Drugs used in the treatment of epilepsy

Question 1

At what age can sodium valproate be given?

Answer 1

Valproate can be safely used in children down to 1 month of age.

Question 2

What kind of seizures can sodium valproate be used for?

Answer 2

Generalised, mixed and partial seizures

Question 3

When is sodium valproate contraindicated?

Answer 3

Severe hepatic or renal failure

Question 4

How does sodium valproate work?

Answer 4

Sodium valproate acts by weakly blocking sodium ion channels. It inhibits GABA transaminase, which would deactivate gamma-Aminobutyric Acid (GABA) and may also stimulate GABA synthesis.

Question 5

Where is valproic acid metabolised?

Answer 5

The liver

75% by the CYP450 system

Question 6

What is valproic acid at room temperature?

Answer 6

Liquid fatty acid but it can be reacted with a base to form a solid salt.

Question 7

How does valproic acid affect platelets?

Answer 7

Interferes with platelet aggregation and can cause blood disorders

Question 8

How many days until valproic acid treatment is effective?

Answer 8

14 days

Question 9

Can valproic acid be used to treat migraines?

Answer 9

Yes

Question 10

What effect does phenytoin have on the enzyme intestinal conjugase?

Answer 10

It inhibits intestinal conjugase and this causes folate deficiency.

Question 11

What is phenytoins half life?

Answer 11

6 - 24hrs

Question 12

Is phenytoin a CYP450 enzyme inducer or inhibitor?

Answer 12

Inducer

Question 13

What are the CVS effects of phenytoin?

Answer 13

Hypotension and arrhythmias so should be administered with cardiac monitoring if giving IV.

Question 14

What effect does phenytoin have on blood glucose?

Answer 14

Phenytoin can cause hyperglycaemia & glycosuria due to insulin inhibition

Question 15

How protein bound is phenytoin?

Answer 15

Highly protein bound, mainly to albumin

Question 16

What kind of kinetics does phenytoin undergo?

Answer 16

Phenytoin follows saturatable first order kinetics which converts to zero order kinetics when the enzyme system is overwhelmed.

It has a narrow therapeutic index and blood levels are therefore monitored.

Question 17

What does SEs does phenytoin toxicity cause?

Answer 17

Toxicity causes blurred vision, mydriasis and brisk tendon reflexes.

Question 18

What is the oral bioavailability of phenytoin?

Answer 18

Bioavailability is good, but oral absorption is slow, variable & can be only partial.

Volume of distribution is approx 70% of body weight.

Question 19

What kind of effect does phenytoin cause on FBC?

Answer 19

Phenytoin causes macrocytic, megaloblastic anaemia due to folate deficiency.

Question 20

Is phenytoin antiarrhythmic?

Answer 20

It is a class Ib antiarrhythmic agent, like Lidocaine.

Question 21

What effect does phenytoin have on thyroid function?

Answer 21

No effect.

But will cause falsely low TFTs after long term treatment.

Question 22

What routes can phenytoin be given effectively?

Answer 22

Not effective IM

PO (slow)

IV

Question 23

Is phenytoin carcinogenic?

Answer 23

No

Question 24

What drug can be given to treat digoxin induced dysrhythmias?

Answer 24

Phenytoin

Question 25

What enzyme metabolises phenytoin?

Answer 25

Hepatic microsomal enzymes

Question 26

What SEs can phenytoin cause?

Answer 26

It can cause rash, horizontal gaze nystagmus, gum overgrowth, acne as well as blood disorders.

Question 27

Is phenytoin still effective if given with the OCP?

Answer 27

Phenytoin is effective in the presence of the OCP but the contraceptive effect may not be effective due to enzyme induction

Question 28

What effect does phenytoin have on excitable membranes?

Answer 28

Stabilises them

Question 29

What is the half life of phenobarbital?

Answer 29

Phenobarbital is extremely long acting, with a half life of 50 - 100 hours or more.

Question 30

What can phenobarbital be used to treat?

Answer 30

All seizures except absence

Question 31

What is the protein binding of phenobarbital?

Answer 31

20-45% protein bound

Question 32

What problems can phenytoin and carbamazepine cause in pregnancy?

Answer 32

Phenytoin is teratogenic and can cause Fetal Hydantoin Syndrome (like Carbamazepine).

Question 33

What is fetal hydantoin syndrome?

Answer 33

FHS causes intra-uterine groth retardation, microcephaly, craniofacial abnormalities and limb defects

Question 34

Is phenobarbital sedating?

Answer 34

Yes, but use has largely been superceded by benzodiazepines.

Question 35

What does phenytoin do to sodium channels?

Answer 35

Phenytoin stabilises sodium channels in their inactive state

Question 36

Where is phenytoin excreted?

Answer 36

In bile, but some is excreted renally

Question 37

CAn phenytoin be used to treat trigeminal neuralgia?

Answer 37

Yes

Question 38

Can sodium valproate cause tremors?

Answer 38

Yes

Question 39

Does sodium valproate cause hair loss?

Answer 39

Yes, in 10% of people

Question 40

Does phenytoin only rarely cause allergic reactions?

Answer 40

No, phenytoin can cause severe allergic reactions and must be given with vigilance.

Question 41

Is carbamazepine safe in pregnancy?

Answer 41

No. Carbamazepine can cause spina bifida & other neurodevelopmental problems after intrauterine exposure

Question 42

What is the half life of carbamazepine?

Answer 42

25-65hrs

Question 43

What effect does carbamazepine have on blood tests?

Answer 43

Carbamazepine can **reduce serum sodium & WBC levels** at normal drug levels, but also cause **life-threatening loss of platelets.**

Question 44

Does carbamazepine increase the risk of lupus?

Answer 44

Lupus risk increases by nearly 90% (probably only in women)!