Introduction:
Adverse drug events can be catastrophic, and their reporting is a must for drug safety monitoring. Pharmacovigilance is a field that monitors and assesses the risk and benefits of any drug. Adverse drug events have been less than five percent in clinical practice. Electronic and paper-based methods have been introduced by the national pharmacovigilance centers to facilitate reporting.
What Is an Adverse Drug Event (ADE)?
Adverse drug events are described as unintended injury or harm due to the use of a drug. They can occur in normal doses in humans. Adverse drug reactions can result in unplanned hospital admissions and can be fatal at times. It also includes medical errors such as miscalculations, difficulty in the interpretation of handwritten prescriptions, and wrong administration of a drug.
What Is an Adverse Drug Reaction?
It refers to the noxious and unintended reaction to a drug in circumstances where it is administered and prescribed properly. Medical errors are not included in this. All adverse reactions can be adverse drug events.
What to Report in an Adverse Drug Reaction (ADR)?
According to the FDA (Food and Drug Administration), the following have to be reported:
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Suspected adverse drug reactions for a new drug (that is, within a period of three years into the market entry).
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Suspected severe adverse drug reactions without considering the time of entry into the market.
These can be the following:
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Adverse drug reactions in children.
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Adverse drug reactions in the elderly.
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ADR reports on the lack of efficacy with medicines in case of life-threatening disease.
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Complementary medicines that are considered safe by the public and given OTC (over-the-counter) may result in serious drug reactions.
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Delayed drug effects may occur after many months or years after drug exposure.
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Drug interactions between two medicines.
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Medication errors, though not causing any adverse event, should be reported.
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Drug overdose resulting in adverse drug reactions.
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Reports pertaining to pregnancy and breastfeeding.
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Teratogenicity of drugs. This refers to the abnormality or malformation of the growing fetus due to drug intake by the mother.
What Are the Types of Adverse Drug Reactions?
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Type A (Augmented): It can be predicted by knowing the pharmacology of the drug, and these tend to be dose-dependent. These reactions can be reversed by reducing the dosage or stopping the drug. An example is bleeding in patients using anticoagulants.
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Type B (Bizzare): This cannot be predicted, and though it is dose-dependent even in mild doses, it can produce certain reactions, such as hypersensitivity. They can be due to allergy or idiosyncrasy (abnormal reaction to drugs). An example is Aspirin-induced asthma.
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Type C (Chronic Use): This appears to be related to the chemical structure of the drug and its metabolism. An example would be Paracetamol toxicity.
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Type D (Delayed): It is also called delayed reaction and can occur after many years of treatment with a drug. An example is Cyclophosphamide leading to bladder carcinoma.
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Type E (End of Use): It occurs after the withdrawal of a particular drug. An example would be seizures that may occur after withdrawing Phenytoin.
How Does an ADE Differ From Side Effects?
A side effect is a known effect caused due to the usage of the drug that will not help in the treatment. An allergy that can occur due to the consumption of a drug can be immune-mediated and considered to be an ADR.
What Are the Types of Allergic Reactions to the Drugs?
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Type 1 (Anaphylactic) Reactions: The drug might induce the synthesis of the IgE (immunoglobulin E) antibodies which are fixed to the mast cells. On the next subsequent exposure, the antigen-antibody complexes will cause degranulation of mast cells. This, in turn, will trigger and release the mediators of inflammation like histamine, prostaglandins, leukotrienes, and platelet-activating factor. These together are responsible for the characteristic signs and symptoms of anaphylaxis, like laryngeal edema, bronchospasm, and hypotension. These can sometimes be fatal. If this allergic reaction develops within minutes of drug exposure, it is called an immediate hypersensitivity reaction. Skin tests will help predict this type of reaction. Penicillins, Lignocaine, Cephalosporins, Procaine, Iron dextran, and Streptomycin are some drugs that are known to cause anaphylaxis.
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Type 2 (Cytolytic) Reactions: The drug will bind to a protein, and together they will act as antigens and facilitate the formation of antibodies. The antigen-antibody complexes, in turn, activates the complement system resulting in cytolysis. Cytolysis refers to the disruption of cells due to excess water diffusion into the cells. This will cause agranulocytosis, thrombocytopenia, and aplastic anemia. It is also seen in mismatched blood transfusions. Some drugs known to have caused cytolytic reactions are Sulfonamides, Phenytoin, Carbamazepine, and Phenylbutazone.
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Type 3 (Arthus) Reaction: The antigen will bind to antibodies that are circulating, and these complexes are deposited on the vessel wall. There it will initiate an inflammatory response that leads to vasculitis. Rashes, fever, arthralgia, lymphadenopathy, and serum sickness are some of the manifestations of Arthus type reaction. Penicillins, Phenytoin, Sulfonamides, Streptomycin, and Heparin, can cause serum sickness.
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Type 4 (Delayed Hypersensitivity): This type of reaction is mediated by immune cells like macrophages and T lymphocytes. The antigen will react with the receptors present in T lymphocytes, which will produce lymphokines. This will cause a local allergic reaction.
What Are the Drugs That Are Likely to Cause Allergy?
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Penicillins.
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Local anesthetics.
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Cephalosporins.
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Salicylates.
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Sulphonamides and other sulpha drugs.
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Radiocontrast media (with iodine).
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Antisera.
What to Report During an ADR?
It is mandatory to document the severity of the allergies or adverse reactions. Severity is categorized into three:
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Mild: It may require minimal therapeutic intervention, such as discontinuation of the drug.
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Moderate: It may require active treatment for the adverse reaction. Further evaluation or testing is done to assess the degree of non-serious complications.
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Severe: It includes serious complications that may result in organ damage, a life-threatening situation, temporary or permanent disability, a condition that may require medical intervention to prevent further damage, or conditions requiring prolonged hospitalization. Conditions that may be fatal are also included.
What Is a Spontaneous ADR Report?
A spontaneous report is considered to be a communication with a pharmaceutical company, the regulatory authority, or the organization. This report describes the suspected adverse drug reaction in the patient who is administered one or more medicines, and which are not concluded in the study.
Conclusion:
Healthcare professionals should take the responsibility to report any drug effect that is undesirable or unexpected that may occur due to medicines, including vaccines and complementary medicines. Patients should also report to the doctor the ill effects caused by any drug. By following this, adverse drug events can be prevented.
