Seizures

Question 1

Hydantoin

• Selectively inhibits sodium channels, restricting sodium entry into hyperactive neurons; effectively suppressing seizure activity
• Contraindicated in pregnancy and those with HLA-B1502 d/t risk of SJS
• Adverse effects: sedation, ataxia, gingival hyperplasia, dysrhythmias

Partial and primary generalized tonic-clonic

Answer 1

Phenytoin

Question 2

Iminostillbenes

• Suppresses high-frequency neuronal discharge in seizure foci by delaying the recovery of sodium channels from their inactivated state
• CNS effects, bone marrow suppression, teratogenic
• Seizures, BPD, and neuralgias
• Monitor sodium levels in HF patients
• Contraindicated in HLA-B1502
• Target levels: 4-12

Anticonvulsant and Mood Stabilizer

Answer 2

Carbamazepine

Question 3

Succinimide

• Drug of choice for absence seizures
• Inhibits low-threshold calcium currents in the thalamus, suppressing the generation of absence seizures
• N/V, drowsiness, dizziness; rare effects include autoimmune disorders and leukopenias

Answer 3

Ethosuximide

Question 4

Phenyltriazine

• Block sodium channels and partially block calcium channels, leading to decreased glutamate release (an excitatory neurotransmitter) to depress seizure activity
• CNS effects, GI effects, SJS
• Therapeutic range: 3-14

Anticonvulsant and Mood Stabilizer

Answer 4

Lamotrigine

Question 5

• Considered first-line drug for all partial and generalized seizures
• May augment the inhibitory influence of GABA or increase GABA concentration in the brain
• Therapeutic responses are often seen at plasma levels of 50 to 100 µg/mL
• Adverse effects: GI effects more common; hepatotoxicity rare
• Causes minimal sedation and coginitive impairment

Highly teratogenic

Answer 5

Valproic acid

Question 6

• Suppresses seizures by potentiating the effects of GABA
• Effective against partial seizures and generalized tonic-clonic seizures but not absence seizures
• Adverse Effects: drowsiness, respiratory depression, osteomalacia
• Induces hepatic drug-metabolizing enzymes CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP3A4, and, to a lesser degree CYP2B6

Answer 6

Phenobarbital

Question 7

• Similar MOA to phenobarbital: active metabolite of phenobarbital
• Effective against tonic-clonic, simple partial, and complex partial seizures
• Is employed in combination with another antiseizure drug, usually phenytoin or carbamazepine
• Therapeutic plasma levels range from 5 to 12 µg/mL
• Serious adverse reactions (acute psychosis, leukopenia, thrombocytopenia, systemic lupus erythematosus) can occur but are rare
  *

Answer 7

Primidone

Question 8

• Antiseizure effects result from blockade of voltage-sensitive sodium channels in neuronal membranes, an action that stabilizes hyperexcitable neurons and thereby suppresses seizure spread
• Is indicated for both monotherapy and adjunctive therapy for management of partial seizures
• CNS effects, hyponatremia,dermatological effects, decreased bone density

Answer 8

Oxcarbemazepine

Question 9

• An analog of GABA but does not directly affect GABA receptors
• May enhance GABA release, thereby increasing GABA-mediated inhibition of neuronal firing
• Its only FDA-approved use in epilepsy is adjunctive therapy of partial seizures (with or without secondary generalization)
• The AAN/AES guidelines also recommend the drug for monotherapy of partial seizures
• The most common side effects are somnolence, dizziness, ataxia, fatigue, nystagmus, and peripheral edema

Answer 9

Gabapentin

Question 10

• Is an analog of GABA, but does not bind with GABA receptors or with benzodiazepine receptors, and hence does not work by mimicking or enhancing the inhibitory actions of GABA
• Can bind with calcium channels on nerve terminals, and can thereby inhibit calcium influx
• Has four approved indications: neuropathic pain associated with diabetic neuropathy, postherpetic neuralgia, adjunctive therapy of partial seizures, and fibromyalgia

Answer 10

Pregabalin

Question 11

• Unique agent that is chemically and pharmacologically different from all other antiseizure drugs; MOA is unknown
• Is approved for adjunctive therapy of (1) myoclonic seizures in adults and adolescents 12 years and older, (2) partial-onset seizures in adults and children 4 years and older, and (3) primary generalized tonic-clonic seizures in adults and children 6 years and older
• Is not metabolized by P450 isoenzymes, and therefore does not interact with other drugs

Answer 11

Levetiracetam

Question 12

• Seizure reduction occurs by four mechanisms: (1) potentiation of GABA-mediated inhibition, (2) blockade of voltage-dependent sodium channels, (3) blockade of calcium channels, and (4) blockade of receptors for glutamate
• FDA approved for (1) adjunctive treatment of adults and children 2 years and older with partial seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome; (2) monotherapy of adults and children 10 years and older with partial seizures or primary generalized tonic-clonic seizures; and (3) prophylaxis of migraine in adults
• Common effects include somnolence, dizziness, ataxia, nervousness, diplopia, nausea, anorexia, and weight loss; metabolic acidosis

Answer 12

Topiramate

Question 13

• Blocks reuptake of GABA by neurons and glia. As a result, the inhibitory influence of GABA is intensified, and seizures are suppressed
• FDA approved only for adjunctive therapy of partial seizures in patients at least 12 years old
• Off-label uses include management of generalized anxiety disorder, multiple sclerosis, neuropathic pain, posttraumatic stress disorder, psychosis, and spasticity
• Common adverse effects are dizziness, somnolence, asthenia, nausea, nervousness, and tremor

Answer 13

Tiagabine

Question 14

• Belongs to the same chemical family as the sulfonamide antibiotics but lacks antimicrobial activity
• Suppresses focal seizure activity and spread
• Approved only for adjunctive therapy of partial seizures in adults
• Most common adverse effects are drowsiness, dizziness, anorexia, headache, and nausea
• Can trigger hypersensitivity reactions, including some that are potentially fatal (e.g., SJS, TEN, fulminant hepatic necrosis)
• Levels can be affected by agents that induce or inhibit CYP3A4

Answer 14

Zonisamide

Question 15

• Increases seizure threshold and suppresses seizure spread
• It is approved for (1) adjunctive or monotherapy in adults with partial seizures (with or without generalization) and (2) adjunctive therapy in children with Lennox-Gastaut syndrome
• Can cause aplastic anemia and liver damage
• Can alter plasma levels of other antiseizure drugs, and vice versa

Answer 15

Felbamate

Question 16

• Benefits appear to derive from slow inactivation of sodium channels
• Indicated for add-on therapy of partial-onset seizures in patients 17 years and older
• The most common adverse effects are dizziness, headache, diplopia, and nasopharyngitis; can also prolong PR interval
• Has few drug interactions

Answer 16

Lacosamide

Question 17

• Benefits derive from inhibiting GABA transaminase, the enzyme that inactivates GABA in the CNS
• Has two indications: (1) add-on therapy of complex partial seizures in adults who are refractory to other drugs and (2) monotherapy of infantile spasms in children ages 6 months to 2 years
• Can cause irreversible damage to the retina, usually manifesting as progressive narrowing of the visual field

Answer 17

Vigabatrin