Week 8: CNS and Drugs of Abuse Flashcards
Acetylcholine: Receptor and function
Receptor: Cholinergic (muscarinic & nicotinic)
Function: PSNS, skeletal muscle, memory
Dopamine: Receptor and function
Receptor: Dopaminergic
Function: Reward circuit, motor control
Serotonin (5-HT): Receptor and function
Receptor: 5-HT (subtypes 1-7)
Function: Digestion, sleep, anxiety, mood, appetite, social behavior
Histamine: Receptor and function
Receptor: Histamine (subtypes 1-4)
Function: Wakefulness
Glutamate: Receptor and function
Receptor: AMPA, NMDA
Function: Major CNS excitatory NT
GABA: Receptor and function
Receptor: GABA (subtypes A & B)
Function: Major brain inhibitory NT
Glycine: Receptor and function
Receptor: Glycine
Function: Major spinal cord inhibitory NT
Pathophysiology of Parkinson disease
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
Carbidopa: Class, indications, MOA, other notes (2)
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
Entacapone: Class, indications, MOA, other notes (2)
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
Levodopa: Class, indications, MOA, AE (10), PK (2)
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
Pramipexole // Rotigotine // Ropinirole: Class, indications, MOA, AE, PK
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)
Pramipexole // Rotigotine // Ropinirole: Compare and contrast
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
Selegiline // Rasagiline: Class, indications, MOA, AE (7)
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
Selegiline: What’s unique?
Metabolites are amphetamine and methamphetamine → CNS excitation and insomnia
Rasagiline: What’s unique?
Carries risk for malignant melanoma
Amantadine: Indications, MOA, AE (3), PK
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
Benztropine: Class, indications, MOA, AE, PK
Donepezil
Galantamine
Rivastigmine
Memantine
Interferon beta
Mitoxantrone
