Cognitive Impairment

Question 0

Methylphenidate (Ritalin)

Answer 0

Class: CNS stimulant, structurally related to amphetamine
MOA: blocks reuptake of NE and DA, may also enhance release of catecholamines
Indication: FDA approved for ADD/ADHD (first line, followed by dextroamphetamine), accumulating evidence for efficacy in TBI
PK: rapidly absorbed when taken po, peak levels in 1-2h, metabolized in liver, excreted in urine
ADR: nervousness, insomnia, potential for dependence and abuse
Interaction: do not use with MAOI, may potentiate the effects of phenobarbital and phenytoin by delaying absorption, increase NE effects of tricyclic antidepressant, increase DA effects of anti-parkinsonian agents, potentiate analgesic effects of meperidine

Question 1

Donepezil (Aricept)

Answer 1

Class: AchE inhibitor
Indication: FDA approved for 1 month, accumulating evidence for efficacy in TBI
PK: well absorbed when taken po, highly protein bound, metabolized partially in liver, then excreted in bile, elimination half life 50-70h
ADR: n/v (10%), sinus bradycardia and 1’ AV block relative contraindications, monitor LFTs
Interaction: agents that inhibit hepatic metabolism via CYP450 (e.g. ketoconazole, quinidine) may increase blood levels of donepezil, inducers of metabolism (phenobarbital, phenytoin, carbamazepine, dexamethasone, rifampin) may decrease therapeutic blood levels

Question 2

Atomoxetine (Strattera)

Answer 2

Class: SNRI
Indication: FDA approved for ADHD
PK: rapid GI absorption, CYP2D6 metabolism
ADR: liver toxicity, suicidal ideation
Interaction: wit CYP2D6 inhibitors (e.g. Quinidine)

Question 3

Amantadine, Memantine

Answer 3

Class: moderate-affinity uncompetitive NMDA antagonist, and dopamine agonist (ropinirole)
Indicated for Parkinson’s Disease (Amantadine), Alzheimer’s Disease (memantine)

Question 4

Modafinil

Answer 4

Class: approved for treatment of excessive daytime somnolence in patients with narcolepsy

• may have a role in tx of post-TBI fatigue and cognitive impairment
• exact MOA include activation of orexin neurons in lateral hypothalamus, indirect dose-dependent reduction of GABA release, increases in glutamate release in VL and VM thalamus, increases in DA in NuAcc.