Phenobarbitone + Phenytoin Pharmacology
Phenobarbitone + Phenytoin
Barbiturates activate inhibitory GABA-A receptors and inhibit excitatory AMPA receptors and produces CNS depression.
17.Exacerbation of Porphyria
5.Obstructive sleeps apnoea
2.Patient with acute or chronic pain
5. Drug abuse
7. Debilitated patients
8. Driving vehicles, operating machines and people involving any other dangerous activities
9. Slowly withdraw the drug with caution
Valproic acid: Increases efficacy of barbiturates. Half life of valproic acid may be decreased.
Chloramphenicol: Efficacy of barbiturates increased. Barbiturates may decrease efficacy of chloramphenicol.
MAOIs: Effects of barbiturates prolonged.
Efficacy of the following drugs decreased by barbiturates: Oral anticoagulants, digitoxin, TCAs, corticosteroids, doxycycline, oral contraceptives and estrogens, acetaminophen, beta-blockers, quinidine, rifampicin, theophylline and metronidazole.
Phenytoin: Effect on phenytoin metabolism is unpredictable.
Frusemide: May produce or aggravate orthostatic hypotension.
Griseofulvin: Interferes with absorption of oral griseofulvin leading to decreased blood levels.
Anticonvulsant (Not used for absence and febrile seizure): 60 - 180 mg / day at bed time or 3 divided doses
Sedation: 30 - 120 mg / day in 2 or 3 divided doses
Insomnia: 100 - 200 mg/ day
Maximum dose: 400 mg / day
Anticonvulsant: 1 - 8 mg / kg body weight / day in single dose or 2 divided dose.
Sedation: 8 - 32 mg/ day
Antiarrhythmic action of Phenytoin is due to its membrane stabilizing effect and blockage of sodium channels. It causes depression of automaticity in ventricular and Purkinje fibres.
At high concentrations Phenytoin
1. Enhances calcium binding to phospholipids in neuronal membrane and results in a more stable neuronal membrane.
2. It enhances the concentration of inhibitory neurotransmitter GABA
3. It inhibits the excitatory glutamate receptors.
All these indicate that Phenytoin limits the development of maximal seizure activity and reduce the spread of the seizure process from the active focus.
Antiarrhythmic action: Phenytoin exerts its action by normalizing sodium entry to Purkinje`s fibers in patient with cardiac glycoside induced arrhythmias.
Distribution: It is very widely distributed in the body in protein bound form.
Metabolism: It is metabolised in the liver to inactive metabolites.
Excretion: It is excreted mainly in urine
4. Slurred speech
6. Decreased coordination
11. Megaloblastic anaemia
15. Coarsening of facial expressions
16. Abdominal discomfort
2. Atrioventricular block
3. Sinus Bradycardia
4. Sino Atrial block
2. Myocardial infarction
4. Renal impairment
5. Diabetic patient
6. Respiratory depression
7. Debilitated patient
8. Slowly withdraw the drug with caution
NEONATES : Use with caution
2. Trigeminal neuralgia,
4. Cardiac arrhythmia
Decreased pharmacological effects of Phenytoin may occur when any of the following drugs are administered comcomitantly with phenytoin: Diazoxide, Barbiturates, Carbamazipine, Rifampicin, Chronic ethanol ingestion, Theophylline, Antacids, Charcoal, Sucralfate, Antineoplastics, Folic acid, Influenza virus vaccine, Loxapine, Nitrofurantoin, Pyridoxine.
Phenytoin may decrease pharmacological effects of the following drugs: Acetaminophen, Amiodarone, Cardiac glycosides, Corticosteroids, Dicoumarol, Doxycycline, Haloperidol, Oestrogens, Methadone, Mexiletine, Oral contraceptives, Quinidine, Frusemide, Cyclosporine, Mebendazole, Non depolarising muscle relaxants, Sulfonylureas, Valproic acid.
Corticosteroids: Systemic manifestation of phenytoin induced hypersensitivity reactions masked.
Dopamine: Severe hypotension.
Meperidine: Decreased analgesic effect and increased toxicity with phenytoin.
Primidone: Pharmacological effects of primidone enhanced.
Warfarin: Pharmacological effects enhanced leading to bleeding disorders.
Lab tests: May interfere with Metyrapone and 1mg Dexamethasone tests.
300mg /day in 3 divided doses with food or milk. If needed dose can be increased to 600 mg / day
Maintenance dose: 300 - 400 mg / day.
Neuritic pain (Trigeminal neuralgia, Migraine): 200 - 600 mg / day in divided doses
Arrhythmia: 50 - 100 mg IV every 10 - 15 minutes
Maximum dose: 15 mg / kg
Anticonvulsant: 5 mg / kg body weight in 2 or 3 divided doses
Maintenance dose: 4 - 8 mg / kg body weight
Maximum dose: 300 mg / day
Children above 6 years: 300 mg / day in 3 divided doses
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