Antiepileptics

Question 1

Why is TDM needed

Answer 1

Avoid toxicity
Optimize dose and therapeutic response
Detect changes in pharmacokinetics
Monitor compliance

Question 2

AED classification

Answer 2

Classical : phenytoin, phenobarbital, carbamazepine, valproate
Newer : lamotrigine, levetiracetam

Question 3

Inducers of CYT P450

Answer 3

Phenytoin
Phenobarbital
Carbamazepine

Question 4

Definition of epilepsy

Answer 4

Brain disorder with aberrant neuronal firing
Abnormal neuronal activity presents as strange sensation, behavior or convulsions with or without LOC
Recurrent (>2) seizures unprovoked by systemic or acute neurological insults

Question 5

Classification of seizures

Answer 5

LOC?
Y- generalized
N- change in consciousness? Y- complex partial, N- simple partial

Question 6

Seizure pathhysiology

Answer 6

Due to imbalance between excitation and inhibition

Excitation- inward flow of Na and Ca2, and glutamate
Inhibition- inward flow of chloride, outward flow of K, and GABA

Question 7

Function of GABA

Answer 7

Binds and stimulates GABA-A receptor
Increases conductance
Influx of chloride causing membrane hyperpolarization
Increase threshold for developing AP
Inhibitory effect

Question 8

General MOA of AEDs?

Answer 8

Affect ion conduction:
Prolongs Na channel inactivation
Increases GABAergic transmission via Cl channels
Glutamate receptor antagonism
Inhibition of calcium current

Question 9

Factors in choosing AED

Answer 9

Seizure - classification
Patient - age, comorbidities, lifestyle, pregnancy risk, preference
Drug - PK profile, interactions, adverse effects, cost, efficacy

Question 10

Drugs that inhibit atonal transmission

Answer 10

Phenytoin
Carbamazepine
Valproate
Lamotrigine

Question 11

Drugs that cause potentiation of GABA receptor

Answer 11

Benzodiazepines - increase Cl channel openings

Phenobarbital - prolongs Cl channel openings and decreases some Na channel openings

Question 12

Drugs that act at the excitatory synapse

Answer 12

Gabapentin

Levetiracetam

Question 13

Which are the pleotropic AEDs and activity

Answer 13

Valproate - increase GABA , inhibit Na channels, augment K channels
Lamotrigine - inhibit Na channels, interfere with glutamate release, inhibit calcium channels

Question 14

ARVs and epilepsy?

Answer 14

Phenytoin and carbamazepine = enzyme-inducing - potential reaction with ARVs –> change to lamotrigine or valproate
If RVD+ and of child bearing age, lamotrigine&raquo_space;> valproate

Question 15

Phenytoin drug characteristics

Answer 15

MOA: Inhibit Na generation –> inhibit AP generation
Highly bound to plasma proteins
Adverse effects: CNS sedation, gum hyperplasia, hirsuitism, skin rash/ hypersensitivity
Interactions: displaced from plasma proteins by valproate. Induces CYT P450
Zero order kinetics - saturable metabolism

Question 16

Carbamazepine drug characteristics

Answer 16

MOA: Inhibits Na channels, inhibits high frequency
Adverse effects: Diplopia and ataxia, idiosyncratic skin reaction, agranulocytosis and aplastic anemia
Interactions: stimulates own metabolism, induces microsomes enzymes

Question 17

Lamotrigine drug characteristics

Answer 17

MOA: inhibits Na channels, Ca channels and glutamate release
Adverse effects: CNS sedation (less), dermatitis (–> fatal)
Interactions: induces CYT P450, levels increased by valproate and decreased by carbamazepine, phenytoin and phenobarbital

Question 18

Phenobarbital drug characteristics

Answer 18

MOA: increases GABA-A receptor opening time
Adverse effects: CNS sedation, skin rash if allergic, tolerance and physical dependence
Interactions: CNS depression, induces CYT p450

Question 19

Valproate drug characteristics

Answer 19

MOA: increases GABA transmission, inhibits Na channels, opens K channels
Highly plasma protein bound
Adverse effects: increases liver enzymes, brith defects
Interactions: displaces phenytoin, inhibits CYT p450

Question 20

Benzodiazepine drug characteristics

Answer 20

MOA: increases frequency of GABA -A receptors
Adverse effects: CNS sedation, tolerance and dependence
Interactions: increases action of other CNS depressants

Question 21

Definition of status epilepticus

Answer 21

5 minutes or more continuous
A. Clinical or EEG seizure activity or
B. Recurrent seizure activity without recover between seizures

Question 22

Management of status epilepticus

Answer 22

Start Rex immediately : BDZs –> phenytoin (20 mg/kg IV diluted in 0.9%NS)–> phenobarbital (20-30 mg/kg)–> RSI with propofol (2-5mg/kg) or thiopental sodium
ABCs
Check blood glucose
Check electrolyte and anticonvulsant levels

Question 23

Epilepsy in pregnancy

Answer 23

Valproate - highest teratogenic risk
Folate supplementation before pregnancy
PK changes in pregnancy therefore adjust dose

Question 24

Goals of therapy

Answer 24

Control seizures
Restore quality of life
Restore neuronal function
Minimize drug adverse effects
Identify and avoid precipitating factors