By the end of this chapter the student will be able to:
Recognize the main practical points regarding the pharmacokinetics, pharmacodynamics, mechanisms of action, clinical use, and adverse effects of the following drug groups:
This chapter reviews the basic and clinical pharmacology of cardiovascular drugs; focusing on practical, relevant points related to their pharmacokinetics, mechanisms of action, clinical use, and adverse effects. Despite the large number of available drugs used in the treatment of cardiovascular diseases, the most commonly used drugs are classified under a few categories of agents. The classification used in this chapter is based on the main mechanism of action of the drug. It should be noted that a single class of drugs can be used in treating more than one disease. As clarified in previous chapters, for managing a particular disease, there may be a number of drugs from different classes that can be used either alternatively, in combination, or during a particular stage of a disease.
Vasodilators are useful agents in the treatment of heart failure and hypertension. Several groups of drugs can lead to vasodilatation; including those inhibiting the renin-angiotensin-aldosterone system (RAAS), direct-acting vasodilators, calcium channel blockers, organic nitrates, and α-adrenergic blockers (discussed under “antiadrenergic agents” in this chapter).
Inhibitors of the Renin-Angiotensin-Aldosterone System
Angiotensin II is one of the most potent vasoconstrictor peptides in the body. Therefore, inhibitors of the renin-angiotensin-aldosterone system (RAAS) are frequently used in the treatment of hypertension and heart failure. It plays an important role in preventing the remodeling of the left ventricle following myocardial infarction. Figure 17.1 summarizes some actions of angiotensin II. Angiotensin-converting enzyme (ACE) inhibitors suppress angiotensin II formation (Fig. 17.2), whereas angiotensin receptor antagonists directly block the receptors of angiotensin II and minimize its effect.
Angiotensin II receptor-mediated effects that increase blood pressure.
Formation of angiotensin II and effects of angiotensin-converting enzyme inhibitors.
Angiotensin-Converting Enzyme Inhibitors
Captopril is the short-acting active prototype of this group. Enalapril is an oral prodrug that is converted by hydrolysis to an active compound, enalaprilat, with effects similar to those of captopril. Enalaprilat itself is available only for intravenous use, primarily for hypertensive emergencies. Lisinopril is a lysine derivative of enalaprilat. Benazepril, fosinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril are other long-acting members of this class. All are prodrugs, like enalapril, and are converted to active agents by hydrolysis, primarily in the liver.
CLINICAL CORRELATION 17.1
Afro-Caribbean patients respond less ...