Overdose opioid

Action on receptors provides numerous examples. Beneficial interactions are sought in overdose, as with the use of naloxone for morphine overdose (opioid receptor), of atropine for anticholinesterase, i.e. insecticide poisoning (acetylcholine receptor), of isoproterelol (isoprenaline) for overdose with a P-adrenoceptor blocker (p-adrenoceptor), of phentolamine for the monoamine oxidase inhibitor-sympathomimetic interaction (a-adrenoceptor). 

Constipation and sedation occur with therapeutic doses constipation should be managed with stool softeners. In overdose, opioids cause a triad of pinpoint pupils, coma, and respiratory depression. 

Wunsch MJ, Cropsey KL, Campbell ED, Knisely JS. OxyContin abuse and overdose. / Opioid Manage 2008 4(2) 73-79. 

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

Opiate overdose is a medical emergency that can result in respiratory and CNS depression. The opioid receptor antagonist naloxone immediately reverses cardiorespiratory depression. However, repeated naloxone administration is required, since the effects of naloxone last for 30 min, while opioid agonists can remain at potentially lethal blood levels for several hours. 

Two opioids are used in the treatment and management of opiate dependence levomethadyl and methadone. Levomethadyl is given in an opiate dependency clinic to maintain control over the delivery of the drug. Because of its potential for serious and life-threatening proarrhythmic effects, levomethadyl is reserved for use in the treatment of addicted patients who have no response to other treatments. Levomethadyl is not taken daily the drug is administered three times a week (Monday/Wednesday/Thursday or Tuesday/Thursday/ Saturday). Daily use of the usual dose will cause serious overdose. 

This drug is used for complete or partial reversal of narcotic depression, including respiratory depression. Narcotic depression may be due to intentional or accidental overdose (self-administration by an individual), accidental overdose by medical personnel, and drug idiosyncrasy Naloxone also may be used for diagnosis of a suspected acute opioid overdosage. 

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. 

The large numbers of opioid receptors in areas of the brainstem such as the solitary tract and adjacent areas are probably related to respiratory effects of opiates, cough suppression and nausea and vomiting. Opiates acting in the brainstem reduce the sensitivity of the respiratory centres to pC02 and this is the most common cause of death from overdose with street use of opiates. 

Figure 5.1 Visualization of the distribution of the DA transporter, D3 receptor, and K2-opioid receptor in the human brain of a drug-free control subject and a representative cocaine overdose victim. (A, B) The DA transporter was measured using [3H]WIN 35,428 (2 nM) as described previously. (C, D) The D3 receptor was measured using [3H]-(+)-7-OH-DPAT (1 nM) in the presence of GTP (300 m/W) to enhance the selective labeling of the D3 receptor subtype over the D2 receptor subtype as described previously. (E, F) The K2-opioid receptor subtype was measured using [125l]IOXY on tissue sections pretreated with BIT and FIT to occlude binding to the p- and 8-opioid receptors, respectively.

Mash D.C., Staley J.K. D3 dopamine and kappa opioid receptor alterations in human brain of cocaine-overdose victims. Ann. N.Y. Acad. Sci. 877 507, 1999. 

Staley J.K., Rothman R.B., Rice K.C., Partilla J., Mash D.C. Kappa2 opioid receptors in limbic areas of the human brain are upregulated by cocaine in fatal overdose victims. J. Neurosci. 17 8225, 1997. 

The answer is c. (Hardman, pp 574—575.) Phencyclidine is a hallucinogenic compound with no opioid activity Its mechanism of action is amphetamine-like. A withdrawal syndrome has not been described for this drug in human subjects. In overdose, the treatment of choice for the psychotic activity is the antipsychotic drug haloperidol. 

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. 

Miosis Morphine causes constriction of the pupil by a direct action on the parasympathetic nerve. Miosis is pathognomonic of opioid (specifically ju agonist) overdose, but mydriasis occurs with respiratory suppression and asphyxiation. 

Naloxone (Narcan). Naloxone, like naltrexone, is a potent opioid receptor blocker. Its primary use has been to reverse opiate toxicity after an overdose. However, some physicians have found it is also useful for a process known as rapid opiate detoxification. Although opiate withdrawal is not life threatening, it can be extremely unpleasant. Most opiate addicts are fearful of the withdrawal symptoms therefore, it usually requires a slow, deliberate detoxification to keep the withdrawal symptoms in check. Rapid opiate detoxification is an alternative approach that keeps the taper and detoxification as brief as possible. In this approach, naloxone is used in conjunction with general anesthesia or a nonopiate sedative such as the benzodiazepine mid-... 

It is worth mentioning that iV-allylic substitution in a number of morphine derivatives, as a rule, leads to antagonistic properties. Naloxone is a few times stronger than nalorphine as an antagonist. It blocks opiate receptors. It eliminates central and peripheral action of opioids, including respiratory depression. Naloxone is used upon overdose of narcotic analgesics.Synonyms for this drug are narkan, talwin, and others. 

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. 

Respiratory depression Accidental overdose with long-acting opioids (eg, methadone, levomethadyl) may result in prolonged respiratory depression. While nalmefene has a longer duration of action than naloxone in fully reversing doses, be aware that a recurrence of respiratory depression is possible. Observe patients until there is no reasonable risk of recurrent respiratory depression. 

Fentanyl transdermal system Fentanyl transdermal systems contain a high concentration of the potent schedule II opioid agonist, fentanyl. Schedule II opioid substances have the highest potential for abuse and associated risk of fatal overdose due to respiratory depression. Fentanyl can be abused and is subject to criminal diversion. The high content of fentanyl in the patches may be a particular target for abuse and diversion. 

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. 

Conversion from CR tablets to parenteral opioids To avoid overdose, follow conservative dose conversion ratios. For patients receiving high-dose parenteral opioids, a more conservative conversion is warranted. 

Abuse of ER dose forms by crushing, chewing, snorting, or injecting the dissolved product will result in the immediate release of the entire daily dose of the opioid and pose a significant risk to the abuser that could result in overdose and death. 

Musshoff et al. [35] developed a method for the enantiomeric separation of the synthetic opioid agonist tramadol and its desmethyl metabolite using a Chiralpak AD column containing amylose tris-(3,5-dimethylphenylcarbamate) as chiral selector and a n-hexane/ethanol, 97 3 v/v (5mM TEA) mobile phase nnder isocratic conditions (1 mL/min). After atmospheric pressure chemical ionization (APCI), detection was carried out in positive-ion MS-MS SRM mode. The method allowed the confirmation of diagnosis of overdose or intoxication as well as monitoring of patients compliance. 

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