Question
Drugs used to treat Parkinsonism. Describe the Mechanism of action and adverse effects of levodopa.
Answer
Drugs used to treat Parkinsonism
| Group | Examples |
|---|---|
| Dopamine precursor | Levodopa (with Carbidopa) |
| Dopamine agonists | Pramipexole, Ropinirole (non-ergot); Bromocriptine (ergot) |
| MAO-B inhibitors | Selegiline, Rasagiline |
| COMT inhibitors | Entacapone |
| Anticholinergics | Trihexyphenidyl |
| Amantadine | Amantadine |
Levodopa — mechanism of action and adverse effects Mechanism: levodopa is the metabolic precursor of dopamine — dopamine itself cannot cross the blood-brain barrier, while levodopa can (via the large neutral amino acid transporter). Once inside the CNS, it is decarboxylated to dopamine by dopa decarboxylase, replenishing striatal dopamine. Always co-administered with a peripheral decarboxylase inhibitor (Carbidopa), which cannot itself cross the blood-brain barrier and so only blocks peripheral conversion — this increases the fraction of an oral dose reaching the CNS intact (allowing a lower dose for the same effect) and reduces peripheral dopamine-mediated adverse effects.
Adverse effects: nausea/vomiting (peripheral dopamine stimulating the chemoreceptor trigger zone — reduced but not eliminated by carbidopa), postural hypotension, cardiac arrhythmias, and — with chronic use — motor fluctuations (“wearing-off” as the therapeutic window narrows with disease progression) and dyskinesias (involuntary movements from pulsatile, non-physiological striatal dopamine receptor stimulation), the rationale for delaying levodopa initiation in younger patients where feasible. Psychiatric effects (hallucinations, confusion) can also occur, particularly in elderly patients.