Parkinson's

Question 1

Most effective drug for PD

• Full therapeutic responses may take several months to develop
• Increases dopamine synthesis in striatum
• When in the brain, the drug undergoes uptake into the remaining dopaminergic nerve terminals that remain in the striatum
• High-protein foods can reduce therapeutic effects
• N/V, dyskinesias, postural hypotension

Answer 1

Levodopa

Question 2

• Inhibits decarboxylation of levodopa in the intestine and peripheral tissues
• No therapeutic effects of its own

Answer 2

Carbidopa

Question 3

Nonergot dopamine agonist

• Used alone in early-stage PD and combined with levodopa in advanced-stage PD
• Binds selectively to dopamine-2 and dopamine-3 receptors
• Also approved for patients with Restless Legs Syndrome (RLS)
• Adverse effects: nausea, dizziness, daytime somnolence, insomnia, constipation, weakness, and hallucinations; sleep attacks

Other similar drugs include ropinirole and rotigotine

Answer 3

Pramiprexole

Question 4

Ergot derivative

• Beneficial effects derive from activating dopamine receptors in the striatum
• In addition to activating dopamine receptors, the ergot drugs cause mild blockade of serotonergic and α-adrenergic receptors
• The most common dose-limiting effects are psychological reactions (confusion, nightmares, agitation, hallucinations, paranoid delusions)
• Also associated with valvular heart disease

Answer 4

Bromocriptine

Question 5

Catechol-O-Methyltransferase Inhibitor

• Selective, reversible inhibitor of COMT indicated only for use with levodopa
• Prolongs the plasma half-life of levodopa and thereby prolongs the time that levodopa is available to the brain
• Can cause dyskinesias, orthostatic hypotension, nausea, hallucinations, sleep disturbances, and impulse control disorders (see Pramipexole)

Similar drug is tolcaptone, but it can cause severe hepatocellular injury, so it is not preferred

Answer 5

Entacapone

Question 6

• Selegiline and rasagiline
• Cannot be combined with tyramine-rich foods

Answer 6

MAO-B Inhibitors

Question 7

• Originally developed as an antiviral agent
• Possible mechanisms include the inhibition of dopamine uptake, stimulation of dopamine release, blockade of cholinergic receptors, antagonism of N-methyl-D-aspartate (NMDA) receptors, and blockade of glutamate receptors
• May be helpful for managing dyskinesias caused by levodopa
• Side effects include CNS effects and livedo reticularis

Answer 7

Amantadine

Question 8

• Benztropine (Cogentin, Kynesia) and trihexyphenidyl
• Helps balance between acetylcholine and dopamine

Answer 8

Centrally acting anticholinergics