Anti-epileptics: Uses, actions and side effects

Question 1

Phenytoin moa

Answer 1

binds to sodium channels increasing their refractory periods

Question 2

phenytoin effect on P450 system

Answer 2

INDUCER of P450 system

Question 3

phenytoin initial side effects

Answer 3

initially: dizziness, diplopia, nystagmus, slurred speech, ataxia
later: confusion, seizures

Question 4

phenytoin chronic side effects

Answer 4

common: gingival hyperplasia (secondary to increased expression of platelet derived growth factor, PDGF), hirsutism, coarsening of facial features, drowsiness
megaloblastic anaemia (secondary to altered folate metabolism)
peripheral neuropathy
enhanced vitamin D metabolism causing osteomalacia
lymphadenopathy
dyskinesia

Question 5

phenytoin idiosyncratic side effects

Answer 5

fever
rashes, including severe reactions such as toxic epidermal necrolysis
hepatitis
Dupuytren’s contracture*
aplastic anaemia
drug-induced lupus

Question 6

phenytoin effects on foetus

Answer 6

associated with cleft palate and congenital heart disease

Question 7

sodium valproate moa

Answer 7

increasing GABA activity

Question 8

Sodium valproate effect on P450 system

Answer 8

P450 inhibitor

Question 9

sodium valproate adverse effects

Answer 9

gastrointestinal: nausea
increased appetite and weight gain
alopecia: regrowth may be curly
ataxia
tremor
hepatotoxicity
pancreatitis
thrombocytopaenia
hyponatraemia
hyperammonemic encephalopathy: L-carnitine may be used as treatment if this develops

Question 10

treatment for hyperammonemic encephalopathy

Answer 10

L-carnitine

Question 11

carbamazepine MOA

Answer 11

binds to sodium channels, increases their refractory period

Question 12

carbamazepine effect on P450 system

Answer 12

P450 enzyme inducer

Question 13

carbamazepine adverse effects

Answer 13

dizziness and ataxia
drowsiness
headache
visual disturbances (especially diplopia)
Steven-Johnson syndrome
leucopenia and agranulocytosis
hyponatraemia secondary to syndrome of inappropriate ADH secretion

Question 14

carbamazepine autoinduction

Answer 14

hence when patients start carbamazepine they may see a return of seizures after 3-4 weeks of treatment.

Question 15

lamotrigine moa

Answer 15

sodium channel blocker

Question 16

lamotrigine adverse effects

Answer 16

Steven-Johnson syndrome

Question 17

topiramate moa

Answer 17

blocks voltage-gated Na+ channels
increases GABA action
carbonic anhydrase inhibition: this results in a decrease in urinary citrate excretion and formation of alkaline urine that favours the creation of calcium phosphate stone

Question 18

topiramate effect on p450 system

Answer 18

inducer of the P450 enzyme CYP3A4

Question 19

topiramate adverse effects

Answer 19

reduced appetite and weight loss
dizziness
paraesthesia
lethargy and poor concentration
rare but important: acute myopia and secondary angle-closure glaucoma

Question 20

ethosuximide moa

Answer 20

blocks T-type calcium channels in thalamic neurons

Question 21

1st line treatment generalised tonic clonic

Answer 21

males: sodium valproate
females: lamotrigine or levetiracetam

Question 22

first line treatment focal seizures

Answer 22

first line: lamotrigine or levetiracetam

Question 23

second line treatment focal seizures

Answer 23

second line: carbamazepine, oxcarbazepine or zonisamide

Question 24

first line treatment absence seizures

Answer 24

ethosuximide

Question 25

Second line treatment absence seizures

Answer 25

male: sodium valproate
female: lamotrigine or levetiracetam
carbamazepine may exacerbate absence seizures

Question 26

myoclonic seizures treatment

Answer 26

males: sodium valproate
females: levetiracetam

Question 27

tonic or atonic seizures management

Answer 27

males: sodium valproate
females: lamotrigine