Paper I
Question
Enumerate four groups of drugs used in the treatment of Parkinson’s disease. Describe the pharmacological actions and adverse effects of levodopa. What is the advantage of combining levodopa with the peripheral decarboxylase inhibitor. (2+3+1= 6)
Answer
Four groups of drugs used in Parkinson’s disease
- Dopamine precursor: Levodopa (with carbidopa)
- Dopamine agonists: Bromocriptine, Pramipexole
- MAO-B inhibitors: Selegiline
- COMT inhibitors: Entacapone
- Anticholinergics: Trihexyphenidyl
- Amantadine (promotes dopamine release)
Pharmacological actions of Levodopa
- Crosses the blood-brain barrier and is converted to dopamine by dopa decarboxylase in the surviving nigrostriatal neurons, replenishing depleted striatal dopamine
- Improves bradykinesia and rigidity most effectively, with lesser effect on tremor
- Improves overall mobility and quality of life, especially in early disease
Adverse effects of Levodopa
- GI: nausea, vomiting, anorexia (due to peripheral dopamine formation)
- Cardiovascular: postural hypotension, arrhythmias
- CNS: dyskinesias (involuntary movements) with long-term use, “on-off” phenomenon/wearing-off effect, psychiatric disturbances (hallucinations, confusion)
- Mydriasis (caution in narrow-angle glaucoma)
Advantage of combining with a peripheral decarboxylase inhibitor (carbidopa)
- Carbidopa does not cross the blood-brain barrier and inhibits peripheral (extracerebral) conversion of levodopa to dopamine
- This increases the fraction of administered levodopa that reaches the brain (allowing a lower dose to be used), and markedly reduces peripheral dopamine-mediated adverse effects (nausea, vomiting, cardiovascular effects)