Adverse drug reactions
A drug’s desired effect is called the expected therapeutic re-sponse. An adverse drug reaction (also called a side effect or ad-verse effect), on the other hand, is a harmful, undesirable re-sponse. Adverse drug reactions can range from mild ones that dis-appear when the drug is discontinued to debilitating diseases that become chronic. Adverse reactions can appear shortly after start-ing a new medication but may become less severe with time.
Adverse drug reactions can be classified as dose-related or patient sensitivity–related. Most adverse drug reactions result from the known pharmacologic effects of a drug and are typically dose-related. These types of reactions can be predicted in most cases.
Dose-related reactions include:
· secondary effects
· iatrogenic effects.
A drug typically produces not only a major therapeutic effect but also additional, secondary effects that can be harmful or benefi-cial. For example, morphine used for pain control can lead to two undesirable secondary effects: constipation and respiratory de-pression. Diphenhydramine used as an antihistamine produces se-dation as a secondary effect and is sometimes used as a sleep aid.
A patient can be hypersusceptible to the pharmacologic actions of a drug. Such a patient experiences an excessive therapeutic re-sponse or secondary effects even when given the usual therapeu-tic dose.
Hypersusceptibility typically results from altered pharmacoki-netics (absorption, metabolism, and excretion), which leads to higher-than-expected blood concentration levels. Increased recep-tor sensitivity also can increase the patient’s response to therapeu-tic or adverse effects.
A toxic drug reaction can occur when an excessive dose is taken, either intentionally or by accident. The result is an exaggerated re-sponse to the drug that can lead to transient changes or more seri-ous reactions, such as respiratory depression, cardiovascular col-lapse, and even death. To avoid toxic reactions, chronically ill or elderly patients often receive lower drug doses.
Some adverse drug reactions, known as iatrogenic effects, can mimic pathologic disorders. For example, such drugs as antineo-plastics, aspirin, corticosteroids, and indomethacin commonly cause GI irritation and bleeding. Other examples of iatrogenic ef-fects include induced asthma with propranolol, induced nephritis with methicillin, and induced deafness with gentamicin.
Patient sensitivity–related adverse reactions aren’t as common as dose-related reactions. Sensitivity-related reactions result from a patient’s unusual and extreme sensitivity to a drug. These adverse reactions arise from a unique tissue response rather than from an exaggerated pharmacologic action. Extreme patient sensitivity can occur as a drug allergy or an idiosyncratic response.
A drug allergy occurs when a patient’s immune system identifies a drug, a drug metabolite, or a drug contaminant as a dangerous foreign substance that must be neutralized or destroyed. Previous ex-posure to the drug or to one with similar chemical characteristics sensitizes the patient’s immune system, and subsequent exposure causes an allergic reaction (hypersensitivity).
An allergic reaction not only directly injures cells and tissues but also produces broader systemic damage by initiating cellular release of vasoactive and inflammatory substances.
The allergic reaction can vary in intensity from an immediate, life-threatening anaphylactic reaction with circulatory col-lapse and swelling of the larynx and bronchioles to a mild reaction with a rash and itching.
Some sensitivity-related adverse reactions don’t result from pharmacologic properties of a drug or from an allergy but are specific to the individual patient. These are called idio-syncratic responses. Some idiosyncratic responses have agenetic cause.