Adverse Drug Reactions (ADRS)

The World Health Organization defines an adverse drug reaction as any response to a drug which occurs at doses normally used in man for prophylaxis, diagnosis, and therapy of disease or for the modification of physiological function.

Adverse reactions are recognized hazards of drug therapy. Adverse drug reactions (ADRS) are important causes of mortality and morbidity in both hospitalized and ambulatory patients. ADR study and its prevention is today’s demand because ADR is the fourth leading cause of death ahead of pulmonary disease, diabetes, AIDS, pneumonia, accidents, and automobile deaths. In many countries ADRs rank among the top 10 leading causes of mortality.

So there is a need to study ADR's seriously to create awareness about ADRs among patients to motivate health care professionals in the hospital to report ADRs to minimize the risk. It is important in detection of lack of efficacy, and detection and prevention of counterfeit and sub stranded products in clinical practice. Early detection, evaluation and monitoring of ADR are essential to reduce harm to patients and thus improve public health

FEATURES OF ADR

The important features of adverse drug reactions are:

1. There is some evidence that a drug is responsible for the reaction
2. It is unintended and occurred at normal doses used clinically
3. The effects of the reaction is either harmful to the patient
4. ADRs are preventable and many healthcare professionals are in a position to identify them at an early stage.

CLASSIFICATION OF ADR

1. Traditional Classification

As proposed by Rawlins and Thompson

• Type A (Augmented): These include the common, pharmacologically predictable, dose related reactions, which improve when the medicine is withdrawn. Eg: Insulin induced hypoglycemia
• Type B (Bugs): These are pharmacologically predictable and they also improve when the medicine is withdrawn but they involve interaction with a microorganism. Eg: Sugar containing medicine promoting dental caries

2. Newer Classification

As proposed by Simon Wills and David Brown

• Type A (Augmented)
• Type B (Bugs)
• Type C (Chemical)
• Type D (Delivery)
• Type E (Exit)
• Type F (Familial)
• Type G (Genetotoxicity)
• Type H (Hypersensitivity)
• Type U (Unclassified)

DETECTION AND MONITORING OF ADRS

• Detection of an ADR is crucial in the management of any patient. Always suspect a drug as cause of symptoms in a patient .all drugs have the potential to cause ADRs although most produce no ill effects in most of the patients. ADRs contribute to overall healthcare costs by increasing morbidity and mortality.
• Adverse event detection systems have included manual methods and a combination of both electronic and manual review process.

METHODS OF MONITORING ADVERSE DRUG REACTIONS

Although all new drugs undergo clinical trials to demonstrate efficacy and detect adverse effects, only the most common ADRs, will probably have been detected by the time the drug is marketed. In addition, clinical trials are unlikely to have been carried out on some groups of patients, such as the elderly or pregnant women. Pharmaceutical products must therefore be monitored after marketing to identify any more unusual, serious or delayed adverse effects. Adverse event detection systems have included manual methods and combination of both electronic and manual review processes.

1. Manual Methods

Manual adverse event detection systems offer the ability to detect a wide array of adverse events, and with some methods, a substantial proportion of events. The systems described below are limited by either physician reluctance to use them or the resource requirements to maintain the system

a. Provider voluntary reporting methods

• Incident reporting
• Prompted spontaneous reporting

b. Provider involuntary reporting methods

• Chart Review
• Observers
• Patient interviews

2. Combined Modalities

3. The UK Yellow Card System

4. Anecdotal reports (Case reports)

5. Cohort studies (Prospective studies)

6. Case-control studies (Retrospective studies)

7. Record linkage studies

8. Hospital-based population studies

9. International ADR reporting

10. Patient-cantered studies.

BASIC PRINCIPLES OF EFFICIENT REPORTING

• Report the adverse reaction immediately after it occurs.
• If possible, take the decision to report whilst the patient is still with you, so that the details can be filled in at once on the reporting form.
• Think about any other factors which may contribute in causing the event such as other prescribed drugs, self-medication, herbal products, food, and chemicals, ask the patient, particularly about other medicines taken.
• If you get any supplementary data later, e.g. if the same patient develops the effect again or if something happens which increases your suspicion or seem to exclude the reaction, please send in a supplementary note immediately using ADRs reporting form with the patient identifiers.
• All reports must have the following four data elements

1. An identifiable patient
2. A suspected adverse effect
3. A named suspected drugs
4. An identifiable reporter

• Always write legibly.

MANAGEMENT OF THE ADVERSE REACTION

• Confirmation of the ADRs indicates what assisted in confirming the suspected adverse reactions.

For example:

1. Drug reactions are confirmed by the disappearance of the reaction after stopping the administration of the drug or reducing the doses.
2. Recovery on withdrawal of the suspected drug(s) if no other drug is withdrawn and no therapy is given.
3. Recovery follows the treatment of the reaction in addition to the withdrawal of the drug.

• Mention the criteria for regarding the reaction as serious.
• Mention any treatment given to the patient after experiencing the ADRs.
• Outcome: indicate the outcome of the adverse reaction by marking X in the appropriate box with dates in case of fatal outcome.

PREVENTIVE MEASURES FOR ADVERSE DRUG REACTION

Comprehensive and ongoing ADR monitoring, evaluating and reporting programs need to be initiated that should focus on the assessment of incidence, prevalence, category, severity, preventability, costs and burdens of adverse drug reactions. This will help ensure that patients receive safe medicines and mortality or morbidity due to ADRs is considerably reduced. The most ideal way to manage ADRs is to prevent its occurrence in predictable cases. However, if it has occurred, therapeutic measures become necessary. Preventive measures are:

1. Never use any drug unless there is good indication. If the woman is pregnant do not use a drug unless the need is imperative.
2. Choose an alternative therapy of relative efficacy and safety. Eg: if patient is allergic to penicillin, choose other alternative like amoxicillin.
3. Using a prophylaxis to other drugs to prevent future ADRs. Eg: penicillin should be injected subcutaneously for skin test to prevent the occurrence of anaphylaxis.
4. Allergy and idiosyncrasy are important causes of adverse drug reactions. Ask if the person had previous reactions. There may also be family history of adverse reactions to drugs that share a common characteristic indicative of inherited disorder. (Eg: Glucose-6- phosphate dehydrogenase deficiency).
5. Ask if the person is already taking other drugs including self-medication drugs interactions may occur.
6. Age and hepatic or renal impairment may alter the metabolism or excretion of drugs so that much smaller doses may be needed. Genetic factors may also be responsible for variations in metabolism.
7. Prescribe a few drugs as possible and give clear instructions to elderly patients or any patient likely to misunderstand complicated instructions.
8. Whenever possible use a familiar drug. With a new drug are particularly alert for or unexpected events.
9. If serious adverse events are liable to occur, warn the patient.
10. Implementation of program designed to educate patient about their medication and potential for ADRs.
11. Documentation of ADRs is necessary to avoid re exposure