doxapram are rare, however, with overdose, hypertension, tachycardia, tremors, spasticity, and hyperactive reflexes have been seen to occur.

Oliceridine should not be given to people with significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; known or suspected gastrointestinal obstruction; or known hypersensitivity to the medication.

In the event of overdose of AG, drowsiness, nausea, vomiting, hypotension, and respiratory depression may occur. Medical attention should be sought urgently. Treatment of AG overdose can include gastric lavage to decrease absorption and dialysis to enhance elimination.

Therefore, even selective mu agonists can cause analgesia under the right conditions, whereas under others can cause none whatsoever.Alvimopan It is also suggested however that the pain modulated by the μ-opioid receptor and that modulated by the δ-opioid receptor are distinct types, with the assertion that DOR modulates the nociception of chronic pain, while MOR modulates acute pain. Evidence for whether delta agonists produce respiratory depression is mixed; high doses of the delta agonist peptide DPDPE produced respiratory depression in sheep, but in tests on mice the non-peptide delta agonist SNC-80 produced respiratory depression only at the very high dose of 40 mg/kg. In contrast both the peptide delta agonist Deltorphin II and the non-peptide delta agonist (+)-BW373U86 actually stimulated respiratory function and blocked the respiratory depressant effect of the potent μ-opioid agonist alfentanil, without affecting pain relief.

Other studies have suggested a role for 5-HT4 agonists in learning and memory, and BIMU-8 was found to increase conditioned responses in mice, so this drug might also be useful for improving memory in humans. Some other selective 5-HT4 agonists such as mosapride and tegaserod (the only 5-HT4 agonists currently licensed for use in humans) have been found not to reduce respiratory depression. On the other hand, another 5-HT4 agonist, zacopride, does inhibit respiratory depression in a similar manner to BIMU-8. This suggests that either the anti- respiratory depression action is mediated via a specific subtype of the 5-HT4 receptor which is activated by BIMU-8 and zacopride, but not by mosapride or tegaserod, or alternatively there may be functional selectivity involved whereby BIMU-8 and zacopride produce a different physiological response following 5-HT4 binding compared to other 5-HT4 agonists.

A decrease in blood pH due to respiratory depression is called respiratory acidosis. An increase in blood pH due to hyperventilation is called respiratory alkalosis (Fig. 11). Figure 11. Alterations in ventilation may result in respiratory acidosis or respiratory alkalosis.

The advantages of general anaesthesia is that it produces complete akinesia, controlled intraocular pressure and safe operating environment. It is the safest option for bilateral surgery. The complications of general anaesthesia are laryngospasm, hypotension, hypercarbia, respiratory depression and cardiac arrhythmia.

An untreated overdose may be fatal, particularly in children. Premortal signs are respiratory depression and cardiac arrest. A specific antagonist is physostigmine which combines a peripheral and a central action. Carbachol can be used to treat atonic bowel and bladder.

Hydrocodone: Respiratory depression, extreme somnolence progressing towards coma, muscle limpness, cold and clammy skin, slow heart rate, low blood pressure, abrupt loss of heart function, and death may occur. Paracetamol: Liver and kidney failure, low blood sugar coma may occur.

In an effort to fully incapacitate the subject and minimize the risk of legal repercussions, the perpetrator may tend to overdose the subject. The subject may also be allergic to the drug used, may be overly sensitive to its effects and side-effects or may also be voluntarily taking a prescription drug that has dangerous interactions with the administered drug. Respiratory depression, coma with or without lethal outcome may occur, especially when the drug co-administered with alcohol. Especially benzodiazepine drugs are known to be extremely dangerous in combination with alcohol, potentially leading to extreme respiratory depression.

If bupivacaine, commonly used for epidural pain control, is inadvertently administered into a vein, it can cause excitation, nervousness, tingling around the mouth, tinnitus, tremor, dizziness, blurred vision, or seizures as well as central nervous system depression, loss of consciousness, respiratory depression and apnea. Bupivacaine has been implicated in cardiac arrests resulting in death when accidentally administered into a vein instead of the epidural space. Large doses of epidural opioids may cause itching and respiratory depression. The sensation of needing to urinate is often significantly diminished or completely absent after administration of epidural local anesthetics or opioids.

Its current investigation as an antagonist for respiratory depression caused by morphine has shown there to be no serious cardiovascular side effects. However, a slight decrease in blood pressure was a more minor effect. Repinotan has been linked with pupil diameter reduction.

The symptoms of an opiate toxidrome include the classic triad of coma, pinpoint pupils, and respiratory depression as well as altered mental states, shock, pulmonary edema and unresponsiveness. Complications include bradycardia, hypotension, and hypothermia. Substances that may cause this toxidrome are opioids.

Side effects can include skin rash, fever, depression, ulcers or sores in mouth or throat, unusual bleeding or bruising, confusion, fast heartbeat, respiratory depression, swelling of feet or lower legs, dizziness, drowsiness, headache, double vision, clumsiness, constipation, diarrhea, nausea, vomiting, unusual weakness.

This could mean that amitraz' effects are reversible or at least are recoverable.Agin, H., Calkavur, S., Uzun, H., & Bak, M. (2004). Amitraz poisoning: clinical and laboratory findings. Indian Pediatrics, 41(5), 482-486 When an amitraz poisoning is lethal, death results from respiratory depression.

PSA can cause several complications. These include allergic reactions, over-sedation, respiratory depression, and hemodynamic effects. These typically depend on the sedative agent used. Some agents are more likely to cause complications than others, but all sedative agents can cause complications if not used properly.

Benzhydrocodone/APAP is contraindicated in patients with significant respiratory depression, bronchial asthma in an unmonitored setting, known or suspected gastrointestinal obstructions (including paralytic ileus). It is also contraindicated in patients that have experienced hypersensitivity to hydrocodone, acetaminophen or any other component in the formulation.

Side effects in animals include transient hypertension, hypotension, and respiratory depression. Further, the decrease of tissue sensitivity to insulin leads to xylazine-induced hyperglycemia and a reduction of tissue glucose uptake and utilization. The duration of effects in animals lasts up to 4 hours.

By itself it is sold in a long-acting formulation. Common side effects include dizziness, sleepiness, nausea, and constipation. Serious side effects may include abuse, low blood pressure, seizures, QT prolongation, respiratory depression, and serotonin syndrome. Rapidly decreasing the dose may result in opioid withdrawal.

The isolation of morphine in the early 1800s was yet another milestone in obstetric anesthesia. However, the drug would not be widely used until the invention of the hypodermic needle in the 1850s. The first to use a hypodermic syringe in the United States was Fordyce Barker, who actually received the syringe from H.J Simpson as a gift during a visit to Edinburgh. Eventually, the use of morphine for pain control during labor lost favor due to its effects of respiratory depression in the newborn and was replaced largely by meperidine, a synthetic narcotic, first made in Germany in 1939, that had less of an effect on respiratory depression.

CX-546 itself has been investigated for other applications, and most notably has been found to show significant efficacy in reversing the respiratory depression produced by sedative drugs such as opioids and barbiturates. No effective respiratory stimulants are currently marketed for this application, with CX-546 being only the third drug discovered (after BIMU-8 and BW373U86) that effectively relieves the respiratory depression induced by fentanyl without reducing the analgesic effects. CX-546 could be developed for this purpose, although it is more likely Cortex will use newer and more potent analogues such as CX-1739 or CX-1763 which are likely to be more suitable for commercial development.

In the short term, death from solvent abuse occurs most commonly from aspiration of vomit while unconscious or from a combination of respiratory depression and hypoxia, the second cause being especially a risk with heavier-than-air vapors such as butane or gasoline vapor. Deaths typically occur from complications related to excessive sedation and vomiting. Actual overdose from the drug does occur, however, and inhaled solvent abuse is statistically more likely to result in life-threatening respiratory depression than intravenous use of opiates such as heroin. Most deaths from solvent abuse could be prevented if individuals were resuscitated quickly when they stopped breathing and their airway cleared if they vomited.

Remifentanil is a specific μ-receptor agonist. Hence, it causes a reduction in sympathetic nervous system tone, respiratory depression and analgesia. The drug's effects include a dose-dependent decrease in heart rate and arterial pressure and respiratory rate and tidal volume. Muscle rigidity is sometimes noted.

Phenoxyethanol is a vaccine preservative and potential allergen, which may result in a nodular reaction at the site of injection. It reversibly inhibits NMDAR-mediated ion currents. Ingestion may cause central nervous system and respiratory depression, vomiting and diarrhea in infants, particularly when combined with chlorphenesin.

Side effects are rare and may include dizziness and gastrointestinal disturbances such as nausea or vomiting. Adverse effects such as constipation, drowsiness, excitation, ataxia and respiratory depression have been reported occasionally or after large doses. The primary safety concerns with pholcodine revolve around death during general anaesthesia.

Modulation of the α1 subunit is associated with sedation, motor impairment, respiratory depression, amnesia, ataxia, and reinforcing behavior (drug-seeking behavior). Modulation of the α2 subunit is associated with anxiolytic activity and disinhibition. For this reason, certain benzodiazepines may be better suited to treat insomnia than others.

Severe headaches and seizures as a result of increased intracranial pressure are not uncommon. Cardiovascular and pulmonary symptoms may also be present as the brain loses function, but might also be associated with bleeding. They can include: hypertension, respiratory depression, arrhythmia and in severe cases cardiac arrest.

Barbiturate overdose is poisoning due to excessive doses of barbiturates. Symptoms typically include difficulty thinking, poor coordination, decreased level of consciousness, and a decreased effort to breathe (respiratory depression). Complications of overdose can include noncardiogenic pulmonary edema. If death occurs this is typically due to a lack of breathing.

Biperiden mimics an atropine intoxication with mydriasis, dryness of mucous membranes, red face, atonic states of bowels and bladder, and hyperthermia in high doses. Central consequences are agitation, confusion, and hallucinations. An untreated overdose may be fatal, particular in children. Premortal signs are respiratory depression and cardiac arrest.

Benzhydrocodone/APAP has the potential for addiction as well as abuse and misuse, which can result in overdose and death. Serious, life-threatening, or fatal respiratory depression can occur. Accidental ingestion can cause a fatal overdose of hydrocodone. Hydrocodone can cause neonatal opioid withdrawal syndrome when taken during pregnancy.

In common with other opioids, oxymorphone overdosage is characterized by respiratory depression, sleepiness progressing to stupor or coma, skeletal muscle weakness, cold and clammy skin, and sometimes slow heart rate and low blood pressure. In a severe case of overdose, apnea, circulatory collapse, cardiac arrest and death can occur.

The most obvious practical use of BIMU-8 is to combine it with opioid analgesic drugs in order to counteract the dangerous respiratory depression which can occur when opioids are used in excessive doses. BIMU-8 does not affect the pleasurable or painkilling properties of opiates, which means that if combined with BIMU-8, large therapeutic doses of opiates could theoretically be given to humans without risking a decrease in breathing rate. Studies have shown BIMU-8 to be effective in rats at counteracting the respiratory depression caused by the potent opioid fentanyl, which has caused many accidental deaths in humans. However, no human trials of BIMU-8 have yet been carried out.

Allylnorpethidine (WIN-7681) is a 4-phenylpiperidine derivative that is related to the opioid analgesic drug pethidine (meperidine). Allylnorpethidine is an analogue of pethidine where the N-methyl group has been replaced by allyl. In many other opioid derivatives, placing an allyl substituent on the nitrogen instead of a methyl will reverse the normal opioid effects, to produce μ-opioid antagonists which among other things reverse the respiratory depression caused by opioid agonists such as morphine. This is not true with allylnorpethidine, as while it does partially reverse the respiratory depression produced by morphine it is actually an active analgesic and has no antagonistic properties( online version) when administered alone, so is instead a partial agonist.

Trefentanil has very similar effects to alfentanil, much like those of fentanyl itself but more potent and shorter lasting. Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear. The risk of respiratory depression is especially high with potent fentanyl analogues such as alfentanil and trefentanil, and these drugs pose a significant risk of death if used outside of a hospital setting with appropriate artificial breathing apparatus available.

A BAC of 0.09% to 0.25% causes lethargy, sedation, balance problems and blurred vision. A BAC from 0.18% to 0.30% causes profound confusion, impaired speech (e.g., slurred speech), staggering, dizziness and vomiting. A BAC from 0.25% to 0.40% causes stupor, unconsciousness, anterograde amnesia, vomiting, and respiratory depression (potentially life- threatening).

Nicomorphine's side effects are similar to those of other opioids and include itching, nausea and respiratory depression. It is considered by doctors to be one of the better analgesics for the comprehensive mitigation of suffering, as opposed to purely clouding the noxious pain stimulus, in the alleviation of chronic pain conditions.

Etomidate is an imidazole derivative, commonly used for the induction of general anesthesia. Effects kick in almost immediately, within 5-15 seconds, and last 5-15 minutes. Etomidate carries sedative effects only; it does not provide pain relief. Side effects of etomidate include myoclonus (involuntary muscle jerking) and respiratory depression.

Hydrocodone causes respiratory depression and miosis. Hydrocodone decreases gastrointestinal (GI) motility by increasing smooth muscle tone and decreasing propulsive contractions, which may result in constipation. Hydrocodone causes dilation of peripheral blood vessels, which can cause hypotension and syncope. Vasodilation coupled with histamine release can result in pruritus, sweating and flushing.

Buprenorphine/naloxone tablet Buprenorphine is a partial opioid receptor agonist. Unlike methadone and other full opioid receptor agonists, buprenorphine is less likely to cause respiratory depression due to its ceiling effect. Treatment with buprenorphine may be associated with reduced mortality. Buprenorphine under the tongue is often used to manage opioid dependence.

Levodropropizine is a cough suppressant. It is the levo isomer of dropropizine. It acts as a peripheral antitussive, with no action in the central nervous system. It does not cause side effects such as constipation or respiratory depression which can be produced by opioid antitussives such as codeine and its derivatives.

The primary medical use of these drugs is as an anesthetic recovery tool or to treat emergency respiratory depression. Other drugs of this category are prethcamide, pentylenetetrazole, and nikethamide. Nikethamide is now withdrawn due to risk of convulsions. Analeptics have recently been used to better understand the treatment of a barbiturate overdose.

Side effects include irregular heartbeat, respiratory depression, and hepatotoxicity. It appears to be safe in porphyria. It is unclear whether use during pregnancy is harmful to the baby, and it is not generally recommended for use during a C-section. Halothane is a chiral molecule that is used as a racemic mixture.

Intravenous doses of nalmefene have been shown effective at counteracting the respiratory depression produced by opioid overdose.Label information. U.S. Food and Drug Administration When nalmefene is used to treat an opioid overdose, doses of nalmefene greater than 1.5 mg do not appear to give any greater benefit than doses of only 1.5 mg.

Side effects may include respiratory depression (decreased breathing), small pupils, sleepiness, and low blood pressure. The risk of overdose is lower with buprenorphine/naloxone than with methadone. However, people are more likely to stop treatment on buprenorphine/naloxone than methadone. Methadone, or buprenorphine alone, are generally preferred when treatment is required during pregnancy.

Contraindications are severe respiratory or liver impairment and acute alcoholism. There are limited accounts of cross-reactivity with opioids, but there is a possibility. Serious central nervous system (CNS) and respiratory depression may also occur with concurrent use of CNS depressants, ingesting alcohol, or other CNS depressing factors while on buprenorphine/naloxone.

In some individuals, the effect of oxygen on chronic obstructive pulmonary disease is to cause increased carbon dioxide retention, which may cause drowsiness, headaches, and in severe cases lack of respiration, which may lead to death. People with lung ailments or with central respiratory depression, who receive supplemental oxygen, require careful monitoring.

Many overdoses occur in people who misuse their medication after being in withdrawal long enough to lose the tolerance to respiratory depression. Less commonly, massive overdoses have been known to cause circulatory collapse. Opioid overdoses can be rapidly reversed through the use of opioid antagonists, naloxone being the most widely used example.

Death Record On July 3, 1888, Blaylock took a lethal dose of laudanum and alcohol. Her death was ruled as "suicide by opium poisoning". A long time abuser of laudanum and alcohol, it is possible she overdosed by accident and died of respiratory depression. The coroner's report of her death is brief.

Levophenacylmorphan is a morphinan derivative that acts as an opioid agonist. It has potent analgesic effects and is around 10x more potent than morphine. Adverse effects associated with its use are those of the opioids as a whole, including pruritus, nausea, respiratory depression, euphoria and development of tolerance and dependence to its effects.

More severe side effects may include respiratory depression (decreased breathing), seizure, addiction, and psychosis. Other side effects may include high heart rate and blood pressure, trouble sleeping, and, rarely, liver toxicity. When use is stopped, withdrawal symptoms may occur. Deaths have occurred with kratom both by itself and mixed with other substances.

Paradoxical behavior is often not recalled by the patient due to the amnesia-producing properties of the drug. In extreme situations, flumazenil can be administered to inhibit or reverse the effects of midazolam. Antipsychotic medications, such as haloperidol, have also been used for this purpose. Midazolam is known to cause respiratory depression.

Sixteen of these were identified as being caused by Chiropsalmus quadrumanus and four by the Portuguese man o' war (Physalia physalis). All these stings were linear in nature, causing both intense pain and systemic symptoms. Apart from pain, the symptoms include cardiac dysfunction and respiratory depression. The rash lasts for several months.

Cow urine is also used in Myanmar and Nigeria as a folk medicine. In Nigeria, a concoction of leaves of tobacco, garlic and lemon basil juice, rock salt and cow urine is used in an attempt to treat convulsions in children. This has resulted in the death of several children from respiratory depression.

The effect of RWJ-394674 when administered in vivo thus produces potent agonist effects at both μ and δ receptors through the combined actions of the parent drug and its active metabolite, with the δ-agonist effects counteracting the respiratory depression from the μ-opioid effects, and the only prominent side-effect being sedation.

This type of respiration is different to respiratory depression, often seen after morphine administration. Hospices sometimes document the presence of Cheyne–Stokes breathing as a patient nears death, and report that patients able to speak after such episodes do not report any distress associated with the breathing, although it is sometimes disturbing to the family.

Arousal of subjects who received gamma-hydroxybutyric acid sometimes even required a painful stimulus; this was not seen in patients who received triazolam or pentobarbital group. During the heavy sedation with gamma- hydroxybutyric acid, the subjects maintained normal respiration and blood pressure. This is often not the case with opioids as they cause respiratory depression.

Reports of overdose in medical literature are generally from abuse, and often involve other drugs as well. Symptoms include vomiting, excessive sweating, periods of stopped breathing, seizures, agitation, loss of psychomotor skills, and coma. Overdose can lead to death due to respiratory depression. People who overdose may die from asphyxiation from their own vomit.

