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Related Concept Videos

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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Hypersensitivity Reactions: Cytolytic Reactions01:01

Hypersensitivity Reactions: Cytolytic Reactions

198
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...
198
Hypersensitivity Reactions: Immune-Complex Reactions01:19

Hypersensitivity Reactions: Immune-Complex Reactions

247
Type III hypersensitivity reactions occur when antigen–antibody complexes form and activate the complement system. Normally, these complexes help the clearance of antigens by phagocytes and red blood cells. However, when large numbers of immune complexes are present, they can deposit in tissues—particularly in the walls of blood vessels—leading to inflammation and tissue injury. These deposits trigger complement activation and neutrophil recruitment, resulting in serum...
247
Allergic Drug Reactions01:27

Allergic Drug Reactions

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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...
1.6K
Drug toxicity: Idiosyncratic Reactions01:16

Drug toxicity: Idiosyncratic Reactions

219
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...
219
Allergic Reactions: Anaphylaxis01:30

Allergic Reactions: Anaphylaxis

267
Anaphylaxis is a severe, life-threatening hypersensitivity reaction mediated by Immunoglobulin E (IgE) antibodies. When IgE binds to allergens, it triggers the release of mediators– histamine, leukotrienes, and prostaglandins from mast cells and basophils. These mediators cause vasodilation, edema, and inflammation, leading to various symptoms.The primary allergens causing anaphylaxis include food items (e.g., peanuts, shellfish), drugs (e.g., penicillin, asparaginase, corticotropin,...
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Adverse reactions associated with systemic polymyxin therapy.

Julie Ann Justo1, John A Bosso

  • 1Department of Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, Columbia and Charleston, South Carolina.

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Polymyxins like colistin and polymyxin B combat resistant infections but cause toxicity. Minimizing nephrotoxicity and neurotoxicity is key, with new monitoring and drug development offering hope.

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Area of Science:

  • Pharmacology and Toxicology
  • Infectious Diseases
  • Nephrology

Background:

  • Systemic polymyxins (colistin, polymyxin B) are vital for treating multidrug-resistant bacterial infections.
  • These antibiotics have a significant history of dose-limiting toxicities, primarily nephrotoxicity and neurotoxicity.
  • Understanding and managing polymyxin toxicity is crucial due to their increasing clinical use.

Purpose of the Study:

  • To review current information on polymyxin toxicity mechanisms, incidence, and risk factors.
  • To summarize strategies for minimizing polymyxin-induced toxicities.
  • To highlight emerging approaches for safer polymyxin use.

Main Methods:

  • Literature review of recent studies on polymyxin toxicity.
  • Analysis of data on nephrotoxicity, neurotoxicity, and hypersensitivity reactions.
  • Examination of emerging therapeutic drug monitoring and novel agent development.

Main Results:

  • Nephrotoxicity is a primary concern, linked to dose and duration of polymyxin therapy.
  • Recent data challenges the notion that colistin is less nephrotoxic than polymyxin B, especially with altered dosing.
  • Neurotoxicities and hypersensitivity reactions are less frequent than nephrotoxicity.

Conclusions:

  • Strategies to minimize polymyxin toxicity are evolving.
  • Therapeutic drug monitoring and development of less toxic polymyxin derivatives are promising.
  • Careful management is essential for effective treatment of multidrug-resistant infections with polymyxins.