VPT 321: Veterinary Neuropharmacology (2+1)

ANTICONVULSANTS 

Epilepsy is a condition frequently reported in dogs and cats. Seizure is the term used for altered brain function, loss of consciousness and increased muscle tone or movement, altered sensations and other neurological changes. Convulsive seizure is the term used for spastic muscle movement with unconsciousness. Convulsions may be due to hypoxia, hypoglycaemia, hypocalcaemia, poisoning by lead, strychnine or organophosphorous compounds and infectious disease like distemper, hydrocephalus, neoplasia or parasitic migration involving the central nervous system.

The pathogenesis of seizures include:

• Altered balance of excitation and inhibition
• Altered resting membrane potential
• The paroxysmal shift: damaged group of neurons will suddenly shift into a depolarized state generating a burst of action potentials

An ideal drug used for the maintenance of antiepileptic action should have

• Long duration of action
• No metabolic tolerance due to liver enzyme induction effect
  • Good oral absorption and subsequent blood brain barrier penetration
  • Effectiveness at subsedative dose rates
  • No major side effects
• An ideal drug used in status epilepticus should have
  • Effective centrally acting muscle relaxant properties
  • Rapid onset of action
  • Suitability for intravenous or intramuscular administration
• For treating any epilepsy a suitable anticonvulsant drug is used

Anticonvulsant drugs

• Phenobarbitone – This was the first drug to be used as an antiepileptic. It is the drug of choice in dogs and cats. Has a slow onset but, longer duration of action. It is a potent inducer of liver microsomal enzymes and is highly protein bound. It is administered once daily.
• Primidone – This is 2-deoxy analog of phenobarbitone. Not preferred to phenobarbitone as hepatotoxicity has been reported.
• Diphenylhydantoin – This is a membrane stabilizing agent used as antiarrythmic and anticonvulsant. Intravenously used in status epilepticus. For general clinical use it is of limited value because of poor absorption and high hepatotoxicity.
• Trimethadione – The major side effect of this drug is photophobia as observed in distemper and hence is not commonly used.
• Valproic acid – This drug has a short half-life in the dog and hence it is not used.
• Carbamazepine – Elimination is too rapid in the dog.
• Diazepam – Drug of choice in status epilepticus. Act by enhancing the inhibitory effects of GABA in the CNS. Has minimal depressant actions on the cardiovascular and respiratory systems. More rapid penetration of the CNS is observed. Metabolic tolerance also occurs readily.
• Clonazepam – Metabolic tolerance does not occur. Passage into the CNS is rapid. But a decreased effectivenesss is noticed with continuous treatment.
• Bromides – Ammonium, potassium and sodium bromide are used to control convulsions.

Note: Drugs contraindicated in epilepic patients – Reserpine, phenothiazines, butyrophenones, metaclopramide, fluorinated quinolones, morphine, methylxanthines and chloramphenicol.