McKenna's Pharmacology for Nursing, 2e

746

P A R T 8  Drugs acting on the cardiovascular system

triglycerides and to increase HDL levels in individuals with primary hyperlipidaemia or mixed lipid disorders. Fenofibric acid is slowly absorbed from the GI tract, with peak levels occurring in 4 to 5 hours; metabo- lised in the liver, it has a half-life of 20 hours and is excreted in the urine. Caution should be used in people with renal impairment, and the drug should be avoided in individuals with severe renal impairment. The most common adverse effects that have been reported are headache, back pain, nausea, diarrhoea, muscle pain, runny nose and respiratory infections. Gallstones have also been reported with this drug. Individuals complain- ing of gallstone-type pain should be screened carefully. There is an increased risk of muscle breakdown and rhabdomyolysis if taken with a statin, and people using this combination need to be monitored closely. Caution must be used with warfarin anticoagulants; increased bleeding can occur. The person should be monitored closely and the dose of the anticoagulant regulated to achieve therapeutic anticoagulation. COMBINATION THERAPY Frequently, if the person shows no response to strict dietary modification, exercise, and lifestyle changes and the use of one lipid-lowering agent, combination therapy may be initiated to achieve desirable serum LDL and cholesterol levels. For example, a bile acid sequestrant might be combined with niacin; the combination would decrease the synthesis of LDLs while lowering the serum levels of LDLs. This combination is thought to help slow the progression of CAD. Numerous fixed-combination therapies are available (see Box 47.6). However, care must be taken not to combine agents that increase the risk of rhabdomyolysis. For example, HMG-CoA reduc- tase inhibitors are not usually combined with nicotinic acid or gemfibrozil. FUTURE THERAPIES Despite advances in treatment, CAD remains the number one killer of adults in Australia. New drugs are being investigated that would address multiple risk factors simultaneously with hopes of cutting risk suc- cessfully. The endocannabinoids are substances present in the body that activate various neurological receptors that seem to be very important in the body’s regulation of appetite, satiety and lipid metabolism. With blocking of the endocannabinoid system, a series of changes occur that would seem to have a very profound effect on many components of the metabolic syndrome. Blocking the endocannabinoid system results in feelings of satiety and decreased appetite, leading to weight loss; decreased release of growth hormone, increased oxygen

and glucose use in the muscle, decreased fat synthesis in the liver, decreased levels of triglycerides and LDLs and increased levels of HDLs, improving the lipid profile; increased sensitivity of insulin receptor sites, leading to decreased blood glucose levels; decreased fat pro- duction and storage; increased levels of adiponectin; and decreased activity of tumour necrosis factor, a pro­ inflammatory agent, and decreased activity of C-reactive protein, which is associated with proinflammatory and prothrombotic states. Rimonabant is an endocannabinoid blocker that has been used in Europe as a weight loss agent. In early studies in the US, it was shown to significantly reduce weight and abdominal adiposity and improve lipid profiles while increasing insulin sensitivity and reducing the proinflammatory and prothrombotic markers. US approval of the drug was denied at one point because of some significant CNS changes that occur, leading to questions of safety. It has since been removed from the market. ■■ Other agents used to lower cholesterol include fibrates, peroxisome proliferator receptor alpha activator and niacin. Often lipid-lowering agents are used in combination to lower the cholesterol at different sites. ■■ Research is being done on the effects of blocking the endocannabinoid system, resulting in weight loss, improved lipid profiles and decreased proinflammatory and prothrombotic states. Questions have not been answered about the safety or effectiveness of drugs that block this system. CHAPTER SUMMARY ■■ CAD is the leading cause of death in the Western world. It is associated with the development of atheromas or plaques in arterial linings that lead to narrowing of the lumen of the artery and hardening of the artery wall, with loss of distensibility and responsiveness to stimuli for contraction or dilation. ■■ The cause of CAD is not known, but many contributing risk factors have been identified, including increasing age, male gender, genetic predisposition, high-fat diet, sedentary lifestyle, smoking, obesity, high stress levels, bacterial infections, diabetes, hypertension, gout and menopause. The presence of many of these factors constitutes metabolic syndrome. ■■ Treatment and prevention of CAD is aimed at manipulating the known risk factors to decrease CAD development and progression. KEY POINTS