Anticonvulsants

Question 0

What drugs are used for status epilepticus

Answer 0

Diazepam (iv)
lorazepam (iv)
phenytoin (iv)
phenobarbital (iv)

Question 1

What drugs are used for infantile seizures

Answer 1

corticosteriods

topiramate

Question 2

What drugs are used for absence seizures

Answer 2

ethosuxidimide
valproic acid
clonazepam

Question 3

Phenytoin (fosphenytoin)

Answer 3

MOA: block repetitive firing but prolonging inactivation of na+ channels
Use: effective for partial and tonic clonic seizures, NOT effective for absence seizures
- not water soluble so cannot be injected
- highly bound to plasma proteins, displaced by phenylbutazone and sulfonamides (can result in large changes in blood levels)
- metabolism saturated at therapeutic levels - displacement of drug from protein when at the therapeutic level can be toxic
- since saturates liver metabolism- there is inhibition of other drug metabolism, namely warfarin
- induces p450 - increases metabolism of oral contraceptives
- carbamazepine increases phenytoin metabolism
- DO NOT USE IN PREGNACY- CAT. D
- gingival hyperplasia, hirsuitiusm, coarsening of facial hair, ild peripheral neuropathy, sedation at high levels, ataxia, nystagmus, double vision

Question 4

fosphenytoin

Answer 4

water-soluble prodrug of phenytoin- can be used parenterally

Question 5

Carbamazepine

Answer 5

MOA: blocks Na channels and inhibits NT release
Use: anticonvulsant- DOC of partial seizures, can be used for tonic clonic seizures, mood stabilizer (used for bipolar disorder), high doses for trigeminal neuralgia
- induces hepatic enzymes CYP3A- inc. metabolism of phenytoin, primidone, ethosuximide, valproic acid, clonazepam, haloperidol, and oral contraceptives, and carbamazepine
- cimetidine, erythromycin, isonazid, fluoxetine inhibit carbamazepine metabolism
- Toxicity: idiosyncratic blood dyscrasias, steven johnson syndrome or toxic epidermal necrolysis if allele HLA-B-1502 present (do genetic testing before use), pregnancy CAT. D

Question 6

Topiramate

Answer 6

MOA: blocks voltage gated Na channels, enhances GABAa, and limits glutamate- inhibits spread of seizures instead of inc. the seizure threshold
USE: broad spectrum use- partial and gen. tonic clonic seizures, absence seizures, west syndrome, lennox gestaut syndrome, bipolar disorder, binge eating, migraine prophylaxsis, alcohol recovery
- pregnancy category C

Question 7

Lamotrigine

Answer 7

MOA: inactivates voltage gates Na channel, acts on N and P/Q Ca channels, decrease release of glutamate,
Use: absence seizures (Ca channels), partial seizures, bipolar disorder, myoclonic seizures
Toxicity: Preg. cat. C

Question 8

Phenobarbital (Primidone)

Answer 8

MOA: Enhances GABAa
Use: partial and generalized tonic clonic seizures
primidone metabolized into phenobarbital
preg. Cat. D- toxic
contraindication in porphyria and pulmonary insufficency

Question 9

Gabapentin (pregabalin)

Answer 9

MOA: GABA analog - augments GABA release (Does not act on receptors), blocks N type Ca channels inhibiting glutamate release
Use: partial seizures and general tonic clonic, neuropathic pain esp diabetic neuropathy, bipolar disorder, fibromyaglia (pregabalin)
- High doses for anticonvulsant, low doses for pain relief
- excreted by kidney
- no drug interactions
- pregnancy category C

Question 10

Levetiracetam

Answer 10

MOA: binds to synaptic vesicular protein (SV2A) and reduces glutamate release while increasing GABA release
Use: partial, myoclonic, generalized tonic clonic
- not metabolized by p450 - few drug interaction

Question 11

Tiagabine

Answer 11

MOA: inhibits GABA uptake esp. in forebrain and hippocampus- prolongs inhibitory action of GABA and potentiates tonic inhibition in brain

use: adjunct in partial seizure therapy
- well absorbed, protein bound
- toxicity: nervousness, difficulty concentrating, pregnancy C

Question 12

Vigabatrin

Answer 12

MOA: irreversible inhibitor of GABA transaminase - increases GABA levels in the presynaptic cleft inc tonic inhibition in the brain

use: refractory adult complex partial seizures and infantile spasms
- preexisting mental condition is contraindication
- irreversible constriction of visual field or retinal damage common

Question 13

Ethosuximide

Answer 13

MOA: block T type Ca channels- part of the rhythmic cortical discharge in thalamic neurons

use: absence seizures
- give twice per day to dec. GI effects
- valproic acid decreases clearance ethosiximide
- toxicity: gastric pain, can cause steven johnson, preg, C

Question 14

valproic acid

Answer 14

MOA: blocks Na channels and high frequency repetitive firing, dec NMDA receptor simulation, inc. GABA levels
Use: DOC for absence and gen. tonic clonic occurring together, atonic, and partial seizures, bipolar disorder, migraine prophylaxis
- inhibits own metabolism at low doses, and inhibits phenobarbital metabolism, dec. elimination of lamotrigine
- displaces phenytoin from plasma proteins
Toxicity: hepatoxicity (CI in pts with liver disease), pancreatitis, Preg Cat. D

Question 15

Clonazepam

Answer 15

Benzo - useful in absence seizures, myoclonic, infantile spasms,
Preg Cat. D (all benzos)

Question 16

Diazepam, lorazepam

Answer 16

Benzo

IV for status epilepticus along with respiratory support

Question 17

Steven Johnson Syndrome

Answer 17

Hypersensitivity reaction consisting of erythema multiforme, arthritis, nephritis, CNS abnormalities, myocarditis 
Drugs that cause this: 
- phenytoin (fosphenytoin) 
- phenobarbital (primidone) 
- ethosuximide 
- valproic acid 
- lamotrigine

Question 18

Pregnancy Category D drugs

Answer 18

Phenytoin, carbamazepine (oxcarbazepine), phenobarital (primidone), ethosuximide, valproic acid, benzodiazepines

Question 19

Pregnancy Category C drugs

Answer 19

Lamotrigine
Gabapentin
Topirimate
Tiagabine