PSYCH - Cognitive Dysfunction (TBI, Alz, Parkinsons, Dementia)

Question 1

What is the mechanism of action for these 3 drugs?

Donepezil
Galantamine
Rivastigmine

Clinical uses?

Answer 1

AChE inhibitor

Donepezil - Alzheimers, TBI
Galantamine - Alzheimers, Dementia, Parkinsons
Rivastigmine - Alzheimers

Question 2

What are some ways to increase ACh in the synaptic cleft?

Answer 2

AChE inhibitor OR CDP-choline (ACh precursor)

Question 3

What is the mechanism of action for methylphenidate (ritalin)?

Clinical uses?

Answer 3

CNS stimulant (blocks reuptake of NE + dopamine)

Clinical Uses: ADHD, TBI

Question 4

What is the mechanism of action for (dextro)amphetamine?

Answer 4

stimulates release of NE, dopamine, and Epinephrine from neurons

Clinical Uses: ADHD, TBI

Question 5

What is the mechanism of action for Atomoxetine and duloxetine?

Clinical uses (hint: same MoA, but different functions!)

Answer 5

blocks NE reuptake

Clinical use:

Atomoxetine: ADHD + TBI related attentional deficits

Duloxetine: Anti-depressant, chronic pain

Question 6

What is the mechanism of action for Amantadine?

Clinical use?
Side Effects

Answer 6

stimulates dopamine release and inhibits dopamine reuptake

Clinical use: Parkinson’s

Side effects: CNS symptoms (ataxia, slurred speech, dizziness)

Question 7

What is the mechanism of action for Memantine?

Clinical use?
side effects?

Answer 7

NMDA antagonist (decreases neuronal excitation via glutamate receptors)

Clinical use: Alzheimers

Side effects: CNS symptoms (agitation, dizziness, headache)

Question 8

What is the mechanism of action for Modafinil?

Clinical use?

Answer 8

unclear, but it may involve:

• stimulation of hypocretin/orexin neurons in lateral hypothalamus
• increase glutamate release in VPL/VPM
• increase dopamine release in nucleus accumbens

Clinical use:

• excess daytime sleepiness (increases mental alertness)
• post-TBI fatigue and cognitive impairment

Question 9

Donepezil

Mechanism of Action:
Clinical use:
Side effects:
Contraindications:

Answer 9

Mechanism of Action: AChE inhibitor

Clinical use: Alzheimers, TBI

Side effects: nausea, vomiting, GI upsets, muscle cramping (treat with tonic water), hepatotoxicity (monitor LFTs)

Contraindications: patients with

• sinus bradycardia
• 1st degree AV block
• medications that increase/decrease CYP enzyme activities

Question 10

Methylphenidate and Dextroamphetamine

Mechanism of Action:
Clinical use:
Side effects:
Contraindications:

Answer 10

Mechanism of Action:

• Methylphenidate - blocks dopamine/NE reuptake
• Dextroamphetamine - stimulate release of NE, dopamine and Epi, and blocks reuptake

Clinical use: ADHD, TBI

Side effects: highly abusable, insomnia, decrease appetite and weight loss, psychosis + hallucinations (with OD)

Contraindications: MAOi

Question 11

Atomoxetine

Mechanism of Action:
Clinical use:
Side effects:
Contraindications:

Answer 11

Mechanism of Action: blocks NE reuptake

Clinical use: ADHD, TBI-related attentional deficits

Side effects: sedation, liver toxicity, suicidal ideation

Contraindications: medications that inhibit CYP2D6