McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 4 7 Lipid-lowering agents

Pharmacokinetics The statins are all absorbed from the GI tract and undergo first-pass metabolism in the liver. They are excreted through faeces and urine. The peak effect of these drugs is usually seen within 2 to 4 weeks. These drugs are most effective when taken at night when the liver is processing the most lipids. These drugs cross the placenta, and most have been found in breast milk. Contraindications and cautions These drugs are contraindicated in the presence of allergy to any of the statins or to fungal by-products or compounds to avoid hypersensitivity reactions . Statins are also contraindicated in people with active liver disease or a history of alcoholic liver disease, which could be exacerbated, leading to severe liver failure, and with pregnancy or breastfeeding, because of the poten- tial for adverse effects on the fetus or neonate. These drugs are labelled as pregnancy category X. Atorvastatin levels are not affected by renal disease, but individuals with renal impairment who are taking other statins require close monitoring. Caution should be used in individuals with impaired endocrine function because of the potential alteration in the formation of steroid hormones. Adverse effects The most common adverse effects associated with these drugs reflect their effects on the GI system: flatulence, abdominal pain, cramps, nausea, vomiting and consti- pation. CNS effects can include headache, dizziness, blurred vision, insomnia, fatigue and cataract develop­ ment, and may reflect changes in the cell membrane and synthesis of cholesterol. Increased concentrations of liver enzymes commonly occur, and acute liver failure has been reported with the use of atorvastatin and flu- vastatin. Pravastatin and simvastatin are not associated with some of the severe liver toxicity that is seen with the other agents. Rhabdomyolysis, a breakdown of muscles whose waste products can injure the glomerulus and cause acute renal failure, is a rare adverse effect but has been known to occur with the use of all of these drugs. MEDSAFE New Zealand has also warned that high dose (80 mg) of simvastatin increases the risk of myopathies. Clinically important drug–drug interactions The risk of rhabdomyolysis increases if any of these drugs is combined with erythromycin, cyclosporin, gem- fibrozil, niacin or antifungal drugs; such combinations should be avoided. Increased serum levels and resultant toxicity can occur if these drugs are combined with digoxin or warfarin; if this combination is used, serum digoxin

Safe medication administration

levels and/or clotting times should be monitored care- fully and the prescriber consulted for appropriate dose changes. Increased oestrogen levels can occur if these drugs are taken with oral contraceptives; the person should be monitored carefully if this combination is used. Serum levels of the drug and the risk of toxicity increase if combined with grapefruit juice. Individuals who are taking HMG-CoA inhibitors need to be cautioned to avoid using grapefruit juice while taking these drugs. Grapefruit juice alters the metabolism of the drugs, leading to an increased serum level of the drug and increased risk for adverse effects, such as the potentially fatal rhabdomyolysis with renal failure. The effects may last for several days, so just drinking the grapefruit juice at a different time of day does not protect the person from risk. Prototype summary: Atorvastatin Indications: Adjunct to diet in the treatment of elevated levels of cholesterol, triglycerides and LDL; to increase HDL cholesterol in people with primary hypercholesterolaemia; treatment of boys and postmenarchal girls age 10 to 17 years of age with familial hypercholesterolaemia and two or more risk factors for CAD; prevention of CAD in adults without clinically evident heart disease but with multiple risk factors to reduce the risk of cardiovascular events. Actions: Inhibits HMG-CoA, causing a decrease in serum cholesterol levels, LDLs and triglycerides and an increase in HDL levels. Pharmacokinetics: Route Onset Peak Duration Oral Slow 1–2 hours 20–30 hours T 1/2 : 14 hours; metabolised in the liver and cells and excreted in bile. Adverse effects: Headache, flatulence, abdominal pain, cramps, constipation, rhabdomyolysis with acute renal failure.

Care considerations for people receiving HMG-CoA reductase inhibitors

Assessment: History and examination

■ ■ Assess for contraindications and cautions: any known allergies to these drugs or to fungal