Comital - General Information
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. Comital has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.
Pharmacology of Comital
Comital 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. Comital reduces the maximal activity of brain stem centers responsible for the tonic phase of tonic-clonic (grand mal) seizures. Comital acts to damp 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.
Comital for patients
Patients taking phenytoin should be advised of the importance of adhering strictly to the prescribed dosage regimen, and of informing the physician of any clinical condition in which it is not possible to take the drug orally as prescribed, eg, surgery, etc.
Patients should also be cautioned on the use of other drugs or alcoholic beverages without first seeking the physician's advice.
Patients should be instructed to call their physician if skin rash develops.
The importance of good dental hygiene should be stressed in order to minimize the development of gingival hyperplasia and its complications.
Do not use capsules which are discolored.
There are many drugs which may increase or decrease phenytoin levels or which phenytoin may affect. Serum level determinations for phenytoin are especially helpful when possible drug interactions are suspected. The most commonly occurring drug interactions are listed below:
1. Drugs which may increase phenytoin serum levels include: acute alcohol intake, amiodarone, chloramphenicol, chlordiazepoxide, diazepam, dicumarol, disulfiram, estrogens, H2-antagonists, halothane, isoniazid, methylphenidate, phenothiazines, phenylbutazone, salicylates, succinimides, sulfonamides, tolbutamide, trazodone.
2. Drugs which may decrease phenytoin serum levels include: carbamazepine, chronic alcohol abuse, reserpine, and sucralfate. Moban brand of Molindone Hydrochloride contains calcium ions which interfere with the absorption of phenytoin. Ingestion times of phenytoin and antacid preparations containing calcium should be staggered in patients with low serum phenytoin levels to prevent absorption problems.
3. Drugs which may either increase or decrease phenytoin serum levels include: phenobarbital, sodium valproate, and valproic acid. Similarly, the effect of phenytoin on phenobarbital, valproic acid and sodium valproate serum levels is unpredictable.
4. Although not a true drug interaction, tricyclic antidepressants may precipitate seizures in susceptible patients and phenytoin dosage may need to be adjusted.
5. Drugs whose efficacy is impaired by phenytoin include: corticosteroids, coumarin anticoagulants, digitoxin, doxycycline, estrogens, furosemide, oral contraceptives, quinidine, rifampin, theophylline, vitamin D.
Drug/Laboratory Test Interactions
Phenytoin may cause decreased serum levels of protein-bound iodine (PBI). It may also produce lower than normal values for dexamethasone or metyrapone tests. Phenytoin may cause increased serum levels of glucose, alkaline phosphatase, and gamma glutamyl transpeptidase (GGT).
Phenytoin is contraindicated in those patients who are hypersensitive to phenytoin or other hydantoins.
Additional information about Comital
Comital Indication: For the control of generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery.
Mechanism Of Action: Comital acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. By promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of post-tetanic potentiation at synapses. Loss of post-tetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas.
Drug Interactions: Not Available
Food Interactions: Avoid alcohol.
Take with food.
Do not take calcium, aluminum, magnesium or Iron supplements within 2 hours of taking this medication.
Generic Name: Phenytoin
Synonyms: 5,5-Dwufenylohydantoina; Difenilhidantoina [Spanish]; Diphenylhydantoine [French]; Diphenylan Sodium; Diphenylhydantoin; Diphenylhydatanoin; DPH; Fenitoina [INN-Spanish]; Phenytoin Sodium; Phenytoine; Phenytoine [INN-French]; Phenytoinum [INN-Latin]; 5,5-diphenylhydantoin; Dihydantoin
Drug Category: Anticonvulsants
Drug Type: Small Molecule; Approved
Absorption: Bioavailability 70-100% oral, 24.4% for rectal and intravenous administration. Rapid rate of absorption with peak blood concentration expected in 1½ to 3 hours.
Toxicity (Overdose): Oral, mouse: LD50 = 150 mg/kg; Oral, rat: LD50 = 1635 mg/kg. Symptoms of overdose include coma, difficulty in pronouncing words correctly, involuntary eye movement, lack of muscle coordination, low blood pressure, nausea, sluggishness, slurred speech, tremors, and vomiting.
Protein Binding: Highly protein bound
Biotransformation: Primarily hepatic
Half Life: 22 hours (range of 7 to 42 hours)
Dosage Forms of Comital: Liquid Intravenous
Chemical IUPAC Name: 5,5-di(phenyl)imidazolidine-2,4-dione
Chemical Formula: C15H12N2O2
Phenytoin on Wikipedia: https://en.wikipedia.org/wiki/Phenytoin
Organisms Affected: Humans and other mammals