in 1940, phenytoin was found to be effective drug - became major first-line antiepileptic drug for partial and secondarily generalized seizures. in 1990s, with good efficacy, fewer toxic effects, better tolerability, and no need for newer drugs blood level monitoring were developed. All antiepileptics increase risk of suicidality! Valproic acid and phenytoin interfere with platelet function! Antiepileptic drugs: block initiation of electrical discharge prevent spread of electrical discharge (most current AED) Na+ channel blockers - stabilize inactive state of Na+ channels (prevent return of Na+ channels to active state) in frequency-dependent manner prevented rapid, repetitive, sustained firing of axons → (normal action potentials are not inhibited!). Most common and most well-characterized mechanism of currently available AEDs! each sodium channel dynamically exists in 3 states: resting - allows Na+ passage into cell (during action potential) - allows increased Na+ influx into cell active state inactive state (during refractory period) - does not allow Na+ passage. Na+ channels action potential – Carbamazepine Oxcarbazepine eslicarbazepine Phenytoin the only AED metabolized through nonlinear, zero-order kinetics. – Fosphenytoin Lamotrigine Zonisamide lacosamide Rufinamide Ca2+ channel inhibitors Ca2+ channels in CNS exist in 3 forms - L, N, T. these channels are small and are inactivated quickly. influx of Ca2+ currents in resting produces partial depolarization of membrane (Ca2+ channels function as of normal rhythmic brain activity), e.g. T-calcium channels “pacemakers” in thalamus. Ca2+ channels - voltage-dependent neurotransmission “pacemakers”, Ethosuximide methsuximide Phenytoin also has some Ca2+ channel blocking activity. GABA enhancers GABA binds to GABAA receptor Cl- influx hyperpolarization (repolarization). → → GABA is produced by glutamate decarboxylation (glutamic acid decarboxylase, GAD).
in 1940, phenytoin was found to be effective drug - became major first-line antiepileptic drug for partial and secondarily generalized seizures. in 1990s, newer drugs with good efficacy, fewer toxic effects, better tolerability, and no need for blood level monitoring were developed. All antiepileptics increase risk of suicidality! Valproic acid and phenytoin interfere with platelet function! Antiepileptic drugs: block initiation of electrical discharge prevent spread of electrical discharge (most current AED) Na+ channel blockers - stabilize inactive state of Na+ channels (prevent return of Na+ channels to active state) in frequency-dependent manner → prevented rapid, repetitive, sustained firing of axons (normal action potentials are not inhibited!). Most common and most well-characterized mechanism of currently available AEDs! each sodium channel dynamically exists in 3 states: resting - allows Na+ passage into cell active state (during action potential) - allows increased Na+ influx into cell inactive state (during refractory period) - does not allow Na+ passage. Na+ channels – action potential Carbamazepine Oxcarbazepine eslicarbazepine Phenytoin – the only AED metabolized through nonlinear, zero-order kinetics. Fosphenytoin Lamotrigine Zonisamide lacosamide Rufinamide Ca2+ channel inhibitors Ca2+ channels in CNS exist in 3 forms - L, N, T. these channels are small and are inactivated quickly. influx of Ca2+ currents in resting produces partial depolarization of membrane (Ca2+ channels function as “pacemakers” of normal rhythmic brain activity), e.g. T-calcium channels in thalamus. Ca2+ channels - “pacemakers”, voltage-dependent neurotransmission Ethosuximide methsuximide Phenytoin also has some Ca2+ channel blocking activity. GABA enhancers GABA binds to GABAA receptor → Cl- influx → hyperpolarization (repolarization). GABA is produced by glutamate decarboxylation (glutamic acid decarboxylase, GAD).
E3.%20Antiepileptic%20Drugs.docx