05.01.1.1 Types

Adverse drug effects have been classified as 3 types; A, B, and C. A is for Augmentation. These side effects are extensions of the drug actions. This can be because the same binding site underlies beneficial and adverse effects of the drug. For instance, digoxin is used to increase the force of the heart beat in people with heart failure. Digoxin is a Na⁺K⁺-ATPase inhibitor. Inhibition of the cardiac Na⁺K⁺-ATPase produces both the beneficial effect (increased heart force) and adverse effects (cardiac arrhythmias) of digoxin on the heart. In addition, Na⁺K⁺-ATPase is present in all cells. Inhibition by digoxin of Na⁺K⁺-ATPase in non-cardiac cells for can cause other adverse effects, such as blurred vision and visual disturbances.

Another example of Type A adverse effects is when drugs that show limited selectivity for a binding site cause a beneficial action at their target binding site but an adverse effect at another binding site. For example, atenolol is a selective β₁-adrenoceptor antagonist that has a beneficial effect (antihypertensive) by blocking the cardiac β₁-adrenoceptor to decrease heart rate and force. However, as atenolol is only selective, not specific, for β₁-adrenoceptors, this means that atenolol will also have some effect at β₂-adrenoceptors. β₂-adrenoceptors mediate bronchodilation and some metabolism relating to glucose. The β₂-adrenoceptor blocking action of atenolol is such that it is contraindicated (not to be used) in asthmatics.

In type B adverse effects, the B is for Bizarre or idiosyncratic, adverse effects. For these adverse effects, we do not know what the exact mechanism is. Type B adverse effects include allergy. As drugs are foreign to the body, it is not surprising that allergic reactions to drugs are common. Drug allergy occurs when the body forms antibodies to a particular drug, causing an immune response when the person is re-exposed to a drug. Thus, the allergic response is small on first exposure, but can be large on subsequent exposure. The reason for asking new patients “Are you allergic to any drugs?” is to avoid major allergic responses. People who are allergic to the penicillins develop a rash on first exposure. In addition, on repeated exposure, people allergic to penicillin develop angioedema (marked swelling of the lips, tongue, and face) and anaphylaxis (respiratory distress, hypotension, unconsciousness).

In type C adverse effects, the C is for Continuous. These adverse effects are a consequence of continuous (long term) use of drug. An example is with the continuous use of some of the older drugs for schizophrenia, such as haloperidol. Schizophrenia is an ongoing condition requiring continuous medication. However, the long term use of haloperidol can lead to tardive dyskinesia. Tardive dyskinesia is uncontrollable lip smacking, tongue darting, constant chewing movements, and tics. Some people also have jerky, uncontrolled movements of arms and legs.