Mechanism of Action: Produces a voltage and frequency dependent blockade of sodium channels in rapidly discharging nerve cells. Thus, it stops sustained repetitive firing such as that occurring during a seizure. Because of this it prevents the spread of seizure discharge.
Therapeutic Use: Simple and complex partial seizures (temporal lobe seizures); generalized tonic-clonic seizures (grand mal). Not effective with absence seizures (may exacerbate absence).
Absorption: Peak blood level reached 24 hours after administration.
Metabolism: Liver (Oxidation by P-450 enzymes).
Half-life: 22-36 hours.
Average Daily Dose (adult): 300 mg
Adverse Effects: Drowsiness, ataxia (muscular incoordination) dysarthria (slurred speech), confusion, insomnia (disturbed sleep patterns), CNS sedation. Phenytoin is contraindicated in those patients who are hypersensitive to phenytoin or other hydantoins.
Drug Interaction: Carbamazepine (Tegretol ) may increase the metabolism of phenytoin causing a well-known decrease in plasma levels of phenytoin. Drugs which increase phenytoin serum levels include alcohol, amiodarone, chloramphenicol, chlordiazepoxide, diazepam, dicumarol, estrogens, cimetidine, methylphenidate (Ritalin), phenothiazines, salicylates, succinimides, sulfonamides and trazadone.
Contraindication: Those patients who are hypersensitive (allergic) to phenytoin and other hydantoins.
References:
- Chi, W., Chua, K. and Kong, K. (2000). Phenytoin-induced asterixis-uncommon or under-diagnosed? Brain Injury. 14(9), 847-?.
- Duritsch, S.W. (1991). Abstract: A randomized double-blind study of phenytoin for the prevention of posttraumatic seizures. Journal of Head Trauma Rehabilitation. 6(4), 67.
- Temkin, N.R., Dikmen, S.S., Wilenski, A.J., Keihm, J., et al. (1990). A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. New England Journal of Medicine. 323(8), 497-502.
Mechanism of Action: Increases the action of the inhibitory neurotransmitter, GABA in the brain. Also appears to inhibit the release of glutamate (an excitatory neurotransmitter) from nerve endings.
Therapeutic Use: Anticonvulsant (partial and generalized tonic-clonic or cortical focal seizures), and emergency control of acute seizures. May also be used as a sedative, hypnotic (sleep aid).
Absorption: Time for peak effect is 15 minutes .Well absorbed, effect begins in one hour or longer and lasts from 10-12 hours.
Metabolism: Metabolized primarily by the hepatic microsomal (P-450) enzyme system and the metabolic products are excreted in the urine primarily.
Half-life: 53-118 hours.
Average Daily Dose (adult): 60-200 mg
Adverse Effects: Sedation or drowsiness, lethargy. In some patients it may produce excitement rather than depression as well as irritability and hyperactivity. If allergic to the drug patients may develop severe skin disorders, such as scarlatiniform or morbilliform rash. Nystagmus and ataxia may occur at high doses. Tolerance and physical dependence are possible with high doses.
Drug Interaction: When combined with other sedative hypnotics such as benzodiazepine or alcohol can produce severe CNS depression leading to coma. Phenobarbital stimulates microsomal liver enzymes involved in the metabolism of other drugs which may require increase in the dose of other drugs such as oral contraceptives.
Contraindication: Patients who are hypersensitive (allergic) to phenobarbital and other barbiturates.
References:
- McNamara, J. O. In Goodman and Gilman s The Pharmacological Basis of Therapeutics 9th Edition. Hardman, J.G. et al. (Eds). McGraw Hill , New York, 1996. pp. 461 - 486.
Mechanism of Action: Mechanism of action to inhibit seizures has not been established. It has been suggested that its activity is related to increased brain levels of GABA.
Therapeutic Use: Treatment of simple and complex partial seizures, absence seizures, generalized tonic-clonic. It is a broad spectrum antiepileptic drug. Also, used in bipolar disorder (manic-depressive psychosis).
Absorption: Time for peak effect is 1-4 hours.
Metabolism: Primarily metabolized in the liver.
Half-life: Half-life of 6-16 hours.
