McKenna's Pharmacology for Nursing, 2e

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P A R T 3  Drugs acting on the immune system

the neonate or mother . The risk for cardiovascular dysfunction is increased with high doses, increasing duration of use and in people with other CV risk factors. The lowest effective NSAID dose should be used for the shortest possible duration; caution should be used with renal or hepatic dysfunction, which could alter the metabolism and excretion of these drugs , and with any other known allergies, which indicate increased sensitivity. • All NSAIDs (including COX-2 inhibitors) have been associated with the development of acute kidney injury. Acute kidney injury is more likely to occur in individuals with other risk factors—particularly hypovolaemic states. Renal function should be monitored in at risk individuals. If acute kidney injury occurs, the NSAID should be stopped. NSAIDs should be avoided in people who develop or have a history of interstitial nephritis. • Colonic ulceration, perforation and haemorrhage have been associated with NSAIDs. NSAID-induced diaphragm strictures are usually found in the ascending colon. Symptoms suggestive of ulceration and diaphragm strictures in the large intestine are chronic diarrhoea, iron deficiency anaemia and weight loss, rather than pain and sub-acute obstruction. Adverse effects People receiving NSAIDs often experience nausea, dys- pepsia, GI pain, constipation, diarrhoea or flatulence caused by direct GI effects of the drug. The potential for GI bleeding is often a cause of discontinuation of the drug. Headache, dizziness, somnolence and fatigue also occur frequently and could be related to prostaglandin activity in the CNS. Bleeding, platelet inhibition and even bone marrow depression have been reported with chronic use and probably are related to the blocking of prostaglandin activity. Rash and mouth sores may occur, and anaphylactoid reactions ranging up to fatal anaphylactic shock have been reported in cases of severe hypersensitivity. Severe cutaneous adverse reactions (SCARs) have been reported with NSAIDs. These include bullous erup- tions, erythema multiforme, epidermal necrolysis, toxic epidermal necrolysis and Stevens–Johnson syndrome. SCARs may cause permanent sequelae such as disfigure- ment, blindness and death. Importantly, these reactions may occur without warning. Clinically important drug–drug interactions There is often a decreased diuretic effect when these drugs are taken with loop diuretics; there is a potential for decreased antihypertensive effect of beta-blockers if these drugs are combined; and there have been reports of lithium toxicity, especially when combined with ibu- profen. People who receive these combinations should

be monitored closely, and appropriate dose adjustments should be made by the prescriber. Avoid the concomitant use of more than one NSAID, or a NSAID with a COX-2 inhibitor and/or an anticoagulant where possible. If such a combination is necessary, a gastro-protective agent such as a proton pump inhibitor should be considered. Prototype summary: Ibuprofen Indications: Relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis; relief of mild to moderate pain; treatment of primary dysmenorrhoea; fever reduction. Actions: Inhibits prostaglandin synthesis by blocking cyclooxygenase-1 and -2 receptor sites, leading to an anti-inflammatory effect, analgesia and

antipyretic effects. Pharmacokinetics: Route Onset

Peak

Duration 4–6 hours

Oral

30 mins

1–2 hours

T 1/2 : 1.8 to 2.5 hours; metabolised in the liver and excreted in the urine. Adverse effects: Headache, dizziness, somnolence, fatigue, rash, nausea, dyspepsia, bleeding, constipation.

P aracetamol Paracetamol ( Dymadon, Panadol ) is used to treat moderate to mild pain and fever and is often used in place of the NSAIDs or salicylates. It is the most frequently used drug for managing pain and fever in children. It is widely available over the counter and is found in many combination products. It can be extremely toxic. It causes severe liver toxicity that can lead to death when taken in high doses. Every year children die from inad- vertent paracetamol overdose when parents give their child more than one OTC drug containing paracetamol or administer a high dose of paracetamol. The US FDA and drug manufacturers have joined forces to produce mass media ads warning parents about this possibility. Therapeutic actions and indications Paracetamol acts directly on the thermoregulatory cells in the hypothalamus to cause sweating and vasodilation; this in turn causes the release of heat and lowers fever. The mechanism of action related to the analgesic effects of paracetamol has not been identified. Paracetamol is indicated for the treatment of pain and fever associated with a variety of conditions, includ- ing influenza; for the prophylaxis of children receiving diphtheria–pertussis–tetanus (DPT) immunisations