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.

INTRODUCTION

• Seizures are finite episodes of brain dysfunction resulting from an abnormal discharge of cerebral neurones
• Epilepsy is a chronic disorder, characterized by recurrent seizures

Classification of seizures

Partial seizures

• Simple partial seizures
• Complex partial seizure
• Partial seizures secondary
generalized

Generalized seizures

Tonic-clonic or grand mal seizure

• Absence seizures or the petit mal
• Tonic seizures
• Atonic seizure
• Clonic & myoclonic seizures
• Infantile spasms

1. Drugs for Generalized Tonic-Clonic Seizures

– 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

1. PHENYTOIN

• 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

MOA

• 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

Cont…

• 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

Drug interaction

• 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

ADRs

• Diplopia & ataxia ( dose-related)
• Nystagmus
• Loss of smooth extraocular pursuit movement
• Gingival hyperplasia
• Hirsutism
• Skin rash
• Fever
• Skin lesions-rare

ADRs 20 to Long term therapy

• 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

ASSIGNMENT

• Read and make notes on carbamazepine and valproic acid under the following subheadings; Pharmacokinetics, Drug interaction and toxicities