Average Daily Dose (adult): 15 mg/kg/day increasing at one week intervals by 5 to 10 mg/kg/day until seizures are controlled.
Adverse Effects: Anorexia; nausea; vomiting (16% of patients); sedation; tremor, ataxia (muscular incoordination); alopecia (hair loss); weight gain and an elevation of liver enzymes is observed in about 40% of patients.
Drug Interaction: May potentiate the action of CNS depressants (ie, alcohol, benzodiazepines, etc.).
Contraindication: Not to be used by individuals with hepatic (liver) disease or dysfunction or in children under 2 years of age because of possible liver damage.
References:
- Wroblewski, B.A., Joseph, A.B., Kupfer, J., & Kalliel, K. (1997). Effectiveness of valproic acid on destructive and aggressive behaviours in patients with acquired brain injury. Brain Injury. 11(1), 37.
- Horne, E. & Lindley, S. (1995). Divalproex sodium (Depakote) in the treatment of aggressive behavior and dyshoria in patients with organic brain syndromes. Journal of Clinical Psychiatry. 56(9), 430-31.
- Geracioti, Jr., T. (1994). Valproic acid treatment of episodic explosiveness related to brain injury. Journal of Clinical Psychiatry. 55(9), 417.
Chayasirisobhon, S. & Russell, M. (1983). Valproic acid and intractable seizures in severely brain-damaged patients. Neurology. 33, 99-101, Jan.
Mechanism of Action: Like phenytoin, it is known to block sustained repetitive firing in a frequency dependent manner. As with phenytoin, this is due to blockade of sodium channels and is believed to be largely responsible for its action.
Therapeutic Use: Epilepsy, in particular partial simple or complex seizures. Also, generalized tonic-clonic seizures. Not effective in absence seizures. Also used in bipolar disorder (manic-depressive psychosis).
Absorption: Slow and erratic absorption.
Time for peak effect: 4-5 hours.
Metabolism: (Oxidation to 10, 11 epoxide [active metabolite]) by liver P-450 enzymes. Inactivated by further oxidation and conjugation.
Half-life: 6-12 Hours.
Average Daily Dose (adult): 400 mg.
Adverse Effects: Dizziness, drowsiness, unsteadiness, nausea, diplopia (double vision), blurred vision. Agranulocytosis and aplastic anemia are rare, but very serious adverse effects. A mild, transient leukopenia (decrease in white cell count) occurs in about 10% of patients, but usually disappears in first 4 months of treatment.
Drug Interaction: Stimulates the metabolism of other drugs like Phenytoin and in fact, stimulates its own metabolism. This may require an increase in dose of other drugs patient is taking.
Contraindication: Should not be used in patients with a history of previous bone marrow depression, hypersensitivity to the drug or known sensitivity to any of the tricyclic compounds, such as amitriptyline, desipramine, imipramine, protriptline, nortriptyline, etc. Use with MAO inhibitors is not recommended.
References:
- Lee, J. (1995). Persistent dystonia associated w/carbamazapine therapy: A case report. Brain Injury Update. 10(7), 51.
- Rivey, M.P., Allington, D.R., Stone, J.D., & Serfoss, M.L. (1995). Alteration of carbamazepine pharmacokinetics in patients with traumatic brain injury.Brain Injury. 9(1), 41.
- Sechi, G.P., Zuddas, M., Piredda, M., Agnetti, V. et al. (1989). Treatment of cerebellar tremors with carbamazepine: A controlled trial with long-term follow-up. Neurology. 39, 1113-1115, Aug.
- Bouvy, P.F., van de Wetering, B.J.M., Meerwaldt, J.D. et al. (1988). A case of organic brain syndrome following head injury successfully treated with carbamazepine. Acta Psychiatrica Scandinavica. 77, 361-363.
- Parmelee, D.X. & O'Shanick, G.J. (1988). Carbamazepine--lithium toxicity in brain-damaged adolescents:Case studies.Brain Injury. 2(4), 305-308.
- Goldberg, R.L. & Buongiorno, P.A. (1982). The use of carbamazepine for the treatment of paraphilias in a brain damaged patient. International Journal of Psychiatry in Medicine. 12(4), 275-279.
