Seizure control

These drugs may cause drowsiness or dizziness. Observe caution when performing hazardous tasks. Do not drive unless die adverse reactions of drowsiness, dizziness, or blurred vision are not significant. Driving privileges will be given by the primary health care provider based on seizure control. 

BC, a 22-year-old woman, was diagnosed 2 years ago with juvenile myoclonic epilepsy. She has been treated with valproate 1500 mg/day. Since starting valproate she has gained 45 pounds (20.5 kg), continues to have occasional myoclonic jerks, had a generalized tonic-clonic seizure 3 months ago, and is sexually active. Additionally, she complains of easily falling asleep during the day. Due to adverse effects, poor seizure control, and the risk of birth defects with valproate, the decision is made to switch to a different antiepileptic drug. 

Encourage patients to keep a seizure calendar that notes the time and day seizures occur and the type of seizure. Comparisons can then be made on a monthly basis to determine the level of seizure control. 

Question patients about common adverse effects of the AEDs they are receiving. Weigh the impact of acute adverse effects against the extent of seizure control achieved. If it is determined that the adverse effects negatively impact a patient more than the extent of seizure control obtained benefits the patient, adjust the therapeutic regimen. Continuously monitor chronic adverse effects of AEDs. 

It is important to evaluate for possible etiologies of status epilepticus and treat any underlying causes in order to optimize seizure control. 

Review laboratory results and correct any underlying abnormalities CT scan (if seizures controlled)... 

Treiman (1998)46 Seizure control Resp/cardiac events Patients with subtle GCSE... 

Goal Seizure control Diazepam 0.15 mg/kg + 55.8% 2.1-31.6% fared worse than patients... 

Alldredge (2001 )47 Seizure control Resp/cardiac events Higher doses used in... 

Misra (2006)48 Seizure control Resp/cardiac events As second line agent,... 

Goal Seizure control Sodium valproate 30 mg/kg 66% 4%/0% valproate controlled... 

Pentobarbital is commonly loaded at a dose of 10 to 15 mg/kg over 1 to 2 hours, followed by a continuous infusion of 0.5 to 4 mg/kg per hour. Therapy can be tapered off after 12 to 24 hours of seizure control as evident on the EEG.35 One metaanalysis reported a lower incidence of treatment failure with pentobarbital (3%) when compared to midazolam (21%) or propofol (20%), although the risk of hypotension requiring vasopressor therapy was higher when pentobarbital was used.36 This relative efficacy for pentobarbital must be considered... 

The sucrose content of oral liquids may cause significant problems when these products are prescribed for long-term therapy (e.g., asthma, seizure control, recurrent infections). Oral liquid preparations can represent a substantial carbohydrate load to children with labile diabetes, particularly if a child is ingesting more than one liquid medication with a high sugar content. 

Cannabinoids appear to have a very complex interaction with seizure activity, exerting both anticonvulsant and proconvulsant effects. Anecdotal testimonies abound (Grinspoon and Bakalar, 1993), but there has been very little controlled human research. In single-case studies both use and withdrawal of marijuana have been linked to the resumption of seizures (Keeler and Reifler, 1967 Consroe et al., 1975). In a randomised placebo-controlled blind study, patients who responded poorly to standard treatments experienced improved seizure control in response to cannabidiol administration. Cannabidiol does not interact with cannabinoid receptors, and animal studies indicate that it has different anticonvulsant effects to other cannabinoids (Cunha et al., 1980). As such it may prove to have useful therapeutic properties. 

Patients should be chronically monitored for seizure control, side effects, social adjustment, drug interactions, compliance, quality of life, and toxicity. 

The success of drug therapy in the treatment of epilepsy is singularly difiScult to assess owing to the extreme variability of the disorder, both in type of seizure pattern and the frequency with which attacks occur. The natural history of the disorder is also notoriously variable, further increasing the difficulties of assessing the contribution made by therapeutic agents. Moreover, the therapeutic aim varies from patient to patient. In one subject, for example, successful therapy may mean complete seizure control, while in another a reduction in seizure frequency from daily to weekly attacks may be considered adequate. 

