ANTICONVULSANTS
Seizures can be controlled if not completely treated by various drugs known as Anticonvulsants mentioned below.
1.Phenytoin (Dilantin)
2.Carbamazepine
3.Phenobarbital
4.Pirimidone
5.Valproic Acid
6.Ethosuximide
7.Benzodiazepine
8.Gabapentin
9.Lamotrigine
1.Phenytoin (Dilantin)
Phenytoin is used in treating tonic/clonic seizures and partial seizures. Chemically it is a hydantoin derivative.
Phenytoin is not effective in treating Absences.
Used in treating Status Epilepticus by intravenous route as an adjunct with diazepam.
Phenytoin is acting by blocking voltage-gated sodium channels and thereby prevent the neurons to get depolarized sufficiently to excite an action potential.
Kinetics and Route
Phenytoin can be administered either by intravenous and oral routes.
Since the absorption through the GI system is slow the oral route may have a longer gestation period to reach the required effects pharmacodynamically.
In contrast the intravenous route is rapid and reaches the required effect within minutes and lasts for 24 hours.
Phenytoin is metabolized in the liver by hydroxylation by the endometrial CYP-450 enzymes such as CYP-3A4 and CYP-2-C19. Watch for toxicity if these two enzymes induced by phenytoin get consumed completely.
Side Effects
1.Gingival Hyperplasia-A major toxicity in which there is a painful enlargement of teeth gum. Folic acid supplementation is recommended
2. Megaloblastic Anemia-Because phenytoin interferes with folic acid metabolism. Folic acid supplementation is required.
3.Hirsutism-Unwanted growth of hair.
4.Diminished deep tendon reflexes in the extremities.
5.Stevens-Jonson Syndrome-Severe skin rashes with cell necrosis with fever and usually a life-threatening reaction.
6.CNS depression
7.Endocrine reactions-Diabetes Insipidus(Watery Urine), Hyperglycemia, glycosuria, and osteomalacia(bone weakness)
Drugs Interactions
The following three drugs are competing with phenytoin for the enzyme CYP-450 successfully, by decreasing its metabolism and thereby increasing its plasma concentration.
1.Chloramphenicol-Anti typhoid
2.Isoniazid-Anti T.B.
3.Cimetidine.-Antihistamine to reduce hyperacidity
Dosage adjustment should be necessary when giving Phenytoin concomitantly with the above drugs.
Carbamazepine by inducing rapid metabolism of phenytoin decreases its plasma concentration. Dosage adjustment of phenytoin is important accordingly if given along with carbamazepine.
Use in Pregnancy and Lactation
Phenytoin is a teratogenic drug as it can cross into the placenta and milk and hence it should not be given during pregnancy and lactation as serious reactions such as prenatal growth deficiencies, congenital malfunctions such as the cleft palate and heart malfunctions may occur.
2.Carbamazepine (Tegretol)
Carbamazepine is a neuroleptic drug that can be used as an antipsychotic agent and to relieve neuropathic pain.
Carbamazepine is effective as well as phenytoin and valproic acid in the treatment of grand mal and petit mal as a drug of choice but not in treating absence seizures and myoclonic seizures.
Mechanism of Action
Very similar to phenytoin
Metabolism and Kinetics
Similar to phenytoin but given orally only
metabolized by the CYP-450 hepatic enzyme system similar to phenytoin but successfully compete with it.
Drug Interactions
The following drugs are competing successfully for CYP-450 enzyme with greater affinity than carbamazepine and hence they increase the carbamazepine plasma level by inhibiting its metabolism.
1.Erythromycin-Antibiotic
2.Isoniazid-Anti-T.B.
3.Propoxyphene-A pain killer
4.Verapamil-Calcium Channel Blocker for B.P
5.Cimetidine-A histamine H-2 receptor blocker used for reducing acid secretion in the stomach.
Hence dosage should be adjusted accordingly.
Side Effects
1. Acutely can cause respiratory depression and coma
2.Liver toxicity-Require frequent liver tests.
3.Aplastic anemia-Lack of blood cells formation due to bone marrow and erythropoietic stem cells damage
4.Agranulocytosis-A deficiency of granulocytes in the blood.
5.Drowsiness
6.Ataxia-Loss of full control of body movements.
7.Nystagmus-Involuntary movements of eyeballs.
3Phenobarbital (Luminol)
Chemically phenobarbital is a barbituric acid derivative.
Mechanism
Phenobarbital enhances the action of GABA at its receptors and thereby inhibiting the neuronal excitation.
Uses
1.Drug of choice for treating febrile seizures.
2.Used to treat grand mal in children
3.Partial seizures
Metabolism and Kinetics
Absorbed well by the oral route. Three fourth of the drug is metabolized in the liver.
It is a potent inducer of the CYP-450 enzyme in the liver.
Care should be taken when given along with any drug metabolized by or inducing this enzyme.
The metabolites are excreted in the urine.
Side Effects
1.Sedation
2.Nystagmus
3.Psychotic reactions
4.Allergic reactions such as serious Stevens-Jonson syndrome
5. Overdosage may result in respiratory depression, coma, and death.
Will be continued.....
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