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Drug Toxicity: Allergic Reactions01:30

Drug Toxicity: Allergic Reactions

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Drug-related allergies are immune-mediated responses triggered by the administration of pharmacological agents. These hypersensitivity reactions are classified based on the immune mechanisms involved. The four primary types—Type I, II, III, and IV—are mediated by different immunological pathways and exhibit distinct clinical manifestations.Type I Hypersensitivity/ IgE-Mediated Reactions: Immunoglobulin E (IgE) immediately mediates Type I hypersensitivity reactions. Upon initial...
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Allergic reactions related to drugs are hypersensitivity responses driven by the immune system and bear no connection to the drug's therapeutic action. While drugs in isolation do not trigger an immune response, they can interact with endogenous proteins to form antigens. These antigens stimulate lymphocytes to produce antibodies. IgE-type antibodies attach themselves to mast cells. Upon subsequent exposure to the same stimulus, the antigen-antibody interaction is initiated, unleashing...
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Drug toxicity: Idiosyncratic Reactions01:16

Drug toxicity: Idiosyncratic Reactions

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Idiosyncratic drug reactions represent abnormal chemical responses that vary significantly among individuals, ranging from extreme sensitivity to low doses to insensitivity to high doses. These reactions often occur due to the drug's covalent binding with serum proteins, forming a foreign hapten that triggers an immunotoxicological response. The variability in drug reactions has a strong pharmacogenetic foundation, with genetic differences crucial in how individuals metabolize drugs. For...
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Hypersensitivities01:30

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Hypersensitivity, also known as a hypersensitivity reaction or allergic reaction, is a condition where the body's immune system reacts abnormally to a foreign substance. Such substances, that cause hypersensitivity are referred to as an allergen, could be something typically harmless to most people, like pollen or certain foods.
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Hypersensitivity Reactions: Cytolytic Reactions01:01

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Type II hypersensitivity involves IgG and IgM antibodies targeting cell surface antigens, leading to cell destruction. This can occur through complement activation, antibody-dependent cell-mediated cytotoxicity (ADCC), or acting as opsonins for phagocytosis. When excessive, these reactions cause significant tissue damage.Drug-induced hemolytic anemia is a common example, where drugs like penicillin or cephalosporins bind to red blood cells, forming drug-protein complexes. These complexes...
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Drug Toxicity: Overview01:00

Drug Toxicity: Overview

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Drug toxicity quantifies the harm a compound causes to an organism, varying by dose and potentially impacting whole systems or specific organs like the liver. Toxic reactions may arise from venomous insect or spider bites, with effects ranging from mild symptoms to severe outcomes such as brain damage or death. Common forms of acute poisoning include ethanol intoxication and overdose of pain or fever medications, with substances like GHB and heroin being particularly lethal at doses close to...
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Multiple Drug Hypersensitivity.

Werner J Pichler1, Yuttana Srinoulprasert, James Yun

  • 1ADR-AC, Bern, Switzerland.

International Archives of Allergy and Immunology
|March 20, 2017
PubMed
Summary
This summary is machine-generated.

Multiple drug hypersensitivity (MDH) is a syndrome of T-cell overstimulation causing prolonged reactions to various drugs. This condition results in diverse, severe symptoms and long-lasting T-cell activation, impacting patients for years.

Keywords:
Drug hypersensitivityDrug rash with eosinophilia and systemic symptomsMaculopapular exanthemaMultiple drug hypersensitivityp-i concept

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Area of Science:

  • Immunology
  • Dermatology
  • Pharmacology

Background:

  • Multiple drug hypersensitivity (MDH) is a clinical syndrome characterized by severe, long-lasting drug hypersensitivity reactions (DHR) to structurally unrelated drugs.
  • MDH often begins with severe exanthems or drug rash with eosinophilia and systemic symptoms (DRESS), followed by subsequent DHRs weeks to years later.
  • The syndrome results from massive T-cell stimulations, leading to persistent T-cell activation.

Purpose of the Study:

  • To define the characteristics and underlying mechanisms of Multiple Drug Hypersensitivity (MDH).
  • To elucidate the clinical presentation and immunological basis of MDH.
  • To identify key T-cell activation markers in MDH patients.

Main Methods:

  • Analysis of clinical presentations and patient histories of MDH.
  • Identification of eliciting drugs through skin and in vitro tests.
  • Assessment of T-cell activation markers, including PD-1+/CD38+ expression on CD4+/CD25low T cells.

Main Results:

  • MDH involves long-lasting DHRs to multiple drugs, often starting with DRESS-like symptoms.
  • Fixed drug combinations like sulfamethoxazole/trimethoprim and piperacillin/tazobactam are frequently implicated.
  • Patients exhibit permanent T-cell activation, indicated by sustained PD-1+/CD38+ expression on specific T-cell subsets, for years.

Conclusions:

  • MDH is a drug-induced syndrome characterized by persistent T-cell hyperresponsiveness to diverse drugs.
  • The p-i mechanism is implicated in drug-induced T-cell stimulation in MDH.
  • Long-term T-cell activation is a hallmark of MDH, contributing to its chronic nature.