Adverse drug reactions (ADRs) are unfavorable responses to medications that pose significant challenges in healthcare. They are prevalent and contribute to increased morbidity, mortality, hospitalizations, and healthcare costs. The U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) recorded over 1.25 million serious adverse events and nearly 175,000 deaths in 2022. ADRs lead to six emergency department visits per 1,000 patients, with 38% resulting in hospitalization, and are implicated in 3 out of every 1,000 hospital admissions leading to patient deaths. Consequently, healthcare professionals must prioritize identifying, treating, and preventing ADRs to mitigate their impact.
The International Conference on Harmonization (ICH), including the World Health Organization (WHO) and the FDA, defines an ADR as an unintended and harmful response to a drug at standard doses used for prophylaxis, diagnosis, therapy, or physiological function modification. In contrast, an adverse drug event is any undesirable occurrence during treatment with a pharmaceutical, regardless of causal relation to the treatment. Thus, an ADR specifically denotes an adverse event with a causal link to a drug. Edwards et al. expanded this definition, emphasizing ADRs as harmful or unpleasant reactions that predict future hazards and necessitate preventive or specific treatment measures.
ADRs are categorized into Type A and Type B reactions, each with subcategories.
Type A reactions result from known pharmacological properties and are common, accounting for 85% to 90% of ADRs. These include:
Type B reactions are unpredictable, not related to known pharmacological properties, and include:
Hypersensitivity Reactions:
| Type of Hypersensitivity Reaction | Mediators & Characteristics | Onset & Symptoms | Drug Examples |
|---|---|---|---|
| Type I | IgE, mast cells, basophils | Immediate; urticarial rash, pruritus, flushing; severe cases may lead to angioedema, hypotension, anaphylaxis | Beta-lactams, quinolones, platinum-containing chemotherapeutic agents |
| Type II | IgG, IgM binding cellular/extracellular matrix antigens | Late onset (5-8 days); cellular destruction, tissue damage | Cephalosporins, penicillin, heparin, apixaban, quinidine, sulfonamides, propylthiouracil, flecainide |
| Type III | Immune complexes, complement activation | Delayed onset (weeks); occurs in tissues like joints, kidneys, blood vessels | Equine-antitoxins, monoclonal antibodies, penicillins, cephalosporins, phenytoin, diphtheria and tetanus vaccines |
| Type IV | T cells; cytokine release by various cells | Delayed onset; subtypes include IVa (macrophages), IVb (eosinophils), IVc (T cells), IVd (neutrophils) | Contact dermatitis, AGEP, SJS, DiHS, DRESS |
Other Immunological Reactions: Include drug-induced autoimmunity and fixed drug eruptions.
Idiosyncratic Reactions: Non-immunologic, often due to genetic variations or exaggerated sensitivity.
Pseudoallergic Reactions: Resemble allergic reactions but lack immunologic initiation, such as vancomycin flushing syndrome.
Certain ADRs, like anaphylaxis, Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), Acute Generalized Exanthematous Pustulosis (AGEP), and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), pose significant morbidity and mortality risks. Anaphylaxis, a Type I hypersensitivity reaction, can be life-threatening and requires prompt identification and causative drug determination. SJS and TEN involve severe skin detachment, while AGEP causes rapid pustule development. DRESS presents with extensive rash and systemic involvement, potentially leading to organ failure.
Understanding and addressing these ADRs is crucial for enhancing patient safety and improving healthcare outcomes.