Phenytoin (Diphenyl-Hydantoin) - PDF

ANTI EPILEPSY DR A.E 1- Phenytoin (Diphenyl-Hydantoin, Epanutin) Kinetics: 1- Absorption: a- Oral: - Irritant (Used after meals) & affected by particle shape & size (Polymorphism). b- I.M. Irregular absorption. c- Slow I.V. in Status epilepticus. 2- Distribution All-over the body. Highly bound t...

ANTI EPILEPSY DR A.E 1- Phenytoin (Diphenyl-Hydantoin, Epanutin) Kinetics: 1- Absorption: a- Oral: - Irritant (Used after meals) & affected by particle shape & size (Polymorphism). b- I.M. Irregular absorption. c- Slow I.V. in Status epilepticus. 2- Distribution All-over the body. Highly bound to plasma albumin (80-90%) 3- Metabolized by Hepatic Microsomal Enzymes glucuronic acid: Hydroxylation then conjugation with a- Small dose First-Order Kinetics Constant t ½ b- Large dose Zero-Order Kinetics t ½ with Dose. Uses : 1- Grand Mal Epilepsy & Partial seizures (No Sedation) 2- Status Epilepticus (15 20 mg / kg body weight Slow I.V.). 3- Treatment of Trigeminal neuralgia. 4- Class-1 Group-B Anti-Arrhythmic Useful in treatment of Ventricular arrhythmia with Heart Block Drug of Choice in Digitalis-Induced arrhythmia * Adverse Effects of Phenytoin: 1- CNS: Confusion & Hallucinations. Ataxia, Nystagmus & Vertigo. 2- GIT: Gastric irritation (highly alkaline) Used after meals. 3-Blood: Megaloblastic anemia& Hypoprothrombinemia 4-Bone: Osteomalacia. 5- Hirsutism (Androgenic effect). 6- Hepatotoxicity. 7- Hypersensitivity 8- Hormones Lymphadenopat Release of A.D.H. & Insulin Hyperglycemia. 9- Gum (Gingival) Hyperplasia especially in Children Irreversible Consult Dentists. 10- During Pregnancy: a- First trimester Teratogenic Fetal Hydantoin Syndrome b- Before labor Hypoprothrombinemia in baby Bleeding Hare lip & Cleft palate Prevented & treated by Vit-K 2 ANTI EPILEPSY DR A.E - Drug Interactions: a- Phenytoin Hepatic Microsomal Enzyme Inducer: - Its own metabolism Tolerance & Failure of Anti-Epileptic activity. - Metabolism of Other Anti-Epileptic drugs e.g. Barbiturates & Carbamazepine. - Metabolism of other drugs e.g. Oral contraceptives. - Metabolism of Folic Acid & Its intestinal absorption Megaloblastic anemia & Toxicity of Methotrexate (Folate antagonist). - Metabolism of Vit D Hypocalcemia Osteomalacia. - Metabolism of Vit K Hypoprothrombinemia. b- HME Inducers e.g. Phenobarbitone & Carbamazepine c- HME Inhibitors e.g. Valproate, Cimetidine & Isoniazide Metabolism of Phenytoin. Metabolism of Phenytoin. d- Phenytoin displaces Thyroxin & Tricyclic Anti-Depressants from plasma proteins. e- Aspirin, Sulfa & Valproate Displace phenytoin from plasma proteins. Fosphenytoin : the prodrug form of phenytoin with the advantage over phenytoin: 1-less vascular irritation 2-ability to be injected faster 3-greater physical compatibility with IV and IM solutions to dilute it 4-can be given IM 3