Mechanism of Action: Unknown
Therapeutic Use: Treatment of partial seizures, and secondary generalized seizures.
Absorption: Well absorbed after oral administration. Bioavailability (absorption) decreases with increasing dose.
Metabolism: Gabapentin is not appreciably metabolized in humans. It is eliminated from the systemic circulation by renal excretion as unchanged drug.
Half-life: 5-9 Hours.
Average Daily Dose (adult): 900 to 1800 mg
Adverse Effects: The most common are somnolence (drowsiness), ataxia (muscular incoordination), dizziness, nystagmus (involuntary rapid eye movements) and fatigue.
Drug Interaction: No significant drug interaction known.
Contraindication: In patients who have demonstrated hypersensitivity to the drug.
References:
- Childers, M. & Holland, D. (1997). Psychomotor agitation following gaberpentin use in brain injury. Brain Injury. 11(7), 537-540.
- Ryback, R. & Ryback, L. (1995). Gabapentin for behavioral dyscontrol. American Journal of Psychiatry. 152(9), 159-161.
Mechanism of Action: Clonazepam is a benzodiazepine like the antianxiety drugs and its action is mediated through enhancement of the inhibitory transmitter, GABA.
Therapeutic Use: Absence seizures (petit mal) and panic disorders.
Absorption: Rapidly and completely absorbed after oral administration. Maximum plasma concentrations are reached within 1-4 hours.
Metabolism: Oxidized in Liver by the P-450 system.
Half-life: 30-40 hours.
Average Daily Dose (adult): 20-80 mg/ml 1.5-10 mg/day.
Adverse Effects: Dizziness, ataxia, drowsiness, tolerance, physical dependence, hypersalivation, drooling, confusion, amnesia (memory loss).
Drug Interaction: Enhances the action of other CNS depressants leading to excessive depression.
Contraindication: Should not be used in patients with a history of sensitivity to benzodiazepines, nor in patients with clinical or biochemical evidence of significant liver disease.
Mechanism of Action: Closely related to the barbiturates, indeed it is converted to phenobarbital and phenylethyl malonamide (PEMA), both of which are active metabolites. At least part of its action is due to enhancing the action of GABA.
Therapeutic Use: Psychomotor (complex partial), focal or tonic- clonic seizures.
Absorption: Rapidly and almost completely absorbed after oral administration, although individual variability can be great. Peak concentrations are observed approximately 3 hours after ingestion.
Metabolism: Approximately 40% of the drug is excreted unchanged in the urine.
Half-life: Variable, mean values ranging from 5-15 hours. Phenobarbital has a half life of 100 hours and PEMA of about 16 hours.
Average Daily Dose (adult): 750-1500 mg/day
Adverse Effects: Drowsiness, ataxia (muscular incoordination), vertigo (dizziness), diplopia, nystagmus.
Drug Interaction: Phenytoin has been reported to increase the conversion of primidone to phenobarbital. Other drug interactions to be anticipated are those for phenobarbital.
Contraindication: Sensitivity to phenobarbital. Safe use during pregnancy has not been determined. Children and geriatric clients may exhibit restlessness.
Lazar, R.B. (M.B. Glenn, Ed.). (1995). Felbamate: Is there a role in the prevention and management of posttraumatic epilepsy?Journal of Head Trauma Rehabilitation. 10(1), 87-89.
Pellock, J.M. (1995). Antiepileptic drug therapy in the United States: A review of clinical studies and unmet needs. Neurology. 45(3), S2-17.
Bontke, C.F. (1993). Anticonvulsant prophylasix for the prevention of late posttraumatic epilepsy.Journal of Head Trauma Rehabilitation. 8(4), 101-107.
Thompson, S.B.N., North, N., & Pentland, B. (1993). Clinical management of a man with complex partial seizures and a severe head injury.Brain Injury. 7(3), 257-262.
Massagli, T.L. (1991). Neurobehavioral effects of phenytoin, carbamazepine, & valproic acid: Implications for use in traumatic brain injury. Archives of Physical Medicine & Rehabilitation. 72, 219-226, Mar.
Anti-Convulsants
