Adverse drug reactions

There are several terms commonly used to describe adverse effects of drug therapy:

An adverse drug reaction (ADR) is an unwanted or harmful reaction experienced following the administration of a drug or combination of drugs under normal conditions of use and is suspected to be related to the drug. An ADR will usually require the drug to be discontinued or the dose reduced.
An adverse event is harm that occurs while a patient is taking a drug, irrespective of whether the drug is suspected to be the cause.
A side-effect is any effect caused by a drug other than the intended therapeutic effect, whether beneficial, neutral or harmful. The term ‘side-effect’ is often used interchangeably with ‘ADR’ although the former usually implies an effect that is less harmful, predictable and may not even require discontinuation of therapy (e.g. ankle oedema with vasodilators).
Drug toxicity describes adverse effects of a drug that occur because the dose or plasma concentration has risen above the therapeutic range, either unintentionally or intentionally (drug overdose).
Drug abuse is the misuse of recreational or therapeutic drugs that may lead to addiction or dependence, serious physiological injury (such as damage to kidneys, liver, heart), psychological harm (abnormal behavior patterns, hallucinations, memory loss), or death.

Adverse drug reactions - basic principles

Any drug that is capable of producing beneficial therapeutic effects can also cause unwanted ‘adverse’ effects. Adverse drug reactions (ADRs) are therefore common and constitute an important public health challenge in their own right. A significant proportion of admissions to hospital are caused by ADRs and hospitalised patients frequently experience ADRs that complicate and prolong their stay. Many of these ADRs can be avoided if greater care is taken. All prescribers need to make a judgment about the likelihood that a patient will either gain from the beneficial effects or experience an ADR before prescribing. Some drugs rarely cause ADRs (e.g. paracetamol) while others frequently do so (e.g. cancer chemotherapy). The decision to prescribe these ‘higher risk’ drugs will depend on the extent of the potential benefits. Although prescribers always face the possibility of causing an ADR the risks of doing so can be minimised by (i) recognition of patient and drug factors that increase the susceptibility and (ii) by counselling patients about early indications that an ADR may be developing.

Understanding adverse drug reactions and drug allergies: principles....

This 22-page open-access article published by Zahra Pourpak et al. in the Journal Recent Patents on Inflammation & Allergy Drug Discovery, describes in detail the WHO definition of adverse drug reactions (ADRs), the common features, classification according to Rawlins and Thompson and beyond. The authors also provide a comprehensive description of predictable Type A, which is dose-related pharmacological effects and the unpredictable, bizarre, Type B hypersensitivity reactions. Tables 1 and 2 detail the common examples of clinical and genetic risks of Type B ADRs. From page 6 onward, the authors describe the details in ADRs reporting. It provides a useful prerequisite link for those who want to explore further about the immunological mechanisms of drug hypersensitivity. In the last 14 pages, the diagnosis of ADRs with specific examples of antibiotics, non-steroidal anti-inflammatory drugs and local anesthetics are discussed. This article provides comprehensive and useful tips for risk detection and reporting, and assessing suspected ADRs or drug allergies in a clinically relevant manner.

Module 1 – Basic principles of adverse drug reactions

This is one of a set of webpages containing key information relevant to understanding the importance of ADRs in modern healthcare. This module contains an introduction, outlines how ADRs are defined in the EU, and includes a case study to test the outcome of your learning process. Suitable for intermediate level learners. These learning resources were developed by the Yellow Card Centre (YCC) Scotland in conjunction with NHS Education for Scotland (NES). The modules are suitable for intermediate level learners.

WHO Medication Safety Curriculum Guide 2019.pdf

The Medication Safety Curriculum Guide was produced to support implementation of the Third WHO Global Patient Safety Challenge: Medication Without Harm, that was launched in 2017. It provides an overview of those aspects of medication safety that should be taught to undergraduate and postgraduate health care students and practicing health professionals, their educators, and relevant professional bodies. Key areas associated with significant patient harm due to unsafe medication practices are presented in detail: Polypharmacy, Transitions of care and High-risk situations.

Adverse drug reactions - categorisation

Adverse drug reactions (ADRs) are a significant cause of morbidity and mortality. They have historically been classified as either Type A or Type B.

Type A ADRs relate to the mechanism of action (i.e. the known pharmacology) of the medication, and are associated with high morbidity and low mortality.
Clinical examples of Type A ADRs are common and physicians often need to reduce the dosages of the medicine so that the patients can tolerate the treatment. Patients can be empowered to be aware of the ADRs and reduce the incidence of unnecessary Type A ADRs.

In contrast, Type B ADRs are idiosyncratic and cannot be predicted from the known pharmacology of a drug. These reactions are associated with low morbidity and high mortality. Formal recording of the incidence of Type B reactions can be life-saving.

Additional categories of ADRs are described in an article by Kaufman that was published in 2016 (PMID: 27507394).

Classifying_Adverse_Drug_Reactions.pdf

This is a set of teaching slides on Adverse Drugs Reactions for beginners. The author defines and classifies "ADRs" and provides common examples of Type A and Type B ADRs. Contributed to the PEP by Chay-Hoon Tan, National University Of Singapore.

Adverse drug reactions (ADRs) are a significant cause of morbidity and mortality. They have historically been classified as either Type A or Type B.

Additional categories of ADRs are described in an article by Kaufman that was published in 2016 (PMID: 27507394).

