Monoamine oxidase inhibitors cardiovascular

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. 

The older tricyclic antidepressants and monoamine oxidase inhibitors also cause withdrawal mania and a variety of other adverse withdrawal effects, including cognitive and emotional disturbances and psychosis. Many of them have strong anticholinergic effects and therefore produce severe anticholinergic rebound on withdrawal, including cardiovascular and gastrointestinal symptoms. I have seen patients who have taken tricyclics for many years and then been unable to withdraw from them. 

Apraclonidine is contraindicated in patients sensitive to clonidine and those taking monoamine oxidase inhibitors. Caution should be exercised in patients with severe cardiovascular disease, including hypertension. The possibility of vasovagal episodes exists during laser surgery, particularly in patients with a history of such events. 

Treatment is basically symptomatic and supportive no specific antidotes are available. Artificial ventilation with 100% humidified oxygen is necessary in cases of respiratory distress. If patient is cyanotic and cyanosis does not respond to oxygen administration, methemoglobin levels should be determined. Methemoglobinemia can be treated by intravenous administration of methylene blue. Support of cardiovascular function may also be required. Bladder damage can be determined by urinalysis. Hypotension may be treated with isotonic intravenous fluids. Dopamine or norepinephrine may be used if hypotension does not respond to infusion of fluids. Convulsions may be treated with intravenous benzodiazepines (diazepam or loraze-pam) phenobarbital may be used if the convulsions are recurrent. Because chlordimeform is a monoamine oxidase inhibitor, foods with large amounts of... 

There are theoretical drug interactions with caffeine and monoamine oxidase inhibitors. Caffeine could increase risk of cardiovascular events when taken with C. aurantium (54). The case report of MI (45) and several of the Canadian reported adverse events included caffeine (46). Synephrine, tyramine, and octopamine are all substrates of monoamine oxidase (55). Taking a monoamine oxidase inhibitor with C. aurantium could increase concentrations of these sympathomimetics, and thus should be avoided. 

Atomoxetine, bupropion, and TCAs are second-line alternatives to the stimulants for treatment of ADHD in children, teens, and adults. The potential benefits of these agents in comparison with stimulants include reduced risk of abuse and somewhat lower potential for sleep disturbance. TCAs are the most dangerous in overdose and pose the greatest risk for cardiovascular side effects. The monoamine oxidase inhibitor tranylcypromine is effective but used infrequently due to the potential for dangerous drug and dietary interactions. Selective serotonin reuptake inhibitors (SSRIs) are not effective for ADHD. ... 

The triptans are contraindicated in patients who have a history of ischemic or vasospastic CAD, cerebrovascular or peripheral vascular disease, or other significant cardiovascular diseases. Because triptans may cause an acute, usually small, increase in blood pressure (BP), they also are contraindicated in patients with uncontrolled hypertension. Naratriptan is contraindicated in patients with severe renal or hepatic impairment. Rizatriptan should be used with caution in patients with renal or hepatic disease but is not contraindicated in such patients. Sumatriptan, rizatriptan, and zolmitriptan are contraindicated in patients who are taking monoamine oxidase inhibitors. 

Cuthbert MF, Vere DW. Potentiation of the cardiovascular effects of some catecholamines by a monoamine oxidase inhibitor. BrJPharmacol (1971) 43, 471P-472P. 

Goldberg, L. I. and Sjoerdsma, A., Effects of several monoamine oxidase inhibitors on the cardiovascular actions of naturally occurring amines in the dog, J. Pharmacol. Exp. Ther. 127, 212 (1959). 

Advanced arteriosclerosis symptomatic cardiovascular disease moderate to severe hypertension hyperthyroidism hypersensitivity or idiosyncrasy to the sympathomimetic amines glaucoma agitated states history of drug abuse during or within 14 days following administration of monoamine oxidase (MAO) inhibitors (hypertensive crises may result). 

Serious toxic reactions with delirium can arise when specific serotonin reuptake inhibitors (SSRIs) are taken with other drugs that increase central and peripheral serotonergic activity. Known as the serotonin syndrome , this reaction consists of excitation, restlessness, fluctuations in consciousness, with tremor, rigidity, myoclonus, sweating, flushing, pyrexia, cardiovascular changes, and rarely coma and death (Sternbach, 1991). The syndrome has occurred when SSRIs have been combined with irreversible monoamine oxidase... 

Levodopa, the metabolic precursor of dopamine, is the most effective agent in the treatment of Parkinson s disease but not for drug-induced Parkinsonism. Oral levodopa is absorbed by an active transport system for aromatic amino acids. Levodopa has a short elimination half-life of 1-3 hours. Transport over the blood-brain barrier is also mediated by an active process. In the brain levodopa is converted to dopamine by decarboxylation and both its therapeutic and adverse effects are mediated by dopamine. Either re-uptake of dopamine takes place or it is metabolized, mainly by monoamine oxidases. The isoenzyme monoamine oxidase B (MAO-B) is responsible for the majority of oxidative metabolism of dopamine in the striatum. As considerable peripheral conversion of levodopa to dopamine takes place large doses of the drug are needed if given alone. Such doses are associated with a high rate of side effects, especially nausea and vomiting but also cardiovascular adverse reactions. Peripheral dopa decarboxylase inhibitors like carbidopa or benserazide do not cross the blood-brain barrier and therefore only interfere with levodopa decarboxylation in the periphery. The combined treatment with levodopa with a peripheral decarboxylase inhibitor considerably decreases oral levodopa doses. However it should be realized that neuropsychiatric complications are not prevented by decarboxylase inhibitors as even with lower doses relatively more levodopa becomes available in the brain. 

Patients taking certain systemic medications are also more sensitive to the pressor effects of phenylephrine. In individuals taking atropine, the pressor effect of phenylephrine is augmented, and tachycardia can occur. Tricyclic antidepressants and monoamine oxidase (MAO) inhibitors also potentiate the cardiovascular effects of topical phenylephrine. The concomitant use of phenylephrine is contraindicated with these agents, even up to 21 days after cessation of MAO inhibitor therapy. Similarly, patients taking reserpine, guanethidine, or methyldopa are at increased risk for adverse pressor effects from topical phenylephrine because of denervation hypersensitivity accompanying the chemical sympathectomy. 

Piperonyl butoxide, isoniazid, and SKF 525A and related chemicals are inhibitors of various xenobiot-ic-metabolizing enzymes. For instance, piperonyl butoxide increases the toxicity of pyrethrum (an insecticide) by inhibiting MFO activity in insects that detoxifies this agent. Isoniazid, when taken along with phenytoin, lengthens the plasma half-life of the antiepileptic drug and increases its toxicity. Iproniazid inhibits monoamine oxidase and increases the cardiovascular effects of tyramine, which is found in cheese and which is normally readily metabolized by the oxidase. 

---