Drugs for partial and generalized tonic-clonic seizures Flashcards
Drugs for partial and generalized tonic-clinic seizures - 7 drugs
Carbamazepine, oxcarbazepine. Phenytoin, fosphenytoin. Phenorbital. Primidone Valproate
Carbamazepine, oxcarbazepine - MOA
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)
Carbamazepine, oxcarbamazepine - indications
Partial seizures and generalized tonic-clonic seizures (1st line).
DOC: trigeminal neuralgia (tic douloureux).
Alternative to lithium for bipolar disease.
Carbamazepine, oxcarbamazepine - contraindications
Hypersensitivity, absence seizures
Carbamazepine - adverse effects
Aplastic anemia
Ataxia, drowsiness, CNS depression.
GI reactions, nausea
Carbamazepine decreases and increases levels of which drugs?
Increased levels: Lithium.
Decreased levels: Carbamazepine, CCBs, clozapine, haloperidol, steroids, theophylline, thyroid and warfarin, lamotrigine, phenytoin, topiramate, valproate.
Phenytoin and fosphenytoin - MOA
Blocks voltage-sensitive Na+ channels by prolonging the inactivation state of these channels. Inhibits repetitive firing from seizure focus.
Phenytoin and fosphenytoin - Indications
Partial seizures and generalized tonic-clonic seizures (1st line)
Phenytoin, forphenytoin - contraindications
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.
Phenytoin, fosphenytoin - adverse effects
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
Phenytoin and fosphenytoin interfere with the metabolism of which endogenous substances?
Collagen, folate, vit D.
Phenytoin increases metabolism of which drugs?
Amiodarone Digoxin Quinidine Steroids Theophylline Vit K Felbamate, lamotrigine, topiramate, valproate.
Phenorbital - contraindications
Hypersensitivity, porphyria, respiratory depression, severe liver disease
Primidone - MOA
Blocks voltage-sensitive Na+ channels, and prevents membrane depolarization.
Enhances GABA-mediated chloride influx.
Primidone - adverse effects
Ataxia Cognitive impairment Dizziness, drowsiness. Drug dependence Rash Respiratory depression.
Valproate - MOA
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.
Valproate - indications
Partial and generalized seizures. Active for all generalized forms of seizures.
Alternative to lithium in manic phase of bipolar disorder.
Prophylaxis of migraines.
Valproate - adverse effects
Drowsiness GI disturbances, nausea, weight gain. Hepatic toxicity Pancreatitis. Liver failure esp in children under 2 years.
Valproate may increase and decrease levels of?
Increase/decrease: carbamazepine, phenytoin.
Decrease metabolism of lamotrigine, phenobarbital, primidone.
Valproate - contraindications
Hepatic disease and hypersensitivity
Levels of carbamazepine is increased by?
Cimetidine, diltiazem, erythromycin, fluroxetine, isoniazid, propoxyphene.
Levels of phenytoin may be increased by?
Chloramphenicol, cimetidine, isoniazid, sulfonamides.
Metabolism of valproate may be decreased/increased by?
Decreased metabolism by salicylates.
Increased metabolism by carbamazepine, lamotrigine, phenytoin.
Drugs for partial and generalized tonic-clinic seizures - safety in pregnancy and main effects on fetus
Carbamazepine: C - neural tube defects. Phenytoin: C - hyantoin syndrome. Phenobarbital: D - bleeding at birth. Primidone: D Valproate: D - neural tube defects.
