McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 2 3 Antiseizure agents

It is indicated for the control of absence seizures (see Table 23.2).

Prototype summary: Ethosuximide Indications: Control of absence seizures.

Pharmacokinetics Ethosuximide is available for oral use. This drug crosses the placenta and enters breast milk (see Contraindica­ tions and cautions). Ethosuximide is readily absorbed from the GI tract, reaching peak levels in 1 to 7 hours. It is metabolised in the liver and excreted in the urine. The half-life of ethosuximide is 30 hours in children and 60 hours in adults. The established therapeutic serum level for ethosuximide is 40 to 100 mcg/mL. Contraindications and cautions Ethosuximide is contraindicated in the presence of allergy to avoid hypersensitivity reactions . Caution should be used with ethosuximide in people with inter­ mittent porphyria, which could be exacerbated by the adverse effects of the drug , and those with renal or hepatic disease, which could interfere with the metab- olism and excretion of the drug and lead to toxic levels. Use during pregnancy should be discussed with the woman because of the potential for adverse effects on the fetus. Another method of feeding the baby should be used if one of these drugs is needed during breastfeeding. Blood dyscrasias, including some with a fatal outcome, have been reported to be associated with use of ethosuximide; therefore, periodic blood counts should be performed. Should signs and/or symptoms of infection (e.g. sore throat, fever) develop, blood count determinations should be considered at that point. Adverse effects Ethosuximide has relatively few adverse effects compared with many other antiepileptic drugs. Many of the adverse effects associated with the succinimides are related to their depressant effects in the CNS. These may include depression, drowsiness, fatigue, ataxia, insomnia, headache and blurred vision. Decreased GI activity with nausea, vomiting, anorexia, weight loss, GI pain and constipation or diarrhoea may also occur. Bone marrow suppression, including potentially fatal pancytopenia, and dermatological reactions such as pruritus, urticaria, alopecia and Stevens–Johnson syndrome may occur as a result of direct chemical irrita­ tion of the skin and bone marrow. Clinically important drug–drug interactions Use of ethosuximide with primidone may cause a decrease in serum levels of primidone. People should be monitored and appropriate dose adjustments made if these two agents are used together.

O ther drugs for treating absence seizures Three other drugs that are used in the treatment of absence seizures do not fit into a specific drug class (Table 23.2). These include acetazolamide ( Diamox , Glaumox ), sodium valproate ( Epilim ) and zonisamide ( Zonegran ) (not available in New Zealand). Therapeutic actions and indications Sodium valproate reduces abnormal electrical activity in the brain and may also increase GABA activity at inhibi­ tory receptors. Acetazolamide—a sulfonamide—alters electrolyte movement, stabilising nerve cell membranes. Another sulfonamide—zonisamide—is a newer agent that inhibits voltage-sensitive sodium and calcium channels, thus stabilising nerve cell membranes and modulating calcium-dependent presynaptic release of excitatory neurotransmitters. See Table 23.2 for usual indications related to these drugs. Pharmacokinetics Sodium valproate, available for oral and IV use, is readily absorbed from the GI tract, reaching peak levels in 1 to 4 hours. It is metabolised in the liver and excreted in the urine with a half-life of 6 to 16 hours. Acetazolamide, which can be given orally, IM or IV, is readily absorbed from the GI tract and is excreted unchanged in the urine with a half-life of 2.5 to 6 hours. Zonisamide, an oral drug, is well absorbed from the GI tract, reaching peak levels in 2 to 6 hours. It is prim­ arily excreted unchanged in the urine, with a half-life of 63 hours. Actions: May act in inhibitory neuronal systems; suppresses the electroencephalographic pattern associated with absence seizures; reduces frequency of attacks. Pharmacokinetics: Route Peak Oral 3–7 hours T 1/2 : 30 hours (children), 60 hours (adults); metabolised in the liver, excreted in the urine and bile. Adverse effects: Drowsiness, ataxia, dizziness, irritability, nervousness, headache, blurred vision, pruritus, Stevens–Johnson syndrome, nausea, vomiting, epigastric pain, anorexia, diarrhoea and pancytopenia.