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)