A.31

Question 1

drugs acting in the extrapyramidal motoric system. Nootropic drugs

Answer 1

1. Drugs used in Parkinson’s disease- Levodopa, Carbidopa, Entacapone, Ropinirole, Pramipexole, Selegiline, Amantadine, Procyclidine
2. Drugs used in Alzheimer’s disease- Rivastigmine, Memantine,
3. Nootropic agents- Piracetam

Question 2

Levodopa+Carbidopa

Answer 2

MOA: levodopa is DA metabolic precursor;
Effect: Levodopa can cross the BBB and ↑DA synthesis in the brain.
Levodopa is converted by DOPA-decarboxylase→ only 1-3% enters the brain due to extensive peripheral metabolism by the enzyme→ give carbidopa, which is a peripheral inhibitor of the enzyme;
IND: Parkinson’s disease;
Pharmacokinetics: good oral absorption, time to reach peak cc: 1-2h;
SEs: Dyskinesia, end of dose phenomenon, hypotension, arrhythmias, nausea, vomiting, depression, psychosis, agitation, anxiety, nightmares; Extra: Narrow therapeutic index, therapeutic consideration→ start as late as possible

Question 3

Ropinirole, Pramipexole

Answer 3

MOA: DA D2 agonist (non-ergot derivatives);
Effect: longer duration of action than levodopa and effective in patients with fluctuations in response to levodopa, Pramipexole is a potential anti-oxidant;
IND: Parkinson’s disease;
SEs: similar to levodopa→ dyskinesia, psychosis, nausea, vomiting;
ROA: p.o, administered 3 times daily

Question 4

Selegiline

Answer 4

MOA: selective+Irreversible MAO-B inhibitor;
Effect: Decreases metabolism of DA→ increased DA activity in the brain, No “cheese effect” as seen in non-selective MAO inhibitors, Neuroprotective (enhancement of scavenger functions);
IND: Parkinson’s disease (early, administered with levodopa), Alzheimer’s disease, depression;
SEs: Dyskinesia, psychosis, insomnia, hypotension

Question 5

Entacapone

Answer 5

MOA: COMT inhibitor;
Effect: inhibits peripheral metabolism of levodopa by inhibiting the COMT enzyme, added to levodopa/carbidopa for enhanced uptake and efficacy; IND: parkinson’s disease;
SEs: related to incresed effects of L-dopa

Question 6

Amantadine

Answer 6

MOA: antiviral drug (influenza prevention);
Effect: uncertain mechanisms: NMDA-R ant., Enhancing DA release / inhibibiting its reuptake, Adenosine A2A-R ant. →disihnibition of D2-mediated effects. weaker than levodopa and tolerance develops against it;
SEs: mainly mental SEs, Livedo reticularis, psychosis, agitation

Question 7

Procyclidine

Answer 7

MOA: M-R antagonist;
Effect: decreases resting tremor and rigidity;
IND: mostly for drug-induced Parkinsonism, parkinson’s disease, extrapyramidal disorders;
SEs: Atropine-like (dry eyes, dry mouth, blurred vision, mydriasis, constipation)

Question 8

Rivastigmine

Answer 8

MOA: AChE inhibitor (centrally acting);
Effect+IND: 1st line agent for Alzheimer’s disease→ provide moderate reduction in rate of loss of cognitive function;
SEs: nausea, vomiting, diarrhea, bradycardia

Question 9

Memantine

Answer 9

MOA: Glutamate NMDA-R blocker;
Effect+IND: stimulation of CNS glutamate Rs appears to be critical in formation of certain memories, but overstimulation may result in excitotoxicity;
SEs: confusion, agitation

Question 10

Piracetam

Answer 10

MOA: interferes with NT release by binding to synaptic vesicle protein (SV2A);
IND: Vascular dementia,used as cognition enhancers and in treatment of ADHD, Parkinson’s disease and schizophrenia

Question 11

Dyskinesia (on/off phenomenon)

Answer 11

levodopa-induced dyskinesia
* On phase→ dyskinesia (uncontrolled movements)
* Off phase→ bradykinesia (slow movements)

Question 12

End of dose phenomenon

Answer 12

shorter duration of action, DA will be less effective as time goes on→ narrowing dose intervals to reach same effect
“cheese effect”- If you take an MAOI and you eat high-tyramine foods, tyramine can quickly reach dangerous levels. This can cause a serious spike in blood pressure and require emergency treatment.