Anticonvulsants

Question 1

Phenytoin

Answer 1

• for tonic-clonic generalized seizures and partial seizures
• suppresses seizures without the sedation of barbiturates
• use-dependent block: binds to the inactivated state of sodium channels
• induces CYP3A4 drugs
• adverse effects: gingival overgrowth in children, rickets/osteomalacia (affects it D and K metabolism and calcium absorption), overdose can cause ataxia, nystagmus, drowsiness, and CV collapse

Question 2

Carbamazepine

Answer 2

• for tonic-clonic generalized seizures and partial seizures
• exacerbates absence and myoclonic seizures
• use-dependent block (binds to the inactivated state of sodium channels)
• induces CYP3A4 drugs so CYP3A4 inhibitors like erythromycin increases carbamazepine levels
• adverse effects: dizziness, ataxia, diplopia, headaches, agranulocytosis, aplastic anemia

Question 3

Valproic Acid

Answer 3

• broad spectrum anticonvulsant also used to treat bipolar disorders and migraine
• use-dependent block
• increases GABA conc and inhibits calcium channels
• crosses membrane barriers –> not recommended for pregnant women
• inhibits the metabolism of itself and other drugs like phenobarbital
• adverse effects: idiosyncratic hepatotoxicity in pts under 2, pancreatitis

Question 4

Ethosuximide (Succinimide)

Answer 4

• for absence seizures (first line)
• dose-dependent inhibition of calcium channels
• metabolized by CYP3A4, so CYP3A4 inhibitors like erythromycin increase plasma levels of succinimide
• crosses membrane barriers –> not recommended for pregnant women
• adverse effects: GI distress, headache, dizziness, skin rash

Question 5

Acetazolamide (carbonic anhydrase inhibitors)

Answer 5

• for absence seizures and catamenial epilepsy
• usually used as an adjunct due to tolerance development
• increases CO2 levels in the brain –> hyper polarization and decreased neuron excitability
• adverse effects: dehydration, risk of kidney stone formation

Question 6

Benzodiazepines

Answer 6

Currently approved by the FDA for seizure treatments: Clobazam, Clonazepam, Clorazepate, Diazepam

• decrease seizure threshold in patients with grand mal epilepsy (generalized tonic-clonic seizures)
• enhance the ability of GABA to open GABAa channels (increases freq of opening)
• many effects on the CNS such as sedation, hypnosis, anesthesia, and anti convulsion - inhibits development and spread of epileptiform activity
• contraindicated in pregnant women; detected in breast milk; can induce withdrawal symptoms and respiratory depression in neonate
• therapeutic index is large –> accommodates a wide range of dosing
• side effect: drowsiness
• additive deleterious effect when taken in combo with another CNS depressant like alcohol
• can induce a paradoxical reaction in elderly and younger patients
• tolerance can develop
• rapid discontinuation can cause serious withdrawal syndromes like convulsions and death
• IV diazepam or lorazepam is first line for status epilepticus treatment followed by phenytoin, phenobarbital, etc

Question 7

Flumazenil

Answer 7

• benzo receptor antagonist
• for benzo overdose in naive patients only
• contraindicated for bento-dependent patients bc it can induce seizures and cardiac side effects

Question 8

Phenobarbital / Primidone

Answer 8

• Primidone is metabolized to phenobarbital
• used to treat generalized tonic-clonic seizures
• other effects: dec BP/HR, rest depressant
• barbiturates increase duration of GABAa channel openings; GABA-mimetic at high concentrations
• inhibit glutamate receptors
• more pronounced CNS depressant effect than benzos
• contraindicated in pregnant women; detected in breast milk
• contraindicated in patients with porphyria (causes an increase in porphyrin precursors)
• metabolites of barbiturates lack pharm activity, unlike benzos
• potential drug interactions due to long-term use causing an increase in liver microsomal enzyme activity - decrease ability of Warfarin to act as an anticoagulant
• additive with other CNS depressants like alcohol
• can develop tolerance
• overdose can’t be treated with Flumenazil

Question 9

Lamotrigine

Answer 9

• uses: partial seizures, bipolar disorder, Lennox-Gastaut syndrome
• can cause Stevens-Johnson in children so it is primarily used in adults
• approved for mono therapy

Question 10

Gabapetin

Answer 10

• uses: partial seizures, chronic pain conditions, migraine

- adjunctive therapy

Question 11

Topiramate

Answer 11

• uses: broad spectrum - effective against refractory partial seizures; migraine
• adjunctive therapy
• can cause weight loss and memory impairment

Question 12

Partial onset seizure with or without secondary generalization

Answer 12

carbamazepine and phenytoin are first line

but however are P450 enzyme inducers

Question 13

Tonic-clonic, myoclonic, absence seizures

Answer 13

valproate is first line
ethoxysuximide also first line for absence seizures

phenytoin and carbamazepine are effective against tonic-clonic but not other types of generalized seizures

Question 14

absence seizures

Answer 14

ethoxysuximide (succinimide) is first line along with valproate
valproate can protect against the tonic-clonic seizures that sometimes develop but rare risk of hepatotoxicity in children under 2 and skin rash (steven johnson)