An overdose or concurrent use with other depressant drugs like benzodiazepines or alcohol commonly results in death from respiratory depression. Opioids act by binding to opioid receptors. They are found principally in the central and peripheral nervous system and the gastrointestinal tract. These receptors mediate both the psychoactive and the somatic effects of opioids.

OxpheneridineCS Patent 109234 is a 4-phenylpiperidine derivative that is related to the opioid analgesic drug pethidine (meperidine). Oxpheneridine is not currently used in medicine. Presumably it has similar effects to other opioid derivatives, such as analgesia, sedation, nausea and respiratory depression. Unlike most opioid derivatives, oxpheneridine is not specifically listed as an illegal drug.

Mitragynine is also known to interact with dopamine D2, adenosine, serotonin, and alpha-2 adrenergic receptors, though the significance of these interactions is not fully understood. Additionally, several reports of mitragynine pharmacology indicate potential biased agonism activity favoring G protein signaling pathways independent of beta - arrestin recruitment, a primary component in opioid induced respiratory depression.

Adverse effects of flunitrazepam include dependency, both physical and psychological; reduced sleep quality resulting in somnolence; and overdose, resulting in excessive sedation, impairment of balance and speech, respiratory depression or coma, and possibly death. Because of the latter, flunitrazepam is commonly used in suicide. When used in late pregnancy, it might cause hypotonia of the foetus.

Repinotan Dose Relationship to Nociception Repinotan has presently been found to be effective at stopping respiratory depression caused by morphine. In addition, it represses nociception at high doses, but enhances nociception at small doses (0.2 micrograms/kg). Repinotan may be applicable to Parkinson's, as it is able to reduce glutamate-induced excitotoxicity and thereby some cell death.

U-69,593 is a drug which acts as a potent and selective κ1-opioid receptor agonist. In animal studies it has been shown to produce antinociception, anti- inflammation, anxiolysis (at low doses), respiratory depression, and diuresis, while having little effect on gastrointestinal motility. It also inhibits the peripheral, though not central secretion of oxytocin and vasopressin in rats.

The sedating/narcotic effect of buprenorphine is increased by other sedating drugs such as other opioids, benzodiazepines, first generation antihistamines, alcohol, and antipsychotics. In addition, opioids and especially benzodiazepines increase the risk for potentially lethal respiratory depression. Strong inhibitors of the liver enzyme CYP3A4, such as ketoconazole, moderately increase buprenorphine concentrations; CYP3A4 inducers can theoretically decrease concentrations of buprenorphine.

Common side effects include vomiting, constipation, sedation, confusion, hallucinations, and injuries related to poor coordination. Serious side effects may include decreased breathing (respiratory depression), serotonin syndrome, low blood pressure, addiction, or coma. Fentanyl works primarily by activating μ-opioid receptors. It is around 100 times stronger than morphine, and some analogues such as carfentanil are around 10,000 times stronger.

Benzodiazepine overdose describes the ingestion of one of the drugs in the benzodiazepine class in quantities greater than are recommended or generally practiced. The most common symptoms of overdose include central nervous system (CNS) depression, impaired balance, ataxia, and slurred speech. Severe symptoms include coma and respiratory depression. Supportive care is the mainstay of treatment of benzodiazepine overdose.

U-47700 has never been studied on humans, but would be expected to produce effects similar to those of other potent opioid agonists, including strong analgesia, sedation, euphoria, constipation, itching and respiratory depression which could be harmful or fatal. Tachycardia was another side effect encountered with U-47700 use. Tolerance and dependence would be expected to develop.

Treatment with high doses of benzodiazepines or barbiturates may cause respiratory depression and respiratory support including intubation and mechanical ventilation is required in these patients. Continuous electroencephalography monitoring is recommended in symptomatic patients. Further treatment for complications of metabolic acidosis, rhabdomyolysis, hyperthermia, or low blood pressure may be required. Metabolic acidosis is treated by administering sodium bicarbonate.

Yet, opioids and benzodiazepines are concurrently dispensed in many settings. As with an overdose of opioid alone, the combination of an opioid and another depressant may precipitate respiratory depression often leading to death. These risks are lessened with close monitoring by a physician, who may conduct ongoing screening for changes in patient behavior and treatment compliance.

Mental Health Research Institute Total Positive and Negative Syndrome Scale scores dropped by 21% compared to placebo. Sodium benzoate, along with phenylbutyrate, is used to treat hyperammonemia. Sodium benzoate, along with caffeine, is used to treat postdural puncture headache, respiratory depression associated with overdosage of narcotics.mayoclinic.org, Caffeine And Sodium Benzoate (Injection Route) and with ergotamine to treat vascular headache.ebi.ac.

Cycloheptane is a cycloalkane with the molecular formula C7H14. Cycloheptane is used as a nonpolar solvent for the chemical industry and as an intermediate in the manufacture of chemicals and pharmaceutical drugs. It may be derived by Clemmensen reduction from cycloheptanone. Cycloheptane vapour is irritating to the eyes and may cause respiratory depression if inhaled in large quantity.

The smallest known dose of TAA that has killed a person is 30 ml. An overdose produces symptoms similar to alcohol poisoning and is a medical emergency due to the sedative/depressant properties which manifest in overdose as potentially lethal respiratory depression. The oral in rats is 1 g/kg. The subcutaneous LD50 in mice is 2.1 g/kg.

Benzhydrocodone/APAP contains acetaminophen, which can cause acute liver failure at high doses (>4000 mg a day in healthy adults). Benzhydrocodone/APAP use with CYP3A4 inhibitors can cause a fatal overdose of hydrocodone. Benzhydrocodone/APAP use with benzodiazepines or other CNS depressants can cause sedation, respiratory depression, coma or death. Benzhydrocodone is a schedule II-controlled substance.

Common adverse effects associated with the use of codeine include drowsiness and constipation. Less common are itching, nausea, vomiting, dry mouth, miosis, orthostatic hypotension, urinary retention, euphoria, and dysphoria. Rare adverse effects include anaphylaxis, seizure, acute pancreatitis, and respiratory depression. As with all opiates, long-term effects can vary, but can include diminished libido, apathy, and memory loss.

Alcohol intoxication, also known as drunkenness or alcohol poisoning, is the negative behavior and physical effects due to the recent drinking of alcohol. Symptoms at lower doses may include mild sedation and poor coordination. At higher doses, there may be slurred speech, trouble walking, and vomiting. Extreme doses may result in a respiratory depression, coma, or death.

Etazocine (NIH-7856) is an opioid analgesic of the benzomorphan family which was never marketed. It acts as a partial agonist of the opioid receptors, with mixed agonist and antagonist effects. In animal studies, it was shown to induce analgesia, dependency, and respiratory depression, with overall effects similar to those of morphine, but with substantially reduced potency in comparison.

Overdose is commonly broken into two categories - liver toxicity (from paracetamol poisoning) and dextropropoxyphene overdose. An overdose of dextropropoxyphene may lead to various systemic effects. Excessive opioid receptor stimulation is responsible for the CNS depression, respiratory depression, aspiration pneumonia, miosis, and gastrointestinal effects seen in propoxyphene poisoning. It may also account for mood- or thought-altering effects.

Combination products are also available with paracetamol (acetaminophen), ibuprofen, naloxone, and aspirin. Common side effects include euphoria, constipation, nausea, vomiting, loss of appetite, drowsiness, dizziness, itching, dry mouth, and sweating. Severe side effects may include addiction, dependence, hallucinations, respiratory depression (a reduction in breathing), bradycardia, and low blood pressure. Those allergic to codeine may also be allergic to oxycodone.

A BAC of 0.09% to 0.25% causes lethargy, sedation, balance problems and blurred vision. A BAC from 0.18% to 0.30% causes profound confusion, impaired speech (e.g. slurred speech), staggering, dizziness and vomiting. A BAC from 0.25% to 0.40% causes stupor, unconsciousness, anterograde amnesia, vomiting, and death may occur due to respiratory depression and inhalation of vomit during unconsciousness.

Overdose and intoxication with benzodiazepines, including clobazam, may lead to CNS depression, associated with drowsiness, confusion, and lethargy, possibly progressing to ataxia, respiratory depression, hypotension, and coma or death. The risk of a fatal outcome is increased in cases of combined poisoning with other CNS depressants, including alcohol.Fruchtengarten L Inchem - Clobazam. Created July 1997, Reviewed 1998.

Combined with an aminoglycoside, it can increase the possibility of ototoxicity, nephrotoxicity and neuromuscular blockage, result in some hearing loss or can continue to deafness. It could be a temporary symptom, but often be permanent. Neuromuscular blockade can lead to skeletal muscle weakness and respiratory depression or paralysis (apnea). Using anti-cholinesterase or calcium salts may release this block.

After being found unconscious at his home in Las Vegas, Nevada, he was transported to Saint Rose Dominican Hospital in Henderson where he later died at age 27. The Canadian Broadcasting Corporation reported on 10 May 2006 that the cause of death was acute pneumonia, exacerbated by respiratory depression brought on by intoxication with the painkiller oxycodone .

Watson SJ, Akil H, Khachaturian H, et al. Opioid systems: Anatomical, physiological and clinical perspectives. In: Opioids Past, Present and Future, Hughes J, Collier HO, Rance MJ, Tyers MB (Eds), Taylor & Francis, London 1984. p.145. Because of its fatal consequences, opioid induced respiratory depression is one of the major limiting factors of its analgesic effects.

Death may occur due to inhalation of vomit (pulmonary aspiration) while unconscious. A BAC from 0.35% to 0.80% causes a coma (unconsciousness), life-threatening respiratory depression and possibly fatal alcohol poisoning. As with all alcoholic beverages, driving under the influence, operating an aircraft or heavy machinery increases the risk of an accident; as such many countries have penalties for drunk driving.

Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Potent pure opioid antagonists such as naltrexone or nalmefene are recommended in the event of accidental human exposure to thiafentanil.Haymerle A, Fahlman A, Walzer C. Human exposures to immobilising agents: results of an online survey. Vet Rec.

Flunitrazepam is a drug that is frequently involved in drug intoxication, including overdose. Overdose of flunitrazepam may result in excessive sedation, or impairment of balance or speech. This may progress in severe overdoses to respiratory depression or coma and possibly death. The risk of overdose is increased if flunitrazepam is taken in combination with CNS depressants such as ethanol (alcohol) and opioids.

Side effects include an irregular heartbeat, respiratory depression, and hepatotoxicity. Like all volatile anesthetics, it should not be used in people with a personal or family history of malignant hyperthermia. It appears to be safe in porphyria. It is unclear whether use during pregnancy is harmful to the baby, and it is not generally recommended for use during a C-section.

Ketamine may be used for postoperative pain management. Low doses of ketamine may reduce morphine use, nausea, and vomiting after surgery. It is especially useful in the prehospital setting, due to its effectiveness and low risk of respiratory depression. Ketamine has similar efficacy to opioids in a hospital emergency department setting for management of acute pain and for control of procedural pain.

Isopropyl alcohol and its metabolite, acetone, act as central nervous system (CNS) depressants. Poisoning can occur from ingestion, inhalation, or skin absorption. Symptoms of isopropyl alcohol poisoning include flushing, headache, dizziness, CNS depression, nausea, vomiting, anesthesia, hypothermia, low blood pressure, shock, respiratory depression, and coma. Overdoses may cause a fruity odor on the breath as a result of its metabolism to acetone.

The observed toxic dose in about 50% of these patients has been 0.3 g to 1.25 g of 12.5% amitraz formulations and 0.5 to 2 g of 20% formulations. The remaining patients took doses up to 10 g. Other frequently occurring symptoms after massive amitraz intoxication are CNS depression, respiratory depression, miosis, hypothermia, hyperglycemia, loss of consciousness, vomiting and bradycardia.

Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear.

Patients with serious medical conditions are at greater chance for negative side effects after receiving PSA. Examples of comorbidities include heart failure, COPD, neuromuscular disease. Use the ASA Classification to predict a patient’s risk for serious complications from PSA, such as hypotension or respiratory depression. Generally, patients with ASA Class III or greater are more likely to suffer such complications.

A BAC of 0.09% to 0.25% causes lethargy, sedation, balance problems and blurred vision. A BAC from 0.18% to 0.30% causes profound confusion, impaired speech (e.g., slurred speech), staggering, dizziness and vomiting. A BAC from 0.25% to 0.40% causes stupor, unconsciousness, anterograde amnesia, vomiting (death may occur due to inhalation of vomit (pulmonary aspiration) while unconscious) and respiratory depression (potentially life-threatening).

Like other TCAs, doxepin is highly toxic in cases of overdose. Mild symptoms include drowsiness, stupor, blurred vision, and excessive dryness of mouth. More serious adverse effects include respiratory depression, hypotension, coma, convulsions, cardiac arrhythmia, and tachycardia. Urinary retention, decreased gastrointestinal motility (paralytic ileus), hyperthermia (or hypothermia), hypertension, dilated pupils, and hyperactive reflexes are other possible symptoms of doxepin overdose.

Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear.

Blisters and burning of the eyes and/or lungs may also occur. This phase is followed by initially myoclonic jerks (muscle jerks) followed by status epilepticus -type epileptic seizure. Death then comes via complete respiratory depression, most likely via the excessive peripheral activity at the neuromuscular junction of the diaphragm. The effects of nerve agents are long lasting and increase with continued exposure.

Dezocine is generally administered intravenously (as Dalgan) to relieve post- operative pain in patients. Because of its high efficacy, it is often administered at a base dose of 0.1 mg/kg. Respiratory depression, a side- effect of dezocine, reaches a ceiling at 0.3-0.4 mg/kg. It has potent analgesic results, and greater pain-relieving ability than morphine, codeine, and pethidine.

Maximum pain relief is generally within an hour with effects up to 24 hours. Side effects may include respiratory depression (decreased breathing), sleepiness, adrenal insufficiency, QT prolongation, low blood pressure, allergic reactions,constipation, and opioid addiction. Among those with a history of seizures, there is a risk of further seizures. Opioid withdrawal following stopping buprenorphine is generally less severe than with other opioids.

Nalbuphine, sold under the brand names Nubain among others, is an opioid analgesic which is used in the treatment of pain. It is given by injection into a vein, muscle, or fat. Side effects of nalbuphine include sedation, sweatiness, clamminess, nausea, vomiting, dizziness, vertigo, dry mouth, and headache. Unlike other opioids, it has little to no capacity for euphoria or respiratory depression.

Prolonged intranasal use often causes opposite effects in the form of rebound congestion with effects such as chronic redness, swelling and rhinitis. Prolonged use thus may result in overuse of the drug. Overdose most often causes slow heart rate. Respiratory depression, low blood pressure, constricted pupils, hypothermia, brief episodes of high blood pressure, drowsiness, headaches and vomiting may also occur.

Betahydroxythiofentanyl has similar effects to fentanyl. Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear.

Doxapram An analeptic, in medicine, is a central nervous system stimulant. The term analeptic typically refers to respiratory analeptics (for example, doxapram). Analeptics are central nervous system stimulants that include a wide variety of medications used to treat depression, attention deficit hyperactivity disorder (ADHD), and respiratory depression. Analeptics can also be used as convulsants, with low doses causing patients to experience heightened awareness, restlessness and rapid breathing.

Use of camazepam is contraindicated in subjects with known hypersensitivity to drug or allergy to other drugs in the benzodiazepine class or any excipients contained in the pharmaceutical form. Use of camazepam should be avoided or carefully monitored by medical professionals in individuals with the following conditions: myasthenia gravis, severe liver deficiencies (e.g., cirrhosis), severe sleep apnea, pre-existing respiratory depression or cronic pulmonary insufficiency.

In humans, GHB has been shown to reduce the elimination rate of alcohol. This may explain the respiratory arrest that has been reported after ingestion of both drugs. A review of the details of 194 deaths attributed to or related to GHB over a ten-year period found that most were from respiratory depression caused by interaction with alcohol or other drugs.Zvosec et al.

Because of their muscle relaxant action, benzodiazepines may cause respiratory depression in susceptible individuals. For that reason, they are contraindicated in people with myasthenia gravis, sleep apnea, bronchitis, and COPD. Caution is required when benzodiazepines are used in people with personality disorders or intellectual disability because of frequent paradoxical reactions. In major depression, they may precipitate suicidal tendencies and are sometimes used for suicidal overdoses.

The various benzodiazepines differ in their toxicity; temazepam appears most toxic in overdose and when used with other drugs. The symptoms of a benzodiazepine overdose may include; drowsiness, slurred speech, nystagmus, hypotension, ataxia, coma, respiratory depression, and cardiorespiratory arrest. A reversal agent for benzodiazepines exists, flumazenil (Anexate). Its use as an antidote is not routinely recommended because of the high risk of resedation and seizures.

Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear. Life-threatening adverse reactions have been observed.

Doxapram is used in intensive care settings to stimulate the respiratory rate in patients with respiratory failure. It may be useful for treating respiratory depression in patients who have taken excessive doses of drugs such as buprenorphine or fentanyl analogues which may fail to respond adequately to treatment with naloxone.Buprenorphine Drug Data Sheet It is equally as effective as pethidine in suppressing shivering after surgery.

In addition to endomorphins, morphine and morphine-like opiates target the μ-opioid receptor. Thus, endomorphins pose significant potential as analgesics and morphine substitutes. In vitro assessment of endomorphins as analgesics reveals similar behavior to morphine and other opiates, where drug tolerance leads to dependence and addiction. Other side effects common to opiates such as vasodilation, respiratory depression, urinary retention, and gastrointestinal reaction develop.

If this system is affected much like the domino effect, many other bodily functions will be triggered. These functions include reduced sexual function as a result of libido reduction, infertility, mood disorders, respiratory depression, osteoporosis and possibly osteopenia. If these functions are affected, the recovery process will be more difficult as it will require constant patient care through the use of more medications, tests and scans.

Early medical trials of humans taking desomorphine have resulted in the finding that, like morphine and most other analgesics of the morphine type, small amounts are highly addictive and tolerance to the drug develops quickly. However, though tolerance to respiratory depression with repeated doses was observed in rats, early clinical trials failed to show any tolerance to these same effects with repeated doses in humans.

Some people may have allergic reactions to codeine, such as the swelling of skin and rashes. Tolerance to many of the effects of codeine, including its therapeutic effects, develops with prolonged use. This occurs at different rates for different effects, with tolerance to the constipation- inducing effects developing particularly slowly for instance. A potentially serious adverse drug reaction, as with other opioids, is respiratory depression.

