Changing beta-blockers in heart failure: when is a class not a class?

Are all the drugs in a class the same? Take the COX-2 inhibitors, for example. Rofecoxib increases the risk of a heart attack or stroke; but do other COX-2 inhibitors, such as celecoxib, do likewise? In other words, is this adverse effect of rofecoxib a class effect? The concept of grouping compounds in classes is useful, because it prompts questions regarding their similarities and differences. But what makes a class?

The short answer is that drug class is best defined by the most important attribute of a drug: its main pharmacological target of action. Because the target is so important, the terms ‘on-target’ and ‘off-target’, originally invented in the context of drug discovery, are sometimes used to differentiate drug actions. However, in colloquial parlance not all drug classes are named according to their target, even in the World Health Organization's Anatomical Therapeutic and Chemical (ATC) drug classification system1 (Table 1). The idea of a class of drugs, even when it is based on the pharmacological target, is one that does not always bear close scrutiny, for several reasons.

Firstly, the main pharmacological target may not be known. Secondly, some classes of drugs, such as monoclonal antibodies, have no common target, although they may have some effects in common, such as adverse effects. Thirdly, some drugs have more than one main target: spironolactone, for example, is an antagonist at aldosterone receptors through its active metabolite canrenone, which is why it is a potassium-sparing …