Drugs for partial and generalized tonic-clonic seizures

Question 1

Drugs for partial and generalized tonic-clinic seizures - 7 drugs

Answer 1

Carbamazepine, oxcarbazepine. 
Phenytoin, fosphenytoin.
Phenorbital.
Primidone
Valproate

Question 2

Carbamazepine, oxcarbazepine - MOA

Answer 2

Blocks voltage-sensitive Na+ channels. Inhibits abnormal electrical spread from the focus by preventing release of excitatory neurotransmission.
Additional mechanism: Block adenosine receptors. Up-regulation of receptors and blocking of norepinephrine reuptake (mood elevating effect)

Question 3

Carbamazepine, oxcarbamazepine - indications

Answer 3

Partial seizures and generalized tonic-clonic seizures (1st line).
DOC: trigeminal neuralgia (tic douloureux).
Alternative to lithium for bipolar disease.

Question 4

Carbamazepine, oxcarbamazepine - contraindications

Answer 4

Hypersensitivity, absence seizures

Question 5

Carbamazepine - adverse effects

Answer 5

Aplastic anemia
Ataxia, drowsiness, CNS depression.
GI reactions, nausea

Question 6

Carbamazepine decreases and increases levels of which drugs?

Answer 6

Increased levels: Lithium.
Decreased levels: Carbamazepine, CCBs, clozapine, haloperidol, steroids, theophylline, thyroid and warfarin, lamotrigine, phenytoin, topiramate, valproate.

Question 7

Phenytoin and fosphenytoin - MOA

Answer 7

Blocks voltage-sensitive Na+ channels by prolonging the inactivation state of these channels. Inhibits repetitive firing from seizure focus.

Question 8

Phenytoin and fosphenytoin - Indications

Answer 8

Partial seizures and generalized tonic-clonic seizures (1st line)

Question 9

Phenytoin, forphenytoin - contraindications

Answer 9

Bradycardia, hypersensitivity, severe AV block/SA dysfunction.
Asians with polymorphism in HLA allele at higher risk of skin reactions (Steven-Johnson syndrome).
Avoid in children.
Absence seizures.

Question 10

Phenytoin, fosphenytoin - adverse effects

Answer 10

Cerebellar symptoms (ataxia, diplopia, nystagmys, slurred speech).
GI disturbances, gingival hyperplasia.
Hirsutism, megaloblastic anemia & other blood cell deficiencies, osteomalacia, psychriatric changes. Steven-Johnson syndrome & toxic epidermal necrosis.
Hypothrombinemia, bleeding

Question 11

Phenytoin and fosphenytoin interfere with the metabolism of which endogenous substances?

Answer 11

Collagen, folate, vit D.

Question 12

Phenytoin increases metabolism of which drugs?

Answer 12

Amiodarone
Digoxin
Quinidine
Steroids
Theophylline
Vit K
Felbamate, lamotrigine, topiramate, valproate.

Question 13

Phenorbital - contraindications

Answer 13

Hypersensitivity, porphyria, respiratory depression, severe liver disease

Question 14

Primidone - MOA

Answer 14

Blocks voltage-sensitive Na+ channels, and prevents membrane depolarization.
Enhances GABA-mediated chloride influx.

Question 15

Primidone - adverse effects

Answer 15

Ataxia
Cognitive impairment
Dizziness, drowsiness.
Drug dependence
Rash
Respiratory depression.

Question 16

Valproate - MOA

Answer 16

Block voltage-sensitive sodium channels and T-type calcium channels.
Increases GABA synthesis and inhibits GABA degradation.
Decrease glutamate synthesis.
Inhibit repetitive firing of neurons.

Question 17

Valproate - indications

Answer 17

Partial and generalized seizures. Active for all generalized forms of seizures.
Alternative to lithium in manic phase of bipolar disorder.
Prophylaxis of migraines.

Question 18

Valproate - adverse effects

Answer 18

Drowsiness
GI disturbances, nausea, weight gain.
Hepatic toxicity
Pancreatitis. 
Liver failure esp in children under 2 years.

Question 19

Valproate may increase and decrease levels of?

Answer 19

Increase/decrease: carbamazepine, phenytoin.

Decrease metabolism of lamotrigine, phenobarbital, primidone.

Question 20

Valproate - contraindications

Answer 20

Hepatic disease and hypersensitivity

Question 21

Levels of carbamazepine is increased by?

Answer 21

Cimetidine, diltiazem, erythromycin, fluroxetine, isoniazid, propoxyphene.

Question 22

Levels of phenytoin may be increased by?

Answer 22

Chloramphenicol, cimetidine, isoniazid, sulfonamides.

Question 23

Metabolism of valproate may be decreased/increased by?

Answer 23

Decreased metabolism by salicylates.

Increased metabolism by carbamazepine, lamotrigine, phenytoin.

Question 24

Drugs for partial and generalized tonic-clinic seizures - safety in pregnancy and main effects on fetus

Answer 24

Carbamazepine: C - neural tube defects. 
Phenytoin: C - hyantoin syndrome.
Phenobarbital: D - bleeding at birth.
Primidone: D 
Valproate: D - neural tube defects.