Codeine is a prodrug which is converted to morphine and acts on μ-opiate receptors. It is converted to morphine by metabolism of CYP2D6 enzymes. Individuals who have lower CYP2D6 activity may not metabolize codeine efficiently enough to experience its analgesic effects. Conversely, individuals with higher CYP2D6 activity may metabolize the drug too quickly and experience dose-related side effects such as sedation and respiratory depression.

Isoflurane, sold under the brand name Forane among others, is a general anesthetic. It can be used to start or maintain anesthesia, however other medications are often used to start anesthesia rather than isoflurane, due to airway irritation with isoflurane. Isoflurane is given via inhalation. Side effects of isoflurane include a decreased ability to breathe (respiratory depression), low blood pressure, and an irregular heartbeat.

An overdose can lead to nervous system shutdown, coma and death. Additional effects are delirium, convulsions, hypertonia, hyperreflexia, vomiting, kidney failure, coma, and death through cardiac or respiratory arrest. It resembles barbiturate poisoning, but with increased motor difficulties and a lower incidence of cardiac or respiratory depression. The standard single tablet adult dose of Quaalude brand of methaqualone was 300 mg when made by Lemmon.

Conversely patients who are poor metabolizers should be given minimal amounts of opioids such as tramadol in order to avoid respiratory depression. Information regarding a patient's CYP2D6 expression can be found by running a genomic test such as 23andMe. This information is also helpful to healthcare professionals so they may modify the dosing of other drugs that may have drug-drug interactions with opioids such as rifampin.

Eyedea died in his sleep on October 16, 2010 in his Saint Paul apartment. He was found dead by his mother, according to a friend. Cause of death was released November 18, 2010 and ruled an accident, from respiratory depression, caused by opiate derivatives, according to the Ramsey County Medical Examiner's Office. The specific drugs found in Larsen's system have not been revealed to the public.

Delorazepam hosts all the classic side-effects of GABAA full agonists (such as most benzodiazepines). These include sedation/somnolence, dizziness/ataxia, amnesia, reduced inhibition, increased talkativeness/sociability, euphoria, impaired judgement, hallucinations, and respiratory depression. Paradoxical reactions including increased anxiety, excitation, and aggression may occur and are more common in elderly, pediatric, and schizophrenic patients. In rare instances, delorazepam may cause suicidal ideation and actions.

Other supportive measures such as the use of vasopressors and oxygen may be indicated to treat cardiac and/or pulmonary failure. Cardiac arrhythmias or arrest will require advanced life-saving measures. Intravenous naloxone or nalmefene, quick-acting opioid antagonists, are the first-line treatment to reverse respiratory depression caused by an overdose of opium tincture. Gastric lavage may be of some use in certain cases.

Romifidine is a drug that is used in veterinary medicine as a sedative mainly in large animals such as horses, although it may be used in a wide variety of species. It is not used in humans, but is closely related in structure to the commonly used drug clonidine. Romifidine acts as an agonist at the α2 adrenergic receptor subtype. Side effects can include bradycardia and respiratory depression.

All parts of the plant, including its tomato- like fruit, are poisonous to varying degrees due to the presence of solanine glycoalkaloids which is a toxic alkaloid and one of the plant's natural defenses. While ingesting any part of the plant can cause fever, headache, scratchy throat, nausea, vomiting, and diarrhea, ingesting the fruit can cause abdominal pain, circulatory and respiratory depression, or even death. : Nettle . Retrieved 2013-JUN-25.

Side effects increase with dosage and include drowsiness, mild stomach ache, lethargy, urinary retention, bradypnea, constipation, nausea, respiratory depression and death. Nausea can be attributed to the presence of noscapine and is more common in first-time or inexperienced users. At high doses, the side effects are dangerous and can cause death through respiratory arrest or inhalation of vomit. Constipation often results from use, as with any opiate.

The adverse effects of pethidine administration are primarily those of the opioids as a class: nausea, vomiting, dizziness, diaphoresis, urinary retention, and constipation. Due to moderate stimulant effects mediated by dopamine and norepinephrine, sedation is less likely compared to other opioids. Unlike other opioids, it does not cause miosis because of its anticholinergic properties. Overdose can cause muscle flaccidity, respiratory depression, obtundation, cold and clammy skin, hypotension, and coma.

Propofol is a non-barbiturate derivative that is thought to act by stimulating inhibitory GABA receptors and blocking excitatory NMDA receptors. It takes 40 seconds for the effects of propofol to kick in, and effects lasts 6 minutes. Propofol has both sedative and amnestic effects, but provides no analgesia. Adverse effects to look out for include hypotension (low blood pressure) and respiratory depression, manifested as mild drops in oxygen saturation levels.

Paracetamol is recommended for the pain treatment. Although nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and opioids such as codeine and tramadol are equally effective, precautions have to be taken because NSAIDs can cause peptic ulcer disease and are bad for kidneys. Opioids can cause respiratory depression for those who are vulnerable. Similarly, in children, paracetamol and NSAIDs can be used except for codeine need to be used with precautions.

Chronic use is reported to be associated with physical deterioration, dependence, abscesses, and skin ulceration, which can be physically debilitating and painful. Hypertension followed by hypotension, bradycardia, and respiratory depression lower tissue oxygenation in the skin. Thus, chronic use of xylazine can progress the skin oxygenation deficit, leading to severe skin ulceration. Lower skin oxygenation is associated with impaired healing of wounds and a higher chance of infection.

Patients already suffering from debilitation are at a much higher risk of respiratory depression. Nonopioid analgesics should be considered in this population. Elderly patients are much more sensitive to adverse effects, such as falls, cognitive impairment and constipation, and should be monitored for such. Decreased renal function associated with aging leads to decreased clearance of the drug, resulting in narrow therapeutic windows and increasing the danger of overdose.

Naloxone effectively treats CNS and respiratory depression caused by opiate/opioid overdose. It allows adequate ventilation for impacted patients, and health professionals administer it intravenously. Naloxone has well-documented effectiveness; as a matter of fact, 575/609 patients (mainly with heroin overdose) showed improved consciousness and respiration within five minutes of treatment. The major downsides to naloxone are the hypersensitivity from the patient and its reaction with substances contaminating opioids/opiates.

Eseroline is a drug which acts as an opioid agonist. It is a metabolite of the acetylcholinesterase inhibitor physostigmine but unlike physostigmine, the acetylcholinesterase inhibition produced by eseroline is weak and easily reversible, and it produces fairly potent analgesic effects mediated through the μ-opioid receptor. This mixture of activities gives eseroline an unusual pharmacological profile, although its uses are limited by side effects such as respiratory depression and neurotoxicity.

A BAC from 0.35% to 0.80% causes coma, life-threatening respiratory depression and possibly fatal alcohol poisoning. The operation of vehicles or machinery while drunk increases the risk of accident, and many countries have laws against drinking and driving. Wines can trigger positive emotions in a short period of time, such as feelings of relaxation and comfort. The context and quality of wine can affect the mood and emotions, too.

It is also stereoselective, with one isomer being much more active. When modeled in three dimensions, the alkene overlays the alkenes found in 14-cinnamoyloxycodeinone and in 14-allyloxycodeinone, re-enforcing the presence of an interaction of the alkene. Allylprodine produces similar effects to other opioids, such as analgesia and sedation, along with side effects such as nausea, itching, vomiting and respiratory depression which may be harmful or fatal.

DPI-3290 was discovered by scientists at Burroughs Wellcome and licensed to Delta Pharmaceutical US Patent 5552404 - Opioid compounds and methods for using same and is a drug that is used in scientific research. It is a potent analgesic drug, which produces little respiratory depression. DPI-3290 acts as an agonist at both μ- and δ-opioid receptor, with an IC50 of 6.2nM at μ and 1.0nM at δ.

Hydrocodone is in U.S. Food and Drug Administration (FDA) pregnancy category C. No adequate and well-controlled studies in humans have been conducted. A newborn of a mother taking opioid medications regularly prior to the birth will be physically dependent. The baby may also exhibit respiratory depression if the opioid dose was high. An epidemiological study indicated that opioid treatment during early pregnancy results in increased risk of various birth defects.

Trefentanil (A-3665) is an opioid analgesic that is an analogue of fentanyl and was developed in 1992. Trefentanil is most similar to short-acting fentanyl analogues such as alfentanil. In comparative studies, trefentanil was slightly more potent and shorter acting than alfentanil as an analgesic, but induced significantly more severe respiratory depression. For this reason trefentanil has not been adopted for clinical use, although it is still used in research.

Ocfentanil (INN; also called A-3217) is a potent synthetic opioid structurally related to fentanyl that was developed in the early 1990s as one of a series of potent naloxone-reversible opioids in an attempt to obtain an opioid that had better therapeutic indices in terms of cardiovascular effects and respiratory depression as compared to fentanyl. Ocfentanil was never developed for medical use despite reasonable results in human clinical trials, but subsequently started to be sold as a designer drug starting in around 2013. Study of the analgesic activity of ocfentanil using the mouse hot plate test (55 °C) gave an ED50 of 0.007 mg/kg compared to 0.018 mg/kg for fentanyl; ocfentanil being approximately 2.5 times as potent as fentanyl in this test. In human volunteers ocfentanil induces effective analgesia at 1 μg/kg, while in doses up to 3 μg/kg, analgesia and respiratory depression occurred in a dose-dependent manner.

Hydroxypethidine (Bemidone) is an opioid analgesic that is an analogue of the more commonly used pethidine (meperidine). Hydroxypethidine is significantly less potent than meperidine as an analgesic, (0.3x meperidine in potency) although it also has NMDA antagonist properties like its close relative ketobemidone. Hydroxypethidine has similar effects to other opioids, and produces analgesia, sedation and euphoria. Side effects can include itching, nausea and potentially serious respiratory depression which can be life- threatening.

Paromomycin belongs to the aminoglycoside drug class and therefore are toxic to the kidneys and to ears. These toxicities are additive and are more likely to occur when used with other drugs that cause ear and kidney toxicity. Concurrent use of foscarnet increases the risk of kidney toxicity. Concurrent use of colistimethate and paromomycin can cause a dangerous slowing of breathing known as respiratory depression, and should be done with extreme caution if necessary.

Central nervous system side effects are quite frequently noted and encompass speech and visual disturbances, mental depression and confusion, hallucinations, headache, insomnia and exacerbation or precipitation of seizures, and increased nervousness. Infrequent cases of respiratory depression or a feeling of suffocation have been observed. Dantrolene often causes sedation severe enough to incapacitate the patient to drive or operate machinery. Gastrointestinal effects include bad taste, decreased appetite, nausea, vomiting, abdominal cramps, and diarrhea.

The safety profile of oliceridine is similar to other opioids. As with other opioids, the most common side effects of oliceridine are nausea, vomiting, dizziness, headache and constipation. Prolonged use of opioid analgesics during pregnancy can result in neonatal opioid withdrawal syndrome. Olinvyk carries a boxed warning about addiction, abuse and misuse; life-threatening respiratory depression; neonatal opioid withdrawal syndrome; and risks from concomitant use with benzodiazepines or other central nervous system depressants.

3-Methylbutyrfentanyl (3-MBF) is an opioid analgesic that is an analog of butyrfentanyl. Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear.

GAL-021 is a drug related to almitrine which acts as a respiratory stimulant, with its mechanism of action primarily thought to involve blocking the BKCa potassium channel, although secondary mechanisms may also be involved. It was developed by Galleon Pharmaceuticals, and is being tested in clinical trials for potential uses in post-operative care, as well as more generally to counteract the respiratory depression which can be a side effect of opioid analgesic drugs.

It also has no role in the management of unknown overdoses. In addition, if full airway protection has been achieved, a good outcome is expected, and therefore flumazenil administration is unlikely to be required. Flumazenil is very effective at reversing the CNS depression associated with benzodiazepines but is less effective at reversing respiratory depression. One study found that only 10% of the patient population presenting with a benzodiazepine overdose are suitable candidates for flumazenil.

This research was described as a compelling example of how modern high-throughput screening techniques can be used to discover new chemotypes with specific activity profiles, even at targets such as the μ-opioid receptor which have already been thoroughly investigated. More recent research has suggested however that at higher doses, PZM21 is capable of producing classic opioid side effects such as respiratory depression and development of tolerance and may have only limited functional selectivity.

A BAC from 0.35% to 0.80% causes a coma (unconsciousness), life- threatening respiratory depression and possibly fatal alcohol poisoning. There are a number of factors that affect when your BAC will reach or exceed 0.08, including how much you weigh, the time frame that you have been drinking, and if you ate within the time of drinking. A 170 lbs male can drink more than a 135 lbs female, before being over the BAC level.

Dexmedetomidine is most often used in the intensive care setting for light to moderate sedation. It is not recommended for long-term deep sedation. A feature of dexmedetomidine is that it has analgesic properties in addition to its role as a hypnotic, but is opioid sparing; thus, it is not associated with significant respiratory depression (unlike propofol). Many studies suggest dexmedetomidine for sedation in mechanically ventilated adults may reduce time to extubation and ICU stay.

Opioids are frequently used non-medically for their euphoric effects or to prevent withdrawal. Side effects of opioids may include itchiness, sedation, nausea, respiratory depression, constipation, and euphoria. Long- term use can cause tolerance, meaning that increased doses are required to achieve the same effect, and physical dependence, meaning that abruptly discontinuing the drug leads to unpleasant withdrawal symptoms. The euphoria attracts recreational use and frequent, escalating recreational use of opioids typically results in addiction.

It is important to keep track of the patient's vital signs, especially oxygen saturation and blood pressure when giving PSA to ensure adequate cardiopulmonary function. Monitors are also useful for PSA safety. These include cardiac monitoring such as electrocardiogram, pulse oximetry, blood pressure cuff, and an end tidal carbon dioxide monitor. Deep sedation resulting in respiratory depression can cause some quantitative changes to these monitors, hence why it is important to monitor them.

One of the first things that can be seen is a rise in end tidal carbon dioxide. This happens well before a drop in oxygen saturation. Depending on the how substantial the respiratory depression, the physician can use supplemental oxygen or other airway interventions to stabilize the patient.. Visual assessment is also an important part of PSA. To quantify the level of consciousness, the physician uses different levels of stimulation and observes the patient's response.

Xylazine overdose is usually fatal in humans. Because it is used as a drug adulterant, the symptoms caused by the drugs accompanying xylazine administration vary between individuals. The most common side effects in humans associated with xylazine administration include bradycardia, respiratory depression, hypotension, transient hypertension secondary to vagus nerve stimulation, and other changes in cardiac output. Xylazine significantly decreases heart rate in animals that are not premedicated with medications that have anticholinergic effects.

Zacopride is a potent antagonist at the 5-HT3 receptor and an agonist at the 5-HT4 receptor. It has anxiolytic and nootropic effects in animal models, with the (R)-(+)-enantiomer being the more active form. It also has antiemetic and pro-respiratory effects, both reducing sleep apnea and reversing opioid- induced respiratory depression in animal studies. Early animal trials have also revealed that administration of zacopride can reduce preference for and consumption of ethanol.

Common side effects associated to opioid use include: sedation, nausea, dizziness, vomiting, constipation, physical dependence, tolerance, and respiratory depression. Of these the most common are constipation & nausea and there are no development of tolerance to these side effects. This is why stool softeners or laxatives (polyethylene glycol, docusate, and senna) are often prescribed with opioids. Less common side effects include: delayed gastric emptying, hyperalgesia, immunologic and hormonal dysfunction, muscle rigidity, and myoclonus.

Zolpidem should not be taken by people with obstructive sleep apnea, myasthenia gravis, severe liver disease, respiratory depression; or by children, or people with psychotic illnesses. It should not be taken by people who are or have been addicted to other substances. Use of zolpidem may impair driving skills with a resultant increased risk of road traffic accidents. This adverse effect is not unique to zolpidem, but also occurs with other hypnotic drugs.

Its use in pregnant and lactating women is advised against, although the available evidence suggests it is unlikely to cause negative effects on fetal development. The lack of evidence from human studies, however, means it is currently impossible to rule out any risk to the fetus and it is known to cross the placenta. Doxepin is secreted in breast milk and neonatal cases of respiratory depression in association with maternal doxepin use have been reported.

Furethidine is a 4-phenylpiperidine derivative that is related to the clinically used opioid analgesic drug pethidine (meperidine). Furethidine is not currently used in medicine and is a Class A/Schedule I drug which is controlled under UN drug conventions. It has similar effects to other opioid derivatives, such as analgesia, sedation, nausea and respiratory depression. In the United States it is a Schedule I Narcotic controlled substance with the ACSCN of 9626.

Morpheridine (Morpholinoethylnorpethidine) is a 4-phenylpiperidine derivative that is related to the clinically used opioid analgesic drug pethidine (meperidine). It is a strong analgesic with around 4 times the potency of pethidine, and unlike pethidine, does not cause convulsions, although it produces the standard opioid side effects such as sedation and respiratory depression. Morpheridine is not currently used in medicine and is a Schedule I drug which is controlled under UN drug conventions.

Diphenoxylate is used to treat diarrhea in adults; it is only available as a combination drug with a subtherapeutic dose of atropine to prevent abuse. It should not be used in children due to the risk of respiratory depression. It does not appear harmful to a fetus but the risks have not been fully explored. It should not be taken with other central depressants like alcohol, as they can increase its risks.

The drug label has warnings with regard to the risk of respiratory depression, anticholinergic toxicity and opioid overdose, the risk of dehydration and electrolyte imbalance that people with severe diarrhea always run, and toxic megacolon in people with ulcerative colitis. Other adverse effects include numbness in the hands and feet, euphoria, depression, lethargy, confusion, drowsiness, dizziness, restlessness, headache, hallucinations, edema, hives, swollen gums, itchiness, vomiting, nausea, loss of appetite, and stomach pain.

After nighttime administration of midazolam, residual 'hangover' effects, such as sleepiness and impaired psychomotor and cognitive functions, may persist into the next day. This may impair the ability of users to drive safely and may increase the risk of falls and hip fractures. Sedation, respiratory depression and hypotension due to a reduction in systematic vascular resistance, and an increase in heart rate can occur. If intravenous midazolam is given too quickly, hypotension may occur.

Fewer visual and auditory hallucinations/disruptions occur with the use of zaleplon than with other Z-drugs, like zolpidem. Anterograde amnesia can occur and can cause one to lose track of the amount of zaleplon already ingested, prompting the ingesting of more than originally planned. However, continuous ingestion is extremely unlikely precisely because of zaleplon's quick onset of action. The combination of alcohol and zaleplon can result in fatal respiratory depression and asphyxiation from vomiting.

It may result in an impaired ability to drive the next day, though it has proven promising when compared to other sedative/hypnotics and next-day residual sedation. It may have advantages over benzodiazepines with fewer adverse effects. Neither zaleplon, nor any nonbenzodiazepine hypnotic class medication should be combined with alcohol, as both modulate GABAA receptor sites, and in a synergistic manner increase the chances of fatal respiratory depression and asphyxiation from vomiting.

