Anti-epileptics I MCQs

Vigabatrin is an irreversible inhibitor of GABA transaminase , thus increases GABAergic activity. It is the DOC for infantile spasms associated with tuberous sclerosis (ACTH is DOC for all other cases). It can result in irreversible visual field defects due to retinal atrophy.

Benzodiazepines facilitate GABA-mediated inhibitory actions. Ethosuximide selectively blocks calcium channels in thalamic neurons. Phenobarbital produces multiple effects, mainly enhancement of GABA-chloride inhibitory activity. Phenytoin selectively blocks the Na+ channel and prolongs the inactivated state. Reference : Basic & Clinical Pharmacology by Bertram G. Katzung, 14th Edition, Page Number- 425.

Vigabatrine, acts by inhibition of GABA transaminase irreversibly → ↑ GABA, used in Refractory focal seizures (adjunctive therapy) and Monotherapy for infantile spasms (West syndrome). It can cause irreversible vision loss in up to 50% of patients; so used only in patients if other anticonvulsants are ineffective. Reference: Basic & Clinical Pharmacology, Fourteenth Edition By Bertram G. Katzung Page number. 431

Topiramate, Blockage of voltage-gated Na+ channels and↑ GABA. Dose-related adverse effects that occur frequently in the first 4 weeks of topiramate therapy are somnolence, fatigue, dizziness, nervousness, and confusion. Acute myopia and angle- closure glaucoma may require prompt drug withdrawal. Urolithiasis occurs in 0.5–1.5% of patients on long-term therapy and is more common in men. In some patients, carbonic anhydrase inhibition is associated with reduced serum bicarbonate that is usually asymptomatic but may result in nonspecific symptoms such as fatigue, anorexia, or nausea and vomiting. Reference: Basic & Clinical Pharmacology, Fourteenth Edition By Bertram G. Katzung Page number 424

This patient is having megaloblastic anemia, probably due to long term phenytoin therapy. She should be given vitamin B12 + folic acid for the same. Long-term use is associated in some patients with coarsening of facial features and with mild peripheral neuropathy, usually manifested by diminished deep tendon reflexes in the lower extremities. Long-term use may also result in abnormalities of vitamin D metabolism, leading to osteomalacia. Reference: Basic & Clinical Pharmacology, Fourteenth Edition By Bertram G. Katzung Page number. 428

Infantile spasms (hypsarrhythmia) Therapy of this condition is unsatisfactory, antiepileptic drugs are generally useless. Corticosteroids(ACTH) afford symptomatic relief but cannot be used for long-term due to adverse effects. Clonazepam, valproate and vigabatrin may afford some relief. Drug of choice for infantile spasms is ACTH whereas infantile spasms associated with tuberous sclerosis are treated with vigabatrin.

Explanation: The most common and significant adverse effect of lamotrigine is a skin rash , which can range from a simple maculopapular rash to life-threatening Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). The risk is heightened by rapid dose escalation or concomitant use with valproate. Explanation of other options: A) Diplopia & B) Tremors: These are more commonly associated with other antiepileptics like carbamazepine or valproate, not lamotrigine. Neutropenia: This is a rare side effect of lamotrigine, not the most common or significant. Key Takeaways: Lamotrigine-induced rash is a major concern requiring careful dose titration. Concomitant valproate use increases lamotrigine levels and the risk of rash.

Ans. 'b' i.e., Can be mixed with saline While phenytoin cannot be injected in a drip of glucose solution, fosphenytoin can be injected with saline and glucose.