McKenna's Pharmacology for Nursing, 2e

307

C H A P T E R 2 0 Anxiolytic and hypnotic agents

In addition, these sedative/hypnotics are contra­ indicated in pregnancy because a predictable syndrome of cleft lip or palate, inguinal hernia, cardiac defects, microcephaly or pyloric stenosis occurs when they are taken in the first trimester. Neonatal withdrawal syndrome may also result. Breastfeeding is also a contra­ indication because of potential adverse effects on the neonate (e.g. sedation). Use with caution in elderly or debilitated people because of the possibility of unpredictable reactions and in cases of renal or hepatic dysfunction, which may alter the metabolism and excretion of these drugs, resulting in direct toxicity. If possible, hypnotics should be avoided in the elderly, because they are at greater risk of becoming ataxic and confused, leading to falls and injury. Dose adjustments usually are needed for such people. See the NZ Formulary http://nzf.org.nz/ nzf_1997.html. Dependence and tolerance (i.e. a gradual escala- tion of dose needed to produce the required effect) occurs with chronic use of all benzodiazepines there- fore stopping treatment after weeks or months causes increased symptoms of anxiety, together with tremor and dizziness. Addiction (i.e. severe psychological dependence which outlasts the physical withdrawal syndrome) which can occur with many drugs of abuse is not a major problem with benzodiazepines. Adverse effects The adverse effects of benzodiazepines are associated with the impact of these drugs on the central and peripheral nervous systems. Nervous system effects include sedation, drowsiness, depression, lethargy, blurred vision, headaches, apathy, light-headedness and confusion. In addition, mild paradoxical excitatory reactions may occur during the first 2 weeks of therapy. Benzodiazepines may occasionally cause marked respiratory depression and facilities for its treatment are therefore essential. The drug flumazenil is used to antagonise the effects of benzodiazepines (refer to Box 20.3). Several other kinds of adverse effects may occur. GI conditions such as dry mouth, constipation, nausea, vomiting and elevated liver enzymes may result. Cardiovascular problems may include hypotension, hypertension, arrhythmias, palpitations and respiratory difficulties. Haematological conditions such as blood dyscrasias and anaemia are possible. Genitourinary (GU) effects include urinary retention and hesitancy, loss of libido and changes in sexual functioning. Because phlebitis, local reactions and thrombosis may occur at local injection sites, such sites should be monitored. Abrupt cessation of these drugs may lead to a with- drawal syndrome characterised by nausea, headache, vertigo, malaise and nightmares.

Clinically important drug–drug interactions The risk of CNS depression increases if benzodiazepines are taken with alcohol or other CNS depressants, so such combinations should be avoided. In addition, the effects of benzodiazepines increase if they are taken with cimetidine, oral contraceptives or disulfiram. If any one of these drugs is used with benzodiazepines, people should be monitored and the appropriate dose adjust- ments made. Finally, the impact of benzodiazepines may be decreased if they are given with theophyllines or ran- itidine. If either of these drugs is used, dose adjustment may be necessary. Actions: Acts in the limbic system and reticular formation to potentiate the effects of GABA, an inhibitory neurotransmitter; may act in spinal cord and supraspinal sites to produce muscle relaxation. Pharmacokinetics: Route Onset Peak Duration Oral 30–60 mins 1–2 hours 3 hours IM 15–30 mins 30–45 mins 3 hours IV 1–5 mins 30 mins 15–60 mins Rectal Rapid 1.5 hours 3 hours T 1/2 : 20 to 80 hours, metabolised in the liver, excreted in urine. Adverse effects: Mild drowsiness, depression, lethargy, apathy, fatigue, restlessness, bradycardia, tachycardia, constipation, diarrhoea, incontinence, urinary retention, changes in libido, drug dependence with withdrawal syndrome. Prototype summary: Diazepam Indications: Management of anxiety disorders, acute alcohol withdrawal, muscle relaxation, treatment of tetanus, antiepileptic adjunct in status epilepticus, preoperative relief of anxiety and tension.

Care considerations for people receiving benzodiazepines

Assessment: History and examination

■ ■ Assess for contraindications or cautions: known allergies to benzodiazepines to prevent

hypersensitivity reactions ; impaired liver or kidney function, which could alter the metabolism and excretion of a particular drug ; any condition that might be exacerbated by the depressant effects of the drugs (e.g. glaucoma, coma, psychoses, shock, acute alcohol intoxication); and pregnancy and breastfeeding.