Cardiovascular effects MAOIs

Gardner DM, Lynd LD Sumatriptan contraindications and the serotonin syndrome. Ann Pharmacother 32 33-38, 1998 Gardner DM, Shulman KI, Walker SE, et al The making of a user friendly MAOI diet. J Clin Psychiatry 57 99-104, 1996 Glassman AH, Bigger JT Cardiovascular effects of therapeutic doses of tricyclic antidepressants a review. Arch Gen Psychiatry 38 815-820,1981... 

Hypertensive crisis often occurs as a result of the interaction of two or more drugs acting via different mechanisms to potentiate the cardiovascular effects of NE. It can also occur as a result of a drug-food interaction involving MAOIs and tyramine-containing foods. Like the serotonin syndrome, hypertensive crisis can be fatal. Prodromal symptoms include the following ... 

Overdoses of MAOIs (e.g., phenylzine and tranylcypromile) cause side effects such as muscles spasms, sweating, and increasing body temperature, and these effects may be fatal. Overdose can be started with stomach wash, and supportive therapy can be performed to treat CNS effects, hyperpyrexia, and cardiovascular effects. Sometimes, overdose can be observed after a long period, and patients should be carefully monitored. Various drugs given to treat overdose are discussed elsewhere. 

Patients with cardiovascular disease (including hypertension), diabetes (risk of hyperglycemia), pregnancy (uterine contractions), prostatism, and anxiety disorders are among those who should not take ma huang at any dose. Drug-herb interactions occur with MAOIs (hypertensive crisis), phenoth-iazines (tachycardia, hypotension), (3-blockers (hypertension) and theophylline (increased CNS effects). Of course, caffeine and other stimulants have an additive effect. 

Trazodone Hydrochloride Trazodone overdose causes severe toxic effects. These effects are severe if taken along with benzodiazepines or alcohol. Trazodone interacts with MAOIs, cardiovascular drugs, CNS depressants, and antiepileptics. 

Monoamine oxidases (both MAO-A and MAO-B) also exist in peripheral tissue, specifically the gastrointestinal tract (GIT). In the GIT, they inhibit the first-pass metabolism of exogenous tyramine. Because of this property, treatment with non-selective irreversible MAOIs can result in the accumulation of tyramine and have the potential to precipitate a dangerous hypertensive crisis, the so-called cheese effect. This effect may occur more frequently in elderly than in younger patients, because the cardiovascular systems of the elderly are already compromised by age. Selective MAO-B inhibitors and reversible MAO-A inhibitors are free from this potentially fatal interaction. 

There are two issues of concern which are associated with irreversible MAOIs involving the display of liver toxicity, particularly with hydrazines, and the permanent inactivation of both MAO-A and -B isoforms. The replacement of MAOs requires protein synthesis which may take up to 14 days. From the antidepressant viewpoint, only a selective blockage of serotonin metabolism may be of interest in order to increase serotonin availability. However, this long-term effect significantly reduces metabolism of a variety of other biogenic amines, which leads to their accumulation, which is not necessarily desired. This leads to an excessive availability of tyramine and others, which ultimately leads to increased release of noradrenaline that may result in the stimulation of cardiovascular sympathetic nervous system activity. As a consequence, potentially fatal hypertensive crises and cerebral haemorrhage can occur (Fig. 18.22). This phenomenon has often been termed the cheese effect, in order to reflect the fact that tyramine is present in a variety of foods such as wine, cheese and other fermented food and drink products. It would appear, however, that under carefully controlled and restricted dietary conditions such a risk can be minimised. 

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