Pharmacology of epilepsy

Question 1

Define epilepsy?

Answer 1

enduring predisposition to generate (recurrent unprovoked) epileptic seizures and the associated cognitive, psychological and social consequences

Question 2

Give examples of causes of provoked seizures?

Answer 2

• drugs

- head trauma

Question 3

To be diagnosed with epilepsy what must you have?

Answer 3

1) 2 unprovoked seizures (more than 24 hours apart)
2) 1 unprovoked seizure and more than 60% risk of further seizures
3) epilepsy syndrome (symptoms of epilepsy

Question 4

Are most people seizure free after taking anti-epileptics?

Answer 4

yes only 36% are considered parmacoresistant

Question 5

Are most people seizure free after taking anti-epileptics?

Answer 5

yes only 36% are considered pharmacoresistant

Question 6

What factors should be considered when choosing an AED?

Answer 6

• Type of seizures
• efficacy
• co-morbidities
• tolerability
• pharmacokinetics

Question 7

What are the three seizure types?

Answer 7

Focal onset
Generalised onset
Unknown onset

Question 8

What is focal onset seizure?

Answer 8

• starts in one area of brain at one point in time

Question 9

How will seizures in frontal lobe present?

Answer 9

• speech disturbance

- motor problems if in motor cortex

Question 10

How will seizures in parietal lobe present?

Answer 10

• sensory disturbance if in somatosensory cortex

Question 11

What are the different targets of the AED’s?

Answer 11

• GABA receptors, open channels resulting in inhibitory response of GABA, inactivating the neurone
• Glutamate receptors (AMPA & NMDA), block transmission reducing excitation

Question 12

What are the main anti-epileptic drugs?

Answer 12

Carbamazepine 
Phenytoin 
Sodium valproate 
lamotrigine 
Levetiracetam 
Topiramate

Question 13

What drugs should be given to those with absence and myoclonic seizures?

Answer 13

Lamotrigine or levetiracetam

- as these work for the seizure type and have least co-morbidities

Question 14

When is sodium valproate used?

Answer 14

• very efficacious
• but lots of side effects
• so used in drug resistant patients

Question 15

What are the problems associated with Carbamazepine?

Answer 15

Hepatic inducer of CYP3A4 so interacts with lots of other drugs
can also cause disturbance of liver function

Question 16

What are the side effects of Carbamazepine?

Answer 16

• Dose dependent: Diplopia, ataxia, sedation and fatigue
• fatigue, nausea, rash and GI disturbances (get with all AED’s)
• Bone marrow suppression, hypersensitivity, hepatic derangement and rash

Question 17

What is the MOA of carbamazepine?

Answer 17

Sodium channel blocker

Question 18

What is the MOA of phenytoin?

Answer 18

Sodium channel blocker

Question 19

What are the side effects of Phenytoin?

Answer 19

acute - ataxia, diplopia, nystagmus, rash, sedation at high levels
chronic - gym hyperplasia, coarse face, hirsutism, osteopenia, low folate and peripheral neuropathy
Exclusive to phenytoin - fever, rash, lymphadenopathy and teratogenic

Question 20

What are the problems with phenytoin?

Answer 20

• hepatic enzyme inducer so interacts widely with other drugs
• any enzyme inhibiting or inducing drugs will change levels of phenytoin

Question 21

What is the major issue with sodium valproate?

Answer 21

teratogenic - can’t give to pregnant women or those trying to get pregnant

Question 22

What is the MOA of sodium valproate?

Answer 22

sodium channel blocker, GABA and glutamate receptor actions

Question 23

What are the side effects of sodium valproate?

Answer 23

generally well tolerated 
most important is teratogenic
VALPROATE
Appetite inc + weight gain
Liver failure
Pancreatitis 
Reversible hair loss
Oedema 
Ataxia 
Teratogenicity, tremor and thrombocytopenia 
Encephalopathy

Question 24

What are the advantages of levetiracetam?

Answer 24

• few side effects
• no sig interactions
• almost no teratogenic properties

Question 25

What are the disadvantages of levetiracetam?

Answer 25

• side effects of irritability and behavioural changes make patients ‘not themselves’

Question 26

What are the side effects of levetiracetam?

Answer 26

• irritability
• anxiety
• fatigue
• dizziness
• behavioural changes
• bone marrow
• (rare) psychosis

Question 27

What is the MOA of lamotrigine?

Answer 27

sodium channel blocker

Question 28

What are the side effects of lamotrigine?

Answer 28

• Stevens-Johnson rash (important as can be fatal)
• insomnia
• less cognitive effects
• stabilises mood so good for patients with depression

Question 29

What are the interactions of lamotrigine?

Answer 29

• combined pill

- valproate

Question 30

What is the MOA of topiramate?

Answer 30

• sodium/calcium channel blocker

- GABA and Glutamate effects

Question 31

What are the side effects of topiramate?

Answer 31

• sedation
• anorexia
• weight loss
• psychiatric
• word finding difficulties
• Possibly teratogenic and rare kidney stones and glaucoma

Question 32

What anti-epileptic drugs are associated with weight gain?

Answer 32

• Valproate

- Topiramate

Question 33

What should be prescribed along with carbamazepine to maintain bone health?

Answer 33

Vitamin D

Question 34

What AEDs are most associated with mental health problems?

Answer 34

• Levetiracetam
• must discuss suicide risk
• some AEDs can interact with anti-depressants (most don’t)

Question 35

What other conditions can carbamazepine be used to treat?

Answer 35

Neuropathic pain (pain caused by damage to somatosensory system)

Question 36

What AEDs are used to treat bipolar disorder?

Answer 36

• carbamazepine
• lamotrigine
• valproic acid

Question 37

What AEDs are used to treat migraine?

Answer 37

Topiramate

Question 38

What AEDs are used to treat Trigeminal neuralgia?

Answer 38

Carbamazepine

Question 39

What AEDs are used to treat obesity?

Answer 39

topiramate

Question 40

What AEDs are used to treat anxiety?

Answer 40

clobazam

pregabalin