MAO inhibitor interaction

Nausea vomiting allergic reactions, including pulmonary infiltration hypotension urticaria fever vesicular rash hypoglycemia headache hemolytic anemia in G-6-PD deficiency and neonates disulfiram-like reaction with alcohol MAO-inhibitor interactions polyneuritis Halofantrine... 

Korn A, Eichler HG, Fischbach Gasic S. Moclobemide, a new reveraible MAO inhibitor - interaction with tyramine and tricyclic antidepressants inhealthy volunteera and depressive patients. Psychopharmacology (Berl) (1986) 88,153-7. 

In addition to halopeiidol, the putative neuroleptics, limcazole (311), lemoxipiide (312), and gevotioline (313) bind to (7-ieceptois as does the dopamine uptake blocker, GBR 12909 (314) and two ligands active at the NMDA receptor, ifenprodil (315) and CNS 1102 (316). NPC 16377, (317) is a selective (7-teceptor ligand. MAO inhibitors and antidepressants also bind to (7-teceptors. Some evidence indicates that (7-teceptors in the brain are in fact a form of cytochrome which may account for the diversity of ligands interacting with (7-sites. 

Chronic use of these irreversible MAO inhibitors has been associated with life-threatening toxicity, ie, hepatotoxicity and hypertensive crisis. Interactions with tyramine contained in food and other drugs have severely limited use of irreversible MAO inhibitors. These MAO inhibitors are also nonselective, inhibiting both MAO-A and MAO-B isoenzymes. Furthermore, they interfere with the hepatic metabolism of many dmgs. 

The adverse side-effects of the TCAs, coupled with their toxicity in overdose, provoked a search for compounds which retained their monoamine uptake blocking activity but which lacked the side-effects arising from interactions with Hj, aj-adreno-ceptors and muscarinic receptors. One of the first compounds to emerge from this effort was iprindole, which has an indole nucleus (Fig. 20.3). This turned out to be an interesting compound because it has no apparent effects on monoamine uptake and is not a MAO inhibitor. This, together with its relatively minor antimuscarinic effects, led to it commonly being described as an atypical antidepressant. Mechanisms that could underlie its therapeutic actions have still not been identified but, in any case, this drug has now been withdrawn in the UK. 

Linezolid Myelosuppression monitor CBC once weekly if more than 2 weeks of therapy Peripheral and/or optic neuropathy has been reported with long-term therapy Mild MAO inhibitor evaluate for potential drug-drug or drug-food interactions... 

The answer is b. (Katzung, p 1130J Fatalities have been reported when fluoxetine and MAO inhibitors (MAOIs) such as tranylcypromine have been given simultaneously The MAOLs should be stopped at least two weeks before the administration of fluoxetine or paroxetine. The mechanism of this interaction is under investigation... 

Other conditions in which ephedra is contraindicated are anxiety disorders, angle-closure glaucoma, prostate adenoma with residual urine volume, pheochromocytoma, and thyrotoxicosis (Gruenwald et al. 1998). Known medications that may interact adversely with ephedrine include heart glycosides, halothane, guanethidine, MAO inhibitors, secale alkaloids, and oxytocin. 

Toxicity is remarkably low for a compound of such activity. In mice, the LDso value is about three times that of chlorpromazine [166] while none of the effects of the latter drug on the myocardium, liver, skin or eye have appeared in the studies of oxypertine. It is, however, still too early to appraise its chronic toxicity in man. As indicated earlier, dangerous interactions are likely to follow concurrent use of a MAO inhibitor, though simultaneous use of anti-Parkinsonism drugs, for example, to control the relatively minor extra-pyramidal symptoms seems to present no unusual problems. Hypotension may occasionally occur with high doses. 

The first drug-drug interaction alert issued by the Committee in 1966 concerned the risks from interactions between preparations containing adrenaline or noradrenaline and monoamine oxidase (MAO) inhibitors used for the treatment of depression. 

Drugs that may interact with dextromethorphan include MAO inhibitors, quinidine, and sibutramine. 

Drugs that may interact with cyclobenzaprine hydrochloride include MAO inhibitors and TCAs. 

Drugs that may interact include MAO inhibitors, barbiturates, tranquilizers, narcotics, and alcohol. 

The pharmacological inhibition of the serotonin eliminating enzyme MAO is used in the therapy of depression and hypertension. Tranylcypromine is an irreversible unselective MAO inhibitor which displays numerous interactions with amine-containing food and monoamine-related drugs, resulting in evenmally fatal hypertensive crisis, cranial hemorrhage, arrhythmias and seizure can occur. The coadministration with speciflc serotonin reuptake inhibitors (SSRI) can result in similar effects and is therefore contraindicated. Moclobemide, on the other hand, is a reversible inhibitor of MAOa, one of the two enzyme subtyppes (MAOa, MAOb) which is void of most interactions see with tranylcypromine. 

