Anti-Epileptic Drugs Flashcards
MOA of Phenytoin
Antagonist to voltage gated Na+ channel and is also secondary Ca2+ channel blocker. This delays the onset of neuron firing.
MOA for Oxcarbazepine
Antagonist to voltage gated Na+ channel
What Na+ voltage gated channel antagonist is preferred for children?
Oxcarbazepine
Phenytoin is used to treat what type of seizures?
All generalized partial and tonic-clonic seizures.
What is phenytoin a BIG NO for?
Treating juvenile myoclonic seizure because PHT aggravates JM seizures
Adverse effects for phenytoin
Gingival hyperplasia and Hirsutism
Phenytoin increases the conversion of of primidone to what compound?
phenobarbital
Concurrent administration of Phenytoin and carbamazepine does what?
Enhances metabolism of each other due to hepatic cytochrome P450 enzymes
Felbamate MOA:
Glutamatergic receptor antagonist
Felbamate is used only in…
1) Lennox-Gastaut Syndrome or
2) in patients highly refractory to other drugs.
Why is febamate rarely used?
Causes hepatic failure
What is the action of felbamate (FBM) on NMDA receptor?
1) FBM inhibits NMDA channel in a use-dependent manner.
2) FBM binds to NR2B and NR1 subunits in a voltage-independent manner.
3) FBM delays the recovery of desensitized NMDA channels. FBM is a weak positive modulator of GABA-AR Cl- current.
List 3 GABA regulating drugs:
Gabapentin, Tiagabine, Vigabatrin
MOA of Gabapentin
Releases GABA from glial cells. New drug, lipophilic, crosses BBB. Does NOT bind to GABA analog GAABA-AR.
MOA for Tiagabine
Inhibits reuptake of GABA by GABA transporter (GAT-1).
MOA for Vigabatrin:
inhibits the metabolism of GABA by GABA transaminase.
Therapeutic uses for Gabapentin:
used for neuropathic pain and migraine, but not effective for controlling seizures.
Therapeutic uses for Tiagabine
Controls tonic clonic seizures for children below 12 years old.
Therapeutic uses for Vigabatrin
First oral drug approved recently for treatment of INFANTILE SPASM and REFRACTORY COMPLEX partial seizures that are not controlled by usual treatments.
Adverse effects of Vigabatrin
VGB causes liver failure, psychotic disorder, suicidal thoughts, and visual field defect.
What are 3 drugs that can be used to treat myoclonic seizures?
Valproic acid, Zonisamide, Lamotrigine
Describe Myoclonic seizures:
1) Common in juvenile, but rare in childhood.
2) Single multiple clonic jerks in the face, neck, upper arms.
3) Most myoclonic seizures originate from the brainstem in the CNS.
What drugs aggravate juvenile myoclonic seizures?
Phenytoin and Carbamazepine
Valproic acid is used for treatment of juvenile myoclonic seizures. What is the mechanism of action?
Blocker of NA+ channel and Ca2+ channel, also decreases GABA metabolism. It prolongs the recovery of voltage-activated Na+ channel from inactivation.
Adverse effects of Valproic acid (VPA)
Hepatotoxic, during pregnancy can cause spina bifida (folic acid deficiency). If pregnant and need to control seizures, give VPA with folate.
What is Zonisamide used to treat and what is the MOA?
Myoclonic seizures: an antagonist to NA+ and Ca2+ channels. It can cause renal stone formation.
What type of seizure can lamotrigine treat and what is the MOA?
A Na+ channel blocker also effective against myoclonic seizure in children with mild side effects of dizziness, rash and headache.
What type of seizure is this? Onset 4-12 years old and continues to adolescnece. Brief and abrupt unconsciousness (5-10sec). High voltage bilaterally synchronous spike-wave discharge is typically 2.5-3.5 Hz.
Absence seizure (Petit Mal)
Drug of choice to treat Absence seizures
Ethosuximide (ESX)
MOA of Ethosuximide
Blocks T-Type Ca+ channel. Known to inhibit GABA-T.
Other drugs for treatment of Absent Seizures
Valporate and Lamotrigine (a Na+ channel blocker)
Current Definition of Status Epilepticus
Seizure activity lasts for 10 min w/o recovery, or two or more seizures within 30 min.
What was once used to treat Status Epilepticus seizures?
Phenobarbital- sedative and hypnotic schedule
What has largely replaced phenobarbital for Status Epilepticus seizures?
Safer benzodiazepines: Lorazepam and Diazepam
Diazepam vs Lorazepam: Which drug has a high lipid solubility?
Diazepam. Lorazepam has low lipid solubility.
Diazepam vs Lorazepam: Which drug has a rapid action onset?
Diazepam. Lorazepam is delayed 2 min
Diazepam vs Lorazepam: Which drug has a longer Anti-epileptic effect?
Lorazepam (6-12 hr). Diazepam last 15-30 min.
Diazepam vs Lorazepam: Which drug has a longer half-life?
Diazepam (20-100 hr-can cause toxicity). Lorazepam (10-20 hrs).
Diazepam vs Lorazepam: WHich drug has less respiratory depression?
Lorazepam. Diazepam has Resp. depression and hypotension.
MOA for Lorazepam and Diazepam?
Binding of benzodiazepine to GABA receptor forms a positive allosteric effector. This stabilizes the receptor conformation to keep Cl- channel open. This increase Cl- ion influx to cause hyperpolarization, which prevents repetitive neuron firing.
Preferred drugs for partial and generalized seizures?
Phenytoin, Oxcarbazepine (child), Gabapentin
Preferred drug for myoclonic seizures?
Valproic Acid (Never Carbamazepine/Phenytoin)
Preferred drug for Absence Seizures?
Ethosuximide (Children, adult)
Preferred drug for Status Epilepticus?
Lorazepam and Diazepam
Preferred drug for infantile spasms?
Vigabatrin
