Parkinson's disease (502/1700)

For a pt presenting with Parkinson’s disease which of the following drugs is most useful in the
management of the tremor?
a. Apomorphine
b. Cabergoline
c. Selegiline
d. Amantadine
e. Benzhexol

answer: E

Currently accepted practice in the management of patients with Parkinson’s disease (PD) is to delay treatment until the onset of disabling symptoms and then to introduce a dopamine receptor agonist. If the patient is elderly, levodopa is sometimes used as an initial treatment.

Dopamine receptor agonists

e.g. Bromocriptine, ropinirole, cabergoline, apomorphine
ergot-derived dopamine receptor agonists (bromocriptine, cabergoline, pergolide*) have been associated with pulmonary, retroperitoneal and cardiac fibrosis. The Committee on Safety of Medicines advice that an echocardiogram, ESR, creatinine and chest x-ray should be obtained prior to treatment and patients should be closely monitored
patients should be warned about the potential for dopamine receptor agonists to cause impulse control disorders and excessive daytime somnolence
more likely than levodopa to cause hallucinations in older patients. Nasal congestion and postural hypotension are also seen in some patients

Levodopa

usually combined with a decarboxylase inhibitor (e.g. carbidopa or benserazide) to prevent peripheral metabolism of levodopa to dopamine
reduced effectiveness with time (usually by 2 years)
unwanted effects: dyskinesia (involuntary writhing movements), 'on-off' effect, dry mouth, anorexia, palpitations, postural hypotension, psychosis, drowsiness
no use in neuroleptic induced parkinsonism

MAO-B (Monoamine Oxidase-B) inhibitors

e.g. Selegiline
inhibits the breakdown of dopamine secreted by the dopaminergic neurons

Amantadine

mechanism is not fully understood, probably increases dopamine release and inhibits its uptake at dopaminergic synapses, weak effect
side-effects include ataxia, slurred speech, confusion, dizziness and livedo reticularis

COMT (Catechol-O-Methyl Transferase) inhibitors

e.g. Entacapone, tolcapone
COMT is an enzyme involved in the breakdown of dopamine, and hence may be used as an adjunct to levodopa therapy
used in conjunction with levodopa in patients with established PD

Antimuscarinics

block cholinergic receptors
now used more to treat drug-induced parkinsonism rather than idiopathic Parkinson's disease
help tremor and rigidity
e.g. procyclidine, benzotropine, trihexyphenidyl (benzhexol)