McKenna's Pharmacology for Nursing, 2e

730 P A R T 8  Drugs acting on the cardiovascular system T he drugs discussed in this chapter lower serum levels of cholesterol and various lipids. These drugs are some- times called antihyperlipidaemic agents used to treat hyperlipidaemia —an increase in the level of lipids in the blood. There is mounting evidence that the inci- dence of coronary artery disease (CAD), the leading killer of adults in the Western world, is higher among people with high serum lipid levels. The cause of CAD is poorly understood, but some evidence indicates that cholesterol and fat may play a major role in disease development. Lipid and triglyceride levels play a role in metabolic syndrome , a collection of factors, including insulin resistance, abdominal obesity, low high-density lipoprotein and high triglyceride levels, hypertension and proinflammatory and prothrombotic states, that has been shown to increase the incidence of CAD. See Table 47.1. ■■ TABLE 47.1 Clinical aspects of the metabolic syndrome Parameter Significant values

it becomes less distensible and less reactive to many neurological and chemical stimuli that would ordinarily dilate or constrict it. As a result, the coronary vessels are no longer able to balance the myocardial demand for oxygen with increased blood supply. More recent evidence indicates that the makeup of the core of the atheroma may be a primary determinant of which ath- eromas might rupture and cause acute blockage of a vessel. The softer, more lipid-filled atheromas appear to be more likely to rupture than the stable, harder cores. Unmodifiable risk factors • Genetic predispositions : CAD is more likely to occur in people who have a family history of the disease, particularly if the disease occurs in relatives younger than the age of 55 years. • Age : The incidence of CAD increases with age. • Gender : Men are more likely than premenopausal women to have CAD; however, the incidence is almost equal in men and postmenopausal women, possibly because of a protective effect of oestrogens (see Box 47.3). Modifiable risk factors • Gout : Increased uric acid levels seem to injure vessel walls. • Cigarette smoking : Nicotine causes vasoconstriction and may have an effect on the endothelium of blood vessels; over time, smoking can lower oxygen levels in the blood. • Sedentary lifestyle : Exercise increases the levels of chemicals that seem to protect the coronary arteries. • High stress levels : Constant sympathetic reactions increase the myocardial oxygen demand while causing vasoconstriction and may contribute to a remodelling of the blood vessel endothelium, leading to an increased susceptibility to atheroma development. • Hypertension : High pressure in the arteries causes endothelial injury and increases afterload and myocardial oxygen demand. • Obesity : This may reflect altered fat metabolism and will increase the heart’s workload. • Diabetes : Diabetics have a capillary membrane thickening, which accelerates the effects of atherosclerosis and abnormal fat metabolism, which increases lipid levels. • Other factors that, if untreated, may contribute to CAD include bacterial infections ( Chlamydia infections have been correlated with onset of CAD, and treatment with tetracycline and fluororoentgenography has been associated with decreased incidence of CAD, indicating a possible bacterial link) and autoimmune processes (some plaques contain antibodies and other products of immune reactions, making autoimmune reactions a possibility). ■■ BOX 47.1  Risk factors for coronary artery disease

Insulin

Fasting blood glucose >7.0 mmol/L

resistance

Abdominal obesity

Waist measurement >94 cm in men; >80 cm in women; >90 cm in men from Middle Eastern, South Asian, Chinese, Asian- Indian, South and Central American backgrounds High density lipoproteins (HDLs) >1.0 mmol/L; any triglycerides (TG) >2.0 mmol/L Blood pressure >130/85 mmHg Increased macrophages, increased levels of interleukin-6 and tumour necrosis factor (TNF) Increased plasminogen activator levels

Lipid

abnormalities

Hypertension

Proinflammatory state

Prothrombotic state

CORONARY ARTERY DISEASE As explained in Chapter 46, CAD is characterised by the progressive growth of atheromatous plaques, or atheromas, in the coronary arteries. These plaques, which begin as fatty streaks in the endothelium, event­ ually injure the endothelial lining of the artery, causing an inflammatory reaction. This inflammatory process triggers the development of characteristic foam cells containing fats and white blood cells that further injure the endothelial lining. Over time, platelets, fibrin, other fats and remnants collect on the injured vessel lining and cause the atheroma to grow, further narrowing the interior of the blood vessel and limiting blood flow. The injury to the vessel also causes scarring and a thickening of the vessel wall. As the vessel thickens,