Pharmacotherapy of Seizure Disorders Flashcards
Epilepsy drugs
Used for…/mechanism
phenytoin
Partial/Generalized/Mech
Partial:
Simple +
Complex +
Generalized:
Tonic-clonic: 1st line
Absence:
Status: 1st line for propylaxis
Mech: ↑Na channel inactivation
Epilepsy drugs
Used for…/mechanism
Carbamazepine
Partial/Generalized/Mech
Also used for…
Causes:
Partial
Simple: 1st line
Complex: 1st line
Generalized
Tonic-clonic: 1st line (with phenytoin)
Absence:
Also used for…
1st line for trigeminal neuralgia
Mech: ↑Na channel inactivation
Causes agranulocytosis
Epilepsy drugs
Used for…/mechanism
Lamotrogine
Partial/Generalized/Mech
Partial
Simple: +
Complex: +
Generalized
Tonic-clonic: +
Absence:
Status:
Mech: Blocks voltage gated Na channels
Epilepsy drugs
Used for…/mechanism
Gabapentin
Partial/Generalized/Mech
Also used for….
Partial
Simple: +
Complex: +
Generalized
Tonic-clonic: +
Absence:
Also used for….
Also used for peripheral neuropathy, bipolar disorder
Mech: Designed as GABA analog but primarily inhibits HVA Ca channels
Epilepsy drugs
Used for…/mechanism
Topiramate
Partial/Generalized/Mech
Partial
Simple: +
Complex: +
Generalized
Tonic-clonic: +
Absence:
Status:
Mech: Blocks Na channels,
↑ GABA action
Epilepsy drugs
Used for…/mechanism
Phenobarbital
Partial/Generalized/Mech
Partial
Simple: +
Complex: +
Generalized
Tonic-clonic: +
Absence:
Status: 1st line in pregnant women, children
Mech: ↑ GABAA action
Epilepsy drugs
Used for…/mechanism
Valproic Acid
Partial/Generalized/Mech
Partial:
Simple: +
Complex: +
Generalized:
Tonic-clonic: 1st line
Absence: +
Status: Also used for myoclonic seizures
Mech:
↑ Na channel inactivation
↑ GABA concentration
Epilepsy drugs
Used for…/mechanism
Ethosuximide
Partial/Generalized/Mech
Partial:
Simple
Complex
Generalized:
Tonic-clonic
Absence: 1st line
Status
Mech:
Blocks thalamic T-Type Ca channels
Epilepsy drugs
Used for…/mechanism
Benzodiazepines
Partial/Generalized/Mech
Partial
Simple
Complex
Generalized Tonic-clonic Absence Status: 1st line for acute also used for seizures of eclampsia (1st line is MgSO4)
Mech: ↑ GABAA action
Epilepsy drugs
Used for…/mechanism
Tiagabine
Partial/Generalized/Mech
Partial:
Simple: +
Complex: +
Generalized:
Tonic-clonic
Absence
Status
Mech: Inhibits GABA reuptake
Epilepsy drugs
Used for…/mechanism
Vigabatrin
Partial
Simple: +
Complex: +
Generalized:
Tonic-clonic
Absence
Status
Mech:
Irreversibly inhibits GABA transaminase → ↑ GABA
Epilepsy drugs
Used for…/mechanism
Levetiracetam
Partial:
Simple: +
Complex: +
Generalized:
Tonic-clonic: +
Absence
Status
Mech:
Unknown, may modulate GABA and glutamate release
Partial seizures
1st line drugs
Simple: carbamazepine
Complex: Carbamazepine
Generalized seizures
1st line drugs
Tonic Clonic: Phenytoin, carbamazepine
Absence: Ethosuximide
1st line for acute seizures/prophylaxis
Acute: benzodiazepines
Proph: Phenytoin
Epilepsy drug toxicities
benzos
Sedation
Tolerance
Dependence
Epilepsy drug toxicities
carbamazepine
Diplopia, ataxia, blood dyscrasias (agranulocytosis, aplastic anemia) liver toxicity teratogenesis induction of cytochrome P450 SIADH Steven-johnson syndrome
