Drugs used in the treatment of epilepsy Flashcards
At what age can sodium valproate be given?
Valproate can be safely used in children down to 1 month of age.
What kind of seizures can sodium valproate be used for?
Generalised, mixed and partial seizures
When is sodium valproate contraindicated?
Severe hepatic or renal failure
How does sodium valproate work?
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.
Where is valproic acid metabolised?
The liver
75% by the CYP450 system
What is valproic acid at room temperature?
Liquid fatty acid but it can be reacted with a base to form a solid salt.
How does valproic acid affect platelets?
Interferes with platelet aggregation and can cause blood disorders
How many days until valproic acid treatment is effective?
14 days
Can valproic acid be used to treat migraines?
Yes
What effect does phenytoin have on the enzyme intestinal conjugase?
It inhibits intestinal conjugase and this causes folate deficiency.
What is phenytoins half life?
6 - 24hrs
Is phenytoin a CYP450 enzyme inducer or inhibitor?
Inducer
What are the CVS effects of phenytoin?
Hypotension and arrhythmias so should be administered with cardiac monitoring if giving IV.
What effect does phenytoin have on blood glucose?
Phenytoin can cause hyperglycaemia & glycosuria due to insulin inhibition
How protein bound is phenytoin?
Highly protein bound, mainly to albumin
What kind of kinetics does phenytoin undergo?
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.
What does SEs does phenytoin toxicity cause?
Toxicity causes blurred vision, mydriasis and brisk tendon reflexes.
What is the oral bioavailability of phenytoin?
Bioavailability is good, but oral absorption is slow, variable & can be only partial.
Volume of distribution is approx 70% of body weight.
What kind of effect does phenytoin cause on FBC?
Phenytoin causes macrocytic, megaloblastic anaemia due to folate deficiency.
Is phenytoin antiarrhythmic?
It is a class Ib antiarrhythmic agent, like Lidocaine.
What effect does phenytoin have on thyroid function?
No effect.
But will cause falsely low TFTs after long term treatment.
What routes can phenytoin be given effectively?
Not effective IM
PO (slow)
IV
Is phenytoin carcinogenic?
No
What drug can be given to treat digoxin induced dysrhythmias?
Phenytoin
What enzyme metabolises phenytoin?
Hepatic microsomal enzymes
What SEs can phenytoin cause?
It can cause rash, horizontal gaze nystagmus, gum overgrowth, acne as well as blood disorders.
Is phenytoin still effective if given with the OCP?
Phenytoin is effective in the presence of the OCP but the contraceptive effect may not be effective due to enzyme induction
What effect does phenytoin have on excitable membranes?
Stabilises them
What is the half life of phenobarbital?
Phenobarbital is extremely long acting, with a half life of 50 - 100 hours or more.
What can phenobarbital be used to treat?
All seizures except absence
What is the protein binding of phenobarbital?
20-45% protein bound
What problems can phenytoin and carbamazepine cause in pregnancy?
Phenytoin is teratogenic and can cause Fetal Hydantoin Syndrome (like Carbamazepine).
What is fetal hydantoin syndrome?
FHS causes intra-uterine groth retardation, microcephaly, craniofacial abnormalities and limb defects
Is phenobarbital sedating?
Yes, but use has largely been superceded by benzodiazepines.
What does phenytoin do to sodium channels?
Phenytoin stabilises sodium channels in their inactive state
Where is phenytoin excreted?
In bile, but some is excreted renally
CAn phenytoin be used to treat trigeminal neuralgia?
Yes
Can sodium valproate cause tremors?
Yes
Does sodium valproate cause hair loss?
Yes, in 10% of people
Does phenytoin only rarely cause allergic reactions?
No, phenytoin can cause severe allergic reactions and must be given with vigilance.
Is carbamazepine safe in pregnancy?
No.
Carbamazepine can cause spina bifida & other neurodevelopmental problems after intrauterine exposure
What is the half life of carbamazepine?
25-65hrs
What effect does carbamazepine have on blood tests?
Carbamazepine can reduce serum sodium & WBC levels at normal drug levels, but also cause life-threatening loss of platelets.
Does carbamazepine increase the risk of lupus?
Lupus risk increases by nearly 90% (probably only in women)!
