Anticonvulsant Flashcards
Phenytoin
Class: Na+ channel blocker
Uses: effective against all seizure types except absence, better for focal and 2’ generalized seizures than 1’ generalized ones
PD: blocks voltage gated sodium channel
PK: can be given po, iv, poorly absorbed in children po, “has zero order kinetics at high doses due to enzymatic saturation, so easy to OD,” hepatic metabolism, variable half life 6-24h, hepatic enzyme inducer
Toxicity: gingivial hyperplasia, osteomalacia, ataxia, need to supplement ca, vit d, vit k, and folate
Phenobarbital
Class: GABA agonist
Use: effective for all seizure types except absence, can be given po, iv. Iv form very useful for status epilepticus.
PD: opens chloride channel, causes hyperpolarization
PK: long half life-100h, needs to be loaded, hepatic metabolism, hepatic enzyme inducer
Toxicity: hyperactivity in children, sedation in adults, joint and connective issue problems
Consideration: not first line AED, bc its cheap. Useful for anxious and insomniac pt.
Benzodiazepine (Diazepem, Lorazepem)
Class: GABA agonist
Use: effective against all seizure types, tolerance develops rapidly/months, drugs of choice for status epilepticus, alcohol withdrawal sx, like seizure, good sedatives and anxiolytics
PK: po or iv, hepatic metabolism, but not major ez inducers, shorter half life compared to phenobarbital
Toxicity: sedation, depression, withdrawal seizures
Dose: for lorazepem, 5mg bid for anxiety, 2-4mg iv for status epilepticus
Carbamazepine
Class: Na+ channel blocker
Use: excellent for focal and 2’ generalized seizures, less effective for 1, generalized seizure, also mood stabilizer for bipolar disorder, works for neuropathic pain, and trigeminal neuralgia
PK: only po, half-life 1/2h, hepatic metabolism, hepatic ez inducer, levels increased by calcium channel blockers, and macrolide abx
Toxicity: structurally similar to TCA, hence anti-cholinergic ADR, blurred vision, sedation, neutropenia, hyponatremia, weight gain
Dose: 400-1600mg qd, in divided doses
Ethosuximide
Class: T-type calcium channel blocker
Use: only for absence seizures
PK: only oral preparation, has good GI absorption, half-life 24-48h, mild hepatic ez inducer, hepatic metabolism
Toxicity: sedation, GI distress, occasional behavioral changes
Valproate
Class: not well understood, may block Na+ channel, probably also affects GABA levels, ca2+ and k+ conductances
Use: very wide spectrum of efficacy, works for all seizure types, most effective for generalized epilepsy, also used for migraine and bipolar disorder
PK: po or iv, half life 15h, hepatic metabolism, not a major ez inducer
Toxicity: GI upset, weight gain, menstrual problems, hair loss, low platelet count, hepatic encephalopathy sometimes but not always assoc with elevated NH3 and carnitine deficiency
Gabapentin
Class: increases GABA levels, may have other mech of actions including blockade of Ca2+
Use: effective against partial and 2’ generalized seizures, not good for 1’ generalized seizures, also a good anxiolytic, sedative, anti-spasmodic, well indicated for peripheral neuropathy, and other painful states
PK: po only, short half-life 6h, well absorbed except at high doses, not metabolized and excreted in urine, few drug interactions, not an ez inducer
Toxicity: sedation, particularly in elderly. Occasional GI distress, and pedal coma
Lamotrigine
Class: probably blocks release of glutamate pre-synaptically, and blocks Na+ channel post-synaptically
Use: broad spectrum efficacy against all seizure types, also works for bipolar disorder, and neuropathic pain
PK: only po, renally excreted after glucoronidation, not a major ez inducer, 1/2 t of 24h
Toxicity: allergic rash 5-10%, other problems minor, not sedating, may cause insomnia
Topiramate
Class: Na+ blocker, GABA agonist, Glutamate antagonist
Use: broad spectrum of efficacy, but not particularly good for absence, good for migraine prevention, some use in neuropathic pain, weight loss
PK: some hepatic metabolism, but mainly renal clearance without change, half-life 24h, po only, not a hepatic ez inducer
Toxicity: sedation, aphasia, parasthesias, kidney stones
Special: originally a drug for diabetes, incidentally discovered as anti-convulsant
Levetiracetem
Class: controversial, ca2+ blocker, interferes with action of sv2 protein which is necessary for exocytosis of neurotransmitter vehicles
Use: broad spectrum of use for focal and generalized seizures, equivalent iv or po dosing
PK: 2/3 renally excreted unchanged, some enzymatic hydrolysis by liver and RBCs to inactive metabolites, not protein-bound, not an ez inducer
Toxicity: cognitive and behavioral sx
Special: favorite anti-epileptic drug in hospitals
