Antiparkinsonian Agents Drug Interactions of Clinical Significance

Abstract

Within the past 3 decades revolutionary changes have taken place in the pharmacological management of Parkinson's disease. Used alone, or often in combination, antiparkinsonian agents can dramatically and meaningfully ameliorate the symptoms of Parkinson's disease. However, with the development of effective therapeutic agents has come the potential for drug interactions; these interactions can produce consequences that range from the inconsequential to incapacitating and even life-threatening. Drug-drug interactions are not a major problem with either the anticholinergic medications or amantadine. However, cumulative anticholinergic toxicity may occur when multiple drugs with anticholinergic properties are utilised concomitantly, and amantadine toxicity can be triggered by drugs that impair its renal clearance. Gastric emptying and levodopa absorption can be significantly altered by medications and dietary contents. A rather extensive array of medications can interfere with dopaminergic function and thus produce clinical parkinsonism or impair the effectiveness of levodopa. The effectiveness of direct dopamine agonists can also be affected by a small group of agents. As a selective monoamine oxidase type B (MAO-B) inhibitor, selegiline (deprenyl) is free of the 'cheese-effect' when employed in recommended dosages. However, potentially life-threatening drug interactions, with both pethidine (meperidine) and with fluoxetine and other antidepressant medications, have been described, presumably occurring via serotonergic mechanisms. Awareness of the potential for drug interactions with antiparkinsonian agents, and prompt recognition of them when they do occur, is vital for the optimum clinical management of Parkinson's disease.

Arzneimittelinteraktionen bei der Antiparkinson-Therapie

“…Ein weiteres Antiparkinsonmittel ist Selegilin, das irreversibel an MAO-B bindet. Es gehört zu den Arzneistoffen, die zumindest in präklinischen Experimenten neuropro- In normaler Dosierung ist bei Selegilin nicht mit einem Cheese-Effekt (Tyramin-Abbauhemmung führt zu hypertensiven Krisen) zu rechnen, da es ja selektiv MAO-B hemmt (1).Tyramin, das man in größeren Mengen in Käse, Fisch und Geflügelleber findet, wird -wenn überhaupt -durch die intestinale MAO-A abgebaut.Als MAO-B-Hemmer geht Selegilin in üblichen Dosierungen keine Interaktion mit Tyramin ein. Pethidin sollte nicht mit Selegilin kombiniert werden.…”

“…Pethidin sollte nicht mit Selegilin kombiniert werden. Muskelrigidität, Delirium, Hyperthermie und Tod wurden beschrieben, vermutet wird ein serotoninerger Mechanismus (1,31). Dextromethorphan, Sertralin, Paroxetin, Venlafaxin, Amitriptylin und der MAO-A-Hemmstoff Moclobemid sollten nicht mit Selegilin kombiniert werden (1,32).…”

“…Muskelrigidität, Delirium, Hyperthermie und Tod wurden beschrieben, vermutet wird ein serotoninerger Mechanismus (1,31). Dextromethorphan, Sertralin, Paroxetin, Venlafaxin, Amitriptylin und der MAO-A-Hemmstoff Moclobemid sollten nicht mit Selegilin kombiniert werden (1,32). Klinisch relevant ist die Interaktion zwischen Selegilin und Moclobemid nicht wegen der Parkinsontherapie-Effizienz, sondern wegen eines bedrohlichen Cheese-Effekts (Tyramin in Nahrung) (33).…”

Safety of Selegiline with Cold Medications

“…Treatment of Parkinson disease includes carbidopa/levodopa and drug classes such as dopamine agonists, catechol-omethyltransferase (COMT) inhibitors, and monoamine oxidase (MAO) inhibitors that increase dopamine concentrations, stimulate dopamine receptors, and enhance the effects of carbidopa/levodopa. 1 Many patients with Parkinson disease ask if they can take nonprescription cold medications with their anti-Parkinson drugs due to a warning that is present on the labels of many cold medications that contain pseudoephedrine, a decongestant, and dextromethorphan, a cough suppressant. This warning states, "Do not use this product if you are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric or emotional conditions, or Parkin-son's disease), or for 2 weeks after stopping the MAOI drug."…”

Drug interactions in the treatment of Parkinson's disease

“…Although selegiline is free of the "cheese effect" when used at the recommended doses [19], potentially lifethreatening drug interactions with both pethidine and fluoxetine [10] have been described. This effect presumably occurs via serotonergic mechanisms [19].…”