Each of the many different synthetic cannabinoids can have different effects at different dosages. The CDC described synthetic cannabinoid overdoses between 2010 and 2015 and of 277 drug overdose patients who reported synthetic cannabinoid as the sole agent, 66.1% reported problems in the central nervous system (e.g., agitation, coma, toxic psychosis), 17% reported cardiovascular problems (e.g., tachycardia, bradycardia), 7.6% reported pulmonary problems (5.4% of which had respiratory depression), and 4% reported acute kidney injury.

Oxeladin is a cough suppressant. It is a highly potent and effective drug used to treat all types of cough of various etiologies. It is not related to opium or its derivatives, so treatment with oxeladin is free of risk of dependence or addiction. Oxeladin has none of the side effects (such as hypnosis, respiratory depression, tolerance, constipation and analgesia) which are present when common antitussives, such as codeine and its derivatives, are used.

Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear. The risk of respiratory depression is especially high with potent fentanyl analogues such as alfentanil and brifentanil, and these drugs pose a significant risk of death if used outside of a hospital setting without an appropriate artificial breathing apparatus available.

Common side effects of brotizolam are typical of hypnotic benzodiazepines and are related to CNS depression, and include somnolence, ataxia, headache, anterograde amnesia, dizziness, fatigue, impairment of motor functions, slurred speech, confusion, and clumsiness. Less common side effects include hypotension, respiratory depression, hallucinations, nausea and vomiting, palpitations, and paradoxical reactions (i.e. aggression, anxiety, violent behavior, etc.). Brotizolam can cause residual side effects the next day such as impaired cognitive and motor functions as well as drowsiness.

In the workplace, people may be exposed to enflurane by breathing it in as a waste anaesthetic gas, swallowing it, eye contact, or skin contact. The National Institute for Occupational Safety and Health (NIOSH) has set a recommended exposure limit (REL) for exposure to waste anaesthetic gas of 2 ppm (15.1 mg/m3) over a 60-minute period. Symptoms of occupational exposure to enflurane include eye irritation, central nervous system depression, analgesia, anesthesia, convulsions, and respiratory depression.

UNODC Bulletin on Narcotics, 1953; Issue 2:36-38. Acetylmorphone is not currently used in medicine, but may have a higher bioavailability than hydromorphone due to its greater lipid solubility, and hence is likely to be more potent than the parent drug, although probably slower acting due to the requirement for deacetylation to the active metabolite hydromorphone. It can be expected to have similar side effects to other opiates, which would include itching, nausea and respiratory depression.

Forensic photographs were shown to the jury on Thursday, February 7, and the jury reacted emotionally. Barbara Sampson of the medical examiner's office said on the stand that the bruises were only hours or days old. It was indicated that a head blow Brown received two days before she died was the cause of her death. "She was unconscious and going into respiratory depression for at least several hours before she died," Dr. Barbara Sampson informed jurors.

Since acetyldihydrocodeine has higher lipophilicity than codeine and is converted into dihydromorphine rather than morphine, it can be expected to be more potent and longer-lasting. It also has a higher bioavailability than codeine. Side effects are similar to those of other opiates and include itching, nausea and respiratory depression. Although an opioid of low to moderate strength and use in medicine elsewhere in the world, acetyldihydrocodeine is a Schedule I controlled substance in the United States.

Dexmedetomidine is a highly selective α2-adrenergic agonist. Unlike opioids and other sedatives such as propofol, dexmedetomidine is able to achieve its effects without causing respiratory depression. Dexmedetomidine induces sedation by decreasing activity of noradrenergic neurons in the locus ceruleus in the brain stem, thereby increasing the activity of inhibitory gamma- aminobutyric acid (GABA) neurons in the ventrolateral preoptic nucleus. In contrast, other sedatives like propofol and benzodiazepines directly increase activity of gamma-aminobutyric acid neurons.

A narcotic antagonist such as naloxone is indicated to reverse respiratory depression and other effects of pethidine. Serotonin syndrome has occurred in patients receiving concurrent antidepressant therapy with selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase inhibitors, or other medication types (see Interactions below). Convulsive seizures sometimes observed in patients receiving parenteral pethidine on a chronic basis have been attributed to accumulation in plasma of the metabolite norpethidine (normeperidine). Fatalities have occurred following either oral or intravenous pethidine overdose.

US Patent 7,208,604 Alfentanil has a pKa of approximately 6.5, which leads to a very high proportion of the drug being uncharged at physiologic pH. This unique characteristic is responsible for its rapid onset. It is an agonist at mu opioid receptors. While alfentanil tends to cause fewer cardiovascular complications than other similar drugs such as fentanyl and remifentanil, it tends to give stronger respiratory depression and so requires careful monitoring of breathing and vital signs.

3-Allylfentanyl is an opioid analgesic that is an analogue of fentanyl. 3-Allylfentanyl has similar effects to fentanyl. Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear.

As with other opioid medications, tolerance and dependence usually develop with repeated doses. There is some clinical evidence that tolerance to analgesia is less with methadone compared to other opioids; this may be due to its activity at the NMDA receptor. Tolerance to the different physiological effects of methadone varies; tolerance to analgesic properties may or may not develop quickly, but tolerance to euphoria usually develops rapidly, whereas tolerance to constipation, sedation, and respiratory depression develops slowly (if ever).

Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Irresponsible use of fentanyl analogues administrated in several times larger doses than recommended, have ended up in a death of hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear.

Butalbital can cause dependence or addiction. Mixing with alcohol, benzodiazepines, and other CNS- depressants increases the risk of intoxication, increases respiratory depression, and increases liver toxicity when in combination with paracetamol (acetaminophen). Use of butalbital and alcohol, benzodiazepines, and other CNS-depressants can contribute to coma, and in extreme cases, fatality. When benzodiazepines are co-administered with barbiturates, the sum effect of the drugs is far greater than would be expected considering the effect of both drugs separately.

One of the reasons apomorphine is a preferred drug is its reversibility: in cases of prolonged vomiting, the apomorphine can be reversed with dopamine antagonists like the phenothiazines (for example, acepromazine). Giving apomorphine after giving acepromazine, however, will no longer stimulate vomiting, because apomorphine's target receptors are already occupied. An animal who undergoes severe respiratory depression due to apomorphine can be treated with naloxone. Apomorphine does not work in cats, who have too few dopamine receptors.

In cases of a suspected lorazepam overdose, it is important to establish whether the person is a regular user of lorazepam or other benzodiazepines since regular use causes tolerance to develop. Also, one must ascertain whether other substances were also ingested. Signs of overdose range through mental confusion, dysarthria, paradoxical reactions, drowsiness, hypotonia, ataxia, hypotension, hypnotic state, coma, cardiovascular depression, respiratory depression, and death. However, fatal overdoses on benzodiazepines alone are rare and less common than with barbiturates.

In a clinical context the route of administration is most commonly intravenous injection; it may also be given by intramuscular or subcutaneous injection, as well as orally in the form of tablets. The onset of effects is usually rapid and lasts for a few hours. Common side effects include respiratory depression (decreased breathing), dry mouth, drowsiness, impaired mental function, constipation, and addiction. Side effects of use by injection can include abscesses, infected heart valves, blood-borne infections, and pneumonia.

Life-threatening overdose of opium tincture owes to the preparation's morphine content. Morphine produces a dose- dependent depressive effect on the respiratory system, which can lead to profound respiratory depression, hypoxia, coma and finally respiratory arrest and death. If overdose of opium tincture is suspected, rapid professional intervention is required. The primary concern is re-establishing a viable airway and institution of assisted or controlled ventilation if the patient is unable to breathe on his own.

Thiafentanil (A-3080, Thianil) is a highly potent opioid analgesic that is an analog of fentanyl, and was invented in 1986. It is similar to carfentanil though with a faster onset of effects, shorter duration of action and a slightly lesser tendency to produce respiratory depression. It is used in veterinary medicine to anesthetise large animals such as impala, usually in combination with other anesthetics such as ketamine, xylazine or medetomidine to reduce the prevalence of side effects such as muscle rigidity.

When taken in prescribed quantities, cough syrup is quite safe but dangers arise in higher doses since promethazine is a depressant of the central nervous system (CNS), and codeine is a respiratory depressant. When codeine is taken in very large amounts, it can cause one to stop breathing. Using alcohol and other drugs alongside lean increases the chance of respiratory depression. Fallieras stated that the concoction does not cause seizures itself, but increases their likelihood in those susceptible to them.

Pralidoxime is only effective in organophosphate toxicity. It has no beneficial effects if the acetylcholinesterase enzyme is carbamylated, as occurs with neostigmine, pyridostigmine, or insecticides such as carbaryl. Pralidoxime has an important role in reversing paralysis of the respiratory muscles but due to its poor blood–brain barrier penetration, it has little effect on centrally-mediated respiratory depression. Atropine, which is choice of drug to antagonise the muscarinic effects of organophosphates, is administered even before pralidoxime during the treatment of organophosphate poisoning.

Overdose of GHB can sometimes be difficult to treat because of its multiple effects on the body. GHB tends to cause rapid unconsciousness at doses above 3500 mg, with single doses over 7000 mg often causing life-threatening respiratory depression, and higher doses still inducing bradycardia and cardiac arrest. Other side-effects include convulsions (especially when combined with stimulants), and nausea/vomiting (especially when combined with alcohol). The greatest life threat due to GHB overdose (with or without other substances) is respiratory arrest.

Oliceridine is a μ-opioid receptor biased agonist developed by Trevena. In cell-based (in vitro) research, oliceridine elicits robust G protein signaling, with potency and efficacy similar to that of morphine, but with less β-arrestin 2 recruitment and receptor internalization . However, recent reports highlight that this might be due to its low intrinsic efficacy , rather than functional selectivity or 'G protein bias' as initially reported. In vivo, it may have fewer adverse effects (including respiratory depression and constipation) compared with morphine.

Dipropanoylmorphine is slightly slower acting than diamorphine and morphine, but longer lasting, and is slightly more potent by weight due to its higher lipophilicity. Side effects are generally relatively mild for an opioid with a similar profile to morphine/heroin and typical of other opioids. The most common side effects associated with dipropanoylmorphine are itching, nausea and respiratory depression. Dipropanoylmorphine is prepared by reacting morphine with propionic anhydride, in an analogous manner to how heroin is produced by reacting morphine with acetic anhydride.

It also contains the alkaloid gloriocine. Within a few hours of the ingestion of a toxic amount of plant material, a victim may experience nausea, vomiting, numbness, and tingling around the mouth, burning in the throat, abdominal pain, and bloody diarrhea, which leads to dehydration. As the toxic syndrome progresses, rhabdomyolysis, ileus, respiratory depression, hypotension, coagulopathy, haematuria, altered mental status, seizures, coma, and ascending polyneuropathy may occur. Longer-term effects include peeling of the skin and prolonged vaginal bleeding in women.

The FDA reviewed the results of two randomized, double-blind, placebo-controlled clinical trials in healthy people, three observational studies, and several studies in animals. One trial showed that using pregabalin alone and using it with an opioid pain reliever can depress breathing function. The other trial showed gabapentin alone increased pauses in breathing during sleep. The three observational studies at one academic medical center showed a relationship between gabapentinoids given before surgery and respiratory depression occurring after different kinds of surgeries.

Dexmedetomidine, sold under the trade name Precedex among others, is an anxiety reducing, sedative, and pain medication. Dexmedetomidine is notable for its ability to provide sedation without risk of respiratory depression (unlike other commonly used drugs such as propofol and fentanyl) and can provide cooperative or semi-rousable sedation. Similar to clonidine, it is a sympatholytic drug that acts an agonist of α2-adrenergic receptors in certain parts of the brain. Veterinarians use dexmedetomidine for similar purposes in treating cats, dogs, and horses.

It is essential for the administering medical professional to be trained in airway management with readily available airway equipment because the drug causes significant respiratory depression and may cause respiratory arrest if given too rapidly or in too high a dose. Other opioid side effects such as heart rhythm irregularity, blood pressure changes and nausea/vomiting can also be present in patients given this drug and should be dealt with accordingly. Sufentanil has been associated with extremely rare instances of life- threatening anaphylaxis.

4-NEMD is a potent sedative drug which acts as a selective alpha-2 adrenergic agonist. It is closely related to dexmedetomidine but is several times more potent. Like other alpha-2 agonists, it produces sedative and muscle relaxant effects but without producing respiratory depression. It is not currently used in medicine but has been researched as the basis for a potential new generation of alpha-2 agonist drugs, which may have selectivity for the different subtypes of the alpha-2 receptor.

Through this pathway, when opiates bind to and activate the mu receptor, there is a decrease transmission of pain signalling. This pathway targeted for the analgesia properties that opiates are known and used for. Other clinically important roles of mu are its involvement in respiratory and cardiovascular functions, gastrointestinal peristalsis, feeding, and mood. These other pathways are important because they explain the side effects of opiate use like respiratory depression at high doses, constipation with chronic use, and addicting properties.

People should not consume alcohol while taking zolpidem, and should not be prescribed opioid drugs nor take such illicit drugs recreationally. Opioids can also increase the risk of becoming psychologically dependent on zolpidem. Use of opioids with zolpidem increases the risk of respiratory depression and death. The US Food and Drug Administration (FDA) is advising that the opioid addiction medications buprenorphine and methadone should not be withheld from patients taking benzodiazepines or other drugs that depress the central nervous system (CNS).

The FDA reviewed the results of two randomized, double-blind, placebo-controlled clinical trials in healthy people, three observational studies, and several studies in animals. One trial showed that using pregabalin alone and using it with an opioid pain reliever can depress breathing function. The other trial showed gabapentin alone increased pauses in breathing during sleep. The three observational studies at one academic medical center showed a relationship between gabapentinoids given before surgery and respiratory depression occurring after different kinds of surgeries.

At high doses there are strong CNS effects and the atropine at such high doses causes typical anticholinergic side effects, such as anxiety, dysphoria, and delirium. Excessive use or overdose causes constipation and can promote development of megacolon as well as classic symptoms of overdose including potentially lethal respiratory depression. In the 1990s its use in children was restricted in many countries due to the CNS side effects, which included anorexia, nausea and vomiting, headache, drowsiness, confusion, insomnia, dizziness, restlessness, euphoria and depression.

In Sweden, physicians had long been discouraged by the medical products agency to prescribe dextropropoxyphene due to the risk of respiratory depression and even death when taken with alcohol. Physicians had earlier been recommended to prescribe products with only dextropropoxyphene and not to patients with a history of drug abuse, depression, or suicidal tendencies. Products with mixed active ingredients were taken off the market and only products with dextropropoxyphene were allowed to be sold. Dextropoxyphene was de facto narcotica labelled.

Phenomorphan is an opioid analgesic. It is not currently used in medicine, but has similar side-effects to other opiates, which include itching, nausea and respiratory depression. Phenomorphan is a highly potent drug due to the N-phenethyl group, which boosts affinity to the μ-opioid receptor, and so phenomorphan is around 10x more potent than levorphanol, which is itself 6-8x the potency of morphine. Other analogues where the N-(2-phenylethyl) group has been replaced by other aromatic rings.

Because decozine has mixed agonist/antagonist effects on mu-, delta-, and kappa-opioid receptors, it has a lowered dependence potential than purely agonistic opiates. It can be prescribed, therefore, in small doses over an extended period of time without causing patients to develop and sustain an addiction. Its efficacy as an analgesic is dose-dependent; however, it displays a ceiling effect in induced respiratory depression at 0.3-0.4 mg/kg. Side effects at lower doses include mild gastrointestinal discomfort and dizziness.

Azidomorphine is an opiate analogue that is a derivative of morphine, where the 7,8 double bond has been saturated and the 6-hydroxy group has been replaced by an azide group. Azidomorphine binds with high affinity to the mu opioid receptor, and is around 40x more potent than morphine in vivo. It has similar effects to morphine, including analgesia, sedation, and respiratory depression. However, its addiction liability has been found to be slightly lower than that of morphine in animal studies.

Lorazepam is not usually fatal in overdose, but may cause respiratory depression if taken in overdose with alcohol. The combination also causes greater enhancement of the disinhibitory and amnesic effects of both drugs, with potentially embarrassing or criminal consequences. Some experts advise that people should be warned against drinking alcohol while on lorazepam treatment, but such clear warnings are not universal. Greater adverse effects may also occur when lorazepam is used with other drugs, such as opioids or other hypnotics.

The chest pain, high blood pressure, and increased heart rate caused by cocaine may be also treated with benzodiazepines. Multiple and escalating dose of benzodiazepines may be necessary to achieve effect, which increases risk of over-sedation and respiratory depression. A review of cocaine cardiovascular toxicity found benzodiazepines may not always reliably lower heart rate and blood pressure. Nitric-oxide mediated vasodilators, such as nitroglycerin and nitroprusside, are effective at lowering blood pressure and reversing coronary arterial vasoconstriction, but not heart rate.

Noracymethadol (INN) is a synthetic opioid analgesic related to methadone that was never marketed. In a clinical trial of postpartum patients it was reported to produce analgesia comparable to that of morphine but with less nausea, dizziness, and drowsiness. Other side effects included salivation, ataxia, and respiratory depression that was reversible by naloxone. Similarly to many of its analogues, noracymethadol is a Schedule I controlled substance in the United States with an ACSCN of 9633 and 2013 annual manufacturing quota of 12 grammes.

Very large doses of anesthetics or analgesics may result in respiratory depression. An epidural injection may be administered at any point of the spine - the specific administration site determines the specific nerves affected, and thus the area of the body from which pain will be blocked. There are multiple techniques to ensure proper placement and use of an epidural catheter. An epidural catheter may remain inserted for several days, but is usually removed when oral therapy becomes a viable alternative.

With doses that usually range from 10 to 150 mg, users are likely to experience effects similar to heroin, morphine, and fentanyl such as euphoria and respiratory depression. When an overdose occurs users often experience tachycardia, hypertension, and seizures. Mice, dogs, and monkeys, have been used in tests which showed the drug was almost equivalently potent to morphine, and had a very steep dose response curve. Rats given 20 mg doses three times a day for five days, experienced withdrawal symptoms similar to other opioids.

Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (hypo meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapnia) and respiratory acidosis. Hypoventilation is not synonymous with respiratory arrest, in which breathing ceases entirely and death occurs within minutes due to hypoxia and leads rapidly into complete anoxia, although both are medical emergencies. Hypoventilation can be considered a precursor to hypoxia and its lethality is attributed to hypoxia with carbon dioxide toxicity.

