Sympathomimetic amines, antidepressant

MAOIs have the most serious pharmacodynamic interactions of any antidepressant class. As discussed earlier, they can cause a hypertensive crisis and the serotonin syndrome. They potentiate the hypertensive effects of most sympathomimetic amines, as well as tyramine, which is the reason for the avoidance of over-the-counter preparations containing such agents, in addition to the tyramine-free diet ( 508, 509). The serotonin syndrome occurs most often when MAOIs are used in combination with SSRIs and venlafaxine but it can also occur when MAOIs are used with tryptophan, 5-hydroxytryptophan, and some narcotic analgesics. In addition, MAOIs can also significantly potentiate the sedative and respiratory depressant effects of narcotic analgesics. 

Tricyclic antidepressants potentiate the pressor effects of directly acting sympathomimetic amines, such as adrenaline (epinephrine) or noradrenaline (norepinephrine), to cause hypertension. Small amounts of these, such as may be present in local anaesthetic solutions, can be dangerous. Tricyclic antidepressants will inhibit the antihypertensive effects of the older anti hypertensive drugs, such as adrenergic neurone-blocking agents, e.g. guanethidine, a-methyl-DOPA, and clonidine. 

Tricyclic antidepressants + directly acting sympathomimetic amines (e.g. noradrenaline, adrenaline) —> hypertension and arrhythmias due to enhancement of the sympathomimetic effects. 

Correct answer = D. MAO inhibitors and aspirin can be taken concurrently. Hypertensive crisis may result from use (concurrently or within 2 weeks) of MAO inhibitors and indirect sympathomimetic amines, such as ephedrine. Concomitant use of MAO inhibitors and tricyclic antidepressants may result in mutual enhancement of effects with the possibility of hyperpyrexia, hypertension, seizures and death. Tyramine-containing foods, such as aged cheeses and beer, may precipitate a hypertensive crisis because of the accumulation and release of stored catecholamines from nerve endings. MAO inhibitors may lead to an exaggerated response to dopamine. 

BETA-2 AGONISTS ANTIDEPRESSANTS -MAOIs t occurrence of headache and hypertensive episodes. Unlikely to occur with modobemide and selegiline Due to impaired metabolism of these sympathomimetic amines due to inhibition of MAO. Modobemide is involved in the breakdown of serotonin, while selegiline is mainly involved in the breakdown of dopamine Be aware. Monitor BP closely... 

Potent Antidepressant Agents. Aralkylhydrazines. In the search for sympathomimetic agents with a greater intensity and duration of action, Biel and coworkers (19, 22) investigated a large number of phenylalkylhydrazines which were patterned structurally after the sympathomimetic amines. In essence, the hydrazine moiety either replaced an amino radical or served to produce a nitrogen isostere of a sympathomimetic amine ... 

Similar caution should be exercised with biogenic amine uptake blockers such as tricyclic antidepressants. Amphetamine is contraindicated in advanced arteriosclerosis symptomatic cardiovascular disease moderate to severe hypertension hyperthyroidism hypersensitivity or idiosyncrasy to the sympathomimetic amines glaucoma agitated states history of drug abuse and during or within 14 days following administration of monoamine oxidase (MAO) inhibitors. 

Some drugs are competitive inhibitors of nonmicrosomal metabolic pathways. Serious reactions have been reported in patients treated with an MAO inhibitor, such as trancypromine or iproniazid, because they usually are sensitive to a subsequent dose of a sympathomimetic amine (e.g., amphetamine) or a tricyclic antidepressant (e.g., amitriptyline), which is metabolized by MAO. 

Drug interactions for the RIMAs include interaction with SSRI antidepressants, which can cause the 5-HT syndrome (see the discussion of SSRIs). The effect of stimulant drugs, such as methylphenidate and dextroamphetamine (used to treat ADHD), may be increased. Some over-the-counter cold and hay fever decongestants (i.e., sympathomimetic amines) can have increased stimulant effects. Selegiline, a selective MAO-B used for Parkinson s disease, should not be used concurrently with the RIMAs. Unlike the irreversible MAOIs, no significant interactions with foods occur, because the selective inhibition of MAO-Adoes not stop the metabolism of tyramine. The RIMAs must not be taken concurrently with a nonreversible MAOI. 

The most signifioant interaotions of organic nitrates are with those agents that cause hypotension, suoh as other vasodilators, alcohol, and tricyclic antidepressants, in which the potential for orthostatio hypotension may arise. On the other hand, concurrent administration with sympathomimetic amines, such as ephedrine and norepinephrine, may lead to a decrease in the antianginal efficacy of the organic nitrates. 

Boakes AJ, Laurence DI Teoh PC, Barar FSK, Benedikter LT, Prichard BNC. Interactions between sympathomimetic amines and antidepressant agents in man. BMJ 913) 1, 311-15. 

An inhibition of the uptake of NA in nerve endings of the sympathetic innervated blood vessels by tricyclic antidepressants can be demonstrated accurately with blood pressure measurements. Potentiation of the NA pressure response and antagonism of the effects of indirectly acting sympathomimetic amines, such as tyramine, are characterized by a rapid onset of action [23]. With proper precautions, these effects can also be studied in man. It must be remembered that these actions are on the peripheral nervous system and provide no guarantee of CNS-activity. 

A potentially related interaction has been reported between tricyclic antidepressants and methylphenidate which acts as an indirectly acting sympathomimetic amine. Cases have been reported (40 ) of patients taking tricyclic antidepressants (imipramine 200 mg, protriptyline 30 mg, and imi-... 

The main problems with early, irreversible MAOIs were adverse interactions with other drugs (notably sympathomimetics, such as ephedrine, phenylpropanolamine and tricyclic antidepressants) and the infamous "cheese reaction". The cheese reaction is a consequence of accumulation of the dietary and trace amine, tyramine, in noradrenergic neurons when MAO is inhibited. Tyramine, which is found in cheese and certain other foods (particularly fermented food products and dried meats), is normally metabolised by MAO in the gut wall and liver and so little ever reaches the systemic circulation. MAOIs, by inactivating this enzymic shield, enable tyramine to reach the bloodstream and eventually to be taken up by the monoamine transporters on serotonergic and noradrenergic neurons. Fike amphetamine, tyramine reduces the pH gradient across the vesicle membrane which, in turn, causes the vesicular transporter to fail. Transmitter that leaks out of the vesicles into the neuronal cytosol cannot be metabolised because... 

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). 

B. Interactions Based on Additive Effects Additive interaction describes the algebraic summing of the effects of two drugs. The two drugs may or may not act on the same receptor to produce such effects. The combined use of tricyclic antidepressants with diphenhydramine or promethazine predictably causes excessive atropine-like effects since all of these drugs have significant muscarinic receptor-blocking actions. Tricyclic antidepressants may increase the pressor responses to sympathomimetics by interference with amine transporter systems. 

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