Parkinson disease (paralysis agitans) (drugs that increase dopamine levels)

Question 1

Drugs for PD - 3 groups of drugs

Answer 1

Drugs that increase dopamine levels.
Dopamine receptor agonists.
Centrally acting ACh receptor antagonists.

Question 2

Drugs that increase dopamine levels in PD - 7 drugs

Answer 2

Levodopa
Carbidopa
Amantadine
Selegiline
Rasagline
Tolcapone
Entacapone

Question 3

When is levodopa effective in PD?

Answer 3

As long as there are dopaminergic neurons are still alive. Counteract all signs of parkinsonism.
Fluctuation in effectiveness: wearing-off effect and on-off effect.

Question 4

Levodopa - indications

Answer 4

Idiopathic PD.
Postencephalitic parkinsonism.
Parksonian symptoms (CO poisoning, manganese intoxication, cerebral atherosclerosis).

Question 5

Pts on …. for PD should not take which vitamin and why?

Answer 5

Levodopa.

Vit B6: enhance peripheral decarboxylation of levodopa.

Question 6

Levodopa - adverse effects

Answer 6

Nausea, vomiting (80%).
Orthostatic hypotension (25%).
Psychotic symptoms (agitation, delirium, distorted thinking, hallucinations).
Dyskinesia, nightmares, vivid dreams, sedation. Euphoria. Arrhythmias

Question 7

Levodopa - interactions

Answer 7

Antacids increase bioavailability.
Anticholinergic drugs reduce peak serum levels.
Antipsychotics decrease effects of levodopa. Nonselective MAOIs cause hypertensive crisis.
Dietary amino acids decrease bioavailability.
Vit B6: enhance peripheral decarboxylation of levodopa.

Question 8

Which antipsychotic can be used in pts with PD and why is this a good choice?

Answer 8

Clozapine less likely to block dopamine receptors and decrease effects of levodopa

Question 9

Levodopa - diet

Answer 9

Protein-restricted diet because dietary amino acids decrease bioavailability and levodopa uptake to the brain.

Question 10

Carbidopa - MOA

Answer 10

Inhibits dopamine synthesis in peripheral tissues by blocking LAAD.
Increase the amount of levodopa that enters the brain.

Question 11

Carbidopa - indications

Answer 11

Reduction in levodopa dosage (by 75 %).

Reduces GI and cardiovascular effects of levodopa.

Question 12

Amantadine - Classification and MOA

Answer 12

Antiviral drug.

Increases dopamine release from nigrostriatal neurons, and inhibits reuptake of dopamine.

Question 13

Amantadine - indications

Answer 13

Influenza.

Adjunct to levodopa in early or mild cases

Question 14

Amantadine - adverse effects

Answer 14

Dry mouth.
Hypotension.
Livedo reticularis
Nausea
Restlessness, sedation, vivid dreams. 
CNS adverse effects are more likely in elderly.

Question 15

Amantadine - interactions

Answer 15

Benzotropine and trihexyphenidyl potentiate CNS effects

Question 16

Selegiline, rasagline - MOA

Answer 16

Inhibits dopamine breakdown by inhibiting MAO-B, preventing oxidation of dopamine.
Decreases formation of hydrogen peroxide.

Question 17

Selegiline - interactions

Answer 17

Meperidine/fluroxetine/other SSRI: severe reactions.

High doses: Interaction with foods containing thyramine.

Question 18

Selegiline - indications

Answer 18

Single treatment for early/mild PD.

Adjunct to levodopa-carbidopa for advanced disease

Question 19

Rasagline - indications

Answer 19

Monotherapy or adjunct for PD

Question 20

Rasagline, selegiline - adverse effects

Answer 20

Confusion
Dyskinesias
Hallucinations
Hypotension
Insomnia
Nausea

Question 21

Tolcapone and entacapone- MOA

Answer 21

Inhibits COMT and prevents conversion of levodopa to 3OMD.

Stabilizes dopamine levels in striatum. Increase efficacy of levodopa, reducing the dosage requirement.

Question 22

Tolcapone - adverse effects

Answer 22

Diarrhea and nausea.

Rare but fatal hepatitis

Question 23

Difference between entacapone and tolcapone

Answer 23

entacapone is more restricted to peripheral tissues, and causes no hepatic toxicity