After the end of this lesson the learner should be able to; Classify types of seizures
Describe the types of drugs in the management of partial seizures.
Explain the mode of action of each of the drugs.
Explain the adverse drug reactions, clinical use & toxicities.
• Seizures are finite episodes of brain dysfunction resulting from an abnormal discharge of cerebral neurones
• Epilepsy is a chronic disorder, characterized by recurrent seizures
Partial seizures
• Simple partial seizures
• Complex partial seizure
• Partial seizures secondary
generalized
Tonic-clonic or grand mal seizure
• Absence seizures or the petit mal
• Tonic seizures
• Atonic seizure
• Clonic & myoclonic seizures
• Infantile spasms
– Phenobarbital (The drugs of choice for generalized tonic-clonic (grand mal) seizures
1. Phenytoin
1. Carbamazepine
2. Valproic acid
• or primidone) is considered to be an alternative agent in adults but to be a primary drug in infants
• Lamotrigine and topiramate are can also be used
• Available for oral and parenteral use
• A non-sedative antiseizure drug (can sedate at very high levels)
• Fosphenytoin; is a pro-drug of phenytoin that is more soluble and is available for parenteral use
• Block Na+, channels and inhibit
generation of rapidly repetitive action potentials
• Has preferential binding to and propagation of the inactivated state of the sodium channels, therefore, has a used dependent effect
• Others actions:
Alter membrane potential
centration of amino acids
Decrease synaptic release of glutamate
Enhance the release of GABA
• Rate and extent of absorption highly dependent on formulation; particle size and additives
• Absorption: Phenytoin sodium is almost completely absorbed orally
• Achieve Peak concentration in 3-12 hrs
• Absorption after IM is unpredictable & drug precipitates in the muscle- the route is not recommended
• Protein binding: Highly bound to plasma proteins (90%)
• Concentration in CSF is proportional to free plasma levels
• Distribution: It accumulates in the brain, liver, muscle and fat • Metabolism: metabolized to inactive
metabolite
• Excretion: in urine; a small proportion excreted unchanged
• Elimination is dose-dependent; at low levels, it obeys first-order kinetic
• Half-life is 12-36 hrs, average 24 hrs
• It takes 5-7 days to reach steady-state at low doses, & 4-6 wks at high doses
• Mainly related to protein binding or to metabolism
• Phenytoin can be displaced by other highly protein-bound drugs like phenylbutazone, sulphonamides
• Protein binding of phenytoin is decreased in renal disease
• Phenytoin has a high affinity for thyroid-binding globulin hence can give false thyroid function test result
• Diplopia & ataxia ( dose-related)
• Nystagmus
• Loss of smooth extraocular pursuit movement
• Gingival hyperplasia
• Hirsutism
• Skin rash
• Fever
• Skin lesions-rare
• coarse facial features,
• Mild peripheral neuropathy that manifests with diminished deep tendon reflexes in the lower extremities
• Abnormalities of Vitamin D metabolism leading to osteomalacia
• Read and make notes on carbamazepine and valproic acid under the following subheadings; Pharmacokinetics, Drug interaction and toxicities
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