PHARMA I LC 5.1: Anti-seizure Drugs – Overview

A comprehensive set of flashcards covering definitions, classifications, pharmacology, mechanisms of action, drug examples, dosing considerations, special topics (teratogenicity, breastfeeding), and surgical/device options related to epilepsy.

What is a seizure?

Due to abnormal electrical discharges in the brain; presentation varies and is not always jerking of limbs.

What is a convulsion?

Intense, involuntary muscle contractions that may or may not be a seizure.

How did ILAE (2005) define epilepsy?

A disorder with an enduring predisposition to generate epileptic seizures and related neurobiologic, cognitive, psychological, and social consequences.

What are the diagnostic criteria for epilepsy?

Two unprovoked seizures >24 hours apart, or one unprovoked seizure with high probability of recurrence over 10 years, or a diagnosed epilepsy syndrome.

What is symptomatic versus idiopathic/genetic epilepsy?

Symptomatic seizures arise from underlying brain pathology; idiopathic/genetic epilepsy is due to genetic defects with often normal imaging.

What is the basic classification of seizure onset?

Focal onset (one brain area) vs Generalized onset (discharges across the brain).

What are absence seizures?

A type of generalized seizure characterized by brief blank stares and impaired awareness.

What is the objective of pharmacologic management of seizures?

Prevent occurrence or recurrence; monotherapy is preferred when possible.

Why is monotherapy preferred in epilepsy treatment?

Maximizes efficacy with fewer adverse effects; reduces drug interactions and complexity before adding another agent.

What factors influence anti-seizure medication selection?

Seizure type, patient characteristics (adverse effects, comorbidities), and patient preferences/costs.

Name the major molecular targets of antiseizure drugs at excitatory glutamatergic synapses.

Voltage-gated sodium and calcium channels; potassium channels; glutamate release; NMDA and AMPA receptor targets.

Name the major targets at the inhibitory GABAergic synapse.

GABA receptors (GABA-A) with positive modulation; GABA transporter-1 (GAT-1) inhibition; GABA transaminase inhibition.

List common sodium channel–blocking antiseizure drugs.

Phenytoin, carbamazepine, lamotrigine, lacosamide, zonisamide, oxcarbazepine, eslicarbazepine.

What is the mechanism of Retigabine (Ezogabine)?

Potassium channel opener that increases presynaptic potassium efflux, promoting hyperpolarization.

Which drugs inhibit voltage-gated calcium channels (T-type) and their use?

Gabapentin and pregabalin; reduce calcium influx and glutamate release.

What is Levetiracetam’s mechanism of action?

Binds SV2A to prevent glutamate release from presynaptic vesicles.

What are Felbamate and Perampanel targeting?

Felbamate acts on NMDA receptors; Perampanel is an AMPA receptor antagonist (glutamate receptor targets).

Which drugs act on GABA-A receptors to enhance inhibition?

Phenobarbital and benzodiazepines (e.g., diazepam, lorazepam, clonazepam) at GABA-A docking sites.

What is Tiagabine’s mechanism and role?

Inhibits GABA reuptake (GAT-1), increasing GABA in the synaptic cleft.

What is a practical drug selection process for ASDs?

Identify seizure type (focal vs generalized), choose a first drug for that type, maximize monotherapy, then add a second drug with a different mechanism if needed.

Carbamazepine (CBZ): brand and MOA

Brand Tegretol; voltage-gated sodium channel blocker; use-dependent blockade on inactivated channels.

CBZ: key pharmacokinetic feature and dosing consideration.

Autoinduction: CBZ induces its own metabolism; concentrations fall after weeks requiring dose increases.

CBZ adverse effects and a major SJS risk factor.

GI upset, dizziness, diplopia; Stevens–Johnson Syndrome risk higher with HLA-B*1502 (common in Asians).

Oxcarbazepine (OXC): main difference from CBZ

Similar sodium-channel blocker with less induction of hepatic enzymes and lower SJS risk, but more hyponatremia risk.

Lamotrigine (LTG): key indications and caution.

