Opioids overdoses

Opioidergic agents. Naltrexone and nalmefene, opioid antagonists with no intrinsic agonist properties, have been studied for the treatment of alcohol dependence. Naltrexone has been studied much more extensively than nalmefene for this indication. In 1984 naltrexone was approved by the FDA for the treatment of opioid dependence, and in 1994 it was approved for the treatment of alcohol dependence. Nalmefene is approved in the United States as a parenteral formulation for the acute reversal of opioid effects (e.g., after opioid overdose or analgesia). 

Major gastrointestinal effects include decreased gut motility and changes in secretion of gastric and intestinal fluids. Morphine and most p receptor agonists cause pupillary constriction. Some tolerance to this effect may develop, but addicts with high opioid levels will still have miosis. Respiratory depression is the usual cause of death from opioid overdose. 

Naltrexone (Trexan) is the only opioid antagonist currently in use for treatment of addiction. Naloxone is used to treat opioid overdose and to test for opioid addiction but has a short half-life and is relatively ineffective orally cyclazocine s dysphoric side effects make it unacceptable (Resnick et al. 1980). Patients who are likely to continue to use naltrexone and to benefit from treatment are those who have established careers (e.g., health professionals) and family support and are well motivated. Up to 70% of such clients are abstinent at 1-year follow-up (Washton et al. 1984). Programs that utili2e additional rehabilitative services have better results than those that provide minimal services. Successful treatment is also associated with taking naltrexone... 

The opioid antagonists naloxone and naltrexone bind to aU three opioid receptors, p, K, and 8. These compounds are antagonists due to their inability to elicit downstream effects of these receptors once bound (Sarton et al. 2008 Yaksh and Rudy 1977). Interestingly, both antagonists have a high binding affinity for MORs. Naloxone is used to reverse the effects of an acute opioid overdose because of its rapid onset of action. Naltrexone elicits similar actions, but has a longer onset and duration of action and hence, is used for the maintenance of treatment for opioid addicts. 

Monoamine oxidase inhibitors can induce hyperpyrexia anchor seizures or opioid overdose symptoms Used in severe pain Do not use transdermal in acute pain... 

Starting doses to be used in cases of opioid overdose. 

Reversal of opioid effects Complete or partial reversal of opioid drug effects, including respiratory depression, induced by either natural or synthetic opioids. Opioid overdose Management of known or suspected opioid overdose. 

Management of known/suspected opioid overdose Use 1 mg/mL dosage strength (green label). The recommended initial dose of nalmefene for nonopioid dependent patients is 0.5 mg/70 kg. If needed, this may be followed by a second dose of 1 mg/70 kg, 2 to 5 minutes later. If a total dose of 1.5 mg/70 kg has been administered without clinical response, additional nalmefene is unlikely to have an effect. 

High potency (HP) injection - HP injection is a highly concentrated solution of hydromorphone intended for use in opioid-tolerant patients. Do not confuse HP injection with standard parenteral formulations of injection or other opioids. Overdose and death could result. 

Perform cardiopnlmonary resuscitation if necessary If victim is in a coma, administer naloxone hydrochloride (in narcotic or opioid overdose) and 50% glucose (in case of insulin shock)... 

Because of its fast onset (minutes), naloxone (Narcan) administered IV is used most frequently for the reversal of opioid overdose. However, it fails to block some side effects of the opioids that are mediated by the ct-receptor, such as hallucinations. The rapid offset of naloxone makes it necessary to administer the drug repeatedly until the opioid agonist has cleared the system to prevent relapse into overdose. The half-life of naloxone in plasma is 1 hour. It is rapidly metabolized via... 

C. The purpose of this question is to clarify the functional significance of the activation of opioid receptor types. Respiratory depression and bradycardia are associated with the ji2-opioid receptor. Mydriasis is associated with the o-receptor, which is no longer thought of as opioid. Opioids, via respiratory depression, induce hypercapnia, a build-up of carbon dioxide. The clinically relevant sign of opioid overdose and opioid use is miosis, pinpoint pupils, mediated by K-receptor activation. 

Known or suspected opioid overdose IV, IM, Subcutaneous Initially, 0.5 mg/70kg. May give 1 mg/70kgin 2-5 min. If physical opioid dependence suspected, initial dose isO. 1... 

