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excerpted from An Algorithm For The Management Of Parkinson's Disease, a supplement of the American Academy of Neurology. Reprinted in Neurology 1994;44:S1-S52. Editors: William Koller, M.D. Ph.D Dee Silver, M.D. Abraham Lieberman, M.D. Anticholinergic Drugs. A balanced interaction exists between effects of dopamine and acetylcholine in the basal ganglia. In PD, dopamine depletion results in a state of cholinergic sensitivity, so that cholinergic drugs exacerbate and anticholinergic drugs improve parkinsonian symptoms.[42] Centrally acting anticholinergic drugs, such as trihexyphenidyl and benztropine [Cogentin], continue to occupy a useful place in the treatment of PD in the era of levodopa and dopamine agonists.[30] Although some anticholinergic drugs (e.g., benztropine) might augment the dopamine effect by inhibiting striatal presynaptic reuptake of dopamine, it is uncertain whether or not this contributes significantly to their mechanism of action. Patients less than 60 years of age: Anticholinergic drugs should be considered for early monotherapy in patients 60 years of age or younger. Patients with tremor-predominant parkinsonism who are not significantly disturbed by akinesia are particularly good candidates for this approach. In many early studies, anticholinergic drugs were reported to be more effective for tremor and rigidity than for akinesia. Although this differential effect of anticholinergic drugs on specific parkinsonian signs has never been adequately studied and is not universally accepted,[43] contemporary clinical experience has been that anticholinergic drugs are useful for resting tremor but of little value in the treatment of akinesia or impaired postural reflexes.[44] Trihexyphenidyl is the most widely used anticholinergic drug, but little evidence suggests that one drug in this class is superior to another in terms of either therapeutic efficacy or side effects. Trihexyphenidyl is initiated at 0.5 to 1.0 mg twice daily and increased gradually to a dosage of 2 to 3 mg three times daily. Benztropine is given in dosages of 0.5 to 1.0 mg twice daily. As with amantadine, anticholinergic drugs should be discontinued gradually to avoid acute exacerbation of parkinsonism,[45] even in patients in whom clinical response does not appear significant. Adverse side effects of anticholinergic drugs are common and often limit their use, irrespective of the patient's age. Peripheral antimuscarinic effects include dry mouth, blurred vision, constipation, nausea, urinary retention, impaired sweating, and tachycardia. Particular caution should be exercised in the presence of prostatic hypertrophy or closed-angle glaucoma. Mild peripheral effects, such as dry mouth and blurred vision, often subside with continued treatment and do not limit therapy. CNS effects-such as sedation, dysphoric effects, memory impairment, acute confusion, and hallucinations-are much more troublesome and usually require discontinuation of medication. Both advanced age and dementia are risk factors for CNS toxicity; therefore, the use of anticholinergic drugs should be limited to patients aged 60 or younger. Even in patients without obvious cognitive side effects, improvement in short-term and long-term memory has been demonstrated after withdrawal of anticholinergic drugs.[30] In summary, anticholinergic drugs are useful for the early treatment of PD in patients 60 years of age or younger in whom resting tremor is the predominant symptom. Because of the high incidence of peripheral and CNS side effects associated with these drugs, their use in patients without tremor and in patients above age 60 or with dementia is not recommended. Patients greater than 60 years of age: As discussed previously, the routine administration of anticholinergic drugs to patients above age 60 is not recommended. Nevertheless, these agents might be useful against specific symptoms in these patients, such as resting tremor that has been resistant to other treatment. If sialorrhea is to be treated with an anticholinergic drug in this population, one which acts peripherally, such as propantheline, should be considered to avoid CNS toxicity. janet paterson 52 now / 41 dx / 37 onset 613 256 8340 po box 171 almonte ontario canada K0A 1A0 a new voice: <http://www.geocities.com/SoHo/Village/6263/> <[log in to unmask]>