Module 2 – Categorisation

This is one of a set of webpages containing key information relevant to understanding the importance of ADRs in modern healthcare. This specific module compares the ABCDE and DoTS (Dose-related, Time related, Susceptibility) systems that are used to classify ADRs, and includes case studies to test the outcome of your learning process. These learning resources were developed by the Yellow Card Centre (YCC) Scotland in conjunction with NHS Education for Scotland (NES). The modules are suitable for intermediate level learners.

Adverse drug reactions - drug allergy

Allergic drug reactions account for only 5 to 10% of all adverse drug reactions. Any medication has the potential to cause an allergic reaction. Skin reactions (e.g. urticaria, erythema) are the most common form of allergic drug reaction, but can also include cough, nausea, vomiting, diarrhea, and headaches, and in severe cases can cause anaphylaxis.

Medscape- Stevens-Johnson Syndrome. Author: C Stephen Foster (2016)

There are many published reports on Stevens-Johnson syndrome (SJS) and the classification can be confusing. This 12-page Medscape article written by Stephen Foster describes the classification, background, clinical presentation, pathophysiology, etiology, epidemiology and prognostic factors of SJS.

This article has many clinical photos on the various presentations of SJS and the severe form, toxic epidermal necrolysis.

The article also contains a list of drugs that are often associated with SJS. This resource serves as good reference for all levels of readers.

Note that users need to register with Medscape for free access, to be able to read the full article.

NICE: Drug allergy: diagnosis and management

Clinical guideline [CG183] Published date: September 2014

This UK guideline covers diagnosing and managing drug allergy in all age groups. Although aimed primarily at healthcare professionals, the Guidelines may also help patients and their carers gain an improved understanding of their drug allergies.

User level: Advanced (healthcare professionals)

Module 3 – Drug allergy classification

This is one of a set of webpages containing key information relevant to understanding the importance of ADRs in modern healthcare. This specific module looks at drug allergy as a sub-group of Type B ADRs. It includes case studies to test the outcome of your learning process. These learning resources were developed by the Yellow Card Centre (YCC) Scotland in conjunction with NHS Education for Scotland (NES). The modules are suitable for intermediate level learners.

Adverse drug reactions - diagnosis and management

ADRs can be difficult to diagnose for many reasons. They may mimic the symptoms of a common illness, they may be rare or unexpected, or in patients with multiple co-morbidities or being treated with several drugs, the drug-related symptoms are not obvious. Healthcare professionals therefore have to be vigilant and alert to drug reactions as a causative factor when there is an absence of alternative clinical explanations for the presenting symptoms. Whilst laboratory investigations, are unlikely to confirm an ADR, they can be useful tools to exclude non-drug causes of the presenting symptoms or signs. Once a diagnosis of ADR is made, management will depend on the category of ADR. Type A ADRs generally respond to a reduction in dosage, whilst Type B ADRs indicate immediate discontinuation of the offending drug.

Module 4 – Diagnosis, interpretation and management

This is one of a set of webpages containing key information relevant to understanding the importance of ADRs in modern healthcare. This specific module outlines some of the underlying difficulties experienced by healthcare professionals in identifying patient presentations as ADRs, and offers solutions to help overcome these difficulties, so as to move towards more accurate diagnosis, interpretation and management of ADRs. The module includes case studies to test the outcome of your learning process. These learning resources were developed by the Yellow Card Centre (YCC) Scotland in conjunction with NHS Education for Scotland (NES). The modules are suitable for intermediate level learners.

Adverse drug reactions - avoiding adverse drug reactions

The risk of developing ADRs arises from a combination of patient-related factors and the drug or drugs being prescribed. The level of risk is minimised by changing prescribing, providing appropriate warnings and undertaking relevant monitoring.

Module 5 – Avoiding adverse drug reactions

This is one of a set of webpages containing key information relevant to understanding the importance of ADRs in modern healthcare. This specific module covers concepts related to recognising, minimising and reporting ADRs, and includes a case study to test the outcome of your learning process. These learning resources were developed by the Yellow Card Centre (YCC) Scotland in conjunction with NHS Education for Scotland (NES). The modules are suitable for intermediate level learners.

eMC (Electronic Medicines Compendium)

By providing open access to Summaries of Product Characteristics (SPCs) for all UK authorised drugs, the eMC is a good first-line resource for information on ADRs. Suitable for beginner/intermediate level learners.

Adverse drug reactions - pharmacovigilance

Pharmacovigilance (or drug safety) is the practice of monitoring the effects of medical drugs after they have been licensed for use. One important goal of this activity is to detect, collate, assess and monitor previously unreported adverse reactions, with the aim of preventing adverse effects and reducing the considerable economic and clinical costs associated with adverse reactions.

Clinical and economic burden of adverse drug reactions.

PubMed link to an open access article published in 2013 in the Journal of Pharmacology & Pharmacotherapeutics. This article highlights the importance of post-marketing drug safety monitoring through pharmacovigilance activities towards the reduction of both the clinical and economic burdens associated with adverse drug reactions. Suitable for intermediate level learners.

Module 6 – Pharmacovigilance

This is one of a set of webpages containing key information relevant to understanding the importance of ADRs in modern healthcare. This specific module covers pharmacovigilance; what it is, and how it contributes to the detection, assessment, understanding and prevention of ADRs, and ultimately contributes towards improved patient safety. The module includes a case study to test the outcome of your learning process. These learning resources were developed by the Yellow Card Centre (YCC) Scotland in conjunction with NHS Education for Scotland (NES). The modules are suitable for intermediate level learners.