GR-113808 is a drug which acts as a potent and selective 5-HT4 serotonin receptor antagonist. It is used in researching the roles of 5-HT4 receptors in various processes, and has been used to test some of the proposed therapeutic effects of selective 5-HT4 agonists, such as for instance blocking the nootropic effects of 5-HT4 agonists, and worsening the respiratory depression produced by opioid analgesic drugs, which appears to be partly 5-HT4 mediated and can be counteracted by certain 5-HT4 agonists.

It is unclear if it helps those who are born at term. In those at high risk of preterm labor a review found that moderate to severe CP was reduced by the administration of magnesium sulphate, and that adverse effects on the babies from the magnesium sulphate were not significant. Mothers who received magnesium sulphate could experience side effects such as respiratory depression and nausea. However, guidelines for the use of magnesium sulfate in mothers at risk of preterm labour are not strongly adhered to.

Benzethidine is a 4-phenylpiperidine derivative that is related to the clinically used opioid analgesic drug pethidine (meperidine, or Demerol). Benzethidine is not currently used in medicine and is a Class A/Schedule I drug which is controlled under UN drug conventions. It has similar effects to other opioid derivatives, such as analgesia, sedation, nausea and respiratory depression. In the United States, the drug is a Schedule I Narcotic Controlled Substance with a DEA ACSCN of 9606 and 2014 annual aggregate manufacturing quota of nil.

Tapentadol is contraindicated in people with epilepsy or who are otherwise prone to seizures. It raises intracranial pressure so should not be used in people with head injuries, brain tumors, or other conditions which increase intracranial pressure. It increases the risk of respiratory depression so should not be used in people with asthma. As with other mu- opioid agonists, tapentadol may cause spasms of the sphincter of Oddi, and is therefore discouraged for use in patients with biliary tract disease such as both acute and chronic pancreatitis.

The combination of tapentadol and alcohol may result in increased plasma concentrations of tapentadol and produce respiratory depression to a degree greater than the sum of the two drugs when administered separately; patients should be cautioned against alcohol consumption when taking tapentadol as the combination may be fatal. Tapentadol should be used with caution in patients who are taking one or more anticholinergic drugs, as this combination may result in urine retention (which can result in serious renal damage and is considered a medical emergency).

Dezocine is generally administered intravenously. It can also be administered in intramuscular doses, and is given singularly rather than continuously. Dezocine has been found to be an effective painkiller comparable to meperidine (pethidine), and so is a more effective analgesic than pentazocine, but causes relatively more respiratory depression than pentazocine. It is a useful drug for the treatment of pain, but side effects such as dizziness limit its clinical application, and it can produce opioid withdrawal syndrome in patients already dependent on other opioids.

When these are used, effects may include anxiolysis (reduction of anxiety), analgesia (pain relief), sedation, somnolence, cognitive/memory impairment, dissociation, muscle relaxation, lowered blood pressure/heart rate, respiratory depression, anesthesia, and anticonvulsant effects. Depressants exert their effects through a number of different pharmacological mechanisms, the most prominent of which include facilitation of GABA or opioid activity, and inhibition of adrenergic, histamine or acetylcholine activity. Some are also capable of inducing feelings of euphoria (a happy sensation). The most widely used depressant by far is alcohol.

When the pressure within the skull (intracranial pressure, abbreviated ICP) rises too high, it can be deadly. Signs of increased ICP include decreasing level of consciousness, paralysis or weakness on one side of the body, and a blown pupil, one that fails to constrict in response to light or is slow to do so. Cushing's triad, a slow heart rate with high blood pressure and respiratory depression is a classic manifestation of significantly raised ICP. Anisocoria, unequal pupil size, is another sign of serious TBI.

As with other GABAergic drugs, combination with other GABAergic drugs, including alcohol, as well as with sedatives in general, possess a significant risk to the user in the form of overdose. Overdose symptoms are similar to those of other GABAergics including excessive sedation and unresponsiveness to stimuli, severe ataxia, amnesia, confusion, agitation, intoxication and inappropriate (potentially violent) behavior. Severe overdoses may present with respiratory depression (and subsequent pulmonary aspiration), coma, and death. Carisoprodol is not detected on all toxicology tests which may delay diagnosis of overdose.

Trimeperidine produces similar effects to other opioids, such as analgesia and sedation, along with side effects such as nausea, itching, vomiting and respiratory depression which may be harmful or fatal. Trimeperidine is in Schedule I of the Controlled Substances Act 1970 of the United States as a Narcotic with ACSCN 9646 with an annual aggregate manufacturing quota of 2 grammes as of 2014. The free base conversion ratio for salts includes 0.883 for the hydrochloride. Promedol increases the activity of the reticular activating system in the brain.

Chloromorphide (α-chloromorphide) is an opiate analog that is a derivative of morphine, where the 6-hydroxy group has been replaced by chlorine. Developed in 1933 in Germany, it has approximately ten times the potency of morphine. It has similar effects to morphine, such as sedation, analgesia, and respiratory depression. Chloromorphide does not appear specifically in the Controlled Substances Act 1970 in the United States, but is presumably Schedule II controlled substance as a form of morphine or an analogue of morphine or morphinan.

Because of their effect on the part of the brain that regulates breathing, opioids can lead to a person having very slow or stopped breathing during overdoses and therefore result in death if left untreated. Opiate overdose symptoms and signs can be referred to as the "opioid overdose triad": decreased level of consciousness, pinpoint pupils and respiratory depression. Other symptoms include seizures and muscle spasms. Sometimes an opiate overdose can lead to such a decreased level of consciousness such that the person will not wake up.

RWJ-394674 is a drug that is used in scientific research. It is a potent, orally active analgesic drug that produces little respiratory depression. RWJ-394674 itself is a potent and selective agonist for δ-opioid receptors, with a Ki of 0.24 nM at δ and 72 nM at μ. However once inside the body, RWJ-394674 is dealkylated to its monodesethyl metabolite RWJ-413216, which is a potent agonist at the μ-opioid receptor and has less affinity for δ (Ki 0.26 nM at μ, 46.7 nM at δ).

3-Methyl-thiofentanyl is an opioid analgesic and analogue of fentanyl. 3-Methyl-thiofentanyl was sold briefly on the black market in the early 1980s, before the introduction of the Federal Analog Act which for the first time attempted to control entire families of drugs based on their structural similarity rather than scheduling each drug individually as they appeared. 3-Methyl-thiofentanyl has similar effects to fentanyl. Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening.

Ciramadol (WY-15,705) is an opioid analgesic that was developed in the late 1970s and is related to phencyclidine, tramadol, tapentadol and venlafaxine. It is a mixed agonist-antagonist for the μ-opioid receptor with relatively low abuse potential and a ceiling on respiratory depression which makes it a relatively safe drug. It has a slightly higher potency and effectiveness as an analgesic than codeine, but is weaker than morphine. Other side effects include sedation and nausea but these are generally less severe than with other similar drugs.

Different measures for pain control have varying degrees of success and side effects to the woman and her baby. In some countries of Europe, doctors commonly prescribe inhaled nitrous oxide gas for pain control, especially as 53% nitrous oxide, 47% oxygen, known as Entonox; in the UK, midwives may use this gas without a doctor's prescription. Opioids such as fentanyl may be used, but if given too close to birth there is a risk of respiratory depression in the infant. Popular medical pain control in hospitals include the regional anesthetics epidurals (EDA), and spinal anaesthesia.

It produces around the same degree of respiratory depression as morphine, but less inhibition of gastrointestinal motility. Animal studies show it to be a potent analgesic which produces significant analgesic effects even at low doses while inducing comparatively few side effects, however it has never been developed for medical use in humans. 6-Methylenedihydrodesoxymorphine is synthesised in two steps; first a Wittig reaction is used, reacting hydrocodone with methylenetriphenylphosphorane and an alkyl lithium reagent in diethyl ether to form 6-Methylenedihydrodesoxycodeine. The 3-methoxy group is then cleaved to hydroxy, by reaction with pyridine.

Side effects are similar to those of other opiates and include itching, nausea and respiratory depression. Related opioid analogues such as nicomorphine and nicodicodeine were first synthesized. The definitive synthesis, which involves treating anhydrous codeine base with nicotinic anhydride at 130 °C, was published by Pongratz and Zirm in Monatshefte für Chemie in 1957, simultaneously with the two analogues in an article about amides and esters of various organic acids. Nicocodeine is almost always used as the hydrochloride salt, which has a free base conversion ratio of .917.

Diacetyldihydromorphine is quickly metabolized by plasma esterase enzymes into dihydromorphine, in the same way that diamorphine is metabolized into morphine. Diamorphine is 1.50–1.80 times the potency of morphine. It shares with other opioids the risk of overdose or (potentially life-threatening) respiratory depression. When strong narcotics are required, and morphine and diamorphine are not an option, it is more common to use better known drugs such as nicomorphine, hydromorphone, levorphanol, oxymorphone or fentanyl which doctors will be more familiar with, and which do not share the stigma associated with either heroin or morphine.

Paradoxical reactions such as anxiety, delirium, combativeness, hallucinations, and aggression can also occur following benzodiazepine overdose. Gastrointestinal symptoms such as nausea and vomiting have also been occasionally reported. Cases of severe overdose have been reported and symptoms displayed might include prolonged deep coma or deep cyclic coma, apnea, respiratory depression, hypoxemia, hypothermia, hypotension, bradycardia, cardiac arrest, and pulmonary aspiration, with the possibility of death. Severe consequences are rare following overdose of benzodiazepines alone but the severity of overdose is increased significantly if benzodiazepines are taken in overdose in combination with other medications.

Therefore, slow administration of flumazenil is necessary to prevent the occurrence of a seizure. These agents are rarely used in the setting of a colonoscopy as 98.8% of colonoscopies use sedatives but only 0.8% of them result in the administration of one of these antidotes. Even if they are rarely used in colonoscopies they are important in preventing the patient from entering a coma or developing respiratory depression when sedatives are not properly dosed. Outside of the colonoscopy setting, these agents are used for other procedures and in the case of drug overdose.

Pentazocine,US Patent 4105659 Analgesia producing benzazocines sold under the brand name Talwin among others, is a painkiller used to treat moderate to severe pain. It is believed to work by activating (agonizing) κ-opioid receptors (KOR) and blocking (antagonizing) μ-opioid receptors (MOR). As such it is called an opioid as it delivers its effects on pain by interacting with the opioid receptors. It shares many of the side effects of other opioids like constipation, nausea, itching, drowsiness and respiratory depression, but unlike most other opioids it fairly frequently causes hallucinations, nightmares and delusions.

As a side effect of medicines or recreational drugs, hypoventilation may become potentially life-threatening. Many different central nervous system (CNS) depressant drugs such as ethanol, benzodiazepines, barbiturates, GHB, sedatives, and opioids produce respiratory depression when taken in large or excessive doses, or mixed with other depressants. Strong opiates (such as fentanyl, heroin, and morphine), barbiturates, and certain benzodiazepines (short acting ones and alprazolam) are known for depressing respiration. In an overdose, an individual may cease breathing entirely (go into respiratory arrest) which is rapidly fatal without treatment.

A law enforcement grade Breathalyzer, specifically an Alco-Sensor IV Drinking enough alcohol to cause a blood alcohol concentration (BAC) of 0.03–0.12% typically causes a flushed, red appearance in the face and impaired judgment and fine muscle coordination. A BAC of 0.09% to 0.25% causes lethargy, sedation, balance problems and blurred vision. A BAC from 0.18% to 0.30% causes profound confusion, impaired speech (e.g., slurred speech), staggering, dizziness and vomiting. A BAC from 0.25% to 0.40% causes stupor, unconsciousness, anterograde amnesia, vomiting and respiratory depression (potentially life- threatening).

Infrequent adverse reactions in patients taking opioids for pain relief include: dose-related respiratory depression (especially with more potent opioids), confusion, hallucinations, delirium, urticaria, hypothermia, bradycardia/tachycardia, orthostatic hypotension, dizziness, headache, urinary retention, ureteric or biliary spasm, muscle rigidity, myoclonus (with high doses), and flushing (due to histamine release, except fentanyl and remifentanil). Both therapeutic and chronic use of opioids can compromise the function of the immune system. Opioids decrease the proliferation of macrophage progenitor cells and lymphocytes, and affect cell differentiation (Roy & Loh, 1996). Opioids may also inhibit leukocyte migration.

Alcohol is a very prominent depressant. Alcohol can be and is more likely to be a large problem among teenagers and young adults. When depressants are used, effects often include ataxia, anxiolysis, pain relief, sedation or somnolence, and cognitive/memory impairment, as well as in some instances euphoria, dissociation, muscle relaxation, lowered blood pressure or heart rate, respiratory depression, and anticonvulsant effects, and even similar effects of General Anaesthesia and/or death at high doses. Cannabis may sometimes be considered a depressant due to one of its components, cannabidiol.

Nitrazepam should be avoided in patients with chronic obstructive pulmonary disease (COPD), especially during acute exacerbations of COPD, because serious respiratory depression may occur in patients receiving hypnotics. As with other hypnotic drugs, nitrazepam is associated with an increased risk of traffic accidents. Nitrazepam is recommended to be avoided in patients who drive or operate machinery. A study assessing driving skills of sedative hypnotic users found the users of nitrazepam to be significantly impaired up to 17 hours after dosing, whereas users of temazepam did not show significant impairments of driving ability.

Brorphine is a piperidine-based opioid analgesic compound. Some of its structural analogs, originally described in 2018, are functionally biased mu opioid receptor agonists, showing reduced side effects, especially lacking respiratory depression, when administered in high doses in mice. Importantly, however, this brominated member of the series, while it is a potent mu opioid agonist, lacks the safety margin seen for several other analogs and is not a functionally biased compound. Brorphine can instead be regarded as a typical opioid agonist, based upon its performance under various assay conditions, including robust arrestin recruitment.

Side effects can include itching, nausea and potentially serious respiratory depression which can be life-threatening. PEPAP has been found to be a potent CYP2D6 inhibitor, which makes it likely to cause adverse interactions with some other drugs, although the inhibitory potency of PEPAP is less than that of MPPP. Both cocaine and methadone are also CYP2D6 inhibitors and could, in theory, potentiate the effect. It is unlikely that the tetrahydropyridine byproducts that may be formed during the synthesis of PEPAP are neurotoxic in the same way as the MPPP byproduct MPTP.

Metonitazene is an analgesic drug related to etonitazene, which was first reported in 1957, and has been shown to have approximately 100 times the potency of morphine by central routes of administration, but if used orally it has been shown to have approximately 10 times the potency of morphine. Its effects are similar to other opioids like fentanyl and heroin, including analgesia, euphoria, sleepiness. Adverse effects include vomiting, and respiratory depression that can potentially be fatal. Because of high dependency potential and dangerous adverse effects it has never been introduced in pharmacotherapy.

Alcohol causes generalized central nervous system depression and associated cognitive, memory, motor, and sensory impairment. It slows and impairs cognition and reaction time, impairs judgement, interferes with motor function resulting in motor incoordination, loss of balance, and slurred speech, impairs memory formation, and causes sensory impairment. At high concentrations, amnesia, analgesia, spins, stupor, and unconsciousness result. At very high concentrations, anterograde amnesia, markedly decreased heart rate, pulmonary aspiration, positional alcohol nystagmus (PAN), respiratory depression, and death can result due to profound suppression of central nervous system function and consequent dysautonomia.

Rarely, more severe symptoms, such as gastrointestinal bleeding, seizures, metabolic acidosis, high blood levels of potassium, low blood pressure, slow heart rate, fast heart rate, atrial fibrillation, coma, liver dysfunction, acute kidney failure, cyanosis, respiratory depression, and cardiac arrest have been reported. The severity of symptoms varies with the ingested dose and the time elapsed; however, individual sensitivity also plays an important role. Generally, the symptoms observed with an overdose of ibuprofen are similar to the symptoms caused by overdoses of other NSAIDs. Correlation between severity of symptoms and measured ibuprofen plasma levels is weak.

Dimepheptanol (INN; Amidol, Pangerin), also known as methadol or racemethadol, is a synthetic opioid analgesic related to methadone. It has similar effects to other opioids, including analgesia, sedation and euphoria, as well as side effects like itching, nausea and respiratory depression. Dimepheptanol is a mixture of two isomers, alphamethadol (α-methadol) and betamethadol (β-methadol). These are also available separately, and this drug has three separate entries in many national and international lists of illegal drugs, which refer to the racemic mixture dimepheptanol, and the two optical isomers.

Pentamorphone (14β-pentylaminomorphinone, RX-77989) is a semi-synthetic opiate derivative related to compounds such as morphine, hydromorphone and oxymorphone. Developed in 1984, it is a potent opioid analgesic several times stronger than fentanyl, and with a similarly fast onset of effects and short duration of action. It was found to produce relatively little respiratory depression compared to other potent opioid agonists, but its analgesic effects were somewhat disappointing in human trials, and while pentamorphone had some slight advantages over fentanyl these were not sufficient to warrant its introduction into clinical use.

Amiphenazole (Daptazile) is a respiratory stimulant traditionally used as an antidote for barbiturate or opiate overdose, usually in combination with bemegride, as well as poisoning from other sedative drugs and treatment of respiratory failure from other causes. It was considered particularly useful as it could counteract the sedation and respiratory depression produced by morphine but with less effect on analgesia. It is still rarely used in medicine in some countries, although it has largely been replaced by more effective respiratory stimulants such as doxapram and specific opioid antagonists such as naloxone.

Concurrent use of these medicines (as well as other benzodiazepines) can interact in a way that is difficult to predict. Drinking alcohol when taking oxazepam is not recommended. Concomitant use of oxazepam and alcohol can lead to increased sedation, severe problems with coordination (ataxia), decreased muscle tone, and in severe cases or in predisposed patients, even to life-threatening intoxications with respiratory depression, coma, and collapse. There is a risk of blood circulation collapse, possibly the same condition as blood circulation syncope, when oxazepam is used in combination with quetiapine, an antipsychotic.

Nordazepam, like other benzodiazepines, easily crosses the placental barrier, so the drug should not be administered during the first trimester of pregnancy. In case of serious medical reasons, nordazepam can be given in late pregnancy, but the foetus, due to the pharmacological action of the drug, may experience side effects such as hypothermia, hypotonia, and sometimes mild respiratory depression. Since nordazepam and other benzodiazepines are excreted in breast milk, the substance should not be administered to mothers who are breastfeeding. Discontinuing of breast-feeding is indicated for regular intake by the mother.

It was tested up to Phase II human trials, but while it produced less respiratory depression than propofol, it had a longer recovery time and was deemed not to have any significant advantages over the older drug. Similarly when Ro48-6791 was compared to midazolam, it had similar efficacy, higher potency and a shorter recovery time, but produced less of a synergistic effect on opioid-induced analgesia and produced more severe side effects such as dizziness after the procedure. Consequently, it was dropped from clinical development, although it is still used in scientific research.