Epilepsy drug toxicities
Ethosuximide
GI distress Fatigue Headache Urticaria Steven Johnson syndrome
EFGH – ethosuximide, fatigue, GI, Headache
Epilepsy drug toxicities
Phenobarbital
Sedation
Tolerance
Dependence
Induction of cytochrome P450
Epilepsy drug toxicities
Phenytoin
Nystagmus Diplopia Ataxia Sedation Gingival hyperplasia Hirsutism Megaloblastic anemia Teratogenesis (fetal hydantoin syndrome) SLE-like syndrome Induction of P450
Epilepsy drug toxicities
Valproic Acid
GI distress
Rare but fatal hepatotoxicity (measure LFTs)
Neural tube defects in fetus (spinal bifida)
Tremor
Weight gain
Contraindicated in pregnancy
Epilepsy drug toxicities
Lamotrigine
Steven-Johnson syndrome
Epilepsy drug toxicities
Gabapentin
Sedation
Ataxia
Epilepsy drug toxicities
Topiramate
Sedation
Mental Dulling
Kidney Stones
Weight Loss
Stevens-Johnson syndrome
Prodrome of malaise and fever followed by rapid onset of erythematous/purpuric macules (oral, ocular, genital)
Skin lesions progress to epidermal necrosis and sloughing
Phenytoin
Mech/clinical use/toxicity
Mech
Use-dependent blockade of Na channels; ↑ refractory period; inhibition of glutamate release from excitatory presynaptic neuron
Clinical Use
Tonic clonic seizures
Also a class IB antiarrhythmic
Toxicity Nystagmus Ataxia Diplopia Sedation SLE-like syndrome Induction of cytochrome P450 Chronic use produces gingival hyperplasia in children, peripheral neuropathy, hirsutism, megaloblastic anemia (↓ folate absorption). Teratogenic (fetal hydantoin syndrome)
Barbiturates
Mech/clinical use/toxicity
Phenobarbital, pentobarbital, thiopental, secobarbital
Mech
Facilitate GABA A action by ↑ duration of CL- channel opening, thus ↓ neuron firing
Clinical Use
Sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental)
Toxicity
Dependence, additive CNS depression effects with alcohol, respiratory or CV depression (can lead to death)
DDI owing to induction of liver P450 enzymes
Treat overdose with sx management (assist respiration, ↑ BP)
Contraindicated in porphyria
Benzos
Mech/clinical use/toxicity
Diazepam, Lorazepam, Triazolam, Temazepam, oxazepam, midazolam, chlordiazepoxide, alprazolam
Mech
Facilitate GABA A action by ↑ frequency of Cl channel opening
↓ REM sleep
most have long half-lives and active metabolites
Clinical Use Anxiety Spasticity Status epilepticus (lorazepam and diazepam) Detox (esp alcohol – DT’s) Night terrors Sleepwalking General anesthetic (amnesia, muscle relaxant) Hypnotic (insomnia)
Toxicity
Dependence, additive CNS depression effects with alcohol. Less risk of respiratory depression and coma than with barbiturates
Tx overdose with flumazenil (competitive antagonist at GABA benzo rec)
Benzodiazepines
Short acting/most addictive
Short acting = TOM
Triazolam
Oxazepam
Midazolam
Also the highest addictive potential
GABA(A)-R
What binds to it
Benzos
Barbs
EtOH
AED
MOA
Benzos
Enhance GABA
AED
MOA
CBZ
Modulate Na channels
AED
MOA
Ethosuximide
Modulate Ca Channels
AED
MOA
felbamate
Enhance GABA
AED
MOA
Gabapentin
Modulate Ca Channels
AED
MOA
Lamotrigine
Modulate Na Channels
AED
MOA
Levetiracetam
Unknown