Lab 3-- Antiepileptic Flashcards
Inital phase
- opening of voltage gated Na channels
- inward movement of Na through depolarization
Second Phase
- inactivation of Na channel
- opening of K channel
- termination of depolarization
Target sites of Antiepileptic drug
- Stabilization of inactive voltage-gated sodium channels
- reducing current through t-type calcium channels
- inhibitng excitatory NT (glutamate)
- enhancing inhibitory NT (GABA)
Epilepsy
- seizure disorder; excessive neural activity in the cerebral cortex
Epilepsy Diagnosis
- electroencephalogram (EEG)
- Computer assisted tomograpy (CT)
- Magnetic resonance imaging (MRI)
Seizure classifications
- Partial (simple, complex, w/ 2nd generalization)
- Generalized (absence, myoclonic, tonic-clonic, tonic, atonic)
Drugs for stabilizing inactive voltage-gated
Na channel
- carbamazepine
- valproate
- lamotrigine
- oxcarbazepine
- topiramate
- phenytoin
Drugs for Ca channel
reduce current through T-type calcium channels
- Valproate
- ethosuximide
Drugs inhibit excitatory NT
(Glutamate; EPSP)
- Lamotrigine
Drugs enhancing inhibitory NT
(GABA: IPSP)
- Barbituates, benxodiazepines, valproate, gabapentin, levetiracetam, topiramate
Pharmacokinetic factors
- Vd
- bioavailability traction
- salt fraction
- albumin concentration (dominant protein in the blood)
- drug clearance
Disease + physiological factors
- type of seizures
- stage of disease
- age
- pregnancy
- drug interaction
Dose adjustments
- Liver/renal disease (alter albumin lvl)
- obesity (adipose tissue increase Vd)
- Metabolism/clearance (liver P450 enzymes)
- Age (Vd)
Vd
- Theoretical value about ability of drug to distribute in the body tissue.
- Generally constant for the drug and can be used to calculate the drug
dosage.
In vitro Vd
- Mimics lipid membrane and blood compartments
- Drug added to system containing n-octanol (lipid phase) and water/buffer
(aqueous phase). System is shaken to allow drug to partition between two
phases
Phenytoin
- for partial and tonic-clonic seizures
- sodium form is less soluble
- Extensively hydroxylated in the liver (CYP2C9)
F value
bioavailability fraction
S value
salt fraction correction
In experiment
- use standard curve to determine before and after extraction phenytoin conc to determine Vd
Phenytoin narrow therapeutic window
- total serum conc: 10-20 mcg/mL
- free phenytoin: 1-2 mcg/mL
- extensively metabolised by CYP2C9
Phenytoin Vd
Adults: 0.7 L/kg
Child: 1.0 L/kg
Dose normalization
to determine whether serum concentration in a
disease state or drug interaction is therapeutic
Exocytosis
- ca influx
- transmitter release
- GABA – stops other NT to release/produce
- glutamate – produce another NT and send to other cells
Underlying causes of Epilepsy
- Stroke, trauma, meningitis, and
hyperthermia - Drug overdose: haloperidol, lidocaine,
and alcohol - Unknown cause: Idiopathic seizure
Tonic clonic
Tonic/Atonic
- Stiffening, falling and jerking
- falling heavly to the ground
Absence seizures
- staring and blingking without falling
myoclonic seizures
- jerking movement of the body
Simple seizures
- seizure activity while alert
Complex seizures
- seizure activity with change in awareness
with secondary generalization seizures
- seizure activity begins in one area and spreads