However, in 2013, Canadian police seized 3 kilograms of acetylfentanyl. As a μ-opioid receptor agonist, acetylfentanyl may serve as a direct substitute for heroin or other opioids. Common side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear.

It may cause serious health problems when overdosed. Signs and symptoms of adverse effects may include any or several of the following: convulsions, respiratory depression (slow or stopped breathing), dilated eye pupils, nystagmus (rapid side-to-side eye movements), erythema (flushed skin), gastrointestinal constipation, nausea, vomiting, paralytic ileus, tachycardia (rapid pulse), drowsiness and hallucinations. Symptoms of toxicity may take up to 12 hours to appear. Treatment of overdose must be initiated immediately after diagnosis and may include the following: ingestion of activated charcoal, laxative and a counteracting medication (narcotic antagonist).

Monitoring of patients actively using delorazepam should never be discontinued even if the patients has been stable on the medication for many months or years. Caution must be used when delorazepam is administered alongside other sedative medications (ex. opiates, barbiturates, z-drugs, and phenothiazines) due to an increased risk of sedation, ataxia, and (potentially fatal) respiratory depression. Although overdoses of benzodiazepines alone rarely result in death, the combination of benzodiazepines and other sedatives (particularly other gabaminergic drugs such as barbiturates and alcohol) is far more likely to result in death.

Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear. A new wave of fentanyl analogues and associated deaths began in around 2014 in the US, and have continued to grow in prevalence; especially since 2016 these drugs have been responsible for hundreds of overdose deaths every week.

Repinotan (BAYx3702), an aminomethylchroman derivative, is a selective 5-HT1A receptor full agonist with high potency and efficacy. It has neuroprotective effects in animal studies, and was trialed in humans for reducing brain injury following head trauma. It was subsequently trialed up to phase II for treatment of stroke, but while side effects were mild and consisted mainly of nausea, repinotan failed to demonstrate sufficient efficacy to justify further clinical trials. However, repinotan continues to be investigated for other applications, and was found to be effective at counteracting the respiratory depression produced by morphine, though with slight reduction in analgesic effects.

Side effects can include blood from mouth, skin rashes, dizziness, sedation, shortness of breath, hypersensitivity reaction, fainting (syncope or near syncope), nausea or vomiting, confusion, loss of short-term memory, drowsiness, changes in blood, allergic reactions, euphoria, dysphoria, abdominal pain, itchiness, easy bruising, bleeding gums, vivid dreams, dry mouth and addiction. Genetic differences between people give rise to differing rates of metabolism of codeine to morphine. In about 5% of people this may happen particularly fast, leading to higher levels of morphine being passed through breast milk in amounts potentially able to cause fatal respiratory depression of a breastfed baby.

Adverse drug reactions (ADRs) are rare when it is administered correctly. Most ADRs relate to administration technique (resulting in systemic exposure) or pharmacological effects of anesthesia, however allergic reactions can rarely occur. Systemic exposure to excessive quantities of ropivacaine mainly result in central nervous system (CNS) and cardiovascular effects – CNS effects usually occur at lower blood plasma concentrations and additional cardiovascular effects present at higher concentrations, though cardiovascular collapse may also occur with low concentrations. CNS effects may include CNS excitation (nervousness, tingling around the mouth, tinnitus, tremor, dizziness, blurred vision, seizures followed by depression (drowsiness, loss of consciousness), respiratory depression and apnea).

UNODC Bulletin on Narcotics 1958 p 23-42. Although it has high potency, long duration, and good therapeutic index (1100 in animal studies),Bulletin on Narcotics October–December 1956 page 37 Ro4-1539 had no particular clinical advantages over other available opioid drugs, and was never commercially marketed. Ro4-1539 has never formally undergone clinical trials in humans, but based on its effects in animals it would be expected to produce effects similar to those of other potent opioid agonists, including strong analgesia, sedation, euphoria, constipation, itching, tachyphylaxis and respiratory depression, which could be harmful or fatal.

This may explain why patients commonly increase doses over time and many eventually take more than one type of benzodiazepine after the first loses effectiveness. Additionally, because tolerance to benzodiazepine sedating effects develops more quickly than does tolerance to brainstem depressant effects, those taking more benzodiazepines to achieve desired effects may suffer sudden respiratory depression, hypotension or death. Most patients with anxiety disorders and PTSD have symptoms that persist for at least several months, making tolerance to therapeutic effects a distinct problem for them and necessitating the need for more effective long-term treatment (e.g., psychotherapy, serotonergic antidepressants).

Supportive measures include observation of vital signs, especially Glasgow Coma Scale and airway patency. IV access with fluid administration and maintenance of the airway with intubation and artificial ventilation may be required if respiratory depression or pulmonary aspiration occurs. Supportive measures should be put in place prior to administration of any benzodiazepine antagonist in order to protect the patient from both the withdrawal effects and possible complications arising from the benzodiazepine. A determination of possible deliberate overdose should be considered with appropriate scrutiny, and precautions taken to prevent any attempt by the patient to commit further bodily harm.

This information is confirmed in the "Report of the Death of an American Citizen" from the U.S. Department of State, Foreign Service, American Embassy in London, made out on October 12, 1973, by Micaela A. Cella, Vice Consul. The report is on record in the U.S. National Archives in College Park, Maryland. A London physician reportedly prescribed and administered two narcotics and a barbiturate for severe arthritic pain, despite the extreme risk of inducing respiratory depression, apnea, and death in a patient with decreased respiratory reserve. Dunn may have needed the drugs in order to tolerate the physical demands of shooting a movie.

Unlike diethyl ether, methoxyflurane is a significant respiratory depressant. In dogs, methoxyflurane causes a dose-dependent decrease in respiratory rate and a marked decrease in respiratory minute volume, with a relatively mild decrease in tidal volume. In humans, methoxyflurane causes a dose-dependent decrease in tidal volume and minute volume, with respiratory rate relatively constant. The net effect of these changes is profound respiratory depression, as evidenced by CO2 retention with a concomitant decrease in arterial pH (this is referred to as a respiratory acidosis) when anesthetized subjects are allowed to breathe spontaneously for any length of time.

It is an agonist for the μ-opioid receptors.Utilization of a radioreceptor assay for the analysis of fentanyl analogs in urine Mario Enrique Alburges Butyrfentanyl has no current legitimate clinical applications; however, it is being sold as designer drug. Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea, and potentially serious respiratory depression which can be life-threatening. Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear.

CYP2D6 converts codeine into morphine, which then undergoes glucuronidation. Life-threatening intoxication, including respiratory depression requiring intubation, can develop over a matter of days in patients who have multiple functional alleles of CYP2D6, resulting in ultra-rapid metabolism of opioids such as codeine into morphine. Studies on codeine's analgesic effect are consistent with the idea that metabolism by CYP2D6 to morphine is important, but some studies show no major differences between those who are poor metabolizers and extensive metabolizers. Evidence supporting the hypothesis that ultrarapid metabolizers may get greater analgesia from codeine due to increased morphine formation is limited to case reports.

Frakefamide (INN) is a synthetic, fluorinated linear tetrapeptide with the amino acid sequence Tyr-D-Ala-(p-F)Phe-Phe-NH2 which acts as a peripherally- specific, selective μ-opioid receptor agonist. Despite its inability to penetrate the blood-brain-barrier and enter the central nervous system, frakefamide has potent analgesic effects and, unlike centrally-acting opioids like morphine, does not produce respiratory depression, indicating that its antinociceptive effects are mediated by peripheral μ-opioid receptors. It was under development for the treatment of pain by AstraZeneca and Shire but was shelved after phase II clinical trials.

Early adjustment side effects may include nausea and vomiting, numbness, blurred vision, stomach pains and temporary dizziness. There are no specific antidotes available for ethchlorvynol, and treatment is supportive with protocols resembling those for the treatment of barbiturate overdose. Overdose may be marked by a variety of symptoms, including confusion, fever, peripheral numbness and weakness, reduced coordination and muscle control, slurred speech, reduced heartbeat, respiratory depression, and in extreme overdoses, coma and death. As with all GABAA receptor agonists, Placidyl can be habit forming and extremely physically addictive (with potentially lethal withdrawal resembling delirium tremens and benzodiazepine withdrawal).

Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear. Life-threatening adverse reactions caused by furanylfentanyl use have been observed in Sweden and Canada. At least seven deaths in Cook County, Illinois, have been linked to furanylfentanyl in 2016, with additional deaths in suburban Chicago in 2017.

Side effects typical of hypnotic benzodiazepines are related to CNS depression, and include somnolence, sedation, drunkenness, dizziness, fatigue, ataxia, headache, lethargy, impairment of memory and learning, longer reaction time and impairment of motor functions (including coordination problems), slurred speech, decreased physical performance, numbed emotions, reduced alertness, muscle weakness, blurred vision (in higher doses), and inattention. Euphoria was rarely reported with its use. According to the U.S. Food and Drug Administration, temazepam had an incidence of euphoria of 1.5%, much more rarely reported than headaches and diarrhea. Anterograde amnesia may also develop, as may respiratory depression in higher doses.

Mirfentanil is a fentanyl derivative with strong selectivity for the μ opioid receptor. At lower doses, it antagonizes the analgesic effects of alfentanil and substitutes for naloxone in morphine-treated monkeys; however, it also reverses naloxone-precipitated withdrawal in pigeons trained to discriminate morphine from naloxone. At high doses, it exhibits analgesic activity which is not fully reversed by opioid antagonists, suggesting that the drug has both opioid and non-opioid mechanisms of action. Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening.

Quinidine is also an inhibitor of the cytochrome P450 enzyme 2D6, and can lead to increased blood levels of lidocaine, beta blockers, opioids, and some antidepressants. Quinidine also inhibits the transport protein P-glycoprotein and so can cause some peripherally acting drugs such as loperamide to have central nervous system side effects, such as respiratory depression, if the two drugs are coadministered. Quinidine can cause thrombocytopenia, granulomatous hepatitis, myasthenia gravis, and torsades de pointes (dangerous heart rhythm),Rapid Interpretation of EKG's 6th Ed., Dubin so is not used much today. Torsades can occur after the first dose.

Adverse drug reactions (ADRs) are rare when it is administered correctly. Most ADRs relate to administration technique (resulting in systemic exposure) or pharmacological effects of anesthesia, however allergic reactions can rarely occur. Systemic exposure to excessive quantities of bupivacaine mainly result in central nervous system (CNS) and cardiovascular effects – CVS effects usually occur at lower blood plasma concentrations and additional cardiovascular effects present at higher concentrations, though cardiovascular collapse may also occur with low concentrations. CNS effects may include CNS excitation (nervousness, tingling around the mouth, tinnitus, tremor, dizziness, blurred vision, seizures) followed by depression (drowsiness, loss of consciousness, respiratory depression and apnea).

Several other compounds such as CX-701, CX-1739, CX-1763 and CX-1837 have also been announced as being under current investigation, and while little information has yet been released about them, CX-1739 is believed to be the most potent compound in this class to date, reportedly some 5x the potency of CX-717. Presently, CX717 is in phase II clinical trials as a possible non-stimulant pharmacotherapy in the treatment of ADHD. As the AMPA receptors also mediate respiratory drive, CX717 is also being investigated as a therapy in opioid-induced respiratory depression and spinal-cord injury.

Embutramide (INN, USAN, BAN) (brand name Embutane) is a potent opioid analgesic and sedative drug that is structurally related to methadone. It was developed by Hoechst A.G. in 1958 and was investigated as a general anesthetic agent, but was found to have a very narrow therapeutic window, with a 50 mg/kg dose producing effective sedation and a 75 mg/kg dose being fatal. Along with strong sedative effects, embutramide also produces respiratory depression and ventricular arrhythmia. Because of these properties, it was never adopted for medical use as an anesthetic as it was considered too dangerous for this purpose.

Because the combination of spastic movements, vomiting, and irregular respiration may compromise the patient's airway, rapidly acting drugs are used to minimize time in this stage and reach Stage 3 as fast as possible. ;Stage 3: In Stage 3, also known as surgical anaesthesia, the skeletal muscles relax, vomiting stops, respiratory depression occurs, and eye movements slow and then stop. The patient is unconscious and ready for surgery. This stage is divided into four planes: :# The eyes roll, then become fixed; :# Corneal and laryngeal reflexes are lost; :# The pupils dilate and light reflex is lost; :# Intercostal paralysis and shallow abdominal respiration occur.

Benzodiazepines require special precaution if used in children and in alcohol- or drug-dependent individuals. Particular care should be taken in pregnant or elderly people, people with substance abuse history (particularly alcohol dependence), and people with comorbid psychiatric disorders. The use of alprazolam should be avoided or carefully monitored by medical professionals in individuals with: myasthenia gravis, acute narrow-angle glaucoma, severe liver deficiencies (e.g., cirrhosis), severe sleep apnea, pre-existing respiratory depression, marked neuromuscular respiratory, acute pulmonary insufficiency, chronic psychosis, hypersensitivity or allergy to alprazolam or other benzodiazepines, and borderline personality disorder (where it may induce suicidality and dyscontrol).

While benzoctamine was made to be an alternative to the benzodiazepine line of anxiolytic drugs, other uses for the drug have been discovered. Due to benzoctamine's ability to tranquilize without causing respiratory depression, scientists are moving forward with studies that test its sedative effects in patients with respiratory failure. In one study that used benzoctamine in a clinical setting, researchers showed that the use of benzoctamine for sedation did not result in changes in forced expiratory volume in one second or carbon dioxide partial pressure PCO2. This confirmed previous statements that claimed the drug did not cause respiratory failure.

3-Methylfentanyl has similar effects to fentanyl, but is far more potent due to increased binding affinity to its target site. Since fentanyl itself is already highly potent, 3-methylfentanyl is extremely dangerous when used recreationally, and has resulted in many deaths among recreational opioid users ingesting the drug. Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear.

Generic hydrocodone/ibuprofen 7.5/200 mg Hydrocodone/ibuprofen' (INNs), sold under the brand name Vicoprofen, is a fixed-dose combination analgesic medication used in short-term therapy to relieve severe pain. Vicoprofen combines the analgesic and antitussive properties of hydrocodone with the analgesic, anti-inflammatory, and antipyretic properties of ibuprofen. In contrast to hydrocodone/acetaminophen combination analgesics such as Vicodin, this hydrocodone/ibuprofen avoids some of the liver toxicity which may occur from acetaminophen, but still presents significant dangers in hydrocodone overdose, namely respiratory depression. Vicoprofen is supplied in a fixed dose combination tablet which contains hydrocodone bitartrate, USP 7.5 mg with ibuprofen, USP 200 mg.

Thiofentanyl is an opioid analgesic that is an analogue of fentanyl. Thiofentanyl was sold briefly on the black market in the early 1980s, before the introduction of the Federal Analog Act which for the first time attempted to control entire families of drugs based on their structural similarity rather than scheduling each drug individually as they appeared. Thiofentanyl is made with the same synthetic route as fentanyl, but by substituting 2-(2-bromoethyl)thiophene for phenethyl bromide in the synthesis. Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening.

Reversing a gray death overdose frequently requires multiple doses of naloxone, whereas a typical overdose of heroin (which is much less potent) typically needs only one dose. This is consistent with the difficulty of overdose reversal seen with high-affinity opioids in the fentanyl chemical family or with buprenorphine. The greater affinity of these substances for the μ-opioid receptor causes less naloxone to bind to receptors, increasing the dosage necessary to counteract the resulting respiratory depression. The difficulty in reversing an overdose of gray death is likely due to the presence of a fentanyl analogue, which reporting seems to corroborate as of December 2018.

Indochinese spitting cobra (Naja siamensis) The Indochinese spitting cobra (Naja siamensis) is a venomous spitting cobra whose venom consists of postsynaptic neurotoxins, metalloproteinases, powerful cardiotoxins, with cytolytic activity, and Phospholipase A2 with a diversity of activities. The of its venom is 1.07-1.42 mg/gram of mouse body weight. Cranial palsy and respiratory depression are reported to be more common after bites by Naja siamensis than by Naja kaouthia. Indochinese spitting cobras will use their venom for self-defense with little provocation, and as the name implies, are capable of spitting venom when alarmed, often at the face and eyes of the animal or human threatening them.

To understand how changes in respiration might affect blood pH, consider the effects of ventilation on PCO2 in the lungs. If one were to hold his or her breath (or breathe very slowly, as in the case of respiratory depression), the blood would continue delivering carbon dioxide to the alveoli in the lungs, and the amount of carbon dioxide in the lungs would increase. On the other hand, if one were to hyperventilate, then fresh air would be drawn into the lungs and carbon dioxide would rapidly be blown out. In the first case, because carbon dioxide is accumulating in the lungs, alveolar PCO2 would become very high.

Hemicrania was mentioned in 1881 in The Therapeutic Gazette Vol. 2, by G.S.Davis, and the incident has been cited in King's American Dispensatory (1898 and later editions) in the description of the strong analgesic Jamaican Dogwood, a relatively low dose of which reportedly produced convulsions and prolonged respiratory depression over six hours in an elderly woman with this condition. In newer times, Hemicrania continua was described in 1981; at that time around 130 cases were described in the literature. However, rising awareness of the condition has led to increasingly frequent diagnosis in headache clinics, and it seems that it is not as rare as these figures would imply.

Sodium oxybate was approved for use by the FDA to treat symptoms of narcolepsy in 2002, with a strict risk evaluation and mitigation strategy (REMS) program mandated by the FDA. The US label for sodium oxybate also has a black box warning because it is a central nervous system depressant and may cause respiratory depression, seizures, coma, or death, especially if used in combination with other CNS depressants, such as alcohol and its use may cause dependence. In Canada and the European Union (EU) it was classified as a Schedule III and a Schedule IV controlled substance, respectively. It was approved for treating symptoms of narcolepsy in Europe in 2005.

The US label for sodium oxybate has a black box warning because it is a central nervous system depressant (CNS depressant) and for its potential for abuse. Other potential adverse side effects include respiratory depression, seizures, coma, and death, especially when it is taken in combination with other CNS depressants such as alcohol. Cases of severe dependence and cravings have been reported with excessive and illicit use of this medication. GHB, the protonated (acidic) form of this salt, has been used to commit drug-facilitated sexual assault and date rape, though the illicit form of GHB typically has different characteristics from pharmaceutical-grade sodium oxybate.

