Parkinson's

Question 1

Levodopa (l-dopa) MOA

Answer 1

MOA - decarboxylated to dopamine in CNS

Dopamine - activated D2 receptors to inhibit adenyl cyclase - striatal neurons

Question 2

Levodopa - Therapeutics Effects

Answer 2

Clinical improvement after several weeks

Tremor is more resistant to therapy

Improvement of dementia

Full therapeutic action - 5-7yrs until neuronal degenration progresses

Question 3

Levodopa Adverse

Answer 3

Neuro - Dyskinesias (repetitive involuntary gross movements)

Akinesias - “End dose/wearing off” improved mobility, rapid return of ridigity and akinesia before end of dosing interval.

“On-off” akinesia - Works then doesn’t, not related to dosing

Behavioral - Anxiety, insomnia, depression, altered greams, visual hallucinations, psychoses

GI - N/V, tolerancemay develop. Attenuated with carbidopa

CV- Postural hypotension, arrhythmias

Mydriasis - acute glaucoma

Question 4

Levodopa Drug Interactions

Answer 4

Action reduced by DA receptor antagonists (antipsychotic/antiemetic dugs)

GI absorption dec by tricyclic antidepressants

Natural aromatic AA dec levodopa absorption

Nonselective MAO-A/MAO-B inhibitors - can cause HTN crisis, hyperthermia

Pyridoxine (Vit B6) - inc conversion of levodopa to dopamine

Question 5

Carbidopa

Answer 5

l-amino acid decarboxylase inhibitor

DOESN’T CROSS BBB

Less l-dopa metabolized in periphery

Dec adverse effects of l-dopa (N/V, CV)

Question 6

Ropinirole / Pramipexole

Answer 6

Dopamine D2 receptor agonists

Prami - D3 agonist as well

As effective as l-dopa, not as long lasting (desensitization of receptors)

Adverse effects, Contraindications - similar to l-dopa

Behavioral disturbances more severe

Question 7

Amantadine

Answer 7

Anti-viral

Potentiates DA action in CNS

Early PD, control of tremor

Adverese - headache, confusion, hallucinations

reversible discoloration of skin (livedo reticularis)

Peripheral edema, urinary retention, CHF

OD - toxic psychosis, convulsions

Question 8

Rasagiline/Selegiline

Answer 8

Selective MAO-B inibitors

Dec DA metabolism in CNS

Rasagiline - 1st line motor fluctuations

*** Shouldn’t be taken with meperidine or SSRI (serotonin syndrome)

Question 9

Entacapone

Answer 9

Selective peripheral inhibitor of COMT

Dec. clearance of l-dopa

Smoother response to l-dopa

Adverese due to too much l-dopa

Question 10

Benzotropine / Diphenhydramie

Answer 10

Anticholinergic

Supress over-activity of cholinergic neurons in basal ganglia

Initial stages of mild PD - younger pts. .