Anti-Epileptic Drugs

They are divided into 3 categories, according to whether they block Na+, Ca2+ or boost GABA receptors.

Na+ channel antagonists:

These agents block sodium channels in the CNS by binding and prolonging inactivated state of channel
– Their action is use dependent, so only active during seizures characterized by excessive neural activity
– They have teratogenic potential and so should be reduced or stopped during pregnancy.

Phenytoin

This has a low therapeutic index with many adverse side effects

Side effects
  • These can be remembered with the acronym PHENYTOIN:

– P450 enzyme inducer
– H
irsutism
– E
nlarged gums (most common side effect)
– N
ystagmus
– Y
ellow browning of skin
– T
eratogenicity ➔ leads to foetal hydantoin syndrome (cleft lip/palate, microcephaly)
– O
steomalacia ➔ Leads to excessive Vitamin D metabolism
– I
nterference with B12 ➔ Anaemia
– N
europathy

Carbamazepine

This is the drug of choice for treating trigeminal neuralgia and partial seizures 

Side effects
  • These can be remembered with the acronym CARBA-MEAN

– Confusion
– A
taxia
– R
ashes (Stevens-Johnson Syndrome)
– B
lurring of vision
– A
granulocytosis
– M
arrow suppression
– E
nzyme (P450 inducer)
– A
DH release (causes SIADH)
– N
eural tube defects (can worsen absence/myoclonic seizures)

Valproic Acid

This is a Na+ channel antagonist that helps to increase GABA activity

Side effects
  • These can be remembered with the acronym VALPROATE

– Vomiting
– A
ppetite up
– L
iver toxicity
– P
ancreatitis
– R
etention of weight
– O
edema
– A
lopecia
– T
eratogenic (NTDs)
– E
nzyme (P450) inhibitor

 Lamotrigine+Topiramate+Levetiracetam(Cepra)

 These are more examples of sodium channel blockers which have anti-epileptic activity. 

Side effects
  • Lamotrigine is associated with Stevens-Johnson syndrome
  • Levetiracetam can lead to depression and suicidal thoughts

Ca2+ Channel antagonists

e.g. Ethosuximide

It is the drug of choice in absence seizures, which selectively inhibits T-type calcium channels  

Benzodiazepines/Phenobarbital

These are the first choice for status epilepticus

ANTI-MIGRAINE DRUGS

In migraine, there is an increase in cerebral activity which releases 5-HT.
– It activates the endothelium by binding 5-HT2 receptors causing vasodilation + sensitizing nerve endings
– 5-HT1D/1B activation inhibits this vasodilation and inflammation of meninges

Triptans

e.g. Sumatriptan, Naratriptan

These are 5-HT1D/1B agonists which cause vasoconstriction, used to treat acute attacks of migraine
– They are most effective if given at the start of the headache, instead of when the aura begins. 

Side effects
  • “Triptan sensations” – tingling, heat, tightness, pressure symptoms
  • Coronary vasospasm so not used in patients with CAD or cerebrovascular disease

Methysurgide/Pizotifen

5-HT2 receptor antagonists which is used in the prophylaxis of migraine

Side effects
  • Methysurgide causes retroperitoneal fibrosis so rarely used

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