MAOIs Sympathomimetics

Irreversible MAOIs + sympathomimetic amines, tyramine-containing foods ("cheese effect") and buspirone — hypertension, possibly leading to stroke. 

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 indirecdy 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 a-adrenoceptors, causes a marked increase in blood pressure the resultant hypertension may be so severe as to cause death. 

Normally, dietary tyramine is broken down in the gastrointestinal tract by MAO and is not absorbed. In the presence of MAOI, however, all of its potent sympathomimetic actions are seen. Other side effects of MAOI include excessive CNS stimulation, orthostatic hypotension, weight gain, and in rare cases hepatotoxicity. Because the monoamine oxidase inhibitors exhibit greater toxicity, yet no greater therapeutic response than other, newer agents, clinical use has been markedly curtailed. The primary use for MAOIs is in the treatment of atypical depressions, eg, those associated with increased appetite, phobic anxiety, hypersomnolence, and fatigues, but not melancholia (2). 

Additive sympathomimetic effects may develop when decongestants are administered with other sympathomimetic drug s (see Chap. 22). Use of the nasal decongestants with the MAOIs may cause hypertensive crisis. Use of a decongestant with beta-adrenergic blocking dragp may cause hypertension or bradycardia. When ephedrine is administered with theophylline, the patient is at increased risk for theophylline toxicity. 

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... 

MAOIs Pharmacodynamic—hypertensive crisis Tyramine-rich foods Sympathomimetics... 

MAO Is have not been evaluated systematically for treatment of PD under the current diagnostic classification and generally are reserved for patients who are refractory to other treatments.48,49 MAOIs have significant side effects that limit adherence. Additionally, patients must adhere to dietary restriction of tyramine and avoid sympathomimetic drugs to avoid hypertensive crisis. 

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. 

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. 

Drugs that may affect repaglinide include CYP 450 inhibitors (eg, clarithromycin, erythromycin, ketoconazole, miconazole), CYP 450 inducers (eg, barbiturates, carbamazepine, rifampin), beta blockers, calcium channel blockers, chloramphenicol, corticosteroids, coumarins, estrogens, gemfibrozil, isoniazid, itraconazole, levonorgestrel and ethinyl estradiol, MAOIs, nicotinic acid, NSAIDs, oral contraceptives, phenothiazines, phenytoin, probenecid, salicylates, simvastatin, sulfonamides, sympathomimetics, thiazides and other diuretics, and thyroid products. 

Drugs that may affect nateglinide include nonsteroidal anti-inflammatory agents (NSAIDs), salicylates, monoamine oxidase inhibitors, rifamycins, MAOIs, and nonselective beta-adrenergic blocking agents, thiazides, corticosteroids, thyroid products, and sympathomimetics. 

Drugs that may be affected by methyidopa include haloperidol, levodopa, lithium, sympathomimetics, MAOIs, anesthetics, and phenothiazines. 

Uses Endogenous depression Action TCA T synaptic CNS levels of serotonin /or norepinephrine Dose Adults. 25 mg PO tid-qid >150 mg/d not OK Elderly. 10-25 mg hs Peds. 6-7 y 10 mg/d 8-11 y 10-20 mg/d >11 y 25-35 mg/d, 4- w/ hepatic insuff Caution [D, +/-] NAG, CV Dz Contra TCA allergy, use w/ MAOI Disp Caps, soln SE Anticholinergic (blurred vision, retention, xerostomia) Interactions T Effects W/ antihistamines, CNS depressants, cimetidine, fluoxetine, OCP, phenothiazine, quinidine, EtOH T effects OF anticoagulants T risk of HTN W/clonidine, levodopa, sympathomimetics T effects W/barbiturates, carbamazepine, rifampin EMS Concurrent use w/ MAOIs have resulted in HTN,... 

Pseudoephedrine (Sudafed, Novafed, Afrinol, Others) [OTC] [Decongestant/Sympothomimetic] Uses Deconge tant Action Stimulates a-adren gic rec tors w/ vasoconstriction Dose Adults. 30-60 mg PO q6—8h Peds. 4 mg/kg/24 h PO qid -1- in renal insuff Caution [C, +] Contra Poorly controlled HTN or CAD, w/MAOIs Disp Tabs, caps, Liq SE HTN, insomnia, tach, arrhythmias, nervousness, tremor Interactions T Risk of HTN crisis W/ MAOIs T effects W/BBs, sympathomimetics X effects W/TCAs -1- effect OF methyldopa, reserpine EMS Found in many OTC cough/cold pr >arations use sympathomimetics w/ caution, may T adverse effects OD May cause N/V, HTN, arrhythmias, and Szs symptomatic and supportive... 

---