McKenna's Pharmacology for Nursing, 2e

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P A R T 4  Drugs acting on the central and peripheral nervous systems

Contraindications and cautions Phenytoin is generally contraindicated in the presence of allergy to avoid hypersensitivity reactions. These agents are associated with specific birth defects and should not be used in pregnancy or breastfeeding unless the risk of seizures outweighs the potential risk to the fetus. In such cases, the mother should be informed of the potential risks. The risk of taking a woman with a seizure disorder off an antiepileptic drug that has stabilised her condi­ tion may be greater than the risk of the drug to the fetus. Discontinuing the drug could result in status epilepticus, which has a high risk of hypoxia for the mother and the fetus. Research has not been able to show the effects of even a minor seizure during pregnancy on the fetus, making it important to prevent seizures during pregnancy if at all possible. Women of childbearing age should be urged to use barrier contraceptives while taking these drugs. If a pregnancy does occur, the woman should receive educational materials and counselling. Caution should be used with elderly or debilitated people, who may respond adversely to the CNS depres- sion , and with people who have impaired renal or liver function which may interfere with drug metabolism and excretion. People with hepatic impairment are at risk for increased toxicity from phenytoin. Other con­ traindications include coma, depression or psychoses, which could be exacerbated by the generalised CNS depression. Abrupt withdrawal of phenytoin in people with epilepsy may precipitate status epilepticus, hence any need for dosage reduction, discontinuation or sub­ stitution of alternative antiepileptic medication should be implemented gradually. Adverse effects The most common adverse effects relate to CNS depres­ sion and its effects on body function: depression, confusion, drowsiness, lethargy, fatigue, constipation, dry mouth, anorexia, cardiac arrhythmias and changes in blood pressure, urinary retention and loss of libido. Specifically, phenytoin may cause severe liver toxicity, bone marrow suppression, gingival hyper­ plasia and potentially serious dermatological reactions (e.g. hirsutism, Stevens–Johnson syndrome), all of which are directly related to cellular toxicity. Clinically important drug–drug interactions Because the risk of CNS depression is increased with phenytoin taken with alcohol, people should be advised not to drink alcohol while they are taking these agents. Always consult a drug reference before any drug is added to or withdrawn from a therapeutic regimen that involves any of these agents. Box 23.4 describes a haz­ ardous drug–herbal therapy interaction associated with antiepileptic medications.

People being treated for epilepsy should be advised not to use the herb evening primrose because it increases the risk of having seizures. People being treated with barbiturates or phenytoin should be advised not to use ginkgo, which could cause serious adverse effects. Herbal and alternative therapies BOX 23.4

B arbiturates and barbiturate - like drugs Barbiturates and barbiturate-like drugs include pheno­ barbitone (generic) and primidone ( Mysoline [not available in New Zealand]). These drugs are associated with significant CNS depression. Therapeutic actions and indications The barbiturates and barbiturate-type drugs inhibit impulse conduction in the ascending reticular activating system (RAS), depress the cerebral cortex, alter cere­ bellar function and depress motor nerve output. They stabilise nerve membranes throughout the CNS directly by influencing ionic channels in the cell membrane, thereby decreasing excitability and hyperexcitability to stimulation. By decreasing conduction through nerve pathways, they reduce the tonic–clonic, muscular and emotional responses to stimulation. Phenobarbitone depresses conduction in the lower brainstem and the cerebral cortex, as well as depressing motor conduction. Actions: Stabilises neuronal membranes and prevents hyperexcitability caused by excessive stimulation; limits the spread of seizure activity from an active focus; has cardiac antiarrhythmic effects similar to those of lignocaine. Pharmacokinetics: Route Onset Peak Duration Oral Slow 2–12 hours  6–12 hours IV 1–2 hours Rapid 12–24 hours T 1/2 : 6 to 24 hours; metabolised in the liver, excreted in the urine. Adverse effects: Nystagmus, ataxia, dysarthria, slurred speech, mental confusion, dizziness, fatigue, tremor, headache, dermatitis, Stevens–Johnson syndrome, nausea, gingival hyperplasia, liver damage, haematopoietic complications, sometimes fatal. Prototype summary: Phenytoin Indications: Control of tonic–clonic and psychomotor seizures; prevention of seizures during neurosurgery; control of status epilepticus.