Sympathomimetic amines indirectly acting

Predictable interactions occur between the MAOIs and any amine precursors, or directly or indirectly acting sympathomimetic amines (e.g. the amphetamines, phenylephrine and tyramine). Such interactions can cause pronounced hypertension and, in extreme cases, stroke. 

The tricyclic antidepressants (e.g., desipramine and amitriptyline) and some phenothiazines block the sympathetic neuronal amine uptake system they thereby would also block the uptake of guanethidine and thus reduce its hypotensive effectiveness. Conversely, guanethidine competitively inhibits the uptake of drugs that are substrates for neuronal uptake, such as the indirectly acting adrenomimetics, or sympathomimetics (see Chapter 10). 

MAO inhibitors increase the catecholamine content of various organs so that more catecholamine is to be released by indirectly acting sympathomimetic amines. 

As of the mid-1990s, use of MAOIs for the treatment of depression is severely restricted because of potential side effects, the most serious of which is hypertensive crisis, which results primarily from the presence of dietary tyramine. Tyramine, a naturally occurring amine present in cheese, beer, wine, and other foods, is an indirectly acting sympathomimetic, that is, it potently causes the release of norepinephrine from sympathetic neurons. The norepinephrine that is released interacts with adrenoceptors and, by interacting with OC-adrenoceptors, causes a marked increase in blood pressure the resultant hypertension may be so severe as to cause death. 

When this enzyme is inhibited, the concentrations of norepinephrine within adrenergic neurons increase and drugs that stimulate its release can bring about an exaggerated response. Interactions between MAO inhibitors and indirectly acting sympathomimetic amines (e.g., amphetamine) develop by this mechanism. If amphetamine is administered to a patient whose stores of norepinephrine have been increased by MAO inhibition, the patient may experience severe headache, hypertension (possibly a hypertensive crisis), and cardiac arrhythmias. The serious consequences associated with these interactions contraindicate the use of these agents in combination. 

Levo-Dromoran levorphanol. levofenfluramine [inn) is the (/Q-form of fenfluramine hydrochloride. It is an (indirect-acting) SYMPATHOMIMETIC amine, levofloxacin ofloxacin, levoleucovorin calcium calcium levofolinale. levomenthol menthol, levomepromazine methotrimeprazine. levomethadone methadone, levomethadyl dimepheptanol. levomethadyl acetate dimepheptanol levacetylmethadol. 

The ephedra alkaloids are all sympathomimetic amines, which means that a host of drug interactions are theoretically possible. In fact, only a handful of adverse drug interactions have been reported in the peer-reviewed literature. The most important of these involve the monoamine oxidase inhibitors (MAOI). Irreversible, nonselective MAOIs have been reported to adversely interact with indirectly acting sympathomimetic amines present in many cough and cold medicine. In controlled trials with individuals taking moclobemide, ephedrine s effects on pulse and blood pressure were potentiated, but only at higher doses than those currently provided in health supplements (137). Ephe-drine-MAOI interaction may, on occasion, be severe enough to mimic pheo-... 

Further studies clarified the operation of mesencephalic enhancer regulation (Knoll and Miklya 1995 Knoll et al. 1996a,b,c). We realized that PEA, the parent compound of (-)-deprenyl, is primarily an endogenous mesencephalic enhancer substance. Since PEA, in higher concentrations, is a highly effective releaser of catecholamines from their intraneuronal stores, this effect covered up completely the enhancer effect of this endogenous amine, which was classified as the prototype of the indirectly acting sympathomimetics. 

It was reported35 that morphine does not act as a S3rm-patholytic on the isolated heart nor does it alter catecholamine levels or the response of the heart to sympathomimetic amines. On the other hand, iu vivo experiments in the dog3° reveal that morphine increased contractile force. This careful study revealed that the improved ventricular performance induced by morphine is indirect and probably the result of sympathoadrenal discharge. 

SELECTIVE MAO-B INHIBITORS Two isozymes of MAO (MAO-A and MAO-B) oxidize monoamines and both are present in the periphery and GI tract MAO-B is the predominant form in the striatum and is responsible for most of the oxidative metabolism of dopamine in the brain. At low-to-moderate doses (10 mg/day or less), selegiline (eldepryl) selectively and irreversibly inhibits MAO-B. Unlike nonspecific inhibitors of MAO (e.g., phenelzine, tranylcypromine, isocarboxazid), selegiline does not inhibit peripheral metabolism of catecholamines and can be taken safely with levodopa. Selegihne does not cause the lethal potentiation of indirectly acting sympathomimetic amines such as dietary tyramine. Doses of selegiline higher than 10 mg daily can produce inhibition of MAO-A and should be avoided. 

Indirectly acting sympathomimetic blocks amine reuptake into nerve endings. Local anesthetic (ester type). Marked CNS stimulation, euphoria high abuse and dependence liability. Tox psychosis, cardiac arrhythmias, seizures. 

After 5 to 10 days of use furazolidone has MAO-inhibitory activity about equivalent to that of the non-selective MAOIs. The concurrent use of furazolidone with indirectly-acting sympathomimetic amines (amfetamines, phenylpropanolamine, ephedrine, etc.) or with tyramine-rich foods and drinks may be expected to result in a potentially serious rise in blood pressure. However, direct evidence of accidental adverse reactions of this kind does not seem to have been reported. The pressor effects of noradrenaline (norepinephrine) are unchanged by furazolidone. 

It is thought that this reaction occurred as a result of excess sympathomimetic amines ephedrine is an indirectly-acting sympathomimetic that causes increased release of noradrenaline selegiline has some MAO-A in-... 

Starke K. Interactions of guanethidine and indirectly-acting sympathomimetic amines. Arch Int Pharmacodyn Ther ( 972) 195, 309-14. 

These sympathomimetic amines act directly on the receptors at the nerve endings, which innervate arterial blood vessels, so that the presence of the MAOI-induced accumulation of noradrenaline within these nerve endings would not be expected to alter the extent of direct stimulation (contrast Sympathomimetics Indirectly-acting , (p.l 147)). The enhancement seen in those patients whose blood pressure was lowered by the MAOI might possibly be due to an increased sensitivity of the receptors, which is seen if the nerves are cut, and is also seen during temporary pharmacological severance . 

Tyramine is formed in foods such as cheese by the bacterial degradation of milk and other proteins, firstly to tyrosine and other amino acids, and the subsequent deearboxylation of the tyrosine to tyramine. This interaction is therefore not associated with fresh foods, but with those which have been allowed to over-ripen or mature in some way, or if spoilage occurs. Tyramine is an indirectly-acting sympathomimetic amine, one of its actions being to release noradrenaline (norepinephrine) from the adrenergic neurones associated with blood vessels, which causes a rise in blood pressure by stimulating their constriction. ... 

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