EXAM #3: ANTICONVULSANTS II Flashcards
What two drugs are Hydantoins?
Phenytoin
Fos-phenytoin
What is the difference between Phenytoin and Fos-phenytoin?
Fos-phenytoin is a prodrug that is more soluble, making it available for IV and IM preparations
What is the effect of Phenytoin on metabolism?
Induction of cytochome p450
What type of elimination does Phenytoin undergo?
Zero-order i.e. system can become SATURATED
What is the mechanism of action of Phenytoin?
1) Blocks Na+ channels by binding the voltage gated Na+ channel in the inactivated state
2) Enhances GABA release
3) Decreases glutamate release
4) Prevents seizure propagation
What are the clinical indications for Phenytoin?
1) Grand mal seizure
2) Patrial seizure
3) Status epilepticus
What is the unique adverse effect that is strongly associated with Phenytoin?
Gingival Hyperplasia
What is Fetal Hydantoin Syndrome?
Teratrogenic syndrome including cleft lip and palate cause by Phenytoin ingestion during pregnancy
What class of drug is Carbamazepine?
Tricyclic
What is the mechanism of action of Carbamazepine?
Inhibition of voltage-gated Na+ channels
What is the effect of Carbamazepine on metabolism?
Potent induction of CYP p450
What is Oxacarbazepine?
New drug with similar structure to Carbamazepine that has FEWER side effects
What are the clinical indications for Carbamazepine?
1) General tonic-clonic seizures
2) Partial seizures
3) Trigeminal neuralgia
4) Bipolar disorder (manic phase)
What is the drug of choice for trigeminal neuralgia?
Carbamazepine
What is the unique side effect of Carbamazepine?
SIADH i.e “Syndrome of Inappropriate ADH Secretion” leading to fluid retention and hyponatremia
Also, like Phenytoin, a potent Teratogen
What is the mechanism of action of Phenobarbital?
Increases the duration of opening of GABA receptors on the post-synpatic cell
What is Phenobarbital commonly clinically used for?
1) Neonatal seizures
2) Seizures in pregnancy
3) Status epileptics
What is Primidone?
Prodrug of Phenobarbital
What type of seizure is Ethosuximide used to treat?
Petite mal
What is the mechanism of action of Ethosuximide?
Blocks pre-synpatic T-type Ca++ channels
What is the second drug used to treat Petite Mal seizures?
Valproic acid
What is the mechanism of action of Valproic acid ?
1) T-type Ca++ channel blocker
2) Inhibition of GABA transaminase (increase GABA in synapse)
What are the unique side effects of Valproic acid ?
1) Hepatotoxic syndrome
2) Teratogenic risk
What is the preferred initial agent for status epilepticus?
Diazepam
Note that this is relatively short acting and requires an additional drug to maintain cessation of seizure activity*
What is the difference between Lorazepam and Diazepam?
Lorazepam is longer acting in status epilepticus
What is the mechanism of action for Diazepam?
Increases the frequency of GABA-A channel opening
What is the mechanism of action of Gabapentin?
Synthetic GABA analog that BLOCKS pre-synapatic Ca++ channels
(Counter-intuitive)
What are the clinical indications for Gabapentin?
1) Grand mal seizure
2) Neuropathic pain
What is Pregablin?
Lyrcia, a newer GABA analog
What is the mechanism of action of Lamotrigine?
Blocks pre-synaptic Na+ and Ca++ channels
What is the unique adverse effect associated with Lamotrigine?
Stevens Johnson Syndrome
What is the mechanism of action of Felbamate?
Blocks Na+ and glutamate receptors
What adverse effects as associated with Felbamate?
- Aplastic anemia
- Liver failure
What is the mechanism of action of Tiagabine?
Inhibits GABA uptake
What are the two major drugs we discussed as muscle-relaxants?
1) Diazepam
2) Baclofen
What is the mechanism of action of diazepam as a muscle relaxant?
Increases frequency of central GABA-A receptor opening to increase central inhibitor effect
What is the difference GABA-A and GABA-B receptors?
A= Cl- ion channel B= GPRC that increases K+ conductance
What is the mechanism of action of Baclofen?
GABA-B receptor agnoist that increases K+ conductance
Clinically, what is the difference between Diazepam and Baclofen?
Baclofen causes less sedation
