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
·
hypersusceptibility
·
overdose
·
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.
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