By Michael Holt, Cynthia Ju (auth.), Jack Uetrecht (eds.)
This booklet offers the present nation of information of simple mechanisms of inauspicious drug reactions (ADRs). the focus is on idiosyncratic drug reactions simply because they're the main tough to accommodate. It begins with a common description of the foremost pursuits for ADRs via an outline of what are almost immediately believed to be mediators and biochemical pathways serious about idiosyncratic drug reactions. there's additionally an outline of a number of examples of ADRs that serve to demonstrate particular points of ADR mechanisms. finally the e-book indicates that finally larger equipment are had to expect which drug applicants are inclined to reason ADRs and which sufferers are at elevated threat. yet at the present examine appears faraway from this goal.
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Extra resources for Adverse Drug Reactions
Some therapeutic proteins such as mouse antibodies are intrinsically immunogenic because they represent foreign macromolecules. Many drugs, however, are neither proteins nor peptides, but are novel, unique structures and have a molecular mass of less than 1 kD. According to classical immunology (Landsteiner and Jacobs 1935), small molecules are not complete antigens and were considered to be incapable of directly inducing an immune response by priming of naı¨ve T cells in their native state. For these agents to become immunogenic they must be chemically reactive (=haptens) and must be able to covalently bind to high molecular mass proteins (hapten-carrier complexes), which then undergo antigen processing and presentation, and are able to induce a novel immune response.
2 Acute Generalized Exanthematous Pustulosis (AGEP) . . . . . . . . . . . . . . . . 3 Bullous Exanthema, Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Drug (-Induced) Hypersensitivity Syndrome (DHS or DiHS) or Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) . . . . . . . . . . . . . 5 Multiple Drug Hypersensitivity Syndrome . .
2006). This p-i concept adapted to the skin could explain: (a) The preferential localization of drug hypersensitivity to the skin following oral or parental drug uptake. Other organs do not have such highly reactive sentinel T cells – and therefore the tissue is not “alarmed”, and activated T cells, even if they would express the appropriate homing receptors, cannot migrate there so easily. (b) The dose dependency of many drug hypersensitivity reactions. Higher concentrations of drugs are more often associated with delayed drug hypersensitivity reactions (Uetrecht 2001), and higher doses would lead to higher tissue concentrations and thus a better stimulation of T cells.
Adverse Drug Reactions by Michael Holt, Cynthia Ju (auth.), Jack Uetrecht (eds.)