Related Experiment Video
Updated: Aug 9, 2026
13:38
Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells
Published on: January 18, 2017
Mechanisms of aspirin sensitivity
1Pneumology and Respiratory Allergy Service, University of Barcelona Hospital Clinic, Villarroel 170, 08036 Barcelona, Barcelona, Spain. cpicado@ub.edu
Current Allergy and Asthma Reports
|April 4, 2006
Summary
Nonsteroidal anti-inflammatory drug (NSAID) intolerance in asthma is linked to altered arachidonic acid metabolism. NSAID-induced reactions may stem from cyclooxygenase-1 inhibition, increasing cysteinyl leukotrienes.
Area of Science:
- Immunology
- Pharmacology
- Biochemistry
Background:
- Some asthma patients experience adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs), including bronchospasm and nasal symptoms.
- These reactions are associated with cyclooxygenase-1 (Cox-1) inhibition, leading to increased cysteinyl leukotrienes (Cys-LTs) via the lipoxygenase pathway.
Purpose of the Study:
- To investigate the metabolic changes in arachidonic acid (AA) associated with NSAID intolerance in asthma.
- To explore the underlying mechanisms connecting NSAID-induced reactions to specific biochemical alterations.
Main Methods:
- Analysis of arachidonic acid metabolism in NSAID-intolerant asthmatic patients.
- Observation of prostaglandin E2 production, leukotriene-C4 synthase expression, and lipoxin production.
- Measurement of basal and provoked Cys-LT levels in NSAID-intolerant versus NSAID-tolerant asthmatics.
Main Results:
- NSAID-intolerant asthmatics show low prostaglandin E2 production, potentially due to deficient Cox-2 regulation.
- Increased expression of leukotriene-C4 synthase and reduced production of lipoxins were observed.
- Higher basal Cys-LT levels and significant increases post-NSAID provocation were noted in intolerant individuals.
Conclusions:
- A distinct pattern of arachidonic acid metabolism characterizes NSAID-intolerant asthmatics.
- An anomaly in cyclooxygenase-2 (Cox-2) regulation is a likely factor contributing to these observed metabolic changes and NSAID hypersensitivity.
Related Concept Videos
01:30Drug toxicity: Drug–Drug Interaction
Drug–drug interactions can precipitate toxicity through multiple mechanisms. Absorption interactions alter how drugs enter the body, exemplified when ranitidine increases the absorption of basic drugs, while cholestyramine decreases the levels of propranolol. Protein binding interactions occur when drugs share the same binding sites on plasma proteins. Drugs like aspirin and warfarin, when bound in excess, can lead to increased free drug concentrations, enhancing the potential for...
01:20Desensitization and Tachyphylaxis
Tachyphylaxis is described as a rapid decrease in response to a drug after repeated or continuous administration of the same drug dose. It is a phenomenon where the body becomes less responsive to a particular substance or intervention over time, requiring higher doses or stronger interventions to achieve the same effect. It results from adaptive changes in the body's receptors, signaling pathways, or physiological processes that occur in response to prolonged exposure to a stimulus.
Several...
Several...
01:16Drug toxicity: Idiosyncratic Reactions
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...
01:25Dose-Response Relationship: Selectivity and Specificity
Drugs exert their therapeutic effects by interacting with receptors, enzymes, or ion channels that are present throughout the human body. The strength and duration of the interaction between a drug and its target receptor are characterized by the selectivity and specificity of the drug. Selectivity refers to a drug's strong preference for its intended target over other targets. For instance, isoprenaline, a non-selective β-adrenergic agonist, interacts with both β1- and β2-adrenergic receptors...
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
01:24Drug Toxicity: Risk factors
Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...