McKenna's Pharmacology for Nursing, 2e

306

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

Barbituates generally depress cortex, RAS and cerebellum

Calculations

BOX 20.2

Cortex

A 3-year-old boy, weighing 25 kg, is prescribed chloral hydrate as a hypnotic at bedtime.The order reads: 50 mg/kg/day PO at bedtime.The drug comes in a syrup form as 1 g/10 mL. How much syrup would you give as the bedtime dose? First, figure out what the correct dose would be: 50 mg/kg × 25 kg = 1250 mg Set up the equation using the available form and prescribed dose, remembering to convert grams to milligrams

Limbic system

RAS

Zolpidem affects serotonin levels in RAS

1250 1000

10 1

×

= 12.5 mL

Cerebellum

Because this is a child, it is good practice to ask another nurse to calculate the correct dosage and then compare your work, so you can double-check the accuracy of your calculations.

Mechanisms not understood: buspirone chloral hydrate dexmedetomidine promethazine

The benzodiazepines used as anxiolytics include alpra- zolam ( Xanax ), bromazepam ( Lexotan ) (not available in New Zealand), clobazam ( Frisium ), diazepam ( Valium ), lorazepam ( Ativan ), oxazepam ( Serepax ), temazepam ( Normison , Temaze ) and triazolam ( Halcion ). Box 20.2 provides an exercise in calculating the dose for a child receiving a sedative/hypnotic. Therapeutic actions and indications The benzodiazepines are indicated for the treatment of the following conditions: anxiety disorders, alcohol withdrawal, hyperexcitability and agitation, and pre­ operative relief of anxiety and tension to aid in balanced anaesthesia. These drugs act in the limbic system and the RAS to make gamma-aminobutyric acid (GABA) more effective, causing interference with neuron firing (Figure 20.1). GABA stabilises the postsynaptic cell. This leads to an anxiolytic effect at doses lower than those required to induce sedation and hypnosis. The exact mechanism of action is not clearly understood. Benzodiazapines reduce muscle spasm by a central action that is inde- pendent of their sedative effect. As increased muscle tone is a common feature of anxiety states and may contribute to the aches and pains, including headaches that often trouble anxious people, the relaxant effect of benzodiazepines may, therefore, be clinically useful. Pharmacokinetics The benzodiazepines are well absorbed from the gastrointestinal (GI) tract, with peak levels achieved in 30 minutes to 2 hours. They bind strongly to plasma protein and their high lipid solubility causes the drug to accumulate gradually in body fat, crossing the placenta and entering breast milk. The benzodiazepines are metabolised extensively in the liver and are eventually excreted as glucoronide conjugates in the urine. Several

GABA

Benzodiazepines, zopiclone GABA effects

Cell firing inhibited, leading to stabilisation

FIGURE 20.1  Sites of action of the benzodiazepines, barbiturates and other anxiolytics.

benzodiazepines are converted into active metabolites, such as N -desmthyldiazepam, which can have a half- life of as long as 60 hours and which accounts for the tendency of many benzodiazepines to produce cumula- tive effects and long hangovers when given at regular intervals. People with liver disease must receive a smaller dose and be monitored closely. Excretion is primarily through the urine. Contraindications and cautions Contraindications to benzodiazepines include allergy to any benzodiazepine; psychosis, which could be exacer- bated by sedation ; and acute narrow-angle glaucoma, shock, coma or acute alcoholic intoxication, all of which could be exacerbated by the depressant effects of these drugs.