Week 12 - Anticonvulsants Flashcards
Hydantoin - Phenytoin (Dilantin): indications
Tonic clonic and partial complex seizures
Grand mal and psychomotor seizures
First line treatment
Hydantoin - Phenytoin (Dilantin): MOA
Inhibit and stabilize electrical discharges in the motor cortex of the brain by increasing the influx of sodium ions during generation of nerve impulses
Hydantoin - Phenytoin (Dilantin): caution and contraindications
- Avoid in sinus bradycardia, 2nd and 3rd degree AV block, Stocks-Adams syndrome (syncope w/ heart block)
- Hypotension and myocardial insufficiency
- Renal and hepatic impairment
- Rebound status epilepticus can occur w/ sudden withdrawal
- Narrow TI
Can phenytoin be used in pregnancy and pediatrics?
Avoid in pregnancy and lactation
Approved in pediatrics
Hydantoin - Phenytoin (Dilantin): ADR
Agitation, ataxia, confusion, dizziness, drowsiness, HA, nystagmus, hypotension, tachycardia, N/V, anorexia, altered taste, gingival hyperplasia, discolored urine
Rare: hypersensitivity reactions, SI, blood dyscrasias
Carbamazepine (Tegretol): indications
Focal and generalized onset seizures
Carbamazepine (Tegretol): MOA
Exact MOA unclear but thought to affect the sodium channels, slowing influx of sodium in the cortical neurons and slowing the spread of abnormal activity
- Depresses neuron transmission in the nucleus ventralis anterior of the thalamus
Carbamazepine (Tegretol): caution and contraindications
- Caution in renal and hepatic impairment
Black box warning
- Development of SJS and toxic epidermal necrolysis in Chinese patients
- Blood dyscrasias
- Dermatologic toxicity
Can carbamazepine be used in pregnancy and pediatrics?
Avoid in pregnancy and lactation
Approved in pediatrics
Carbamazepine (Tegretol): ADR
Drowsiness, dizziness, ataxia, N/V, skin rash, pruritus, constipation, tremor
Bone marrow depression, impaired thyroid function, liver damage
Rare: behavior changes, SI, multi-organ hypersensitivity reactions, hepatotoxicity
Lamotrigine: indications
Adjunctive treatment (w/ valproic acid, phenytoin)
- Partial seizures
- Primary generalized tonic clonic seizures
Lamotrigine: MOA
Thought to affect voltage-sensitive sodium channels and inhibit presynaptic release of glutamate and aspartate in the neuron
Lamotrigine: caution and contraindications
- Rebound status epilepticus can occur w/ sudden withdrawal
- Caution in renal and hepatic impairment
Black box warning
- Serious skin reactions
Can lamotrigine be used in pregnancy and pediatrics?
Avoid in pregnancy and lactation
Approved in children >2 years
Lamotrigine: ADR
GI - N/V, constipation
CV - chest pain, peripheral edema
CNS - somnolence, fatigue, dizziness, anxiety, insomnia, HA, amblyopia, nystagmus
Derm - rashes
Rare: SI, blood dyscrasias, multi-organ hypersensitivity reactions
Zonisamide: indications
Partial seizures in adults
Zonisamide: MOA
Exact MOA unknown
Blocks voltage dependent sodium and chloride channels
Zonisamide: ADR
Somnolence, anorexia, dizziness, HA, agitation, memory difficulties
Rare: aplastic anemia, agranulocytosis
Zonisamide: caution and contraindications
- Avoid if hypersensitivity to sulfonamides
- Avoid w/ sulfa allergy
- Rebound seizures can occur w/ sudden withdrawal
- Caution in renal and hepatic impairment
Can zonisamide be used in pregnancy and pediatrics?
Avoid in pregnancy and lactation
Approved for pediatrics >16 years
Succinimides - Ethosuximide, Methsuximide: indication
Absence seizures
Succinimides - Ethosuximide, Methsuximide: MOA
Decrease nerve impulses and transmission in the motor cortex
Suppresses seizures by delaying calcium influx into neurons
Succinimides - Ethosuximide, Methsuximide: ADR
- GI distress
- CNS - sedation, ataxia, lethargy
- HA
- Rash
- Pruritus
- Mood changes
- Agranulocytosis, aplastic anemian granulocytopenia
Succinimides - Ethosuximide, Methsuximide: caution and contraindications
- Rebound seizures can occur with sudden withdrawal
- Caution in renal and hepatic impairment
Can succinimides be used in pregnancy and pediatrics?
