McKenna's Pharmacology for Nursing, 2e

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

Gender considerations

BOX 25.2

Prototype summary: Dantrolene Indications: Control of clinical spasticity resulting from upper motor neuron disorders; preoperatively to prevent or attenuate the development of malignant hyperthermia in susceptible people; IV for management of fulminant malignant hyperthermia. Actions: Interferes with the release of calcium from the sarcoplasmic reticulum within skeletal muscles, preventing muscle contraction; does not interfere with neuromuscular transmission. Pharmacokinetics: Route Onset Peak Duration Oral Slow 4–6 hours 8–10 hours IV Rapid 5 hours 6–8 hours T 1/2 : 9 hours (oral), 4 to 8 hours (IV); excreted in the urine. Adverse effects: Drowsiness, dizziness, weakness, fatigue, diarrhoea, hepatitis, myalgia, tachycardia, transient blood pressure changes, rash, urinary frequency. ■ ■ Assess for contraindications or cautions for the use of the drug including any known allergies to prevent hypersensitivity reactions ; cardiac depression; epilepsy; muscle weakness; respiratory depression, which could be exacerbated by the effects of these drugs ; pregnancy and breastfeeding, which require cautious use ; renal or hepatic dysfunction, which could alter the metabolism and excretion of the drug ; and local infections (if using botulinum toxins) to prevent exacerbation of the infections . ■ ■ Assess temperature; skin colour and lesions; CNS orientation, affect, reflexes, bilateral grip strength and spasticity; respiration and adventitious sounds; pulse, electrocardiogram (ECG) and cardiac output; bowel sounds and reported output; and liver and renal function tests to determine baseline status before beginning therapy and for any potential adverse effects. ■ ■ Refer to the Critical thinking scenario for a full discussion of care for a person who is receiving a direct-acting skeletal muscle relaxant. Care considerations for people receiving a direct-acting skeletal muscle relaxant Assessment: History and examination

effects. Such adverse GI effects may include GI irritation, diarrhoea, constipation and abdominal cramps. Dantro- lene may also cause direct hepatocellular damage and hepatitis that can be fatal. Urinary frequency, enuresis and feelings of urinary urgency reportedly occur, and crystalline urine with pain or burning on urination may result. In addition, several unusual adverse effects may occur, including acne, abnormal hair growth, rashes, photosensitivity, abnormal sweating, chills and myalgia. The botulinum toxins have been associated with anaphylactic reactions; with headache, dizziness, muscle pain and paralysis; and with redness and oedema at the injection site. Adverse effects associated with use of botulinum toxin type A for cosmetic purposes include headache, respiratory infections, flulike syndrome and droopy eyelids in severe cases. Pain, redness and muscle weakness have also been reported. The reactions tend to be temporary, but there have been reports of reactions that lasted several months. Clinically important drug–drug interactions If dantrolene is combined with oestrogens, the inci- dence of hepatocellular toxicity is apparently increased. If possible, this combination should be avoided. If the botulinum toxins are used with other drugs that inter- fere with neuromuscular transmission—neuromuscular junction (NMJ) blockers, lincosamides, quinidine, mag- nesium sulphate, anticholinesterases, succinylcholine or polymyxin—or with aminoglycosides, there is a risk of additive effects. If any of these must be given in combi- nation, extreme caution should be used. Understanding the risks of liver damage with dantrolene Dantrolene (Dantrium) is associated with potentially fatal hepatocellular injury. When liver damage begins to occur, people often experience a prodrome, or warning syndrome, which includes anorexia, nausea and fatigue. The incidence of such hepatic injury is greater in women and in individuals older than 35 years of age. In women, a combination of dantrolene and oestrogen seems to affect the liver, thus posing a greater risk. Women of all ages may be at increased risk, because those entering menopause may be taking hormone replacement therapy. People older than 35 years of age are at increasing risk of liver injury because of the changing integrity of the liver cells that comes with age and exposure to toxins over time. If a particular woman needs dantrolene for relief of spasticity, she should not be taking any oestrogens (e.g. birth control pills, hormone replacement therapy) and she should be monitored closely for any sign of liver dysfunction. For safer relief of spasticity in these women, baclofen may be helpful.