Week 8: CNS and Drugs of Abuse

Question 1

Acetylcholine: Receptor and function

Answer 1

Receptor: Cholinergic (muscarinic & nicotinic)
Function: PSNS, skeletal muscle, memory

Question 2

Dopamine: Receptor and function

Answer 2

Receptor: Dopaminergic
Function: Reward circuit, motor control

Question 3

Serotonin (5-HT): Receptor and function

Answer 3

Receptor: 5-HT (subtypes 1-7)
Function: Digestion, sleep, anxiety, mood, appetite, social behavior

Question 4

Histamine: Receptor and function

Answer 4

Receptor: Histamine (subtypes 1-4)
Function: Wakefulness

Question 5

Glutamate: Receptor and function

Answer 5

Receptor: AMPA, NMDA
Function: Major CNS excitatory NT

Question 6

GABA: Receptor and function

Answer 6

Receptor: GABA (subtypes A & B)
Function: Major brain inhibitory NT

Question 7

Glycine: Receptor and function

Answer 7

Receptor: Glycine
Function: Major spinal cord inhibitory NT

Question 8

Pathophysiology of Parkinson disease

Answer 8

Degeneration of neurons in the substantia nigra that supply dopamine to the striatum

In movement:
- Dopamine (DA) = inhibitory
- ACh = excitatory

Dec. DA = unopposed ACh actions = symptoms

Question 9

Carbidopa: Class, indications, MOA, other notes (2)

Answer 9

Class: Decarboxylase inhibitor
Indications: Taken WITH levodopa
MOA: Inhibits decarboxylase to allow more levodopa to reach CNS
- Decreases peripheral AE of levodopa, but increases CNS AE
- No therapeutic effects alone and does not cross BBB

Question 10

Entacapone: Class, indications, MOA, other notes (2)

Answer 10

Class: COMT inhibitor
Indications: Taken WITH levodopa
MOA: Inhibits COMT to allow more levodopa to reach CNS
- Decreased peripheral adverse effects, but increases CNS AE
- No therapeutic effects alone

Question 11

Levodopa: Class, indications, MOA, AE (10), PK (2)

Answer 11

Indications: Use for severe PD
- Most effective (but effects diminish over 5 years)
- Not used in mild cases d/t AE
MOA: Prodrug that is converted into dopamine in the CNS presynaptic terminals
AE:
- N/V
- Dyskinesia
- CV effects: postural orthostatic hypotension early in treatment and dopamine peripherally can cause B1 stimulation & dysrhythmia risk
- Psychosis (reduce dose or use 2nd gen antipsychotic)
- CNS (anxiety/agitation, cognitive impairment)
- Harmless darkening of sweat and urine
- Contraindications:
- MAOIs (risk for severe HTN)
PK:
- DA requires transporters to cross BBB (competes with amino acids)
- To get into CNS: COMT inhibitors, decarboxylase inhibitors, avoid high protein meals

Question 12

Pramipexole // Rotigotine // Ropinirole: Class, indications, MOA, AE, PK

Answer 12

Class: Dopamine agonists
- Nonergot alkaloids
Indications: First line for mild-moderate PD; or taken with levodopa in severe disease
- No dyskinesia risk
MOA: Direct agonism of dopamine RECEPTORS in striatum
- Dopamine receptor selective (fewer adverse effects)
AE:
- N/V
- Dizziness
- Daytime somnolence
- Constipation
- Weakness
- Hallucinations
- If experience N/V, don’t take 5-HT antagonists (can cause orthostatic hypotension) OR dopamine receptor antagonist (opposite effect)

Question 13

Pramipexole // Rotigotine // Ropinirole: Compare and contrast

Answer 13

All: Used with mild PD or with L-dopa in severe PD

MOA:
- Pramipexole and Ropinirole: Binds selectively to D2 and D3 receptor subtypes
- Rotigotine: Exact MOA unknown, likely activation of DA receptors in substantia nigra

AE:
- Pramipexole and Rotigotine: N/V, dizziness, daytime somnolence, constipation, weakness, hallucinations
- Ropinirole: Same AE but AEs are more common, unless used with L-dopa

Question 14

Selegiline // Rasagiline: Class, indications, MOA, AE (7)

Answer 14

Class: MAO-B inhibitors
Indications: First line for mild-moderate PD
MOA: Selective, irreversible binding of MAO-B
- At high doses, MAO-B inhibitors lose their selectivity, and may inhibit MAO-A which breaks down NE and 5-HT
AE:
- HTN in high doses (MAO-A inhibition)
- Orthostatic hypotension
- Dizziness
- GI effects
- Drug Interactions:
- Can intensify L-Dopa
- Opioids: increased AE, serotonin syndrome risk
- SSRIs: serotonin syndrome risk

Question 15

Selegiline: What’s unique?

Answer 15

Metabolites are amphetamine and methamphetamine → CNS excitation and insomnia

Question 16

Rasagiline: What’s unique?

Answer 16

Carries risk for malignant melanoma

Question 17

Amantadine: Indications, MOA, AE (3), PK

Answer 17

Indications: PD
MOA: Increases dopamine availability… through uncertain mechanism
- Promotes release, may also inhibit uptake
AE:
- CNS effects (confusion, dizziness, anxiety)
- Peripheral effects (anticholinergic)
- >1 month: livedo reticularis (mottled discoloration)
PK: Rapid responses, short DOA

Question 18

Benztropine: Class, indications, MOA, AE, PK

Question 19

Donepezil

Question 20

Galantamine

Question 21

Rivastigmine

Question 22

Memantine

Question 23

Interferon beta

Question 24

Mitoxantrone

Question 25

Dalfampridine

Question 26

Phenytoin

Question 27

Fosphenytoin

Question 28

Carbamazepine

Question 29

Valproate

Question 30

Ethosuximide

Question 31

Phenobarbital

Question 32

Oxcarbazepine

Question 33

Lamotrigine

Question 34

Gabapentin

Question 35

Pregabalin

Question 36

Levetiracetam

Question 37

Topiramate

Question 38

Tiagabine

Question 39

Baclofen

Question 40

Dantrolene

Question 41

Cyclobenzaprine

Question 42

Disulfiram

Question 43

Naltrexone

Question 44

Acamprosate

Question 45

Nicotine replacement therapy

Question 46

Bupropion

Question 47

Varenicline

Question 48

Methadone

Question 49

Buprenorphine

Question 50

Flumazenil

Question 51

Marijuana