Seizure control is improved in many patients when the dose of phenytoin, and blood concentration, is increased, although the occurrence of toxic symptoms may limit this process. Baylis (B7) and co-workers examined the monthly fit frequency in 47 children with severe epilepsy in whom the only change in medication was in the dose of phenytoin, which in each case was sufficient to produce a rise in blood phenytoin... 

The conclusion seems inescapable that random measurements of plasma phenytoin levels are useless apart from detecting suspected drug defaulters or confirmation of gross toxicity. The optimum concentration for any individual patient must be determined and regular monitoring carried out thereafter to check that this level is maintained. Thus it should be possible to improve seizure control even in severely affected patients without precipitating toxicity. 

While regular monitoring of plasma phenytoin levels can result in improved seizure control, the benefit derived from measuring other commonly prescribed anticonvulsant drugs is difficult to assess. Phenobarbitone, primidone, and carbamazepine will be discussed briefly. 

Buchanan and Allen (B29) failed to demonstrate a relation between plasma phenobarbitone levels and seizure control in 128 children managed on an out-patient basis, but the significance of their findings is difficult to assess. Their results referred to single determinations carried... 

The relation between the drug levels and seizure control is not clear, and opinion is divided whether primidone exerts anticonvulsant activity solely as the metabolite phenobarbitone (B15, 06) or as native primidone, as suggested by experimental (Gl) and clinical (B7, B17) studies. 

Little is known as yet about the pharmacokinetics of carbamazepine in humans although preliminary reports suggest slow absorption (M21) and marked variations in blood levels during a day in some subjects (M15). Blood levels varying from trace quantities to 12 /ig/ml have been found in patients taking 400-1000 mg daily (P3), but no relation between the level observed and the dose was apparent. In the studies so far published carbamazepine blood levels have not correlated with seizure control (P3), but all the subjects wore receiving additional anticonvulsant drugs. 

Single daily dosage - In adults, if seizure control is established with divided doses of three 100 mg extended phenytoin sodium capsules daily, once/day dosage with 300 mg may be considered patient compliance is essential on a once/day regimen. Only extended phenytoin sodium capsules are recommended once/day. 

Absorption/Distrlbutlon - Phenytoin is slowly absorbed from the small intestine. Rate and extent of absorption varies and is dependent on the product formulation. Bioavailability may differ among products of different manufacturers. Administration IM results in precipitation of phenytoin at the injection site, resulting in slow and erratic absorption, which may continue for up to 5 days or more. Plasma protein binding is 87% to 93% and is lower in uremic patients and neonates. Volume of distribution averages 0.6 L/kg. Phenytoin s therapeutic plasma concentration is 10 to 20 mcg/mL, although many patients achieve complete seizure control at lower serum concentrations. 

Epilepsy Monitor the clinical state and EEC at regular intervals because deterioration in seizure control and EEC changes have occurred in patients taking this drug. 

Petroff, O. A., Mattson, R. H., Behar, K. L., Hyder, F., and Rothman, D. L. (1998). Vigabatrin increases human brain homocarnosine and improves seizure control. Ann. Neurol. 44, 948-952. 

With some drugs, particularly those with a long half life, a loading dose may be useful in order to achieve a therapeutic level more rapidly. For example, the half-life of phenobarbital in the neonate is long, approximately 120 hours, with steady-state concentrations achieved in two to three weeks. A slowly-infused loading dose can be efficacious in achieving seizure control within minutes, typically followed by maintenance infusion and subsequent transition to oral therapy daily. 

Although relationship between serum concentrations and seizure control is not well established and not used clinically, proposed therapeutic concentrations are 20-80 ng/ml potentially toxic concentrations greater than 80 ng/ml... 

Adjunctive therapy for seizure control PO Initially, 300 mg 3 times a day. May titrate... 

Seizure control in patients receiving enzyme-inducing antiepileptic drug (ElAEDs), hut not valproic acid PO Recommended as add-on therapy 50 mg once a day for 2 wk, followed by 100 mg/day in 2 divided doses for 2 wk. Maintenance Dosage may be increased by 100 mg/day every week, up to 300-500 mg/day in 2 divided doses. 

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