Week 10 (Test 4) Flashcards
(56 cards)
What mechanisms can be used by AED’s to reduce excessive excitation?
A. Prevent repetitive action potential propagation of seizure discharges by inactivation of voltage-gated sodium channels B. Reduce excessive presynaptic glutamate release –binding to presynaptic Ca2+ channels at the a2d subunit – binding to presynaptic vesicle SV2A protein C. Block AMPA glutamate receptors
What mechanisms can be used by AED’s to increase inhibition?
A. Increase GABA-mediated neurotransmission 1. Enhancing post-synaptic GABA-A Receptor function 2. Increasing GABA synthesis 3. Reducing GABA breakdown B. Activate inhibitory potassium channels
Side effects of Sodium Channel AEDs:
- Double vision (diplopia), jerky eye movements (nystagmus) -Coordination problems (ataxia) and dizziness (vertigo)
- Sleepiness, lethargy, cognitive slowing
These problems are dose-dependent and reversible
Describe the metabolism of Phenytoin.
–95% hepatic, by a cytochrome P450 enzyme (CYP2C9)
–elimination is first order (concentration-dependent) until P450 enzymes saturated, then
–slows to zero-order – fixed amount metabolized per hour
•a small increase in dose can result in very high drug levels
What’s the mechanism of action of Phenytoin?
•Sodium channel inactivation
What are the long term adverse effects of Phenytoin?
gingival hyperplasia
osteopenia
What’s the mechanism of action of Carbamazepine?
Sodium channel inactivation
What are the long term adverse effects of Carbamazepine?
–aplastic anemia (rare)
–rash
–hyponatremia (low sodium)
What’s the mechanism of action of Valproic Acid (Depakote)?
•Sodium Channel inactivation
a good choice if you can’t tell whether the patient has a focal or generalized seizure disorder
Valproic Acid (Depakote)
What are the common adverse effects of Valproic acid (Depakote)?
–“fat, shaky, bald, yellow”
•weight gain (fat)
•Tremor (shaky)
•hair loss (bald)
•jaundice (yellow)
What is a very common side effect of Lamotrigine?
rash
What’s the mechanism of action of Topiramate (Topamax)?
sodium channel inactivation
What are the adverse effects we need to know for Topiramate (Topamax)?
–confusion/psychosis (“dopamax”)
–Renal stones (avoid in pts w/ history of renal stones)
What’s the mechanism of action of Gabapentin?
decreases presynaptic glutamate release by binding to a2d subunit of the voltage gated calcium channel
What’s the mechanism of action of Levatiracetam (Keppra) ?
–Binds to SV2A synaptic vesicle protein
•inhibits excessive neurotransmitter release
What are the adverse effects of Levatiracetam (Keppra)?
–Somnolence (sleepiness), ataxia, weakness (rare)
Irritability/personality change
What’s the mechanism of action of Perampanel (Fycompa)?
•Non-competitive AMPA glutamate receptor antagonist
–Only AED with this mechanism
What’s an important side effect of Perampanel (Fycompa)?
–risk of serious neuropsychiatric events: Violent thoughts or threatening behavior including homicidal ideation
What’s the mechanism of action of Phenobarbital?
–Enhances GABAa receptor currents
–also sodium channel inactivation
What are the adverse effects of phenobarbital ?
–sedation, cognitive slowing, dizziness, mood change
–paradoxical hyperactivity in kids
What’s the mechanism of action of Ezogabine?
–Activates voltage gated K+ channel
–Leads to hyperpolarization, decreased excitability
What are the adverse effects of Ezogabine?
–Urinary Retention
–Vision and skin problems
•Turns skin blue! (rare)
What is unique about the pharmacokinetics of Carbamazepine?
–Autoinduces cytochrome P450
•Increases expression of the same isozymes that metabolize it
•Start with low dose and increase gradually over 2-3 weeks.
