Management of Adverse drug reactions

What is Adverse Drug Reactions?

An adverse drug reaction is a "response to a drug that is noxious and unintended and occurs at doses normally used in humans for prophylaxis, diagnosis, or therapy of diseases or for the modification of physiological function." It is important to note that there is a causal link between the drug and the adverse drug reaction. In summary, an adverse drug reaction refers to harm directly caused by the drug at normal doses during regular use.

Diagnosis of Adverse Drug Reaction:

Adverse drug reactions (ADRs) can mimic various "traditional diseases" and manifest in different systems of the body. Patients admitted to the hospital with drug-related problems may exhibit symptoms such as weakness, drowsiness, biochemical or hematological abnormalities (e.g., acute kidney injury, electrolyte imbalance, anemia), bleeding, gastrointestinal disturbances, hypoglycemia, or healthcare-associated infections like Clostridium difficile. However, rarer manifestations like drug-induced lupus, fixed drug eruptions, drug-induced eosinophilia, or angioedema require vigilance and suspicion on the part of the clinician to identify the causative agent. A comprehensive medication history plays a fundamental role in identifying any possible connection between the presenting complaint or subsequent findings and an ADR, as well as preventing future ADRs. Various criteria can aid in attributing causality to a specific drug.

Medication history elements that may assist clinical assessment of adverse drug reaction (ADR) probability.

Question	Clinical relevance
Have you taken the medication before without adverse effects?	Prior drug exposure doesn’t entirely rule out an ADR, although tolerating treatment previously may make hypersusceptibility reactions less likely
Did anything else change around the time of possible ADR other than the suspected drug (eg other treatments, over-the-counter medicines, disease progression)	Examination of whether there are alternative causes (other than the suspected drug) that could on their own have caused the reaction
Did the reaction occur only after the drug was started?	While not all ADRs occur immediately or early in therapy (ie on drug challenge), an effect occurring before drug exposure is good counter evidence
Did the reaction resolve when the drug was stopped (or when a specific treatment was given)?	Effects that disappear when treatment is stopped (de-challenge) may increase suspicion of an ADR unless an irreversible reaction
Was there ever intentional or accidental use of the drug following an ADR?	An ADR occurring on re-exposure to a drug increases the probability of a causal relationship

Adapted from the original criteria described by Naranjo et al. (1981).

In some cases, specific investigations can assist in the diagnosis of an ADR by providing objective evidence of the reaction and confirming a drug-induced disease. For example, organ-specific damage accompanied by intracellular tissue deposition of the drug or its metabolite (e.g., indinavir crystalluria and nephropathy).

Treatment of Adverse Drug Reaction:

Prudent and safe prescribing is crucial in reducing errors that can contribute to ADRs. Treatment plans should consider and mitigate any possible adverse effects. For example, co-prescribing folic acid with methotrexate can reduce the incidence of adverse effects associated with folate deficiency, and monitoring electrolytes and renal function when using renally active drugs or diuretics. These examples can help prevent treatment-emergent adverse effects, although they may have limitations due to inadequate or ambiguous monitoring recommendations. It is important to remember that prudent prescribing may also involve avoiding the use of drugs altogether, and the treatment plan should always consider non-pharmacological or conservative options.

Overall, a systems approach involving multiple strategies and including the patient and all healthcare professionals is necessary to reduce the risk of ADRs and prevent "avoidable" reactions in practice.

Management of Adverse Drug Reaction:

Altering the dosage regimen or discontinuing a medicine suspected of causing an ADR are common methods of managing ADRs in practice. However, the approach to managing an ADR may vary among clinicians. Under EU legislation, the approval of all new medicines onto the market must now be accompanied by a robust risk management plan from the marketing authorization holder. This plan may involve the development of specific treatments for managing particular ADRs, as well as ongoing safety trials. An example of this is the development of antidotes for direct oral anticoagulant-induced bleeding. Table 2 presents notable examples of approaches for managing specific ADRs.

Table 2: Examples of agents used in the management of specific adverse drug reactions.

Specific treatments	Drug/drug class causing ADR	Clinical effect of treatment	Clinical context
Naloxone	Opioids	Antidote for opioid toxicity	Widely used for treatment of overdosage with opioids in a non-medical setting and reversal of postoperative respiratory depression
Icatibant	ACE inhibitors	Treatment for life-threatening angioedema affecting airway/head and neck	This selective bradykinin B2 receptor antagonist has proven to reduce the time to complete resolution of angioedema
Idarucizumab	Dabigatran	Antidote for the reversal of direct oral thrombin inhibitor	Novel humanised monoclonal antibody fragment developed as specific reversal agent, promptly restoring dabigatran-prolonged coagulation parameters to baseline values
Intravenous lipid emulsion (Intralipid®)	Local Anaesthetics (eg lidocaine)	Treatment for systemic toxicity from local anaesthetic agents (eg severe cardiotoxic effects)	Reduce adverse effects resulting from inadvertent local anaesthetic overdoses, intravascular injections, or rapid absorption effects from injections in highly vascular sites

ACE = angiotensin-converting enzyme; ADR = adverse drug reaction

References:

1. https://www.pbm.va.gov/PBM/vacenterformedicationsafety/tools/AdverseDrugReaction.pdf

2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297296/

3. https://cdsco.gov.in/opencms/export/sites/CDSCO_WEB/Pdf-documents/Consumer_Section_PDFs/ADRRF_2.pdf

 Student Name: Mohammad Afzal

Student ID:046/032023

Qualification: M pharm 

e-Mail ID: afzalulrehmanmohammad@gmail.com