A number of biased agonists, such as those at muscarinic M2 receptors tested as analgesics or antiproliferative drugs, or those at opioid receptors that mediate pain, show potential at various receptor families to increase beneficial properties while reducing side effects. For example, pre-clinical studies with G protein biased agonists at the mu opioid receptor show equivalent efficacy for treating pain with reduced risk for addictive potential and respiratory depression. Studies within the chemokine receptor system also suggest that GPCR biased agonism is physiologically relevant. For example, a beta-arrestin biased agonist of the chemokine receptor CXCR3 induced greater chemotaxis of T cells relative to a G protein biased agonist.

4-Phenylfentanyl is an opioid analgesic that is a derivative of fentanyl. It was developed during the course of research that ultimately resulted in super- potent opioid derivatives such as carfentanil, though it is a substantially less potent analogue. 4-Phenylfentanyl is around eight times the potency of fentanyl in analgesic tests on animals, but more complex 4-heteroaryl derivatives such as substituted thiophenes and thiazoles are more potent still, as they are closer bioisosteres to the 4-carbomethoxy group of carfentanil. Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening.

Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear. As acrylamide derivatives are often used in drug discovery to make covalent inhibitors which will bind irreversibly to its target, acrylfentanyl is claimed to be naloxone resistant. However, acute intoxications with acrylfentanyl on mice threatened by naloxone (2 mg/kg) have shown that acrylfentanyl could be displaced from the opioid receptor.

A BAC from 0.35% to 0.80% causes a coma (unconsciousness), life-threatening respiratory depression and possibly fatal alcohol poisoning. As with all alcoholic drinks, drinking while driving, operating an aircraft or heavy machinery increases the risk of an accident; many countries have severe criminal penalties against drunk driving. A 2016 systematic review and meta-analysis found that moderate ethanol consumption brought no mortality benefit compared with lifetime abstention from ethanol consumption. Some studies have concluded that drinking small quantities of alcohol (less than one drink in women and two in men) is associated with a decreased risk of heart disease, stroke, diabetes mellitus, and early death.

Semorphone (Mr 2264) is an opiate analogue that is an N-substituted derivative of oxymorphone. Semorphone is a partial agonist at μ-opioid receptors. It is around twice the potency of morphine, but with a ceiling effect on both analgesia and respiratory depression which means that these effects stop becoming any stronger after a certain maximum dose. It is not currently used in medicine, and is not a controlled drug, although it might be considered to be a controlled substance analogue of oxymorphone on the grounds of its related chemical structure in some jurisdictions such as the United States, Canada, Australia and New Zealand.

Pheneridine is a 4-Phenylpiperidine derivative that is related to the opioid analgesic drug pethidine (meperidine). Pheneridine is not currently used in medicine. Presumably it has similar effects to other opioid derivatives, such as analgesia, sedation, nausea and respiratory depression, however unlike most opioid derivatives it is not specifically listed as an illegal drug, although it would probably be regarded as a controlled substance analogue of pethidine on the grounds of its related chemical structure in some jurisdictions such as the United States, Canada and Australia, and would be classified as a "Pethidine Analogue" under the New Zealand Misuse of Drugs Act Class C7.

Yin's team showed that morphine causes inflammation by binding to the protein lymphocyte antigen 96, which, in turn, causes the protein to bind to an immune system receptor called Toll-like receptor 4 (TLR4).Making morphine work better, Nature 2012, 484: 419 The morphine-induced TLR4 activation attenuates pain suppression by opioid and enhances the development of opioid tolerance and addiction, drug abuse, and other negative side effects such as respiratory depression. The Yin group has developed drug candidates that can improve opioid-based pain management therapies.Drahl, C. Small Molecules Target Toll-Like Receptors, C&EN; 2012, 90: 33 On June 23, 2014, BioLineRx Ltd.

Combination with SSRIs/SNRIs, SRAs, serotonin receptor agonists may lead to potentially lethal serotonin syndrome. Combination with MAOIs may also result in an adrenergic storm. Use of tapentadol with alcohol or other sedatives such as benzodiazepines, barbiturates, nonbenzodiazepines, phenothiazines, and other opiates may result in increased impairment, sedation, respiratory depression, and death. Tapentadol is partially metabolized by the hepatic enzymes CYP2C9, CYP2C19, and CYP2D6 so it innately has interactions with drugs that enhance or repress the activity/expression of one or more of these enzymes, as well as with substrates of these enzymes (due to competition for the enzyme); some enzyme mediators/substrates require dosing adjustments to one or both medications.

This can cause users to misjudge the intake of one or both of the drugs, sometimes fatally. Because the stimulant effects of cocaine wear off far more quickly than the depressant effects of heroin or morphine, fatal respiratory depression often occurs when the full effects of a heroin or morphine overdosage are felt in isolation. Due to the countering effect of the cocaine, a fatally high opioid dose can be unwittingly administered without immediate incapacitation, thus providing a false sense of tolerance until it is too late. This form of delayed opioid overdose is believed to be the most common mechanism of death in speedball overdoses.

Inflamed tissue has a lower pH value (~5–7) than non-inflamed tissue (7.4). Through computer simulation, scientists found a way to make the fentanyl analog only affect inflamed tissue via the addition of fluorine to the chemical structure. In experiment, it was shown that NFEPP produced injury-restricted analgesia in rats with different types of inflammatory pain without exhibiting typical opiate effects, including respiratory depression, sedation, constipation, and chemical seeking behavior. As a result, NFEPP has the potential to reduce opioid addiction and dependency, as there is no effect on users who are not actually suffering from pain, as the chemical does not interact with non-inflamed brain tissue.

The poly-drug use of powerful depressant drugs poses the highest level of health concerns due to a significant increase in the likelihood of experiencing an overdose, which may cause fatal respiratory depression. A 1990 study found that diazepam has a higher misuse potential relative to many other benzodiazepines and that some data suggest that alprazolam and lorazepam resemble diazepam in this respect. Anecdotally, injection of alprazolam has been reported, causing dangerous damage to blood vessels, closure of blood vessels (embolization) and decay of muscle tissue (rhabdomyolysis). Alprazolam is not very soluble in water—when crushed in water it does not fully dissolve (40 µg/ml of H2O at pH 7).

Nalodeine, also known more commonly as N-allylnorcodeine, is an opioid antagonist (specifically, an antagonist of the μ-opioid receptor) that was never marketed but is notable as the first opioid antagonist to be discovered. It was first reported in 1915, and this was followed by the clinical introduction of nalorphine (N-allylnormorphine) in 1954, naloxone (N-allyloxymorphone) in 1960, and naltrexone (N-methylcyclopropyloxymorphone) in 1963. Nalmefene (6-desoxy-6-methylene-naltrexone), another structurally related opioid antagonist derivative, was also subsequently introduced, in 1996. In animals, nalodeine both reverses morphine- and heroin-induced respiratory depression and acts as a respiratory stimulant in its own right (i.e.

Parafluorofentanyl (4-Fluorofentanyl) is an opioid analgesic being an analogue of fentanyl developed by Janssen Pharmaceutica in the 1960s. 4-Fluorofentanyl was sold briefly on the US black market in the early 1980s, before the introduction of the Federal Analog Act which for the first time attempted to control entire families of drugs based on their structural similarity rather than scheduling each drug individually as they appeared. 4-Fluorofentanyl is made with the same synthetic route as fentanyl, but by substituting para- fluoroaniline for aniline in the synthesis. Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening.

The name of this drug is also given as 3,6-dipropanoylmorphine and its 6-mono-acetylated homologue is also a longer-acting heroin-like drug, as are 3,6-diformylmorphine and 6-formylmorphine. Dipropanoylmorphine, though rarely used, is considered to be a safer and less addictive alternative to morphine. Studies and clinical trials comparing dipropanoylmorphine to morphine have produced results that indicate the incidence of side-effects are far more common with morphine. Respiratory depression, euphoria, excessive sedation and somnolence (so-called 'nodding' by recreational opioid users), constipation, miosis (pinpoint pupils), nausea, bradycardia, behavioral disturbances, and severe physical and psychological dependence on morphine is more likely with the use of morphine versus dipropanoylmorphine.

PZM21 is an experimental opioid analgesic drug that is being researched for the treatment of pain. It is claimed to be a functionally selective μ-opioid receptor agonist which produces μ-opioid receptor mediated G protein signaling, with potency and efficacy similar to morphine, but with less β-arrestin 2 recruitment . However, recent reports highlight that this might be due to its low intrinsic efficacy , rather than functional selectivity or 'G protein bias' as initially reported. In tests on mice, PZM21 was slightly less potent than morphine or TRV130 as an analgesic, but also had significantly reduced adverse effects, with less constipation than morphine, and very little respiratory depression, even at high doses.

Tonazocine (WIN-42,156) is an opioid analgesic of the benzomorphan family which made it to phase II clinical trials for the treatment of postoperative pain, but development was apparently ceased and ultimately it was never marketed. Tonazocine is a partial agonist at both the mu-opioid and delta- opioid receptors, but acting more like an antagonist at the former and more like an agonist at the latter. It lacks most of the side effects of other opioids such as adverse effects on the cardiovascular system and respiratory depression, but it can cause sedation (although to a lesser degree of typical opioids), and in some patients it may induce hallucinations (probably via binding to and activating the κ-opioid receptor).

Unlike conventional opioid agonists, RB-101 also failed to produce respiratory depression, which suggests it might be a much safer drug than traditional opioid painkillers. RB-101 also powerfully potentiated the effects of traditional analgesics such as ibuprofen and morphine, suggesting that it could be used to boost the action of a low dose of normal opioids which would otherwise be ineffective. RB-101 itself is not orally active and so has not been developed for medical use in humans, however modification of the drug has led to newer orally acting compounds such as RB-120 and RB-3007, which may be more likely to be adopted for medical use if clinical trials are successful.

While a further study suggests that ocfentanil may be as effective as morphine in post-operative relief, Ocfentanil was also studied as a supplement to general anaesthesia, in which the researchers concluded that it appears to be similar in action to fentanyl, with 3 μg/kg of ocfentanil approximately equivalent to 5 μg/kg of fentanyl. Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear.

The authors suggested that tianeptine may be acting as a biased agonist of the MOR and that this may be responsible for its atypical profile as a MOR agonist. However, there are reports that suggest that withdrawal effects resembling those of other typical opioid drugs (including but not limited to depression, insomnia, and cold/flu- like symptoms) do manifest following prolonged usage of dose usage far beyond the medical range. In addition to its therapeutic effects, activation of the MOR is likely to also be responsible for the abuse potential of tianeptine at high doses that are well above the normal therapeutic range. When co- administered with morphine, tianeptine prevents morphine-induced respiratory depression without impairing analgesia.

IBNtxA, or 3-iodobenzoyl naltrexamine, is an atypical opioid analgesic drug derived from naltrexone. In animal studies it produces potent analgesic effects that are blocked by levallorphan and so appear to be μ-opioid mediated, but it fails to produce constipation or respiratory depression, and is neither rewarding or aversive in conditioned place preference protocols. These unusual properties are thought to result from agonist action at a splice variant or heterodimer of the μ-opioid receptor, rather than at the classical full length form targeted by conventional opioid drugs.Keck TM, Uddin MM, Babenko E, Wu C, Moura-Letts G. Abuse Liability and Anti-Addiction Potential of the Atypical Mu Opioid Receptor Agonist IBNtxA.

Acetoxyketobemidone (O-Acetylketobemidone) is an opioid analgesic that is an acetylated derivative of ketobemidone. It was developed in the 1950s during research into analogues of pethidine and was assessed by the United Nations Office on Drugs and Crime but was not included on the list of drugs under international control, probably because it was not used in medicine or widely available. Nevertheless, acetoxyketobemidone is controlled as an ester of ketobemidone, which is included in Schedule I of the Single Convention on Narcotic Drugs of 1961. Presumably acetoxyketobemidone produces similar effects to ketobemidone and other opioids, such as analgesia and sedation, along with side effects such as nausea, itching, vomiting and respiratory depression which may be harmful or fatal.

14-Phenylpropoxymetopon (PPOM) is an opiate analogue that is a derivative of metopon which has been substituted with a γ-phenylpropoxy group at the 14-position. It is a highly potent analgesic drug several thousand times stronger than morphine, with a similar in vivo potency to etorphine. The 14-phenylpropoxy substitution appears to confer potent μ-opioid agonist activity, even when combined with substitutions such as N-cyclopropyl or N-allyl, which normally result in μ-opioid antagonist compounds. It has never been used in humans, but would be expected to produce effects similar to those of other potent opioid agonists, including strong analgesia, sedation, euphoria, constipation, itching and respiratory depression which could be harmful or fatal.

Disulfiram (sold under the trade name Antabuse) is a drug used to support the treatment of chronic alcoholism by producing an acute sensitivity to ethanol (drinking alcohol). Disulfiram works by inhibiting the enzyme acetaldehyde dehydrogenase, causing many of the effects of a hangover to be felt immediately following alcohol consumption. Disulfiram plus alcohol, even small amounts, produces flushing, throbbing in the head and neck, a throbbing headache, respiratory difficulty, nausea, copious vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, fast heart rate, low blood pressure, fainting, marked uneasiness, weakness, vertigo, blurred vision, and confusion. In severe reactions there may be respiratory depression, cardiovascular collapse, abnormal heart rhythms, heart attack, acute congestive heart failure, unconsciousness, convulsions, and death.

In patients taking opioids regularly it is essential that the opioid is only partially reversed to avoid a severe and distressing reaction of waking in excruciating pain. This is achieved by not giving a full dose but giving this in small doses until the respiratory rate has improved. An infusion is then started to keep the reversal at that level, while maintaining pain relief. Opioid antagonists remain the standard treatment for respiratory depression following opioid overdose, with naloxone being by far the most commonly used, although the longer acting antagonist nalmefene may be used for treating overdoses of long-acting opioids such as methadone, and diprenorphine is used for reversing the effects of extremely potent opioids used in veterinary medicine such as etorphine and carfentanil.

Metopon (5-methylhydromorphone)US Patent 2178010 is an opioid analogue that is a methylated derivative of hydromorphone which was invented in 1929 as an analgesic. Metopon is sometimes used in medicine, although longer acting than hydromorphone, Metopon is less potent and its oral bioavailability is fairly low. Generally, Metopon has few advantages to distinguish it from other, more commonly used opioid analgesics, although it does have a slightly lower tendency to produce nausea and respiratory depression compared to morphine. In Canada, as of 1948, the hydrochloride of metopon (free base conversion ratio 0.891, molecular weight 335.8) was available only for oral administration for malignant pain and for maintenance of those habituated to morphine; the only dosage form available was singly scored 8 mg tablets.

Piritramide (R-3365, trade names Dipidolor, Piridolan, Pirium and others) is a synthetic opioid analgesic (narcotic painkiller) that is marketed in certain European countries including: Austria, Belgium, Czech Republic, Germany and the Netherlands. It comes in free form, is about 0.75x times as potent as morphine and is given parenterally (by injection) for the treatment of severe pain. Nausea, vomiting, respiratory depression and constipation are believed to be less frequent with piritramide than with morphine (the gold standard opioid against which other opioids are compared and contrasted), and it produces more rapid-onset analgesia (pain relief) when compared to morphine and pethidine. After intravenous administration the onset of analgesia is as little as 1–2 minutes, which may be related to its great lipophilicity.

The Mexican common name (also spelled ) derives from the Nahuatl , meaning "the plant with the nodding head" (in reference to the nodding seed capsules of Datura species belonging to section Dutra of the genus). Datura species are native to dry, temperate, and subtropical regions of the Americas and are distributed mostly in Mexico, which is considered the centre of origin of the genus. Datura ferox was long thought native to China, Datura metel to India and southeast Asia, and Datura leichardthii to Australia; however, recent research has shown these species to be early introductions from Central America. All species of Datura are poisonous and potentially psychoactive, especially their seeds and flowers which can cause respiratory depression, arrhythmias, fever, delirium, hallucinations, psychosis, and even death if taken internally.

Tapentadol, with some structural similarities to tramadol, presents what is believed to be a novel drug working through two (and possibly three) different modes of action in the fashion of both a traditional opioid and as an SNRI. The effects of serotonin and norepinephrine on pain, while not completely understood, have had causal links established and drugs in the SNRI class are commonly used in conjunction with opioids (especially tapentadol and tramadol) with greater success in pain relief. Dosing of all opioids may be limited by opioid toxicity (confusion, respiratory depression, myoclonic jerks and pinpoint pupils), seizures (tramadol), but opioid-tolerant individuals usually have higher dose ceilings than patients without tolerance. Opioids, while very effective analgesics, may have some unpleasant side-effects.

Levallorphan (INN, BAN) (brand names Lorfan, Naloxifan, Naloxiphan), also known as levallorphan tartrate (USAN), is an opioid modulator of the morphinan family used as an opioid analgesic and opioid antagonist/antidote. It acts as an antagonist of the μ-opioid receptor (MOR) and as an agonist of the κ-opioid receptor (KOR), and as a result, blocks the effects of stronger agents with greater intrinsic activity such as morphine whilst simultaneously producing analgesia. Levallorphan was formerly widely used in general anesthesia, mainly to reverse the respiratory depression produced by opioid analgesics and barbiturates used for induction of surgical anaesthesia whilst maintaining a degree of analgesia (via KOR agonism). It is now less commonly employed for this purpose as the newer drug naloxone tends to be used instead.

Examples of such compounds include nalorphine and levallorphan. However, the analgesic effects from these specific drugs are limited and tend to be accompanied by dysphoria, most likely due to additional agonist action at the κ-opioid receptor. As they induce opioid withdrawal effects in people who are taking, or have recently used, opioid full agonists, these drugs are generally considered to be antagonists for practical purposes. The weak partial agonist effect can be useful for some purposes, and has previously been used for purposes such as long-term maintenance of former opioid addicts using nalorphine, however it can also have disadvantages such as worsening respiratory depression in patients who have overdosed on non- opioid sedatives such as alcohol or barbiturates.

Etonitazene is an analgesic drug, first reported in 1957, that has been shown to have approximately one thousand to one thousand five hundred times the potency of morphine in animal models, but only sixty times the potency in humans. One of several benzimidazole opioids, etonitazene is structurally related to clonitazene, in which the p-ethoxybenzyl group is replaced by a p-chlorobenzyl group; however, clonitazene itself is only three times as potent as morphine. Because it is characterized by a strong dependency potential and a tendency to produce profound respiratory depression, it is not used in humans. It is, however, useful in animal models for addiction studies, particularly those requiring the animals to drink or ingest the agent, because it is not as bitter as opiate salts like morphine sulfate.

