Clinical pharmacology, side effects of drugs

1. Domina Petric, MD
Introduction to drug hypersensitivity
reactions involving skin

2. Adverse drug reactions (ADR)
ADR can be classified into type A and type B
reactions.
• Type A reactions: predictable, common,
dose-dependent and related to the
pharmacologic actions of the drug.
• Type B reactions: unpredictable, uncommon,
more or less dose independent within the
therapeutic range and usually not related to
the pharmacologic actions of the drug.
Rawlins and Thompson 1991 2

3. Type A reactions
•It is estimated that approximately 80%
of ADRs belong to the type A category.
Examples are:
•gastrointestinal bleeding after
treatment with NSAIDs
•bradycardia with β-blocker treatment
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4. Type B reactions
Immune-mediated or allergic drug reactions
(hypersensitivity reactions) are type B reactions.
Type B reactions account for 15-20% of all ADR.
Type B reactions are difficult to predict and are often not recognized until
a drug is marketed and widely used in humans.
Lazarou et al. 1998 4

5. Hypersensitivity reactions
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6. Hypersensitivity reactions
• Drug intolerance: an undesired drug effect
produced by the drug at therapeutic or
subtherapeutic doses.
• Idiosyncratic reactions: reactions that are not
explainable in terms of the known pharmacologic
actions of the drug, but are probably due to some
individual genetic predisposition.
• Allergic or hypersensitivity reactions: reactions
that are dependent on one or more immunological
mechanisms.
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7. Allergic reactions
The effector phase of allergic
reactions can be classified
according to Coombs and Gell
into four reactions.
Coombs and Gell 1968 7

8. Allergic reactions
Type I reactions
that are mediated
by drug-specific
IgE antibodies
(mostly
immediate-type
hypersensitivity
reactions).
Type II and III
reactions are
cytotoxic and
immune complex
reactions,
mediated by
drugs pecific IgG
or IgM antibodies.
Type IV reactions
are mediated by
drug-specific T
lymphocytes
(mostly delayed-
type
hypersensitivity
reactions).
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9. • Hausmann O. Schnyder B. Pichler WJ. Drug
Hypersensitivity Reactions Involving Skin. In:
Uetrecht. J. Adverse Drug Reactions.
Springer;2010.p.29-57.
Literature