Parkinson Drugs

Question 1

What is Parkinson disease characterized by clinically and what is the etiology?

Answer 1

• Resting tremor
• Muscular rigidity
• Bradykinesia
• Gait impairment

Etiology: loss of neurons of the dopaminergic nigrostriatal pathway

Question 2

What are the action os D1 and D2 receptors and which is more important in Tx of Parkinson’s Disease?

Answer 2

D1 receptors: increase adenylyl cyclase

D2 receptors: decrease adenylyl cyclase, decrease Ca2+ conductance, increase K+ conductance

Question 3

Levodopa MOA, AE, PK, CI

Answer 3

MOA: transported into CNS and converted to dopamine in brain

AE: peripheral conversion causing N/V, cardiac arrhythmias, hypotension

PK: rapidly absorbed in small intestines; food can delay appearance in plasma; certain amino acids can compete with absorption in gut and BBB (prevent high protein diet)

CI: vitamin B6, nonspecific MAOIs > HTN crisis, psychotic pts, antipsychotic drugs, angle-closure glaucoma,

Question 4

Carbidopa MOA

Answer 4

MOA: dopa decarboxylase inhibitor that does not cross BBB

Question 5

What is the DOC for parkinson’s disease and AE?

Answer 5

Levodopa + Carbidopa

decline in response to drugs duirng 3-5th year of therapy bc loss of dapaminergic nigrostriatal neurons

AE:

• GI: anorexia, N/V
• CV: tachycardia, ventricular extrasystoles, hypotension
• CNS: visual/auditory hallucination, dyskinesia, mood changes, depression, anxiety, agitation

Question 6

Explain the Wearing-Off Reactions and The On-Off Phenomenom with Tx?

Answer 6

• Wearing-Off Reactions (End-of-Dose Akinesia) is fluctuations related to timing of levodopa intake
• The On-Off Phenomenom is flucuations unrelated to timing of doses and can be Tx with Apomorphine (SC a nonergot DA) but emetogenic so recommended to give Trimethobenzamide

Question 7

Bromocriptine MOA

Answer 7

MOA: D2 agonist; ergot dopamine agonist

Question 8

Pramipexole & Ropinirole MOA, uses

Answer 8

MOA: dopamine agonist; nonergot dopamine agonst

Uses: increasingly being used as initial Tx for PD in younger pts because older are more vulnerable to AE of cognitive effects

Question 9

Rotigotine MOA

Answer 9

MOA: dopamine agonist (nonergot) available transdermal

Question 10

What are the AE of dopamine agonists?

Answer 10

GI: anorexia, N/V, constipation, dyspepsia, bleeding from peptic ulcers

CVS: postural hypotension, arrhythmias, peripheral edema, painless digital vasospasm (ergot)

Dyskinesias, Mental disturbances (confusion, hallucination, delusions)

Ergot DA: pulmonary infiltrates, pleural/retroperitoneal fibrosis, erythromelalgia

Pramipexole, Ropinirole, Rotigotine: uncontrollable somnolence

Question 11

Deprenyl (Selegiline) MOA, AE

Answer 11

MOA: irreversibly inhibits MAO-B; adjunct to levodopa

AE: metabolized to methamphetamine and amphetamine so can cause insomia

Question 12

Rasagiline MOA

Answer 12

MOA: inhibitor of MAO-B

Question 13

Tolcapone & Entacapone MOA, AE

Answer 13

MOA: inhibition of COMT > decreased metabolism of levodopa > decreased plasma 3-O-methyldopa > increased uptake of levodopa

AE: fulminating hepatic necrosis (tolacapone) becauase acts on CNS and periphery COMT

Question 14

Amantadine MOA, AE

Answer 14

MOA: antiviral with unclear action but increases release of dopamine, antagonist at cholinergic receptors, and antagonist at NMDA receptor

AE: Livedo reticularis; restlessness, agitation, confusion, hallucination, acute toxic psychosis, peripheral edema

Question 15

Benztropine Mesylate & Trihexyphenidyl MOA

Answer 15

MOA: centrally acting antimuscarinic; adjuvant that may improve tremor, rigidity, and drooling

Question 16

Choice of treatment for Parkinson’s disease?

Answer 16

• Levodopa + Carbidopa
• Dopamine agonist are next most effective used before levodopa or as adjuvant (nonergot prefered)
• Addition of COMT inhibitor or MAO-B inhibitor
• Antimuscarinic