Sampson also indicated that Brown probably had progressive respiratory depression and perhaps had made moaning and groaning sounds, and was also gasping for air. Sampson further indicated that subdural hematoma was the mechanism of her death. A specialist for the ACS, Vanessa Rhoden, had reported that on December 1, 2005, she had witnessed early signs of abuse in Brown but was rebuffed by Rodriguez. Rodriguez had told Rhoden that he had taken Brown to the hospital, and then used foul language to address her and end the conversation. This revelation took defense lawyer Schwartz off-guard during the Tuesday, February 19 trial portion because he had called Rhoden to the stand to show the court and the jury that there was no cause for alarm at that time.

Patient SafetyNet is a remote monitoring and notification system designed for patients on medical/surgical care floors. A large study by Dartmouth-Hitchcock Medical Center showed Patient SafetyNet helped clinicians achieve a 65% reduction in distress codes and rescue activations and a 48% decrease in patient transfers to intensive care units (ICU), yielding a savings of 135 Intensive Care Unit (ICU) days annually for an annual opportunity-cost savings of $1.48 million. In 2020, Dartmouth- Hitchcock published a retrospective study showing that over ten years of using Patient SafetyNet, there were zero patient deaths and no patients were harmed by opioid-induced respiratory depression while continuous monitoring with Masimo SET was in use. ECRI Institute gave Dartmouth its Health Devices Achievement Award for its use of Patient SafetyNet to prevent "severe patient harm".

Hydromorphinol (RAM-320, 14-Hydroxydihydromorphine), also is an opiate analogue that is a derivative of morphine, where the 14-position has been hydroxylated and the 7,8- double bond saturated. It has similar effects to morphine such as sedation, analgesia and respiratory depression, but is twice as potent as morphine and has a steeper dose-response curve and longer half- life. It is used in medicine as the bitartrate salt (free base conversion ratio 0.643, molecular weight 471.5) and hydrochloride (free base conversion ratio 0.770, molecular weight 393.9) It is also called α-Oxymorphol, and oxymorphol is itself a mixture of hydromorphinol and 4,5α-Epoxy-17-methylmorphinan-3,6β,14-triol, β-Oxymorphol, which is different at position 6 on the morphine carbon skeleton. Hydromorphinol was developed in Austria in 1932.

An opioid epidemic is the overuse or misuse of addictive opioid drugs with significant medical, social and economic consequences, including overdose deaths. Opioids are a diverse class of moderately strong painkillers, including oxycodone (commonly sold under the trade names OxyContin and Percocet), hydrocodone (Vicodin, Norco) and a very strong painkiller, fentanyl, which is synthesized to resemble other opiates such as opium-derived morphine and heroin. The potency and availability of these substances, despite their high risk of addiction and overdose, have made them popular both as medical treatments and as recreational drugs. Due to their sedative effects on the part of the brain which regulates breathing, the respiratory center of the medulla oblongata, opioids in high doses present the potential for respiratory depression and may cause respiratory failure and death.

Nefopam is effective for prevention of shivering during surgery or recovery from surgery. Nefopam was significantly more effective than aspirin as an analgesic in one clinical trial, although with a greater incidence of side effects such as sweating, dizziness and nausea, especially at higher doses. The estimated relative potency of nefopam to morphine indicates that 20 mg of nefopam HCl is the approximate analgesic equal of 12 mg of morphine with comparable analgesic efficacy to morphine, or oxycodone, while nefopam tends to produce fewer side effects, does not produce respiratory depression, and has much less abuse potential, and so is useful either as an alternative to opioid analgesics, or as an adjunctive treatment for use alongside opioid (or other) analgesics. Nefopam is also used to treat severe hiccups.

Benzoctamine’s main clinical use is for the treatment of anxiety, and evidence points to it being as effective as other clinical anxiety drugs, in particular diazepam. In the treatment of symptoms of mild anxiety due to psychoneurosis, a daily dosage of 30 to 80 g of benzoctamine was shown to be just as effective as 6–20 mg of diazepam. In another study one group of patients were given 10g of benzoctamine three times a day, while another group was given 5 mg of diazepam, and the treatments were equivalent. While these studies point to higher doses of benzoctamine being needed to exert the same pharmacological effects, the drug is still popular because of its ability to act as an anxiolytic without producing the common respiratory depression associated with other sedative drugs.

R-4066 (Spirodone) is a drug which is an analogue of the opioid analgesic methadone, or more accurately norpipanone, where the metabolically labile dimethylamino group has been replaced by a piperidinospiro group. Developed by Janssen Pharmaceutica, it is around 212x more potent than methadone as an analgesic in animal tests, with an effective oral dosage of 0.07 mg/kg, but is shorter acting, with a duration of action of around 3 hours. If the ketone function is reduced and acetylated, the racemate 106 x methadone and has an analgesic duration of 20.5 hours compared to 8 hours for methadone. R-4066 has never been used in humans, but would be expected to produce effects similar to those of other potent opioid agonists, including strong analgesia, sedation, euphoria, constipation, itching and respiratory depression which could be harmful or fatal.

WAY-100635 has also been found to increase the analgesic effects of opioid drugs in a dose-dependent manner, in contrast to 5-HT1A agonists such as 8-OH-DPAT which were found to reduce opioid analgesia. However, since 5-HT1A agonists were also found to reduce opioid-induced respiratory depression and WAY-100635 was found to block this effect, it is likely that 5-HT1A antagonists might worsen this side effect of opioids. Paradoxically, chronic administration of the very high efficacy 5-HT1A agonist befiradol results in potent analgesia following an initial period of hyperalgesia, an effect most likely linked to desensitisation and/or downregulation of 5-HT1A receptors (i.e. analogous to a 5-HT1A antagonist-like effect). As with other 5-HT1A silent antagonists such as UH-301 and robalzotan, WAY-100635 can also induce a head-twitch response in rodents.

Mambalgins are believed to trap ASICs in a closed conformation. In tests performed on laboratory mice, mambalgins have the in vivo effect of analgesia without the toxic effects seen with most 3FTx proteins, and in particular, without the clinical manifestations associated with inhibition of nicotinic acetylcholine receptors, the targets of most 3FTx proteins including mambalgins' closest relatives. Furthermore, the analgesic effects of mambalgins does not confer side effects such as respiratory depression and drug tolerance, both associated with opioid analgesics. Summary of the different pathways that mambalgins and PcTx1 follow (non-opioid and opioid pathways) In addition to mambalgins, at least three other peptides from three different taxa have been identified as interacting with ASICs: PcTx1, from the South American tarantula Psalmopoeus cambridgei; APETx2, from the sea anemone Anthopleura elegantissima; and MitTx, a heterodimer from the snake Micrurus tener tener.

It thus seems likely that while δ-opioid agonists can produce respiratory depression at very high doses, at lower doses they have the opposite effect, a fact that may make mixed mu/delta agonists such as DPI-3290 potentially very useful drugs that might be much safer than the μ agonists currently used for pain relief. Many delta agonists may also cause seizures at high doses, although not all delta agonists produce this effect. Of additional interest is the potential for delta agonists to be developed for use as a novel class of antidepressant drugs, following robust evidence of both antidepressant effects and also upregulation of BDNF production in the brain in animal models of depression. These antidepressant effects have been linked to endogenous opioid peptides acting at δ- and μ-opioid receptors, and so can also be produced by enkephalinase inhibitors such as RB-101.

Diphenpipenol is an opioid analgesic drug invented in the 1970s by Dainippon Pharmaceutical Co. It is chemically a 1-substituted-4-(1,2-diphenylethyl)piperazine derivative related to compounds such as MT-45 and AD-1211, but diphenpipenol is the most potent compound in the series, with the more active (S) enantiomer being around 105 times the potency of morphine in animal studies. This makes it a similar strength to fentanyl and its analogues, and consequently diphenpipenol can be expected to pose a significant risk of producing life-threatening respiratory depression, as well as other typical opioid side effects such as sedation, itching, nausea and vomiting. Diphenpipenol has been offered for sale online as a designer drug, though analysis of a sample of supposed diphenpipenol found it to instead contain a structural isomer with much weaker opioid activity, and it is unclear if genuine diphenpipenol has actually been sold.

The infiltration of a solution of anaesthesia- and tumescence-inducing drugs can present medical complications such as a fluid overload of the tissues, the inadequate replacement of the infiltrated solution, and the partitioning (separation) of a single infiltration into several pools, which then are removed by suction lipectomy. Moreover, during anaesthesia, maintaining the patient's stable blood pressure can be difficult, which increases the possibility of bleeding, and the possibility that anaesthetic toxicity can occur if excessive doses are administered by infiltration; the symptoms are manifested as central nervous system (CNS) occurrences of drug-induced anxiety, apprehension, restlessness, nervousness, disorientation, confusion, dizziness, blurred vision, tremors, nausea, vomiting, shivering, and seizures; likewise, as manifestations of drowsiness, unconsciousness, respiratory depression, and respiratory arrest. Furthermore, the toxicity symptoms of a tumescence-inducing drug (e.g. epinephrine) might cause such CNS symptoms, for which reason the operative application of a tumescent drug is limited throughout the operation.

After the war, all German patents, trade names and research records were requisitioned and expropriated by the Allies. The records on the research work of the I.G. Farbenkonzern at the Farbwerke Hoechst were confiscated by the U.S. Department of Commerce Intelligence, investigated by a Technical Industrial Committee of the U.S. Department of State and then brought to the US. The report published by the committee noted that while methadone was potentially addictive, it produced less sedation and respiratory depression than morphine and was thus interesting as a commercial drug. In the early 1950s, methadone (most times the racemic HCl salts mixture) was also investigated for use as an antitussive. Isomethadone, noracymethadol, LAAM, and normethadone were first developed in Germany, United Kingdom, Belgium, Austria, Canada, and the United States in the thirty or so years after the 1937 discovery of pethidine, the first synthetic opioid used in medicine.

With the sole exception of nalorphine, all of the preceding are used as analgesics (by virtue of the fact that both MOR and KOR agonism independently confer pain relief). However, these opioid analgesics have atypical properties in comparison to the prototypical pure MOR full agonist opioid analgesics, such as less or no risk of respiratory depression for MOR partial agonists and antagonists, reduced or no euphoria, abuse potential, and dependence liability with MOR partial agonists/antagonists, and use- and dose-limiting side effects such as dysphoria and hallucinations with KOR agonists. In addition, by virtue of its KOR antagonism, buprenorphine (as buprenorphine/samidorphan (ALKS-5461) or buprenorphine/naltrexone to block its MOR agonism) is under investigation for the treatment of depression and cocaine dependence, as are other KOR antagonists such as CERC-501 (LY-2456302) and, previously, JDTic and PF-4455242 (both discontinued due to toxicity concerns).

Sublingual forms of dihydroetorphine are used in China at doses ranging from 20 to 40μg repeated every 3-4 hours, and are reported to cause strong analgesia and relatively mild side effects compared to other opioids, although all the usual opioid side effects such as dizziness, sedation, nausea, constipation, and respiratory depression can occur. Transdermal patches of dihydroetorphine have also been developed. Dihydroetorphine is considered to be somewhat less addictive than many other opioids, and it is also sometimes used in China as a substitute maintenance drug for opioid addicts, in a similar way to how the related drug buprenorphine is used in western nations. It is presumably controlled as an "ester, ether, salt ..." of etorphine in the United States under the Controlled Substances Act 1970 and/or its pieces of the morphine carbon skeleton put it under the "morphine rule" thereof and/or the 1986 analogues act; it does not have its own ACSCN.

The response of TLR4 to opioid drugs has been found to be enantiomer-independent, so the "unnatural" enantiomers of opioid drugs such as morphine and naloxone, which lack affinity for opioid receptors, still produce the same activity at TLR4 as their "normal" enantiomers. This means that the unnatural enantiomers of opioid antagonists, such as (+)-naloxone, can be used to block the TLR4 activity of opioid analgesic drugs, while leaving the μ-opioid receptor mediated analgesic activity unaffected.) This may also be the mechanism behind the beneficial effect of ultra-low dose naltrexone on opioid analgesia. Morphine causes inflammation by binding to the protein lymphocyte antigen 96, which, in turn, causes the protein to bind to Toll-like receptor 4 (TLR4). The morphine-induced TLR4 activation attenuates pain suppression by opioids and enhances the development of opioid tolerance and addiction, drug abuse, and other negative side effects such as respiratory depression and hyperalgesia.

Other studies have shown that signal extraction technology pulse oximetry results in fewer arterial blood gas measurements, faster oxygen weaning time, lower sensor utilization, and lower length of stay. The measure-through motion and low perfusion capabilities it has also allow it to be used in previously unmonitored areas such as the general floor, where false alarms have plagued conventional pulse oximetry. As evidence of this, a landmark study was published in 2010 showing that clinicians at Dartmouth-Hitchcock Medical Center using signal extraction technology pulse oximetry on the general floor were able to decrease rapid response team activations, ICU transfers, and ICU days. In 2020, a follow-up retrospective study at the same institution showed that over ten years of using pulse oximetry with signal extraction technology, coupled with a patient surveillance system, there were zero patient deaths and no patients were harmed by opioid-induced respiratory depression while continuous monitoring was in use.

As an example, while its parent peptide, [Met]enkephalin, has an in vivo half-life of merely seconds, metkefamide has a half-life of nearly 60 minutes, and upon intramuscular administration, has been shown to provide pain relief that lasts for hours. Likely on account of its δ-opioid activity, clinical trials have found metkefamide to possess less of a tendency for producing many of the undesirable side effects usually associated with conventional opioids such as respiratory depression, tolerance, and physical dependence. However, it has been shown to cause some additional side effects that are considered unusual for standard opioid analgesics like sensations of heaviness in the extremities and nasal congestion—though these were not considered to be particularly distressing—and it has also been shown to raise the seizure threshold in animals. In any case, clinical development was not further pursued after phase I clinical studies and metkefamide never reached the pharmaceutical market.

Benzylfentanyl (R-4129) is a fentanyl analog. It was temporarily placed in the US Schedule I by emergency scheduling in 1985 due to concerns about its potential for abuse as a designer drug, but this placement was allowed to expire and benzylfentanyl was formally removed from controlled substance listing in 2010, after the DEA's testing determined it to be "essentially inactive" as an opioid.Correction of Code of Federal Regulations: Removal of Temporary Listing of Benzylfentanyl and Thenylfentanyl as Controlled Substances Benzylfentanyl has a Ki of 213 nM at the mu opioid receptor, binding around 1/200 as strong as fentanyl itself,Utilization of a radioreceptor assay for the analysis of fentanyl analogs in urine Mario Enrique Alburges though it is still slightly more potent than codeine. Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea, and potentially serious respiratory depression which can be life-threatening.

Recent studies indicate that targeting NOP is a promising alternative route to relieving pain without the deleterious side effects of traditional MOP-activating opioid therapies. In primates, specifically activating NOP through systemic or intrathecal administration induces long-lasting, morphine-comparable analgesia without causing itch, respiratory depression, or the reinforcing effects that lead to addiction in an intravenous self-administration paradigm; thus eliminating all of the serious side-effects of current opioid therapies. Several commonly used opioid drugs including etorphine and buprenorphine have been demonstrated to bind to nociceptin receptors, but this binding is relatively insignificant compared to their activity at other opioid receptors in the acute setting (however the non-analgesic NOPr antagonist SB-612,111 was demonstrated to potentiate the therapeutic benefits of morphine). Chronic administration of nociceptin receptor agonists results in an attentuation of the analgesic and anti- allodynic effects of opiates; this mechanism inhibits the action of endogenous opioids as well, resulting in an increase in pain severity, depression, and both physical and psychological opiate dependence following chronic NOPr agonist administration.

In this survey of 82 street-recruited IDU's who had experienced one or more heroin overdose events, 51% reported soliciting emergency assistance, 87% were in favor of participating in an overdose training program, 35% predicted they would feel comfortable using greater amounts of heroin if they had narcan in their possession, 62% would be less inclined to call 911 for an overdose, 30% would leave an overdose victim after naloxone resuscitation, and 46% might not be able to dissuade the victim from using heroin again to alleviate withdrawal symptoms induced by naloxone. Another article published by van Dorp, raised concerns that i) "the induction of an acute withdrawal syndrome (the occurrence of vomiting and aspiration is potentially life threatening)" – and that could lead to abandonment by a narcan provider/friend; ii) "the effect of naloxone may wear off prematurely when used for treatment of opioid-induced respiratory depression and require multiple doses and long-term vigilance". "Risks warranting the cautious use of naloxone and adequate monitoring of the cardiorespiratory status of the overdose person after naloxone administration where indicated".

The physician Muhammad ibn Zakariya al-Razi of Persian origin ("Rhazes", 845–930 CE) maintained a laboratory and school in Baghdad, and was a student and critic of Galen; he made use of opium in anesthesia and recommended its use for the treatment of melancholy in Fi ma-la-yahdara al-tabib, "In the Absence of a Physician", a home medical manual directed toward ordinary citizens for self-treatment if a doctor was not available. The renowned Andalusian ophthalmologic surgeon Abu al-Qasim al-Zahrawi ("Abulcasis", 936–1013 CE) relied on opium and mandrake as surgical anaesthetics and wrote a treatise, al-Tasrif, that influenced medical thought well into the 16th century. The Persian physician Abū ‘Alī al-Husayn ibn Sina ("Avicenna") described opium as the most powerful of the stupefacients, in comparison to mandrake and other highly effective herbs, in The Canon of Medicine. The text lists medicinal effects of opium, such as analgesia, hypnosis, antitussive effects, gastrointestinal effects, cognitive effects, respiratory depression, neuromuscular disturbances, and sexual dysfunction.

GRIs can induce a wide range of psychological and physiological effects, including a general and subjective alteration in consciousness, dizziness, blurry vision, diplopia or double vision, nystagmus or involuntary eye movements, amblyopia or "lazy eye", tinnitus or "ear ringing", sedation, drowsiness or somnolence, narcolepsy, tiredness or weakness, fatigue or lethargy, aches and pains, headache, nausea and vomiting, gastrointestinal disturbances, shakiness, disorientation, diminished awareness, impaired attention, focus, and concentration, decreased drive and motivation, stuttering and slurring of speech, confusion, cognitive and memory impairment, mood lift or drop, depression, anxiolysis, disinhibition, stress reduction, euphoria or dysphoria, irritability, aggression, anger or rage, increased appetite and subsequent weight gain, ataxia or impaired coordination and balance, muscle relaxation, trembling or muscle tremors and spasms, paresthesia or "pins and needles", analgesia, respiratory depression, and dyspnea or shortness of breath, among others. However, many of these properties are dependent on whether the GRI in question is capable of crossing the blood-brain-barrier (BBB). Those that do not will only produce peripheral effects. GRIs such as CI-966 have been characterized as hallucinogens with effects analogous to those of the GABAA receptor agonist muscimol (a constituent of Amanita muscaria (fly agaric) mushrooms) when administered at sufficient doses.