40 - Antiepileptics Flashcards
Only free drug is active:
Most important ones?
Phenytoin
Valproate
Order of Phenytoin
Zero
Order of other drugs
First
Area under the curve
Measure of drug absorbed
Time to reach steady state
Requires 4 - 7 half lives
Time for elimination if drug stopped
4 - 7 half lives
Carbamazepine - Hepatic
Induces its own metabolizers
Valproic Acid
Inhibits P450s
Which drugs are protein-bound?
Phenytoin
Valproate
Phenytoin
90% Protein Bound
Change in binding can lead to toxicity (low albumin, combination with valproate)
Metabolized by cytochrome P450s with INDUCTION
Zero order kinetics at higher doses
Common reason fro Phenytoin toxicity
Zero order kinetics
At a point (in the clinically relevant range), a TINY increase in dose leads to a HUGE increase in concentration
Consequences of Phentyoin Pharmacokinetics
Protein binding leads to misleading total level (in presence of other protein binding drugs, or if low albumin)
Metabolism affected by many other drugs
If in zero-order kinetic zone, small changes in dose lead to large changes in level.
Anti-Epileptic Drugs - Partial Seizures and GTCs
Carbamazepine Phenytoin Gabapentin Oxycarbazepine Pregabalin Lacosamide?
Anti-Epileptic Drugs - Broad Spectrum
Valproate Lamotrigine Topiramate Zonisamide Levetiracetam Rufinamide Clobazam
Anti-Epileptic Drugs - Absence Seizures Only
Ethsoximide
Mechanisms of Action
Neurotransmission: Increasing inhibition or decreasing excitation
Multiple suspected mechanisms
Drugs with “same” mechanism are not equivalent
Mechanisms have rarely been “proven”
Broad categories of mechanisms for NeuroTransmitter Drugs
Sodium Channels
Calcium Channels
GABA System
Glutamate Receptors
Phenytoin
Complicated pharmacokinetics Multiple drug interactions SFX - Hirsutism SFX - Neuropathy SFX - Increases osteoporosis IV available
Carbamazepine
Fewer interactions
Positive mood effects
Auto-Induction (over a month, their levels fall)
Folks dropped out of the trial with this one because of toxicity, though seizure free rates were similar
