ADR

Adverse Drug Reaction (ADR)

Unintended, harmful events attributed to the use of medicines. This includes authorised use, error, misuse, off-label or unlicensed use.

Undesirable/Unwanted Effects (or Side Effects)

Toxic (harmful) and non-toxic drug effects observed with drug therapy, may be expected.

Toxicity

All possible toxic drug effects with any use/dose (poisoning and overdoses included).

Dose Related ADRs (Type A)

Predictable or intrinsic ADRs. They are common (80-95% of cases), usually have low mortality, are an extension of pharmacological effects (predictable toxic effects), and their severity is proportional to dose. They can often be treated or prevented by dose adjustment.1. same receptor same tissue2. same receptor diff tissu3. diff receptor

Unrelated to Dose ADRs (Type B)

Unpredictable or idiosyncratic ADRs. They are less common (5-15% of cases), have higher mortality, are not related to the known pharmacology of the drug, and their severity is disproportionate to the dose. Examples include hypersensitivity reactions and Stevens Johnson Syndrome/Toxic Epidermal Necrolysis.

Genetic ADRs

Adverse reactions where a patient's genetic make-up predisposes them to the reaction.

Allergic ADRs

Immunologic reactions resulting from previous sensitization to a particular chemical or one structurally related.

Chronic Effects (Type C ADRs)

ADRs seen with long-term drug use, such as toxicity due to dose accumulation or dependence.

Delayed Effects (Type D ADRs)

ADRs with a delayed onset, such as carcinogenicity or teratogenicity.

End of Treatment Effects (Type E ADRs)

ADRs seen when a drug is stopped.

Failure of Treatment (Type F ADRs)

Adverse outcomes where the drug does not produce the intended therapeutic effect.

DoTs

An acronym referring to factors contributing to failure of therapy: Dose of drug, Time course of reaction, and Susceptibility factors. This is a more inclusive categorization that considers diagnosis and prevention.

Pharmacovigilance

The science and activities relating to the detection, assessment, understanding and prevention of adverse events or any other drug-related problem (World Health Organization definition).

Clinical Trials (in ADR Monitoring)

Studies during drug development that can assess incidence rates of ADRs, confirm causal associations, and account for differences in patient populations. They often compare drugs.

Prescription-linked Databases

Databases (e.g., GPRD, Medicare, PacifiCare) that are part of regulatory bodies and provide unbiased, large amounts of information (complete patient records) which can be used to monitor ADRs and study comparative groups.

Cohort Studies

Studies that follow a group of people (e.g., with and without a disease, taking and not taking a drug) prospectively or retrospectively to determine the risk of ADRs.

Case-Control Studies

Studies that compare individuals with an ADR to individuals without the ADR to identify potential drug exposures or other risk factors.

Market Withdrawals

The removal of a drug from the market due to safety issues, such as teratogenicity (Thalidomide, Diethylstilbestrol), hepatotoxicity (Ticrynafen, Troglitazone), or cardiac arrhythmia (Grepafloxacin, Cisapride, Terfenadine, astemizole).

Causality Assessment (in ADRs)

Determining the degree of probability that a drug caused a specific adverse event, often complicated by the presence of other drugs and underlying diseases.

Severity of ADR

A factor clinicians must consider when managing ADRs, ranging from mild and self-limiting to severe and life-threatening.

Seriousness of Disease

A factor clinicians must consider when managing ADRs, weighing the potential harm of the ADR against the need to treat the underlying condition.

Alternative Treatment Options

A factor clinicians must consider when managing ADRs, evaluating whether safer or more effective alternatives are available.

Benefit vs. Harm (of Treatment)

The fundamental consideration in managing ADRs, weighing the therapeutic benefits of a drug against the potential harm caused by its adverse effects.

effects of the same receptor in same tissues

warfarin. toxicities result as extension of drug theraputic action

effects of same receptor in different tissue

digoxin. treatment of heart failure causes an inc force of contraction. Impairs renal function

effects mediated by different receptor subtypes

BAdrenergic drugs. Multiple Rs can be tissue and physiologically distinct

Type 1: Anaphylactic or Hypersensitivity (immediate)

This involves an allergen (drug) reacting with IgE antibody on mast cells and basophils, leading to the release of histamine, leukotrienes, and prostaglandins. Examples include hives, airway constriction, and penicillin allergy

Type 2: Cytotoxic/complement-fixing

This type involves antibody (IgG) interaction with antigen (drug) on the cell surface (blood cells), resulting in complement fixation and cell lysis. Examples include hemolytic anemia with methyldopa, agranulocytosis with sulfas, and thrombocytopenic purpura with ASA or phenytoin

Type 3: Toxic Immune-Complex

This involves antigen-antibody complexes depositing on target tissue cells, leading to complement activation, neutrophil attraction, and tissue destruction. Examples include serum sickness, glomerulonephritis, and reactions to allopurinol, captopril, penicillins, and phenytoin

Type 4 Cell-mediated (delayed)

This type involves an allergen (the drug) plus sensitized lymphocytes leading to the release of cytokines. It can cause eczematous and contact dermatitis (e.g., with topical antihistamines or PABA) and delayed hypersensitivity reaction syndrome (fever, rash, internal organ involvement), as seen with aromatic anticonvulsants like phenytoin and carbamazepine, sulfonamides, allopurinol, and NSAIDs, as well as Stevens Johnson Syndrome/Toxic Epidermal Necrolysis

Post marketing surveillance

1. spontaneous reporting 2. use of databases 3. cohort studies 4. case control studies