Lab 3-- Antiepileptic

Question 1

Inital phase

Answer 1

• opening of voltage gated Na channels
• inward movement of Na through depolarization

Question 2

Second Phase

Answer 2

• inactivation of Na channel
• opening of K channel
• termination of depolarization

Question 3

Target sites of Antiepileptic drug

Answer 3

• Stabilization of inactive voltage-gated sodium channels
• reducing current through t-type calcium channels
• inhibitng excitatory NT (glutamate)
• enhancing inhibitory NT (GABA)

Question 4

Epilepsy

Answer 4

• seizure disorder; excessive neural activity in the cerebral cortex

Question 5

Epilepsy Diagnosis

Answer 5

• electroencephalogram (EEG)
• Computer assisted tomograpy (CT)
• Magnetic resonance imaging (MRI)

Question 6

Seizure classifications

Answer 6

• Partial (simple, complex, w/ 2nd generalization)
• Generalized (absence, myoclonic, tonic-clonic, tonic, atonic)

Question 7

Drugs for stabilizing inactive voltage-gated
Na channel

Answer 7

• carbamazepine
• valproate
• lamotrigine
• oxcarbazepine
• topiramate
• phenytoin

Question 8

Drugs for Ca channel

reduce current through T-type calcium channels

Answer 8

• Valproate
• ethosuximide

Question 9

Drugs inhibit excitatory NT

(Glutamate; EPSP)

Answer 9

• Lamotrigine

Question 10

Drugs enhancing inhibitory NT

(GABA: IPSP)

Answer 10

• Barbituates, benxodiazepines, valproate, gabapentin, levetiracetam, topiramate

Question 11

Pharmacokinetic factors

Answer 11

• Vd
• bioavailability traction
• salt fraction
• albumin concentration (dominant protein in the blood)
• drug clearance

Question 12

Disease + physiological factors

Answer 12

• type of seizures
• stage of disease
• age
• pregnancy
• drug interaction

Question 13

Dose adjustments

Answer 13

• Liver/renal disease (alter albumin lvl)
• obesity (adipose tissue increase Vd)
• Metabolism/clearance (liver P450 enzymes)
• Age (Vd)

Question 14

Vd

Answer 14

• 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.

Question 15

In vitro Vd

Answer 15

• 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

Question 16

Phenytoin

Answer 16

• for partial and tonic-clonic seizures
• sodium form is less soluble
• Extensively hydroxylated in the liver (CYP2C9)

Question 17

F value

Answer 17

bioavailability fraction

Question 18

S value

Answer 18

salt fraction correction

Question 19

In experiment

Answer 19

• use standard curve to determine before and after extraction phenytoin conc to determine Vd

Question 20

Phenytoin narrow therapeutic window

Answer 20

• total serum conc: 10-20 mcg/mL
• free phenytoin: 1-2 mcg/mL
• extensively metabolised by CYP2C9

Question 21

Phenytoin Vd

Answer 21

Adults: 0.7 L/kg
Child: 1.0 L/kg

Question 22

Dose normalization

Answer 22

to determine whether serum concentration in a
disease state or drug interaction is therapeutic

Question 23

Exocytosis

Answer 23

• ca influx
• transmitter release
• GABA – stops other NT to release/produce
• glutamate – produce another NT and send to other cells

Question 24

Underlying causes of Epilepsy

Answer 24

• Stroke, trauma, meningitis, and
  hyperthermia
• Drug overdose: haloperidol, lidocaine,
  and alcohol
• Unknown cause: Idiopathic seizure

Question 25

Tonic clonic
Tonic/Atonic

Answer 25

• Stiffening, falling and jerking
• falling heavly to the ground

Question 26

Absence seizures

Answer 26

• staring and blingking without falling

Question 27

myoclonic seizures

Answer 27

• jerking movement of the body

Question 28

Simple seizures

Answer 28

• seizure activity while alert

Question 29

Complex seizures

Answer 29

• seizure activity with change in awareness

Question 30

with secondary generalization seizures

Answer 30

• seizure activity begins in one area and spreads