Phenytoin-antiepilleptic drug and its pharmacology

Description:-

Matched Synonyms:-  Diphenylhydantoin 

An anticonvulsant that is used in a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.

This compound belongs to the class of organic compounds known as phenylhydantoins. These are heterocyclic aromatic compounds containing an imiazolidinedione moiety substituted by a phenyl group.

Pharmacodynamics:-

Phenytoin is an antiepileptic drug which can be useful in the treatment of epilepsy. The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. Phenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of tonic-clonic (grand mal) seizures. Phenytoin acts to dampen the unwanted, runaway brain activity seen in seizure by reducing electrical conductance among brain cells. It lacks the sedation effects associated with phenobarbital. There are some indications that phenytoin has other effects, including anxiety control and mood stabilization, although it has never been approved for those purposes by the FDA. Phenytoin is primarily metabolized by CYP2C9.

Pharmacokinetics:-

Absorption:- Bioavailability 70-100% oral, 24.4% rectal. Rapid rate of absorption with peak blood concentration expected in 1½ to 3 hours.

Protein binding:- Highly protein bound, 90%

Metabolism:- Primarily hepatic. The majority of the dose (up to 90%) is metabolized to 5-(4'-hydroxyphenyl)-5-phenylhydantoin (p-HPPH). This metabolite undergoes further glucuronidation and is excreted into the urine. CYP2C19 and CYP2C9 catalyze the aforementioned reaction. 

Side Effects:-

• Headache
• Nausea
•  Vomiting
•  Constipation
•  Dizziness
• Feeling of spinning
•  Drowsiness
•  Trouble sleeping or nervousness
• Phenytoin may cause swelling and bleeding of the gums

Uses:-

Phenytoin is used to prevent and control seizures (also called an anticonvulsant or antiepileptic drug). It works by reducing the spread of seizure activity in the brain.

Drug Interactions:-

1. 2-mercaptobenzothiazole + phenytoin = The serum concentration of Phenytoin can be increased when it is combined with 2-mercaptobenzothiazole.

2. 3,4-Methylenedioxyamphetamine  + phenytoin = The serum concentration of Phenytoin can be decreased when it is combined with 3,4-Methylenedioxyamphetamine.

3. 3,4-Methylenedioxymethamphetamine  + phenytoin = The serum concentration of Phenytoin can be decreased when it is combined with 3,4-Methylenedioxymethamphetamine.

4. 4-Androstenedione  + phenytoin = The serum concentration of 4-Androstenedione can be decreased when it is combined with Phenytoin.

5. 7-Nitroindazole  + phenytoin = The risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Phenytoin.

6. Abiraterone  + phenytoin = The serum concentration of Abiraterone can be decreased when it is combined with Phenytoin.

7. Abiraterone  + phenytoin = The serum concentration of Phenytoin can be increased when it is combined with Abiraterone.

8. Aceclofenac  + phenytoin = The metabolism of Aceclofenac can be increased when combined with Phenytoin.

9. Acenocoumarol  + phenytoin = Phenytoin may increase the anticoagulant activities of Acenocoumarol.

REFERENCE:-Tripathi K D"Essential of medical pharmacology",7th edition ,page no-412,413-15,421,422,423,424