Spectrum of Undesired Effects of Drugs

The spectrum of undesired effects of chemicals is broad. In therapeutics, for example, each drug produces a number of effects, but usually only one effect is associated with the primary objective of the therapy; all the other effects are referred to as undesirable effects or side effects. However, some of these side effects may be desired for another therapeutic indication. Some side effects of drugs are always deleterious to the well-being of humans. They are referred to as the adverse, deleterious, or toxic effects of a drug.

 

 

1. Allergic Reactions

Chemical allergy is an immunologically mediated adverse reaction to a chemical resulting from previous sensitization to that chemical or to a structurally similar one. The terms hypersensitivity, allergic reaction, and sensitization reaction are used to describe this situation. Once sensitization has occurred, allergic reactions may result from exposure to relatively very low doses of chemicals; therefore, population-based dose–response curves for allergic reactions seldom have been obtained. However, for a given allergic individual, allergic reactions are dose-related. Sensitization reactions are sometimes very severe and may be fatal.

Most chemicals and their metabolic products are not sufficiently large to be recognized by the immune system as foreign substances and thus must first combine with an endogenous protein to form an antigen (or immunogen). This type of molecule is called a hapten. The hapten-protein complex (antigen) is then capable of eliciting the formation of antibodies. Subsequent exposure to the chemical results in an antigen–antibody interaction, which provokes typical manifestations of allergy that range in severity from minor skin disturbance to fatal anaphylactic shock.

2. Idiosyncratic Reactions

Chemical idiosyncrasy refers to genetically determined abnormal reactivity to a chemical. The response observed is usually qualitatively similar to that observed in all individuals but may take the form of extreme sensitivity to low doses or extreme insensitivity to high doses of the chemical.

3. Immediate versus Delayed Toxicity

Immediate toxic effects occur or develop rapidly after a single administration of a substance, whereas delayed toxic effects occur after the lapse of some period of time. Carcinogenic effects of chemicals usually have long latency periods, often 20 to 30 years after the initial exposure, before tumors are observed in humans.

4. Reversible versus Irreversible Toxic Effects

Some toxic effects of chemicals are reversible, and others are irreversible. If a chemical produces pathological injury to a tissue, the ability of that tissue to regenerate largely determines whether the effect is reversible or irreversible. For liver, with its high regeneration ability, most injuries are reversible, whereas injury to the central nervous system (CNS) is largely irreversible because the differentiated cells in the CNS cannot be replaced. Carcinogenic and teratogenic effects of chemicals, once they occur, usually are considered irreversible toxic effects.

5. Local versus Systemic Toxicity

Another distinction between types of effects is made on the basis of the general site of action. Local effects occur at the site of first contact between the biological system and the toxicant. In contrast, systemic effects require absorption and distribution of a toxicant from its entry point to a distant site at which deleterious effects are produced. Most substances except highly reactive materials produce systemic effects. For some materials, both effects can be demonstrated.

Most chemicals that produce systemic toxicity usually elicit their major toxicity in only one or two organs, which are referred to as the target organs of toxicity of a particular chemical. The target organ of toxicity is often not the site of the highest concentration of the chemical.

Target organs, in order of frequency of involvement in systemic toxicity, are the CNS; the circulatory system; the blood and hematopoietic system; visceral organs such as the liver, kidney, and lung; and the skin. Muscle and bone are seldom target tissues for systemic effects.