McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 2 3 Antiseizure agents

Pharmacokinetics Phenobarbitone, which is available in oral and parenteral forms, is well absorbed from the GI tract, metabolised in the liver and excreted in the urine. This drug has very low lipid solubility, giving it a slow onset and a very long duration of activity. The plasma half-life is 90 to 100 hours in adults, and 65 to 70 hours in children, but is greatly prolonged in neonates. The therapeutic serum level range is 15 to 40 mcg/mL. Primidone, available only as an oral agent, is well absorbed from the GI tract, metabolised in the liver to phenobarbitone metabolites and excreted in the urine. It tends to have a longer half-life than phenobarbitone. The therapeutic serum levels are 5 to 12 mcg/mL. Bar­ biturates readily cross the placenta and, if administered IV, fetal blood concentrations are approximately equal to maternal serum concentrations. Phenobarbitone is excreted into breast milk. Contraindications and cautions Contraindications and cautions for barbiturates are the same as those discussed for hydantoins. Phenobarbi­ tone should not be administered to elderly people who exhibit nocturnal confusion or restlessness from sedative hypnotic drugs or to persons who are known to be, or are likely to become, dependent on sedative hypnotic medications. Adverse effects The most common adverse effects associated with barbiturates relate to CNS depression 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. Because barbitu­ rates and barbiturate-like drugs depress nerve function, they can produce sedation, hypnosis, anaesthesia and deep coma. The degree of depression is dose related. At doses below those needed to cause hypnosis, these drugs block seizure activity. In addition, phenobarbitone may be associated with physical dependence and withdrawal syndrome. The drug has also been linked to severe dermatological reac­ tions and the development of drug tolerance related to changes in drug metabolism over time. Clinically important drug–drug interactions Because the risk of CNS depression is increased when barbiturates are 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 or withdrawn from a therapeutic regimen that involves any of these agents.

B enzodiazepines Some benzodiazepines are used as antiepileptic agents. These include clonazepam ( Rivotril , Paxam [in New Zealand]) and diazepam ( Valium ). Therapeutic actions and indications The benzodiazepines may potentiate the effects of GABA, an inhibitory neurotransmitter that stabilises nerve cell membranes. These drugs, which appear to act primarily in the limbic system and the RAS, also cause muscle relaxation and relieve anxiety without affecting cortical functioning substantially. The benzodiazepines stabilise nerve membranes throughout the CNS to decrease excitability and hyperexcitability to stimula­ tion. By decreasing conduction through nerve pathways, they reduce the tonic–clonic, muscular and emotional responses to stimulation. In general, these drugs have limited toxicity and are well tolerated by most people. (See Chapter 20 for the use of benzodiazepines as sedatives and anxiolytics.) See Table 23.2 for usual indi­ cations for each of these agents. Clonazepam may lose its effectiveness within 3 months (affected individuals may respond to dose adjustment). Prototype summary: Phenobarbitone Indications: Long-term treatment of generalised tonic–clonic and cortical focal seizures; emergency control of certain acute convulsive episodes (status epilepticus, tetanus, eclampsia, meningitis); anticonvulsant treatment of generalised tonic– clonic seizures and focal seizures (parenteral). Actions: General CNS depressant; inhibits impulse conduction in the ascending RAS; depresses the cerebral cortex; alters cerebellar function; depresses motor output; and can produce excitation, sedation, hypnosis, anaesthesia and deep coma. Pharmacokinetics: Route Onset Duration Oral 30–60 mins 10–16 hours IM, SC 10–30 mins 4–6 hours IV 5 mins 4–6 hours T 1/2 : 79 hours; metabolised in the liver, excreted in the urine. Adverse effects: Somnolence, insomnia, vertigo, nightmares, lethargy, nervousness, hallucinations, insomnia, anxiety, dizziness, bradycardia, hypotension, syncope, nausea, vomiting, constipation, diarrhoea, hypoventilation, respiratory depression, tissue necrosis at injection site, withdrawal syndrome.