ANTIEPLEPTICS
AnticonvulsantsEpilepsy
is a common neurological abnormality affecting about 1% of the human population. Epilepsy is a chronic, usually life-long disorder characterized by recurrent seizures or convulsions and usually, episodes of unconsciousness and/or amnesiaWhat is seizure
Seizures are finite episodes of brain dysfunction resulting from abnormal discharge of cerebral neurons.Types of seizures
classified as: general vs. focal seizures; seizures with or without loss of consciousness;The causes of seizures
Head trauma. Meningitis. Childhood fevers, Seizures often occur in hyperthermia (febrile seizures are very common in infants). Brain tumors. Degenerative diseases of the cerebral circulation.6- Toxic manifestation of the action of central nervous system (CNS) stimulants and certain other drugs. 7- Eclampsia, uremia, hypoglycemia. 8- frequently as a part of the abstinence syndrome of individuals physically dependent on CNS depressants.
Phenytoin
Discovered in 1938
Phenytoin Therapeutic uses
Generalized tonic–clonic seizures. partial seizures with complex symptoms.Mechanism of Action
enhance inactivation of voltage- gated sodium and calcium channel and limit the spread of electrical excitation by inhibiting sustained high-frequency firing of neurons.Pharmacokinetic
phenytoin absorption is slow but usually complete. Phenytoin is highly bound (about 90%) to plasma proteins. It displays zero-order (or saturation) kinetics in its metabolismAdverse effects of phenytoin
usually result from overdosage. 1- Nystagmus , ataxia, vertigo, and diplopia (cerebellovestibular dysfunction). 2- Higher doses lead to altered levels of consciousness and cognitive changes.Adverse effects of phenytoin
3- Idiosyncratic reactions may be seen shortly after therapy has begun. Skin rashes are most common. Exfoliative dermatitis or toxic epidermal necrolysis 4- Megaloplastic anemia occur because drug interferes with Vit B12 metabolism and hepatic necrosis.5- Gingival hyperplasia
Gingival hyperplesia
Gingival hyperplasiaGingival hyperplasia
occurs in up to 50% of patients.6 - Thickening of subcutaneous tissue, coarsening of facial features, and enlargement of lips and nose , are often seen in patients receiving long-term phenytoin
7 - phenytoin is Teratogenic in humans, but the mechanism is not clear.
CarbamazepineIs a tricyclic compound Closely related to Imipramine and other antidepressants.
Carbamazepine Mechanism of Action
Carbamazepine, like phenytoin, blocks sodium channels at therapeutic concentrations and inhibits high-frequency repetitive firing in neurons . It also acts presynaptically to decrease synaptic transmission.Carbamazepine Clinical Uses:
Drug of choice for both partial seizures and generalized tonic-clonic seizures ( not sedative). It can be used with phenytoin in many patients who are difficult to control. Very effective in Trigeminal neuralgia and other neuropathic pain. useful in mania (bipolar disorder).
Carbamazepine Adverse Effects
dose-related diplopia and ataxia. mild gastrointestinal upsets. Unsteadiness. idiosyncratic blood dyscrasias including fatal cases of a plastic anemia and agranulocytosis -The mild and persistent leukopenia. -The most common idiosyncratic reaction is an erythematous skin rash.Carbamazepine
The overall incidence of toxicity seems to be low at usual therapeutic doses.Drug Interactions
It induce the enzymes that metabolize other anticonvulsant drugs, including phenytoin, Primidone, phenobarbital, valproic acid, Clonazepam, and Ethosuximide.A common drug–drug interaction is between carbamazepine and the macrolide antibiotics erythromycinPhenobarbital
Is the oldest of the currently available anti seizure drugs (sedative effects).Phenobarbital Chemistry
The four derivatives of barbituric acid clinically useful as antiseizure drugs are: phenobarbital, mephobarbital, metharbital, primidoneMechanism of Action
The exact mechanism of action of phenobarbital is unknown. Phenobarbital binds to an allosteric regulatory site on the GABA A receptor. Phenobarbital also blocks excitatory responses induced by glutamate.
Clinical Use
Treatment of partial seizures and generalized tonic-clonic seizures, The drugs of choice for seizures only in infantsToxicity
Sedation Ataxia Nystagmus Vertigo Nausea and vomiting rashes Agitation and confusion Rebound seizures on discontinuanceValproic Acid
Sodium valproate, also used as the free acid; valproic acid, was found to have antiseizure properties Chemistry Valproic acid is one of a series of fatty carboxylic acids that have antiseizure activityMechanism of Action
reduces the propagation of abnormal electrical discharge in the brain. It may enhance GABA action at inhibitory synapses.Clinical Use
Treatment of myoclonic seizures. The drug diminishes absence seizures but is a second choice because of its hepatotoxic potential. Reduces the incidence and severity of tonic-clonic seizuresToxicity
Nausea and vomiting. Sedation, ataxia, and tremor. Hepatic toxicity may cause a rise in hepatic enzymes in plasma, which should be monitored frequently. It does not induce Cytochrome P-450 enzyme synthesis.
Rash and alopecia may occur Bleeding times may increase because of both thrombocytopenia and an inhibition of platelet aggregation. Valproic acid inhibits phenobarbital metabolism, thereby increasing circulating levels of that barbiturate.