10 21 2014 Anti-epileptic drugs Flashcards
what are the mechanisms by which anti-seizure drugs try to work
- Increase GABA
- Decrease Glutamate release from pre-synaptic vessel or signaling at post-synaptic ( AMP receptors)
- Decrease frequency of Na+, Ca2+ voltage gated channels
What drugs are used for partial seizures (simple and complex)
- Carbamazepine
- Phenytoin
- Valproate
NEW DRUGS: all of them
What drugs are used for Partial with secondarily generated tonic-clonic seizures?
- Carbamazepine
- phenytoin
- valproate
- Primidone
NEW Drugs: ALL of them
Drugs used to treat absence seizure
- Ethosuximide
- Valproate
- clonazepam
NEw Drug: Lamotrigine
Drugs used to treat Myoclonic seizures
- Valproate
- Clonazepam
New Drug: Levetiracetam
Drugs used in Tonic- Clonic seizures
- Carbamazepine
- Phenobarbital
- Phenytoin
- Primidone
- Valproate
NEW DRugs: Lamotrigine, Levetiracetam, Topiramate
Drugs used in status epilepticus
- Phenobartital
2. Diazepam
Mechanism of Action of Phenytoin
- block voltage gated Na+ (presynaptic) inactive phase
- Reduces K+ and Ca2+ = changes membrane potential
= Inhibits release of Glutamate and increases release of GABA
Pharmacokinetics of Phenytoin
- Delivery
- Bind to plasma?
- where is it metabolized?
- oral, IV, IM (intramuscular)
- 90% bind to plasma
- Liver to inactive metabolites and excreted in urine
Drug interactions of Phenytoin
- Valproate competes for protein binding sites and inhibits phenytoin metabolism
- induce microsomal enzymes responsible for metabolism of many drugs
Toxicity of Phenytoin
Diplopia, ataxia, gingival hyperplasia (face), hirsutism, neuropathy, nystagmus.
Sedation at really high levels.
Sedation at really high levels.
- LONG TERM TOXICITIES
Mechanism of Carbamazepine
Structure is similar to tricylic-antidepressants
- decrease Na+ current (voltage gated)
- decrease release of glutamate
Pharmacokinetics of Carbamazepine
- delivery
- metabolism
given orally
induces it own metabolism P450 enzymes (CYP2C, CYP3A, UGT)
Drug Interactions of Carbamazepine
- Phenobarbital, Phenytoin, Valproate increase metabolism of Carbamazepine.
- may enhance transformation of Phenytoin
- may lower concentration of other anti-seizure drugs
Toxicity of Cabamazepine
Drowsiness, blurred vision, diplopia, headache, dizziness, ataxia, nausea and vomiting.
- cognitive effects can interfere with learning
- hyponatremia
- Stevens- Johnson Syndrome: rare disorder in skin and mucosa
Mechanism of Valproic Acid ( Valproate)
- prolongues inactivation of voltage gated Na+
- blocks T-type Ca2+ receptors
= Increases GABA release
= inhibits tonic hind limb extension during maximal electroshock seizures
Pharmacokinetics of Valproic Acid
- delivery and rate of absorption
- Bind to proteins?
- Where and what enzyme(s) help with metabolism
- Absorbed rapidly and completely after oral
- can also be given IV - 90% binds to plasma proteins
- T1/2 = 15hrs
- Hepatic metabolism via UGT enzymes
Drug interactions of Valproate
inhibits metabolism of phenytoin, phenobarbital, lamotrigine an lorazepam
- can displace other drugs from albumin (ex phenytoin)
Undesirable effect of Valproate
causes severe/ fatal hepatic toxicity in children
Mechanism of Ethosuximide
blocks T-Type Ca2+
- this is the pacemaker current for thalamic neurons that are responsible for generating rhythmic cortical discharge of an absence attack
Drug interactions of Ethosuximide
Valproic acid decreases ethosuximide clearance and higher stead-state concentrations owing to inhibition of metabolism
Toxicity of Ethosuximide
GI: pain, n/v
lethargy, fatigue
Headache, dizziness, hiccups, and euphoria
Stevens-Johnson sundrome
Mechanism of Phenobarbital
blocks Na+, Ca 2+
- allosteric regulation of GABAa receptor : ENHANCES GABA current and DECREASES GLUTAMATE
Pharmcokinetics of Phenobarbital
- Oral: complete but slow, very long half life (can also be delivered IV)
- 40-60% is bound by plasma proteins
- 25% is eliminated by kidneys
- inactivated by hepatic microsomal enzymes (CYP2C9)
- also induces UGT enzymes
