Adverse reactions following medical treatments are frequent and known. Physicians prefer the term ‘adverse reaction’ over ‘side effect’ because the latter suggests effects beyond pharmacological actions. Studies indicate that 5% to 30% of patients experience adverse events that are unpleasant experiences reported by the patients and not necessarily due to a specific medicine. Therefore, understanding their mechanisms is often elusive and requires systematic study in developing causality assessment between the medicine and the adverse reaction reported. An adverse drug reaction (ADR) refers to the unpleasant experience associated with the drug therapy such as gastric discomfort, skin rash etc. Sometimes, few people tend to be sensitive to a few medicines and develop allergic reactions. This phenomenon is also known as Drug hypersensitivity, and it develops when one’s immune mechanism overreacts. Allergic reactions are then manifested as severe skin rash, redness etc. Such an exaggerated immune response is the result of excessive activation of IgE antibodies. In such a situation one may require treatment for the symptoms and among few it subsides with time.
Adverse drug reactions are classified as follows:
- Type A- Pharmacologically predicted – i.e. due to actions of the drug itself, but which occur in excess.
- Type B- Idiosyncratic and Unpredictable (Includes drug allergy)
- Type C- Arising from Chronic (long term) use of the medicines
- Type D- Delayed Toxicity
- Type E- Drug-drug interactions
- Type F- Failure of therapy
Some categories of medications are known to have a high occurrence of adverse events. These categories include nonsteroidal anti-inflammatory drugs (NSAIDs) consumed to relieve pain, antimicrobials (which fight bacteria) consumed to treat infectious diseases, anticonvulsants (used in epilepsy management), anaesthetic agents (inducing loss of sensation with or without loss of consciousness), and drugs affecting muscles and nerves.
Pharmaceutical manufacturers play a crucial role in monitoring adverse drug reactions (ADRs) associated with their products. When adverse drug reactions are identified, pharmaceutical manufacturers are obligated to report these findings to regulatory authorities such as the FDA (Food and Drug Administration) in the United States or the EMA (European Medicines Agency) in Europe. Even after a drug has been approved and is on the market, pharmaceutical manufacturers must continue to monitor for adverse reactions through post-market surveillance programs.
Adverse drug reactions can vary significantly across different populations globally. Conducting global clinical trials allows researchers to uncover how genetic, ethnic, environmental, and lifestyle factors influence the occurrence and severity of ADRs. For example, a medication might have a higher incidence of a specific adverse reaction in Asian populations compared to European populations. Global clinical trials provide a more comprehensive assessment of a drug’s safety profile by including diverse patient populations. This is particularly important for detecting rare or unexpected adverse events that may not surface in smaller, more homogeneous trials. Many regulatory bodies, such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), require global clinical trials to assess a drug’s safety and efficacy for approval.
Diagnosis of an adverse drug reaction are by following ways:
- Clinical history- When considering the cause of an adverse drug reaction (ADR), doctors may inquire about the clinical symptoms encountered, as well as their timing and duration concerning the administration of the medication. They will also try to find out other possible factors responsible for adverse drug reactions such as other medicines, supplements consumed etc.
- Laboratory investigations- Tests to identify potential adverse drug reactions (ADRs) involving the immune system may involve specific assays to quantify antibody levels and various skin tests. Diagnosing drug allergy or hypersensitivity can be challenging and often necessitates consultation with a specialized clinical expert known as an immunologist. This option is considered only for severe cases.
The primary consideration for all suspected adverse drug reactions is discontinuing the suspected medication. When patients are taking multiple drugs, the choice to cease a medication should balance the necessity of the drug with its potential to cause the observed adverse effects.
A thorough understanding of the mechanisms behind Adverse Drug Reactions (ADRs) is crucial for both drug development and patient care. Avoiding drugs that are metabolized through specific metabolic or enzymatic pathways can help prevent the formation of reactive metabolites, which are often responsible for many drug hypersensitivity reactions. For this reason, many drug-drug interactions studies are undertaken during drug development programs in animal models to elucidate the metabolic pathways. During clinical development program safety assessment is performed to understand expected adverse effects with the drug, its incidence and mitigation plans. When it comes to patient care, factors such as age, sex, human leukocyte antigen (HLA) type, as well as kidney and liver function, should be taken into account by healthcare providers when deciding on drug therapy and dosages. In the unfortunate event of an ADR, it is vital to investigate the underlying mechanism to prevent a recurrence in the future. It is important to note that the options for investigating ADRs are likely to expand rapidly as ongoing research in this area progresses.
