Anticonvulsant drug therapy

Generally, anticonvulsants reduce the excitability of the neurons (nerve cells) of the brain. When neuron excitability is decreased, seizures are theoretically reduced in intensity and frequency of occurrence or, in some instances, are virtually eliminated. For some patients, only partial control of the seizure disorder may be obtained with anticonvulsant drug therapy. 

Wilson JT, Wilkinson GR. Delivery of anticonvulsant drug therapy in epileptic patients assessed by plasma level analyses. Neurology 1974 24(7) 614-23. 

Tolman, K. G., Jubiz, W., Sannella, J. J., Madsen, J. A., Belsey, R. E., Goldsmith, R. S., and Preston, J. W., Osteomalacia associated with anticonvulsant drug therapy in mentally retarded children. Pediatrics 56, 45-51 (1975). 

In the neonate with hemorrhagic disease of the newborn, the administration of vitamin K raises the concentration of these clotting factors to the level normal for the newborn infant and controls the bleeding tendency within -6 hours. The routine administration of 1 mg phylloquinone intramuscularly at birth is required by law in the U.S.. This dose may have to be increased or repeated if the mother has received anticoagulant or anticonvulsant drug therapy or if the infant develops bleeding tendencies. Alternatively, some clinicians treat mothers who are receiving anticonvulsants with oral vitamin K prior to delivery (10-20 mg/day for 2 weeks). 

The adverse effects on bone caused by chronic anticonvulsant drug therapy have been reviewed [46 ]. 

Monitoring and Managing Adverse Reactions Drowsiness is a common adverse reaction of the anticonvulsant drug , especially early in therapy Therefore, the nurse should assist the patient with all ambulatory activities. The nurse helps tire patient to arise from the bed slowly and sit for a few minutes before standing. Drowsiness decreases with continued use ... 

Spontaneous reports of osteoporosis, osteopenia, bone fractures, and delayed healing of bone fractures have been seen in the isotretinoin population. While causality to isotretinoin has not been established, an effect cannot be ruled out. Physicians should use caution when prescribing isotretinoin to patients with a genetic predisposition for age-related osteoporosis, a history of childhood osteoporosis conditions, osteomalacia, or other disorders of bone metabolism. This would include patients diagnosed with anorexia nervosa and those who are on chronic drug therapy that causes drug-induced osteoporosis/osteomalacia and/or affects vitamin D metabolism, such as systemic corticosteroids and any anticonvulsants. 

Carbamazepine also can induce the enzymes that metabolize other anticonvulsant drugs, including phenytoin, primidone, phenobarbital, valproic acid, clonazepam, and ethosuximide, and metabolism of other drugs the patient may be taking. Similarly, other drugs may induce metabolism of carbamazepine the end result is the same as for autoinduction, and the dose of carbamazepine must be readjusted. A common drug-drug interaction is between carbamazepine and the macrolide antibiotics erythromycin and trolean-domycin. After a few days of antibiotic therapy, symptoms of carbamazepine toxicity develop this is readily reversible if either the antibiotic or carbamazepine is discontinued. 

Somnolence, dizziness, ataxia, fatigue, and nystagmus Discontinuation of gabapentin and/or addition of an alternative anticonvulsant drug to existing therapy should be done gradually over a minimum of 1 week... 

BD and other forms of NCL are relatively rare, occurring in an estimated two to four of every 100,000 live births in the US [www.ninds.nih.gov]. There is currently no specific treatment for BD and current therapy simply alleviates the symptoms of the disease. Anticonvulsant drugs alleviate the associated seizures, and occupational therapy helps individuals compensate for the loss of vision, physical and mental abilities. Because BD involves the deterioration of neuronal cell tissue, it is a candidate for cellular therapy. 

L. Bossi, Fetal effects of anticonvulsants, in P.L. Morselli, C.E. Pippenger and J.K. Penry (Eds.), Antiepileptic Drug Therapy in Pediatrics, Raven Press, New York, 1983, pp. 37-64. 

Drug therapy includes the use of anticonvulsant or anti-epileptic drugs, such as sodium valproate, sodium phenytoin, lamotrigine, vigabatrin. 

Failure of contraceptive therapy and breakthrough bleeding have been noted repeatedly in patients concurrently taking various enzyme-inducing anticonvulsant drugs (305,314). These include phenytoin, primidone, ethosux-imide, phenobarbital, and carbamazepine. The specific isozyme responsible for metabolic 2-hydroxylation of ethinylestradiol is CYP3A4, which is induced by... 

A number of important characteristics exist that distinguish drug therapy in infants from adult medication protocols. For example, after intramuscular administration, drug absorption is partially dependent on blood flow in the muscle bed. Abnormal drug absorption following intramuscular injection can occur in premature infants, in whom muscle mass is small and blood flow to the musculature is poor. Examples of adverse effects attributed to altered drug absorption are the reactions of infants to cardiac glycosides and anticonvulsants. 

Topiramate is routinely administered orally, absorbed rapidly, and metabolized minimally, but its disposition is affected by CyP 2C19. Serum concentrations of other anticonvulsant drugs are not significantly affected by the concurrent administration of topiramate, with the exception in individual patients on phenytoin who exhibit increased phenytoin plasma concentrations after addition of topiramate. Co-administration of phenytoin or carbamazepine decreases topiramate serum concentrations. Changes in cotherapy with phenytoin or carbamazepine (e.g., addition or withdrawal) for patients stabilized on topiramate therapy may require topiramate dose adjustment. As with other... 

Valproic acid is rapidly and almost completely absorbed after oral administration. Peak concentrations occur 1 to 4 hours after an oral dose. The principal metabolite, 2-n-propyl-3-ketopentanoic acid, is created by action of CyP 2C19 and has anticonvulsant activity comparable to that of valproic acid, although this metabolite does not accumulate in plasma the exact cytochrome enzyme isomer involved in metabohsm has not been identified. The single-dose half-life is 16 hours in healthy adults, but this decreases to 12 hours on chronic therapy and may be as short as 8 hours in children. In neonates and in hepatic disease, when metabolism is reduced, the half-life becomes prolonged. Valproic acid is highly protein bound (93%). In circumstances when competition for protein binding increases, such as in uremia, cirrhosis, or concurrent drug therapy, the percent of free valproic acid increases. 

Serum alkaline phosphatase elevation and other indices, both biochemical and radiological, of rickets and osteomalacia are more common in patients receiving anticonvulsant drugs than in control subjects (B13, C16, C37, R16, TIO). The severity of these abnormalities has been reported to relate directly to the duration of therapy (K35, TIO), to the... 

---