Pharm - parkinsons & cognitive enhancers

Question 0

Carbidopa

Answer 0

oral, used to help treat parkinsonism;

Mech: blocks peripheral metabolism of Levodopa –> promotes levodopa entrance to brain.

Question 1

Levodopa

Answer 1

oral dopamine precursor, used for parkinsonism.
Mech: metabolized to DA in brain (and peripherally).
SE: orthostatic hypotension, nausea/vomiting (bc of peripheral DA & NE toxicity); Dyskinesia, psychosis
* usually given w/ carbidopa to increase BBB crossing.

Question 2

Sinemet

Answer 2

oral, = levodopa + carbidopa; #1 most effective parkinsonism Tx;
Mech: Levodopa = dopamine precursor, Carbidopa decreases peripheral metabolism of Levodopa –> increase levodopa in brain.
SE: dyskinesia, psychosis; possible orthostatic hypertension & nausea

Question 3

Tolcapone

Answer 3

oral COMT inhibitor, used to treat parkinsonism;
Mech: decrease L-Dopa elimination, increase half-life, & bioavailability (blocks peripheral metabolism of inactive dopamine metabolite)
SE: Liver failure (monitor regularly)

Question 4

Entacapone

Answer 4

oral COMT inhibitor, used to treat parkinsonism;
Mech: decrease L-dopa elimination, increase half-life and bioavailability –> reduce pharmacodynamic rebound or on-off effect
(blocks peripheral metabolism of inactive dopamine metabolite)

Question 5

Stalevo

Answer 5

oral, = Levodopa + carbidopa + Entacapone; used to treat parkinsonism;
Mech: 3 drug combo to increase efficacy of dopamine replacement
SE: diskinesia, psychosis, (less) orthostatic hypotension & nausea

Question 6

trihexyphenidyl

Answer 6

oral anticholinergic, used for early stages of Parkinson’s & tremors;
Mech: inhibits motion suppressing neurons
* very good for increasing smoothness of mvmt.
SE: “SLUD” (Decreases: Salivation, Lacrimation, Urination, and Defecation), esp. in elderly.

Question 7

Bromocriptine

Answer 7

oral ergoline, D2 agonist; used to treat parkinsonism & hyperprolactinemia from PD.
Mech: synthetic dopamine mimic
* longer half-life than L-dopa
SE: fibrosis, dyskinesias, hallucinations

Question 8

Pramipexole

Answer 8

oral, non-ergoline synthetic dopamine;
= to treat parkinsonism or restless leg syndrome.
Mech: D3 > D2 agonist
SE: (not fibrosis) dyskinesias, hallucinations, sleep attacks, nausea, insomnia, constipation

Question 9

Ropinirole

Answer 9

oral, non-ergoline synthetic dopamine, used to treat parkinsonism and restless leg syndrome.
Mech: D3 > D2 agonist (replaces DA to inhibit mvmt inhibition pathway)
SE: (not fibrosis) dyskinesias, hallucinations, sleep attacks, nausea, insomnia, constipation

Question 10

Amantidine

Answer 10

oral dopamine enhancer, used for parkinsonism;

Mech: increases DA release from surviving substancia nigra afferents, also blocks glutamate.

Question 11

Selegiline

Answer 11

MAO-B inhibitor, used for parkinsonism;
Mech: inhibits brain metabolism of DA into DOPAC
SE: interacts w/ antidepressants (tricyclics)!
* expensive and not as effective as L-dopa

Question 12

Rasagiline

Answer 12

MAO-B & A inhibitor, used for parkinsonism;
Mech: inhibits brain metabolism of DA to DOPAC
SE: Serotonin syndrome, tyramine food interactions, contraindicated if hepatic insufficiency

Question 13

Apomorphine

Answer 13

powerful dopamine agonist; = IV, subcut, intramuscular… (not oral)
Use: for parkinsonism emergency “off”-state rescue in immbobile patient.
Mech: D1/D2 agonist

Question 14

Drug classes used for alzheimer’s prevention (3)

Answer 14

1. NSAIDs - Aspirin, Naproxen
2. Statins (ie: Lovastatin)
3. Antihypertensives

Question 15

Tacrine

Answer 15

Oral cognitive enhancing prototype drug (for Alzheimer’s)
Mech: Reversible cholinesterase inhibitor (take 4x/day)
* non-selective (CNS & PNS)
SE: liver toxicity (!), cholinergic effects (ataxia, urinary incotinence, diarrhea, nausea, vomiting)
** no longer on market**

Question 16

Donepezil

Answer 16

oral cognitive enhancing drug (for Alzheimer’s)
Mech: reversible cholinesterase inhibitor (take 1x/day)
* CNS selective
SE: liver toxicity only w/ drug-drug interactions (competitive P450 metabolism)
* best for patients NOT on multi-drug regimens*

Question 17

Rivastigmine

Answer 17

oral cognitive enhancing drug (for Alzheimer’s)
Mech: reversible cholinesterase inhibitor (take 2x/day)
* CNS selective!
SE: cholinergic effects (diarrhea, nausea, urinary incontinence)
(*NO liver toxicity or drug-drug interactions)
* best for patients who ARE on multi-drug regimens)

Question 18

Galantadine

Answer 18

oral cognitive enhancing drug (for Alzheimer’s),
* non-selective (CNS & PNS)
Mech: reversible cholinesterase inhibitor (take 2x/day) AND potentiates nACh Rs
SE: hepatotoxicity only w/ drug interactions, cholinergic effects (diarrhea, nausea, urinary incontinence)

Question 19

Memantine

Answer 19

oral cognitive enhancer (for Alzheimer’s)
Mech: NMDA antagonist & blocks chronic Glutamate neurotoxicity (but allows pulsatile GLU for learning)
* added benefit when combo w/ reversible cholinesterase inhibitors*