Adverse drug reactions (ADRs) are a significant concern in clinical practice, impacting patient safety and treatment outcomes. The World Health Organization (WHO) defines an ADR as “A response to a drug which is noxious and unintended, and which occurs at doses normally used for prophylaxis, diagnosis, or therapy of disease or the modification of physiologic function.”
Risk factors for adverse drug reactions
Several factors can predispose individuals to ADRs, including:
- Patient-related Factors:
- Age: Elderly patients and infants are more susceptible to ADRs due to differences in pharmacokinetics and pharmacodynamics.
- Gender: Women may experience ADRs more frequently than men.
- Genetics: Genetic polymorphisms can affect drug metabolism and response.
- Co-morbidities: The presence of multiple diseases can increase the risk of ADRs.
- Drug-related Factors:
- Polypharmacy: The use of multiple medications increases the risk of drug-drug interactions.
- Dosage and Duration: Higher doses and prolonged use of drugs can elevate the risk of ADRs.
- Route of Administration: Parenteral routes may cause more severe reactions compared to oral administration.
Classification of adverse drug reactions
ADRs can be broadly classified into two main types:
- Type A (Augmented) reactions: these reactions are dose-dependent and related to the pharmacological action of the drug. They are often predictable and preventable and are associated with high morbidity and low mortality.
- Type B (Bizarre) reactions: these reactions are unpredictable, dose-independent, not related to the pharmacological action of the drug, and often idiosyncratic. They are associated with low morbidity and high mortality.
Type A Reactions
Type A reactions can occur in any individual given a sufficient dose. Type A reactions are common and constitute 85% to 90% of ADRs. These reactions can be categorised as follows:
Drug overdoses: Overdose occurs when an excessive amount of a drug is consumed. An example of a type A ADR due to a drug overdose is hypoglycaemia from insulin or oral hypoglycaemic use. Insulin and sulfonylureas lower blood glucose levels, and excessive dosing or overdose can, therefore, lead to hypoglycaemia.
Side effects: Side effects are defined as “a predictable or dose-dependent effect of a drug that is not the principal effect for which the drug was used.” An example of a type A ADR due to side effects is nephrotoxicity with aminoglycoside therapy. Aminoglycosides accumulate in renal proximal tubular cells, causing cellular damage and nephrotoxicity, especially at higher doses or with prolonged use.
Drug interactions: Drug interactions are reactions between drugs and other drugs, foods, supplements, or diseases. An example of a type A ADR due to drug interaction is the co-administration of theophylline with certain antibiotics, notably macrolides (e.g., erythromycin, clarithromycin) and fluoroquinolones (e.g., ciprofloxacin. These can inhibit CYP1A2, leading to increased plasma levels of theophylline. This inhibition results in a higher concentration of theophylline in the blood, which can cause toxicity.
Type B Reactions
Type B adverse drug reactions (ADRs) are less common but often more serious and unpredictable than Type A reactions. These reactions can be categorised as follows:
Hypersensitivity reactions: These reactions are the commonest type of type B ADR, constituting approximately 5% to 10% of all ADRs. Hypersensitivity reactions are further categorised into the following types:
- Type I hypersensitivity reactions – these are mediated by immunoglobulin E, mast cells, and basophils and are immediate in onset. Anaphylaxis with penicillin is a common example.
- Type II hypersensitivity reactions – these occur when IgG or IgM binds cellular or extracellular matrix antigens. They are late in onset, and symptoms typically appear 5 to 8 days after drug exposure. Drug-induced thrombocytopaenia following heparin administration is an example of this type of reaction.
- Type III hypersensitivity reactions – these are mediated by immune complexes and the activation of complement. Similar to type II reactions they are delayed in onset but can take weeks for symptoms to appear. Serum sickness following the use of monoclonal antibodies is an example of this type of reaction.
- Type IV hypersensitivity reactions – these are mediated by T cells and are delayed in onset. Stevens-Johnson syndrome (SJS) following sulphonamide usage is an example of this type of reaction.
Other immunological reactions: Drug-induced autoimmunity may occur after drug exposure and lead to autoimmune diseases. An example of this type of reaction is the lupus-like disease that can develop following exposure to isoniazid.
Pseudoallergic reactions: These resemble allergic drug reactions, but they are not initiated by immunologic mechanisms. They are also sometimes referred to as “nonimmune hypersensitivity reactions.” These reactions occur due to the direct activation of inflammatory cells. Vancomycin flushing syndrome is a commonly encountered example of this type of reaction.
Idiosyncratic reactions: These are type B reactions that are not mediated by immunological or inflammatory mechanisms. They can arise because of genetic anomalies, for example, dapsone-induced haemolysis in a patient with G6PD deficiency, or exaggerated sensitivity at low doses, such as tinnitus after a single dose of aspirin.
Reporting adverse drug reactions
ADRs are an important concern in healthcare, and their reporting is crucial for monitoring the safety of medications.
The Yellow Card Scheme is the primary mechanism for collecting information on suspected ADRs in the UK. It is designed to monitor the safety of all healthcare products, including prescription medicines, vaccines, over-the-counter medicines, and herbal remedies. The scheme plays a vital role in identifying and evaluating potential safety concerns related to medications.
Thank you to the joint editorial team of www.mrcgpexamprep.co.uk for this article.
