Opioids monoamine oxidase inhibitors

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

Drug withdrawal reactions - tricyclic antidepressants, monoamine oxidase inhibitors, benzodiazepines, barbiturates, alcohol, opioids. 

Morphine and other opioids exhibit intense sedative effects and increased respiratory depression when combined with other sedatives, such as alcohol or barbiturates. Increased sedation and toxicity are observed when morphine is administered in combination with the psychotropic drugs, such as chlorpromazine and monoamine oxidase inhibitors, or the anxiolytics, such as diazepam. 

The combination of pethidine with monoamine oxidase inhibitors (MAOIs) can cause serious adverse reaction, which can present in two distinct forms. The excitatory form is characterised by sudden agitation, delirium, headache, hypo- or hypertension, rigidity, hyperpyrexia, convulsions and coma. It is thought to be caused by an increase in cerebral 5-HT concentrations because of inhibition of monoamine oxidase. This is potentiated by pethidine, which blocks neuronal uptake of 5-HT. The depressive form, which is frequently severe and fatal, consists of respiratory and cardiovascular depression and coma. It is the result of the inhibition of hepatic microsomal enzymes by the MAOI, leading to accumulation of pethidine. Phenoperidine should also be avoided in patients taking MAOI drugs but other opioids appear to be safe. 

Monoamine oxidase inhibitors Relative contraindication to all opioid analgesics because of the high incidence of hyperpyrexic coma hypertension has also been reported. 

The opioid derivatives most commonly used as antitussives are dextromethorphan, codeine, levopropoxyphene, and noscapine (levopropoxyphene and noscapine are not available in the USA). They should be used with caution in patients taking monoamine oxidase inhibitors (see Table 31-5). Antitussive preparations usually also contain expectorants to thin and liquefy respiratory secretions. Importantly, due to increasing reports of death in young children taking dextromethorphan in formulations of over-the-counter "cold/cough" medications, its use in children less than 6 years of age has been banned by the FDA. Moreover, due to variations in the metabolism of codeine, its use for any purpose in young children is being reconsidered. 

Drugs and chemicals are known to cause activated interaction. The depressant action of opioid drugs is enhanced by drugs acting on the central nervous system (CNS) such as alcohol, anesthetics, anxiolytics, hypnotics, tricyclic antidepressants, and antipsychotics. Concomitant administration of opioid analgesics and monoamine oxidase inhibitors (MAOIs) should be avoided, or extra care should be taken if such a therapy is inevitable. Fatal reactions are reported when treated along with selegiline. Interactions also are reported with cyclizine, cimetidine, mexiletine, cisapride, metoclopramide, or domperidone. 

Adverse effects Large doses of meperidine cause tremors, muscle twitches, and rarely, convulsions. The drug differs from opioids in that in large doses it dilates the pupil and causes hyperactive reflexes. Severe hypotension can occur when the drug is administered postoperatively. When used with major neuroleptics, depression is greatly enhanced. Administration to patients taking monoamine oxidase inhibitors (see p. 123) can provoke severe reactions such as convulsions and hyperthermia. Meperidine can cause dependence, and can substitute for morphine or heroin in use by addicts. Cross-tolerance with the other opioids occurs. 

There is a risk of hypertension, tachycardia, hyperpyrexia, and coma with the concurrent administration of opioids and monoamine oxidase inhibitors (SEDA-19, 83). 

Opioid analgesics interact with non-selective monoamine oxidase inhibitors, causing nervous system excitation and hypertension (70). These interactions have been reviewed (SEDA-18, 14). 

Concomitant use of some opioid analgesics, such as pethidine or dextropropoxyphene, with the selective monoamine oxidase inhibitors selegiline and moclobe-mide can enhance their nervous system toxicity (71). 

Opioids interact with monoamine oxidase inhibitors, causing CNS excitation and hypertension (72). 

Tricyclic antidepressants, monoamine oxidase inhibitors Over-the-counter antihistamines, decongestants Allergies (preservatives, penicillins, sulfonamides, neomycin, opioids)... 

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). 

Monoamine oxidase inhibitors (MAOI) are not completely selective for MAO and impair the metabolism of tricyclic antidepressants, of some sympathomimetics, e.g. phenylpropanolamine, amfetamine, of opioid analgesics, especially pethidine, and of mercaptopurine. 

Interactions. Morphine (also pethidine and possibly other opioids) is potentiated by monoamine oxidase inhibitors. Any central nervous system depressant (including alcohol) will have additive effects. Patients recently exposed to neuromuscular blocking agents (unless this is adequately reversed, e.g. by neostigmine) are particularly at risk from the respiratory depressant effects of morphine. The effect of diuretic drugs may be reduced by release of antidiuretic hormone by morphine. Useful interactions include the potientating effect on pain relief of tricyclic antidepressants and of dexamfetamine. 

In patients with reduced respiratory reserve, such as those with emphysema, severe obesity, cor pulmonale, and kyphoscoliosis, opioids must be used with caution. The relative benefits and harms of using opioids in patients taking monoamine oxidase inhibitors, those with a history of drug abuse, asthma, hepatic impairment, hypotension, raised intracranial pressure, or head injury, and during pregnancy or breast feeding, should be carefully considered. Dextropropoxyphene, pethidine, and methadone should be used with caution (SEDA-21, 85). 

Meperidine IM 50-1 50 mg q 3 h IV 5-10 mg q 5 min prn Use in severe pain Oral not recommended Do not use in renal failure May precipitate tremors, myoclonus, and seizures Monoamine oxidase inhibitors can induce hyperpyrexia and/or seizures or opioid overdose symptoms... 

Gonadotropin-releasing hormone analogs Benzodiazepines Tricyclic antidepressants Monoamine oxidase inhibitors Hz-Receptor antagonists Opioids Other Verapamil... 

General consideration oxymorphone should be started at 1/3 to 1/2 of the usual dose in patients who are concurrently receiving other CNS depressants including sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, and alcohol, because respiratory depression, hypotension, and profound sedation or coma may result. No specific interaction between oxymorphone and monoamine oxidase inhibitors has been observed, but caution in the use of any opioid in patients taking this class of drugs is appropriate. 

Receptor interactions preclinical studies have shown that duloxetine is a potent inhibitor of serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine reuptake. Duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histamin-ergic, opioid, glutamate, and GABA receptors. Duloxetine does not inhibit monoamine oxidase (MAO). 

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