Epilepsy

Epilepsy

1. Partial Seizures

   • May lead to Secondary Generalized Serizure
   • Simple
     • Without alteration of conciousness
   • Complex
     • With alteration of consciousness
   • Secondarily Generalized Seizures
     • Loss of consciousness. Involves both hemispheres. Tonic (extending rigidity) and clonic (jerking extremities) phases
   • Medication
     • Carbamazepine
       • Fewer side-effects than phenytoin Well absorbed Strong enzyme-inducing agent- many interactions with other drugs 
       • Side effects include sedation, ataxia, mental disturbances, mild generalised erythematous rash and water retention
     • Valproate
       • Increases GABA by: (i) Weak inhibitor of enzymes that inactivate GABA, such as GABA transaminase. (ii) May stimulate synthesis of GABA (iii) May decrease GABA turnover (iv) weak blocker of Na+ channels (v) May block NMDA-mediated responses
       • • Side effects include baldness, teratogenicity, weight gain and liver damage - liver function should be managed • Valproate has metabolic effects and increases plasma lamotrogine levels • There may be an increased risk of poly-cystic-ovary syndrome associated with valproate
     • Phenytoin
       • Acts mainly by block of Na+ channels • Metabolism of phenytoin shows the characteristic of saturation • Range of plasma concentration for effectiveness prior to the appearance of side effects is ~40-100 μmol/l
       • Side effects begin to appear at plasma concentrations of ≥100 μmol/l and severe reactions at plasma concentrations of ≥150 μmol/l) Side effects include confusion, gum hyperplasia, skin rashes, anaemia and teratogenesis 

2. Primarily Generalized Seizures

   • Absence (Petit Mal)
     • Brief interruption of consciousness <10 seconds
     • Medication
       • Ethosuximide
         • Mechanisms of action: Blocks of T-type Ca2+ channels • Side effects include nausea and anorexia • Cautions include avoiding abrupt withdrawal, hepatic and renal impairment
       • Lamotrigine
       • Valproate
   • Tonic-clonic (Grand Mal)
     • Sequences of tonic and clonic phases
     • Medication
       • Valproate
       • Carbamazepine
       • Lamotrigine
         • Mechanism of action: -Blocker of Na+ channels -Inhibits the release of glutamate • Effective in treating absence epilepsy • Side effects include sedation, dizziness, ataxia and skin rashes (Stevens-Johnson syndrome) • Cautions include close monitoring in the effect of skin rashes, consideration for withdrawal
       • Phenytoin
   • Myclonic
     • Sudden involuntary muscle contraction
   • Atonic
     • Loss of muscle tone

3. Status Epilepticus

   • Continuous seizures lasting at least 30 minutes.
   • Medication
     • Lorazepam
       • High potency benzodiazepine  •Tolerance and dependance can develop from long term administration •Mechanism of action: positive allosteric modulator of GABA(A)receptors •Side effects include sedation and withdrawal symptoms
     • Diazepam
       • Tolerance can develop with long term administration • Mechanism of action: positive allosteric modulator of GABA(A) receptors • Side effects include sedation and withdrawal symptoms
     • Clonazepam
       • Tolerance can develop •Mechanism of action: positive allosteric modulator of GABA(A)receptors •Side effects include sedation and withdrawal symptoms