Anti Epileptics

Question 1

Name 3 short term treatment options for acute epilepsy

Answer 1

Lorazepam
Diazepam
Phenytoin

Question 2

Name two drug classes used in the long term management of epilepsy

Answer 2

Voltage gated sodium channel blockers

Drugs that enhance GABA mediated inhibition

Question 3

Name 3 examples of voltage gated sodium channel blockers

Answer 3

Carbamazepine
Phenytoin
Lamotrigine

Question 4

Name 2 examples of drugs that enhance GABA mediated inhibition

Answer 4

Valproate

Benzodiazepines

Question 5

What is the mechanism of action of VGSCB

Answer 5

Bind to channel on inside of membrane (can only get in during depolarisation), leaves channel in inactivated state, therefore firing frequency decreases
They increase inactivation state
This prevents propagation of the impulse

Question 6

What caution do you need to be wary of in carbamazepine and phenytoin?

Answer 6

Both induce CYP450, therefore increases metabolism of common drugs such as warfarin, COCP, corticosteroids, phenytoin, carbamazepine.
Therefore their plasma concentration decreases. (Incl itself).

Question 7

What do you need to wary of phenytoin regarding its pharmacokinetics?

Answer 7

It does not follow linear PKs when at therapeutic levels (it does when sub therapeutic).

Question 8

What type of seizures can phenytoin and carbamazepine be useful for?

Answer 8

Generalised tonic clonic, all partial.

Not good for absent.

Question 9

What monitoring is needed for most anti epileptic drugs?

Answer 9

Regular bloods- measuring free plasma conc (toxicity etc), bone profile

Question 10

Name 4 side effects of carbamazepine + phenytoin

Answer 10

Ataxia, drowsiness, dizziness
Variation in BP
N + V, rash, hyponatraemia

Gingival hyperplasia (phenytoin only)

Question 11

What is the rare, severe side effect of carbamazepine

Answer 11

Severe bone marrow suppression, resulting in neutropenia

Question 12

What drug is contraindicated for phenytoin and why?

Answer 12

Cimetidine

Increases plasma conc of phenytoin

Question 13

Name 4 benefits of Lamotrigine over other drugs?

Answer 13

Fewer ADRs, 
Rash, dizzy, ataxia, somnolence, nausea
Also safer in pregnancy 
Also useful in absent seizures too
No induction of CYP450, therefore fewer DDIs

Question 14

What is the mechanism of action of benzodiazepines?

Answer 14

Bind to their own site in GABA receptor.
Leads to increase of Cl- into the neurone, thus increasing the threshold for an action potential.

Positive allosteric effect, meaning when either one is bound, increases each others binding.

Question 15

What PKs do benzodiazepams follow?

Answer 15

Linear

Question 16

ADRs of benzodiazepines

Answer 16

Sedation, tolerance, aggression, confusion, impaired coordination, dependence, withdrawal, resp and CNS depression when stopped abruptly.

Question 17

What can be used to reverse a benzodiazepines overdose/simply reverse effects?

Answer 17

IV Flumazenil 300-600mcg.

Question 18

What are benzodiazepines used for in epilepsy?

Answer 18

Status epilepticus (Lorazepam, diazepam)
Abscence, short term use (clonazepam)

Question 19

What is the mechanism of action of valproate (in brief)

Answer 19

VGSCB, Ca2+ blocker, inhibition of GABA inactivating enzymes, stimuli of GABA synthesising enzymes (therefore more GABA)

Question 20

List 4 ADRs of valproate

Answer 20

Sedation, ataxia, tremor, weight gain, increase in transaminase LFTs
Rarely- liver failure

Question 21

List 3 main DDIs of valproate

Answer 21

Antidepressants typically inhibit action of valproate
Antipsychotics typically antagonise valproate as they lower convulsive threshold
Aspirin increases plasma conc of valproate due to competitive binding.

Question 22

How do you need to monitor valproate?

Answer 22

Plasma conc is not closely associated with efficacy

Therefore need to monitor for blood, metabolic and hepatic disorder

Question 23

What is the difference between benzodiazepines and barbiturates, regarding mechanism of action?

Answer 23

Benzodiazepines- increase frequency of Cl- channels

Barbiturates- increase duration of Cl- channel opening