Focal and generalized seizures; preferred during breastfeeding; risk of SJS; slow titration essential.

Valproic acid (VPA): spectrum and major teratogenic concerns.

Broad-spectrum; not ideal for women of reproductive age due to neural tube defects, cognitive issues, and autism risk with first-trimester exposure.

Valproate drug interactions and cautions.

Inhibits metabolism of PB, ESL, LTG; displaces PHT from proteins; dose adjustments needed when coadministered.

Topiramate (TPM): key features and pregnancy risk.

Multiple mechanisms; adverse cognitive effects; risk of oral clefts with first-trimester exposure; reduced contraceptive efficacy.

Ethosuximide (ESM): indication and mechanism.

First-line for absence seizures; blocks T-type calcium channels; not available in the Philippines.

Lamotrigine and pregnancy planning.

LTG preferred in women of reproductive age due to lower teratogenic risk compared with VPA; 1–2% baseline teratogenicity still present.

Levetiracetam (LEV): dosing and mood effects.

Keppra; broad spectrum; minimal drug interactions; potential behavioral/mood changes (irritability, aggression, depression).

Gabapentin (GBP) vs Pregabalin (PGB): key differences.

Both modulate voltage-gated calcium channels; GBP has lower bioavailability and less effectiveness for seizures; PGB is 100% absorbed; more commonly used for neuropathic pain.

Drugs for generalized onset seizures: Valproate and LTG combination caveat.

LTG synergy with VPA increases LTG half-life; require careful titration to avoid toxicity.

Levetiracetam dosing and safety in elderly.

Typically 500–1000 mg/day starting, up to 3 g/day; predictable pharmacokinetics with minimal interactions; monitor mood changes.

Drugs for myoclonic seizures: recommended choices.

Valproate, levetiracetam, zonisamide, topiramate, lamotrigine (avoid most sodium channel blockers).

Drugs for atonic seizures (drop seizures): core options.

Valproate and lamotrigine; sometimes topiramate, felbamate, lamotrigine; clobazam and rufinamide as adjuncts.

Clobazam (Onfi): role and status in the Philippines.

Benzodiazepine for LGS; adjunctive for atonic/focal seizures; not universally available in IV form in some regions.

West Syndrome treatment: vigabatrin facts.

Vigabatrin increases GABA by inhibiting GABA transaminase; effective for infantile spasms but risk of irreversible retinal toxicity; monitor vision.

Status epilepticus: definitions and first-line therapy.

Convulsive SE >5 minutes; nonconvulsive SE >10 minutes. First-line: lorazepam or diazepam; second-line: IV phenytoin or valproate; third-line: phenobarbital, propofol, midazolam.

Electrical stimulation devices: VNS and RNS.

Vagus Nerve Stimulation detects/counteracts seizures via the vagus nerve; RNS provides responsive brain stimulation similar to a pacemaker for seizures.

Ketogenic diet in epilepsy.

High-fat diet, mainly for children; initiation requires hospital admission due to seizure risk during transition.

Breastfeeding safety with antiseizure meds.

LEV, GBP, LTG, TPM commonly present in breast milk; generally safe; VPA and PB/PH may have concerns; high protein binding limits transfer for some drugs.

Withdrawal of antiseizure drugs: general principles.

Consider genetic epilepsy may require lifelong meds; idiopathic epilepsy may allow taper after 2 years seizure-free; taper slowly over 1–3 months to avoid rebound seizures.

Pharmacoresistant epilepsy: when to consider surgery.

Seizures persist with two appropriate drugs at max tolerated doses; consider adding a third drug or moving to surgical options if resistant.

Surgical options for epilepsy: lobectomy, callosotomy, lesionectomy.

Lobectomy removes a brain lobe; callosotomy disconnects hemispheres; lesionectomy removes a lesion; used when seizures are focal and surgical candidacy is met.

Vagus nerve stimulation (VNS) aside from RNS: practical use.

Common implant for epilepsy treatment; detects abnormal impulses on the vagus nerve and modulates activity to prevent seizure spread.