Phenelzine Levodopa

WARNING Cases of fulminant liver failure resulting in death have occurred Uses Adjunct to carbidopa/levodopa in Parkinson Dz Action COMT inhibitor slows levodopa metabolism Dose 100 mg PO tid w/ 1st daily levodopa/carbidopa dose, then dose 6 12 h later -1- w/ renal impair Caution [C, ] Contra Hqjatic impair, w/ nonselective MAOI Disp Tabs SE Constipation, XCTOstomia, vivid dreams, hallucinations, anorexia, N/D, orthostasis, liver failure, Rhabdomyolysis Interactions T Effects OF CNS dqjressants, SSRIs, TCAs, warfarin, EtOH t risk of hypotensive crisis W/ nonselective MAOIs (phenelzine, tranylc5 promine) EMS Has been associated w/ liver failure and death may experience hallucinations concurrent EtOH use can T CNS dqjression T effects of warfarin severe D is common sevoal wks afto starting OD May cause NA and dizziness... 

Interactions The vitamin pyridoxine (B6) increases the peripheral breakdown of levodopa and diminishes its effectiveness (Figure 8.6). Concomitant administration of levodopa and monoamine oxidase (MAO) inhibitors, such as phenelzine (see p. 124), can produce a hypertensive crisis caused by enhanced catecholamine production therefore, caution is required when they are used simultaneously. In many psychotic patients, levodopa exacerbates symptoms, possibly through the buildup of central amines. In patients with glaucoma, the drug can cause an increase in intraocular pressure. Cardiac patients should be carefully monitored because of the possible development of cardiac arrhythmias. Antipsychotic drugs are contraindicated in parkinsonian patients, since these block dopamine receptors and produce a parkinsonian syndrome themselves. 

E. Nonspecific MAO-inhibitors, such as phenelzine, are a useful adjunct to levodopa therapy. 

Correct answer = D. Carbidopa inhibits the peripheral decarboxylation of levodopa, permitting lower dosage. Chlorpromazine blocks the dopamine receptor site in the brain and therefore blocks the beneficial effects of levodopa. Vitamin B6 enhances the peripheral decarboxylation of levodopa. Dopamine does not itself cross the blood-brain barrier. Phenelzine inhibits the metabolism of norepinephrine and serotonin and may produce a hypertensive crisis. 

Adrenaline, apomorphine, ascorbic acid, benserazide, dihydralazine, dobutamine, dodecyl gallate, dopamine, ethylnoradren-aline, hexoprenaline, hydralazine, iproniazid, isocarboxazid, isoetharine, isoniazid, isoprenaline, levodopa, meban-azine, methyldopa, methyldopate, nialamide, noradrenaline, phenelzine, procarbazine, protokylol, rimiterol... 

DA agonists levodopa, bromocriptine, ropinirole, pramipexole, selegiline AAAD inhibitor carbidopa M-blockers benztropine, trihexiphenidyl MAOIs phenelzine, tranylcypromine TCAs amitriptyline, imipramine, clomipramine SSRIs fluoxetine, paroxetine, sertraline Others bupropion, mirtazapine, nefazodone, trazodone... 

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. 

Similar cases of severe, acute hypertension, accompanied in most instances by flushing, throbbing and pounding in the head, neck and chest, and light-headedness have been described in other case reports and studies involving the concurrent use of levodopa with pargyline, nialamide, tranylcypromine, phenelzine and isocarboxazid. ... 

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