Anti-Convulsant Flashcards
What is a seizure in terms of neuronal activity?
Excessive, synchronous neuronal activity reflecting increased excitation and/or decreased inhibition in affected neurons.
What is the primary goal of anti-convulsant drugs?
To balance neuronal activity by reducing excitation and/or enhancing inhibition.
How do newer anti-convulsant drugs differ from older ones?
They have novel mechanisms of action.
What are the main pharmacological targets for seizure treatment?
Ligand-gated (glutamate, GABA) and voltage-gated ion (sodium, calcium) channels.
How do drugs targeting voltage-gated sodium channels help control seizures?
They stabilize the inactive state of sodium channels, limiting excessive activity without affecting action potentials.
What is the mechanism of slow inactivation for sodium channels?
Constricting the channel.
Which drug works through slow inactivation of sodium channels?
Lacosamide.
What is the mechanism of fast inactivation for sodium channels?
Closing the inactivation gate using the “ball and chain” mechanism.
Which drugs work through fast inactivation of sodium channels?
Phenytoin and Carbamazepine.
What is the effect of ethosuximide on T-type calcium channels?
It decreases calcium influx at T-type calcium channels, inhibiting their role in regulating cortical excitation.
How can neurotransmitter release be regulated through high voltage-activated calcium channels?
By targeting the α2δ subunit, which regulates calcium channel activity and number.
Which drugs act on the α2δ subunit of N, P/Q calcium channels?
Gabapentin and pregabalin.
How do gabapentin and pregabalin affect neurotransmitter release?
They bind to the α2δ subunit, reducing calcium influx and decreasing neurotransmitter release.
How can neurotransmitter release be regulated through SV2A?
By targeting synaptic vesicle protein 2A (SV2A), which influences vesicular neurotransmitter release.
Which drug acts on SV2A to regulate neurotransmitter release?
Levetiracetam.
How does levetiracetam affect neurotransmitter release?
It binds to SV2A, decreasing vesicular release of neurotransmitters in a stimulation-dependent manner.
How can synaptic excitation be reduced by targeting NMDA and AMPA receptors?
By reducing sodium and calcium influx through these receptors.
How does felbamate affect NMDA receptors?
It reduces sodium and calcium influx through the NMDA receptor.
How can GABA neurotransmission be enhanced to control seizures?
By enhancing GABA actions at GABAA receptors, inhibiting GABA reuptake, or reducing GABA breakdown.
How does perampanel affect AMPA receptors?
It acts as a non-competitive AMPA receptor antagonist, reducing sodium and calcium influx.
Which drug inhibits GABA reuptake?
Tiagabine (targets GAT-1).
Which drug inhibits GABA breakdown?
Vigabatrin (targets GABA transaminase, GABA-T).
How do GABAA receptor positive allosteric modulators (PAMs) enhance GABA actions?
They allow chloride to enter the neuron, hyperpolarizing and inhibiting it.
Which drugs act as GABAA receptor positive allosteric modulators?
Phenobarbital (barbiturate), clobazam (benzodiazepine), and ganaxolone (neurosteroid site).
What is Epidiolex?
A 98% cannabidiol (CBD) extract from cannabis, used to control seizures.
Is Epidiolex a psychoactive compound?
No, it does not produce a “high” because it does not directly activate cannabinoid CB1 receptors at pharmacologically relevant concentrations.
What are the proposed mechanisms of action for Epidiolex in seizure control?
Modulation of intracellular calcium via GPR55 and TRPV1 receptors.
What are the major mechanisms of action of fenfluramine in seizure control?
It acts as a serotonin (5-HT) releaser, a 5-HT2 agonist, and modulates ion channels through a novel receptor.
Which anti-convulsant drug is associated with gingival hyperplasia?
Phenytoin.
Why should anti-convulsant drugs not be discontinued abruptly?
Sudden discontinuation can lead to seizures.
Which anti-convulsants induce hepatic enzymes, including CYP3A4?
Phenytoin, carbamazepine, and phenobarbital.
How do anti-convulsants affect oral contraceptives?
They induce CYP3A4, increasing metabolism of oral contraceptives and reducing their effectiveness, which may lead to unplanned pregnancy.
What are the potential teratogenic effects of phenytoin and some other anti-convulsants?
Spina bifida and cleft palate.