Acute administration of opioids, particularly in non-tolerant individuals, produces a syndrome of intoxication characterized by pupillary dilation and initial euphoria, followed by apathy, psychomotor retardation, slurred speech, and impaired attention and memory. Opioid overdose can produce fatal respiratory depression and thus is a medical emergency. 

Overdosing causes stupor and coma. Pulmonary edema occurs, and froth can be seen coming from the nose and mouth. An antidote for an opioid overdose is naloxone (Nar-can ), which can rapidly displace the opioid from the receptor. Overuse of dextromethorphan can induce euphoria, sedation, ataxia, increased awareness, sweating, elevated blood pressure, arrhythmia, hallucinations, and coma. Some of the dextromethorphan effects resemble those of phencyclidine. 

It is inactive orally because of high first pass metabolism in liver. Metabolised by glucuronidation in liver. The main use of naloxone is in the treatment of acute opioid overdose (acute morphine poisoning). It also precipitates withdrawal syndrome when administered to morphine addicts. The constricted pupils of addicts dilate after administration of naloxone. This has been used as a diagnostic tool for opioid addiction. 

All pure p agonist opioids produce a dose-related depression of ventilation. Pure K agonists have little effect on respiration. The primary effect of opioids is a reduction in the sensitivity of the respiratory centre to C02. They also depress the medullary and peripheral chemoreceptors. Initially, respiratory rate is affected more than tidal volume, which may even increase. With increasing doses respiratory rhythmicity is disturbed resulting in the irregular, gasping breathing characteristic of opioid overdose. The hypoxic drive to ventilation is also depressed by opioids. 

The first drug in this class was nalorphine (/V-allylmorphine). Nalorphine is equipotent with morphine but produced severe psychotomimetic activity, which precluded its use as an analgesic. Until the discovery of naloxone it was widely used for its antagonist properties in the treatment of opioid overdose. The dysphoric side effects of some of this class of drugs is thought to be due to binding to the non-opioid a receptor. 

Constriction of the pupils is seen with virtually all opioid agonists. Miosis is a pharmacologic action to which little or no tolerance develops (Table 31-3) thus, it is valuable in the diagnosis of opioid overdose. Even in highly tolerant addicts, miosis is seen. This action, which can be blocked by opioid antagonists, is mediated by parasympathetic pathways, which, in turn, can be blocked by atropine. 

Intravenous injection of naloxone dramatically reverses coma due to opioid overdose but not that due to other CNS depressants. Use of the antagonist should not, of course, delay the institution of other therapeutic measures, especially respiratory support. 

The major application of naloxone is in the treatment of acute opioid overdose (see also Chapter 58). It is very important that the relatively short duration of action of naloxone be borne in mind, because a severely depressed patient may recover after a single dose of naloxone and appear normal, only to relapse into coma after 1-2 hours. 

Naloxone Antagonist at P-, 5, and receptors Rapidly antagonizes all opioid effects Opioid overdose Duration 1-2 h (may have to be repeated when treating overdose) Toxicity Precipitates abstinence syndrome in dependent users... 

Naloxone Nonselective antagonist of opioid receptors Reverses the acute effects of opioids can precipitate severe abstinence syndrome Opioid overdose Effect much shorter than morphine (1-2 h), therefore several injections required... 

Opioids (opium, morphine, heroin, meperidine, methadone, etc) are common drugs of abuse (see Chapters 31 and 32), and overdose is a common result of using the poorly standardized preparations sold on the street. See Chapter 31 for a detailed discussion of opioid overdose and its treatment. 

Analgesic efficacy and clinical use Levallorphan (Leimgruber et al., 1973) is an opioid antagonist with a minor agonistic component and practically no analgesic action. It has been used as one of the first relative pure antagonists for the treatment of opioid overdose, to reverse opioid central depression and to antagonize opioid-induced respiratory impairment (Foldes et al., 1969). 

As a Schedule II opioid narcotic, meperidine is highly addictive. Treatment for opioid overdose usually involves administration of an opioid antagonist such as Narcan (naloxone), which reverses or blocks the effects of the drug. However, in some cases, those who overdose on meperidine do not respond well to opioid antagonists. 

Naloxone is being used to reverse the potentially lethal respiratory depression caused by neurolept analgesia or opioid overdose. Among other pharmacological effects, naloxone antagonizes the blood pressure drop in various forms of shock [29-32], reverses neonatal hypoxic apnoea [26], counteracts chronic idiopathic constipation [34], reduces the food intake in humans [35, 36] and shows beneficial effects in CNS injuries [37]. 

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