Pharm: Seizures Flashcards
Diazepam
“Valium”
= Benzodiazepine (clonazepam, lorazepam)
** Given IV for status epilepticus!!!
MOA: enhance GABA-mediated Cl- influx and enhance the generation of inhibitory membrane potentials
PK: extremely lipophilic
USE: Status epilepticus, myoclonic, partial, generalized tonic-clonic seizures
ADR: can cause sedation/drowsiness and decreased respiratory drive
Carbamazepine
“Tegretol”
MOA: prolongs inactivated state of Na+ channel
PK: potent CYP inducer
** Autoinduction **
USE: Partial seizures, generalized tonic-clonic, trigeminal neuralgia, mania in bipolar disorder
Unique ADRs: hyponatremia, blood dyscrasias (agranulocytosis), *** leukopenia, SJS
Ethosuximide
“Zarontin”
- MOA: reduces low threshold Ca2+ (T-type) current
PK: long t1/2 40 hours
USE: ** ONLY Absence seizures
Unique ADRs: gastric distress
Gabapentin
“neurontin”
MOA: bind α2δ subunit of voltage-gated N-type Ca2+ channels, decrease Ca2+ entry, decrease synaptic release of glutamate
PK: not metabolized
USE: Partial seizures, generalized tonic-clonic, neuropathic pain, post-herpetic neuralgia
Unique ADRs: headache, tremor
Lamotrigine
“Lamictal”
MOA: prolongs inactivated state of Na+ channel
USE: Partial seizures, generalized tonic-clonic, bipolar disorder
Unique ADRs: skin rash
Levetiracetam
“Keppra”
MOA: binds synaptic vesicular protein SV2A. Modifies synaptic release of glutamate and GABA.
USE: Partial seizures, generalized tonic-clonic, myoclonic seizures
Unique ADRs: serious mood and behavioral changes (less common)
Phenytoin
= “Dilantin”
MOA: prolongs inactivated state of Na+ channel
- highly protein bound!!
- CYP2C9/19 metabolism
USE: (this is the go to, works for everything but absence) Partial seizures, generalized tonic-clonic
Unique ADRs: gingival hyperplasia, hirsutism
- Cardiac effects: hypotension, bradycardia, arrhythmia
- can cause SJS
Valproic Acid
- Divalproex
= “Depakote”
MOA: prolongs inactivated state of Na+ channel, may block NMDA receptor mediated excitation, may increase levels of GABA
PK: highly protein bound
USE: (ALL ! )Absence seizures, myoclonic seizures, generalized tonic-clonic, partial seizures, status epilepticus, bipolar disorder, migraine prophylaxis
Unique ADRs: GI distress, fine tremor, weight gain and hair loss!
simple partial seizure
= minimal, normal consciousness, presered awareness
complex partial seizure
- localized onset but discharge becomes widespread; almost always involving limbic system
- Patient may have automatisms (lip smacking, swallowing, fumbling, scratching), memory loss, or aberrant behavior.
secondarily generalized seizure
- Partial seizure immediately precedes a generalized tonic-clonic seizure.
tonic-clonic
= grand-mal seizure
(1) Sudden, sharp tonic contraction followed by rigidity and clonic movements.
(2) Patient may cry/moan, lose sphincter control, bite tongue, or develop cyanosis.
(3) After seizure, patient may have altered consciousness, drowsiness, or confusion (postictal).
absence seizure
= petit mal
(1) Sudden onset and abrupt cessation; altered consciousness; a blank stare.
(2) Occurs in young children through adolescence.
myoclonic seizure
Brief, shock-like muscle contractions; occur in wide variety of seizures
atonic seizure
(1) Sudden loss of postural tone: head drop, fall to floor, slumping.
(2) Many patients wear helmets to prevent head injury.
three MOAs of AED’s (anti-eleptic drugs)
Limit sustained, repetitive firing of neurons, mediated by promoting the inactivated state of voltage-gated Na+ channels
Enhanced γ-aminobutyric acid (GABA) mediated synaptic inhibition, mediated by presynaptic or postsynaptic actions
Inhibition of voltage-gated Ca2+ channels
which are highly protein bound?
phenytoin, valproic acid
common ADR’s amongst all?
Sedation Dizziness Blurred or double vision Difficulty concentrating Ataxia
what to watch out for w/ warfarin?
- phenytoin
- carbamazepine
autoinduction?
carbamazepine
tx for partial seizures?
Carbamazepine
lamotrigine
oxcarbazepine
levetiracetam
topiramate
“topamax”
MOA: actions on Na+ channels, GABAA receptors, high-voltage Ca2+ currents, may act on glutamate/NMDA receptors
Partial, generalized tonic-clonic, Lennox-Gastaut, infantile spasms, absence seizures, migraine
Unique ADRs: paresthesias, nervousness, weight loss
tx of primary generalized tonic clonic seizure
Valproate –or– lamotrigine –or– levetiracetam
Absence seizure tx?
Ethosuximide –or– valproate
Atypical absence, myoclonic or atonic tx?
Valproate –or– lamotrigine –or– levetiracetam
DDI’s of phenytoin?
Protein binding (sulfonamides)
Competes for metabolism CYP2C9 (warfarin) & 2C19
Also results in enzyme induction (oral contraceptives)
DDI’s of carbamazepine?
Enzyme induction (phenytoin, oral contraceptives)
DDI’s of Valproic Acid?
Enzyme inhibition (carbamazepine)
DDI of Lamotrigine?
Oral contraceptives may decrease lamotrigine concentrations
AED’s and pregnancy?
- Interactions with oral contraceptives
Effectiveness of OCs reduced by (likely due to induction of CYP3A4):
- carbamazepine, oxcarbamazepine, phenobarbital, phenytoin, primidone, rufinamide - Potential teratogenic effects:
- Increased risk of congenital malformations: phenytoin, valproate, topiramate
look at questions!
at end of slide