May continue therapy during pregnancy w/ close monitoring
Avoid in lactation
Approved in pediatrics >3 years
Valproic acid: indications
- Focal (partial) onset seizures
- Generalized onset seizures
- Focal onset impaired awareness
- Absence seizures
Valproic acid: MOA
Increases GABA availability and enhances the action of GABA
Mimics its action at the postsynaptic sites
Valproic acid: ADR
HA, drowsiness, dizziness, N/V, tremor, visual disturbance, weight gain, behavioral changes
Rare: hypersensitivity reactions, SI, brain atrophy
Valproic acid: caution and contraindications
Rebound seizures can occur w/ sudden withdrawal
Black box warning
- Hepatotoxicity
- Severe pancreatitis
Can valproic acid be used in pregnancy and pediatrics?
Avoid in pregnancy and lactation
Avoid in children <2 years
Gabapentin: indications
Focal seizures
Gabapentin: MOA
Thought to be a GABA analogue that binds to unknown receptors in the brain
Gabapentin: ADR
- Dizziness
- Drowsiness
- Fatigue
- Ataxia
- Peripheral edema
- Abnormal thinking
Gabapentin: caution and contraindications
- Caution on renal impairment
- Caution in patients w/ substance abuse history
- Rebound seizures can occur w/ sudden withdrawal
Can gabapentin be used in pregnancy and pediatrics?
Only if benefits outweigh risks in pregnancy and lactation
Avoid in children <3 years
Topiramate: indications
- Focal seizures
- Primary generalized tonic clonic seizures
Topiramate: MOA
MOA unclear but may block sodium channels or potentiate GABA
Topiramate: ADR
- Ataxia
- Paresthesia
- Dizziness
- Somnolence
- Difficulty concentrating
- Mood changes
- Weight loss
Topiramate: caution and contraindications
- Caution in renal and hepatic impairment
- Rebound seizures can occur with sudden withdrawal
Can topiramate be used in pregnancy and pediatrics?
Avoid in pregnancy
Use only if benefits outweigh risks in lactation
Avoid in children <3 months
Levetiracetam: indications
- Focal onset seizures
- Generalized onset seizures
Levetiracetam: MOA
MOA unclear but may inhibit burst firing w/o affecting normal neuronal excitability
Levetiracetam: ADR
- Somnolence
- Dizziness
- Nervousness
- Mood disturbances
Rare: SI
Levetiracetam: caution and contraindications
- Caution in renal impairment
- Rebound seizures can occur w/ sudden withdrawal
Can levetiracetam be used in pregnancy and pediatrics?
Caution in pregnancy and avoid in lactation
Avoid in children <1 month
Factors that precipitate seizures
Sleep deprivation, high caffeine intake, hyperventilation, stress, hormonal changes, sensory stimuli, drug/alcohol use, infections, fever, metabolic disorders
- Anticonvulsants can be used to treat mood disorders
General MOA of anticonvulsants
- Stimulate influx of chloride ions (associated w/ GABA)
- Delaying the influx of sodium
- Delaying the influx of calcium
Phenytoin (Dilantin): drug interactions
- Levels of phenytoin will increase w/
- Cimetidine, diazepam, acute alcohol intake, valproic acid, allopurinol
- Levels of phenytoin will decrease w/
- Barbituates, antacids, calcium, chronic alcohol use
- Phenytoin will cause decreased effects in…
- Carbamazepine, estrogens, acetaminophen, corticosteroids, levadopa, sulfonylureas, cardiac glycosides
True/False: Providers should give patients phenytoin (Dilantin) IV or IM in primary care setting when needed
False
Phenytoin (Dilantin): monitoring
TSH
Need to asses OTC drugs such as ibuprofen, antacids
Phenytoin (Dilantin): patient education
- Avoid driving if not seizure free for more than 1 year
- Monitor oral hygiene
- Phenytoin hypersensitivity syndrome (fever, skin rash, lymphadenopathy)
- Occurs at 3-8 weeks of treatment
Total serum concentration of phenytoin and associated adverse events
- >20mcg/mL: far lateral nystagmus
- >30mcg/mL: 45 degrees lateral gase nystagmus and staxia
- >40mcg/mL: decreased mentation and lethargy
- >100mcg/mL: lethal
Carbamazepine: drug interactions
- Grapefruit juice
- Drug levels increase w/
- Propoxyphene (Darvocet), cimetidine, erythromycin, clarithromycin, verapamil, hydantoins (e.g. phenytoin)
- Drug levels decrease w/
- Beta blockers, warfarin, doxycycline, succinimides, haloperidol
Lamotrigine: drug interactions
Levels decrease by - barbiturates, estrogens, phenytoin, mefloquine
Levels increase by - alcohol, carbamazepine, CNS depressants, valproic acid
Lamotrigine: patient education
- Avoid alcohol, OTC drugs
- Maintain adequate hydration
- Avoid driving
- Controversy about d/c medications after a few years being seizure-free
- Neurologist should make final decision
