Regarding The Adverse Effect Of Cabergoline Used In Treatment Of Parkinson's Disease

A 64-year-old man with a history of Parkinson's disease is reviewed in clinic and a decision has been made to start him on cabergoline. Which one of the following adverse effects is most strongly associated with this drug?
A. Optic neuritis
B. Transient rise in liver function tests
C. Pulmonary fibrosis
D. Renal failure
E. Thrombocytopenia

Answer:
C. Pulmonary fibrosis

Discussion:
Parkinson's disease: management : 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
 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)