Anti-epileptic drugs

Question 1

Management of epilepsy:

Name 3 drugs target the inactive (intermediate) state of Na channels

Answer 1

Phenytoin
Carbamazepine
Sodium valproate

Question 2

Which Na channels should not be used in absence seizures, as they may exacerbate these types of seizures? [2]

Answer 2

Phenytoin
Carbamazepine

Question 3

Explain the DDI effect that phenytoin and carbamazepine have on other drugs [3]

Answer 3

Phenytoin and carbamazepine:
* both induce metabolizing liver enzymes.
* These liver enzymes are involved of transformation of many drugs / increased metabolism
* which may result in the loss of efficacy of other drugs (other drugs may need an increase in dose as a response)

Question 4

Explain what is meant by phenytoin’s dose dependent / zero order / saturation kinetics characteristics

Answer 4

Most drugs have first order elimination (rate of elimination is proportional to the plasma concentration).

However, with phenytoin, as the dose of drug is increased, because of saturated enzymes, the rate of elimination is no longer proportional to the concentration of drug in the plasma (i.e. there is saturation & so only a finite amount can be eliminated).

When this happens, small increases in drugs can cause large increases in plasma concentration

Question 5

Antiepileptic drugs:

Name two calcium channels that are used as anti-epileptic drugs [2]

Answer 5

Ethosuximide

Gabapentin / pregabalin (in the PBL)

Question 6

Gabapentin and pregablin target which subunit of the calcium channel?

Answer 6

alpha 2 delta subunit

Question 7

AEDs

What type of drug class does clonazepam belong to? [1]

State clonazepams MoA [1]

Answer 7

Benzodiazepines - GABA(A) receptor

positive allosteric modulators: enhance the frequency of GABA channel opening. (more GABA; causes more inhibition)

Question 8

AEDs

What type of drug class does phenobarbitone and stiripentol belong to? [1]

What is MoA? [1]

Answer 8

phenobarbitone and stiripentol:

• Drug class: Barbiturates: GABAA receptor positive allosteric modulators
• . Phenobarbitone (leads to microsomal enzyme induction)
  Enhances the duration of GABA channel opening. (more GABA; causes more inhibition

Question 9

AEDs

Which drug inhibits GABA metabolism? [1]

Answer 9

Vigabatrin

Question 10

Which drug inhibits GABA reuptake via the GAT-1 transporter? [1]

It is generally used as an add-on therapy

Answer 10

Tiagabine

Question 11

What happen to 1/3rd of epilepsy patients with AEDs? [1]

Answer 11

1/3rd become treatment resistant (if so, reassess drug choice)

Question 12

Status elipeticus is a medical emergency. Name two drugs used to treat this conditon [2]

Answer 12

Lorezepam (IV)
Diazepam (IV)

Question 13

Alternatives to AEDs

Name 3 surgical procedures that could be used to treat epilepsy [3]

Answer 13

Lobe resection
Corpus callasotomy (reduces propogation of seizures from one cerebral hemisphere to the next)
Functional hemispherectomy

Question 14

Name 5 consequences of chronic epilepsy beyond seizures [5]

Answer 14

Suffer from tiredness, mood problems, depression, sexual problems, physical activity problems

Question 15

Alternatives to AEDs

Name a type of diet that could help epilepsy [1]

Name a drug class for a potential new AED [1]

Answer 15

Keto diet

Cannabidiol

Question 16

How may it be possible to one day predict seizures? [1]

Answer 16

Long term ambulatory EEG to predict seizures

Question 17

Which of the following type of channel does carbamazepine target?

Ca2+
GABA
Na+
Glutamate

Answer 17

Which of the following type of channel does carbamazepine target?

Ca2+
GABA
Na+
Glutamate

Question 18

Which of the following type of channel does pregabalin target?

Ca2+
GABA
Na+
Glutamate

Answer 18

Which of the following type of channel does pregabalin target?

Ca2+
GABA
Na+
Glutamate

Question 19

What is the MoA of Levetiracetam? [1]

Answer 19

Binds synaptic vesicle protein SV2A causing a reduction in conduction in neurones

Question 20

Name a drug that predominately blocks Na+ channels, but also acts on Ca2+ channels and causes the presynaptic inhibition of glutamate release.

Answer 20

Lamotrigine

(hint: tri gated?)

Question 21

AEDs

Focal Seizures Treatment:

First line: [] or []
Second line: [] or []

Answer 21

First line: carbamazepine or lamotrigine
Second line: sodium valproate or levetiracetam

Question 22

Management of tonic-clonic seizures is with:

First line: []
Second line: [] or []

Answer 22

Management of tonic-clonic seizures is with:

First line: sodium valproate
Second line: lamotrigine or carbamazepine

Question 23

Which drugs are used for absence seizures? [2]

Answer 23

ethosuximide, sodium valproate

Question 24

Myoclonic seizures:

First line: [1]
Other options: [3]

Answer 24

First line: sodium valproate
Other options: lamotrigine, levetiracetam or topiramate

Question 25

Describe the MoA of sodium channel active drugs like phenytoin and carbamazepine [1]

Answer 25

Stabilises Na+ channels inactivated state to decrease excitability

Question 26

Explain MoA of Sodium valproate [3]

Answer 26

Potentiates GABA receptor;
Stops breakdown of GABA
Blocks voltage gated sodium channels and T-type calcium channels