Tricyclic antidepressants sympathomimetics

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... 

In addition to this serious diet-drug interaction, irreversible MAOIs also potentiate the effects of sympathomimetic drugs like ephedrine found in over-the-counter cold remedies and recreational stimulants like amphetamine. The MAOIs also interact with drugs that increase synaptic concentrations of 5-HT, such as the tricyclic antidepressant clomipramine and the herbal SSRI antidepressant St John s wort (Hypericum spp.). The resulting serotonin syndrome is characterised by hyperthermia and muscle rigidity. While devoid of these side effects the reversible MAO-A inhibitor moclobemide has yet to establish itself as a first-line alternative to the SSRIs. 

Drugs that may be affected by dronabinol include amphetamines, cocaine, sympathomimetics, anticholinergics, antihistamines, tricyclic antidepressants, alcohol, sedatives, hypnotics, psychomimetics, disulfiram, fluoxetine, and theophylline. 

Drugs that may be affected by SSRIs Drugs that may be affected by SSRIs include alcohol, benzodiazepines, beta blockers, buspirone, carbamazepine, cisapride, clozapine, cyclosporine, diltiazem, digoxin, haloperidol, hydantoins, lithium, methadone, mexiletine, nonsedating antihistamines, NSAIDs, olanzapine, phenothiazines, phenytoin, pimozide, procyclidine, ritonavir, ropivacaine, sumatriptan, sulfonylureas, sympathomimetics, tacrine, theophylline, tolbutamide, tricyclic antidepressants, and warfarin. 

Drugs that may be affected by lithium include phenothiazines, sympathomimetics, iodide salts, neuromuscular blocking agents, and tricyclic antidepressants. 

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). 

Medications with serotonergic activity may also have other monaminergic or sympathomimetic activity. Combining MAOIs with these medications may result in a complex side effect profile. For example, combining meperidine or dextromethorphan with MAOIs may result in respiratory depression, in addition to symptoms of serotonin excess. Furthermore, interactions between MAOIs and tricyclic antidepressants (TCAs) more commonly result in potentiating shared adverse events such as othostatic hypotension, as opposed to hyperadrenergic crises or the serotonin syndrome. 

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. 

Drug treatments include sympathomimetic stimulants, anticholinergics, tricyclic antidepressants and synthetic antidiuretics. Of these, imipramine and desmopressin have been found to be the most effective. 

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. 

Monoamine oxidase inhibitors (MAOI) are not completely selective for MAO and impair the metabolism of tricyclic antidepressants, of some sympathomimetics, e.g. phenylpropanolamine, amfetamine, of opioid analgesics, especially pethidine, and of mercaptopurine. 

Interactions of sympathomimetics with other vasoactive drugs are complex. Some drugs block the reuptake mechanism for noradrenaline in adrenergic nerve terminals and potentiate the pressor effects of noradrenaline e.g. cocaine, tricyclic antidepressants or highly noradrenaline-selective reuptake inhibitors such as roboxetine. Others deplete or destroy the intracellular stores within adrenergic nerve terminals (e.g. reserpine and guanethidine) and thus block the action of indirect S5unpathomimetics. 

Clinically important, potentially hazardous interactions with albuterol, alpha-blockers, amitriptyline, amoxapine, atenolol, beta-blockers, carteolol, chlorpromazine, clomipramine, cocaine, desipramine, doxepin, ephedra, ergotamine, furazolidone, halothane, imipramine, insulin detemir, MAO inhibitors, metoprolol, nadolol, nortriptyline, oxprenolol, penbutolol, phenelzine, phenoxybenzamine, phenylephrine, pindolol, prazosin, propranolol, protriptyline, sympathomimetics, terbutaline, thioridazine, timolol, tranylcypromine, tricyclic antidepressants, trimipramine, vasopressors... 

Clinically important, potentially hazardous interactions with alprazolam, amphetamines, astemizole, clarithromycin, clozapine, desipramine, dexibuprofen, dextroamphetamine, diethylpropion, droperidol, duloxetine, erythromycin, haloperidol, imipramine, isocarboxazid, linezolid, lithium, MAO inhibitors, mazindol, meperidine, methamphetamine, midazolam, moclobemide, nortriptyline, phendimetrazine, phenelzine, phentermine, phenylpropanolamine, phenytoin, pimozide, pseudoephedrine, selegiline, serotonin agonists, sibutramine, St John s wort, sumatriptan, sympathomimetics, tramadol, tranylcypromine, trazodone, tricyclic antidepressants, troleandomycin, tryptophan, zolmitriptan... 

Clinically important, potentially hazardous interactions with amitriptyline, amoxapine, amphetamines, bupropion, citalopram, clomipramine, cyproheptadine, desipramine, dextroamphetamine, dextromethorphan, diethylpropion, dopamine, doxepin, entacapone, ephedra, ephedrine, epinephrine, fluoxetine, fluvoxamine, ginseng, imipramine, levodopa, mazindol, meperidine, methamphetamine, nefazodone, nortriptyline, paroxetine, phendimetrazine, phentermine, phenylephrine, pizotifen, propoxyphene, protriptyline, pseudoephedrine, rizatriptan, sertraline, sibutramine, sumatriptan, sympathomimetics, tramadol, tricyclic antidepressants, trimipramine, tryptophan, venlafaxine, zolmitriptan... 

The risk of serotonin syndrome may be increased shortly after dosage increases of SSRIs or when drug interactions increase serotonin activity. Concomitant or proximal use of SSRIs, tricyclic antidepressants, or monoamine oxidase inhibitors may cause serotonin syndrome. Further, the addition of certain drugs, such as tryptophan, dextromethorphan, cocaine, or sympathomimetics, to SSRI therapy may increase the risk of developing serotonin syndrome." ... 

Antidepressants selective serotonin reuptake inhibitors, tricyclic antidepressants Antihypertensives felodipine Antibiotics quinolones, isoniazid Bronchodilators albuterol, theophylline Corticosteroids prednisone Dopa agonists levodopa Herbals ma huang, ginseng, ephedra Nonsteroidal anti-inflammatory drugs ibuprofen Stimulants amphetamines, methylphenidate, caffeine, cocaine Sympathomimetics pseudoephedrine Thyroid hormones levothyroxine Toxicity anticholinergics, antihistamines, digoxin Withdrawal alcohol, sedatives... 

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