Due to the frequent unwanted effects and, in case of tranylcypromine, the numerous and dangerous interactions MAO-inhibitors are more and more replaced by the much less problematic SSRIs. Compounds belonging to this group are citalopram, escitalopram, fluoxetine, paroxetine and sertraline. They are used clinically in the therapy of depression, bulimia and obsessive-compulsive disorders. All SSRIs show a slow onset of action (1-2 weeks). They may induce insomnia and weight loss. The antidepressant ven-lafaxine inhibits both, serotonin and noradrenaline re-uptake and might therefore additionally induce hypertension. 

By tritiation experiments, Cesura et al. have shown that both molecules bind exclusively to the active site of the enzyme and behave as mechanism-based reversible MAO inhibitors [66,67], The selectivity for MAO A of Ro 41-1049 (15) appears to be higher than that of clorgyline, which loses its selectivity and also inhibits MAO B at micromolar concentrations [6b], The common N-2-aminoethylcarboxamide group present in the Ro derivatives seems to interact... 

Can antidepressants such as tricyclics or buproprion augment the effect of stimulants on nondepressed children with ADHD Randomized controlled trials have yet to address this question. Nonetheless, such combinations are common in clinical practice. One case report showed leukopenia in a child treated with a combination of MPH and tricyclics for 4 months, although the doses were not specified (Burke et ah, 1995). Another case report indicated that obsessive-compulsive symptoms developed secondary to the combination of MPH and tricyclics (Pataki et ah, 1993). On a cautionary note, MPH has been found to interact with guanethidine to produce paradoxical hypotension. Patients on monoamine oxidose (MAO) inhibitors are likely to develop hypertensive crises if given a stimulant. 

When an SSRI agent is used with a MAO inhibitor, a dangerous pharmacodynamic interaction may occur. The combination of increased stores of monoamine together with reuptake inhibition leads to a phenomenon termed serotonin syndrome. This syndrome, which arises from a marked increase in synaptic serotonin, is clinically... 

Hyperpyrexia and hypertension have been observed with the use of pethidine and MAO inhibitors. Pethidine is the opioid most commonly associated with an adverse reaction with MAOIs. Although only a small proportion of patients taking MAOIs will react adversely to pethidine, there is no sure way of predicting those in whom the combination could produce severe, life-threatening reactions. These can present in two distinct forms. The excitatory form is characterised by sudden agitation, delirium, headache, hypotension or hypertension, rigidity, hyperpyrexia, convulsions and coma. It is possibly caused by an increase in cerebral 5-HT concentrations due to inhibition of MAO. This is potentiated by pethidine, which blocks neuronal uptake of 5-HT. The depressive form, which is frequently severe and fatal, presents as respiratoiy and cardiovascular depression and coma. It is the result of a reduced breakdown of pethidine due to the inhibition of hepatic /V-demethylase by MAOIs, leading to accumulation of pethidine. The risk of adverse reactions to pethidine may be less likely with the newer, specific MAO-A inhibitors. Interactions with other opioids, such as morphine and pentazocine, have been reported, but are less common. Other opioids appear to be safe in combination with MAOIs, with the possible exception of phenoperidine, which is metabolised to pethidine, norpethidine and pethidinic acid. 

Drug interactions NSAIDs Salicylates Sulfonamides Chloramphenicol Probenecid Coumarins MAO inhibitors Beta-blockers Thiazides and other diuretics Corticosteroids Phenothiazines Thyroid products Estrogens Oral contraceptives Phenytoin Nicotinic acid Sympathomimetic Calcium channel blockers Isoniazid Miconazole... 

One old-fashioned augmentation strategy that has fallen out of favor in recent years is to combine with great caution a TCA and an MAO inhibitor (the cautious combo in Fig. 7—30). Given its potential dangers (e.g., sudden hypertensive episodes, orthostatic hypotension, drug and dietary interactions, obesity), as well as the wide variety of other antidepressant combinations available today, this combination is rarely necessary or justified. 

Monamine oxidase (MAO) inhibitors are antidepressants that can interact with sympathomimetic appetite depressants. Patients must discontinue using MAO inhibitors two weeks before taking these diet pills. Use of MAO inhibitors while taking anorectics will cause a sharp rise in blood pressure. 

Ephedra has negative interactions with cardiac heart glycosides, halothene, guanethidine, MAO inhibitors, and secale alkaloid derivatives or oxytocin. 

From the evidence available to date, the reversible, short-acting MAO inhibitor moclobemide, which is available in several countries (but not the USA), appears to be relatively free of this interaction. (The selective MAO-B inhibitor selegiline loses selectivity at antidepressant dosage. Because its action is on the enzyme that metabolizes dopamine, it is most useful in the treatment of Parkinson s disease [Chapter 28 Pharmacologic Management of Parkinsonism Other Movement Disorders].)... 

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