Neurological drugs

Question 1

levadopa/carbidopa (Sinemet)

Answer 1

Class: dopamine precursor/replacement

MoA: levadopa: transforms into DA after crossing BBB into the striatum. carbidopa: decreases breakdown of levadopa in intestines making more available to brain.

Uses: 1st line for moderate-severe PD. May take weeks-months to be effective. Effects wear off after a number of years.

Considerations: Do not give with high protein foods or on empty stomach. increased risk of HTN crisis with MAOIs. Increased beneficial effects with anticholinergics (less AcH for DA to compete with). Decreased effects w/ 1st gen antipsychotics.

Drug holidays recommended intermittently.

AEs: dose-dependent. HA, anxiety, N/V, dyskinesias, impulse control issues, O-HTN, dysrhythmias, psychosis, darkened body fluids, depression, malignant melanoma.

Question 2

pramipexole (Mirapex)

Answer 2

Class: dopamine receptor agonist

MoA: directly stimulates DA receptors.

Uses: 1st line early treatment for PD by itself. Combined with Sinemet for more progressed disease. Allows for fewer off-times when taken w/ Sinemet.

Considerations: Antiemetics decrease effect. Ensure good renal function. Do not stop abruptly.

AEs: N/V, dizziness, sleepiness, hallucinations, impulsive behaviors, O-HTN, edema, HF, dyskinesia, dystonia, double vision, dry mouth, urinary incontinence, constipation.

Question 3

entacopone (Comtan/ Tasmar)

Answer 3

Class: COMT inhibitor

MoA: Catechol-O-methyltransferase is an enzyme that breaks down levadopa. Inhibiting enzyme allows more levadopa to be available in brain.

Uses: Used in combo w/ Sinemet to increase half life.

Considerations: Do not give w/ MAOIs. Do not stop abruptly. Monitor liver function.

AEs: Liver failure, disorientation. Most other effects result from increased levodopa levels.

Question 4

selegiline (Emsam, Zelapar)

Answer 4

Class: MAO-B inhibitor

MoA: MAO-B inactivates DA in striatum, inhibition leads to increased DA available levels

Uses: Used alone for early PD, w/ Sinemet for more severe.

Considerations: Contraindicated w/ SSRIs. Higher doses inhibit MAO-A as well causing overstimulation of CNS & possible HTN crisis + stroke. Avoid foods containing tyramine and sympathomimetics.

AEs: Insomnia, dizziness, O-HTN, HTN crisis, stroke

Question 5

benztropine (Cogentin)

Answer 5

Class: Centrally acting anticholinergic

MoA: Reduces ACh in basal ganglia to restore DA-ACh balance to reduce rigidity, akinesia & tremors.

Uses: Combined w/ other PD meds.

Considerations: Use caution in pts over 60.

AEs: Mad as a hatter, hot as a hare, dry as a cracker. Opposite of DUMBBELLS.

Question 6

donepezil (Aricept)

Answer 6

Class: Cholinesterase inhibitor

MoA: Prevents breakdown of ACh, making more available at cholinergic synapses, enhancing transmission of neurons not yet destroyed by AD. Works only for 1 in 12 for about a year.

Uses: Mild alzheimers, myasthenia gravis

Considerations: Caution w/ asthma & COPD.

AEs: DUMBBELLS

Question 7

memantine (Namenda)

Answer 7

Class: NMDA antagonist

MoA: Adjusts effects of glutamate (major excitatory NT) at NMDA receptors. This blocks Ca2+ influx into neuron when glutamate is low and allowing Ca2+ influx when glutamate is low, resulting in prevention of cell death from unlimited Ca2+ influx.

Uses: Treat moderate-severe alzheimers

Considerations: Do not give pts w/ severe renal impairment as metabolites are toxic.

AEs:
Very mild. Dizziness, HA, diarrhea/constipation, confusion, anxiety, fatigue, hallucinations. Hyper/hypotension, Urinary incontinence, cough.