ADVERSE DRUG REACTIONS

By: HASHMI FURQAN

 General

•        There should be a basic and clear idea between side-effects and the adverse drug reactions.

 

SIDE EFFECTS

Expected, well known reaction resulting in little or no change in patient management e.g. drowsiness or dry mouth due to administration of certain antihistamines, or nausea associated with certain anticancer drugs.

 

•        Side effect can be defined as an effect with a predictable frequency and an effect whose intensity and occurrence are related to the size of the dose

ADVERSE DRUG REACTIONS

•        WHO—defines ADRs as;

•        “Any response to a drug which is noxious, unintended and occurs at doses used for prophylaxis, diagnosis or therapy of disease, or for the modification of physiological function.”

•        FDA—defines,

•        “A serious drug event (events relating to drugs and devices) as one in which, the patient outcome is death, life threatening, hospitalization, disability, or congenital anomaly, or required intervention to prevent permanent impairment or damage.”

WHO / FDA Classification of ADRs

 

•        TYPE-A REACTIONS

•        TYPE-B REACTIONS

 

TYPE-A REACTIONS

•        Qualitatively normal but augmented                        

•        Unrelated to the primary therapeutic effects.

•        Predictable from pharmacology of a drug

•        Dose dependent

•        Do not usually cause serious illness

•        Identified before a drug is marketed.

•        Some have latency e.g. teratogenicity.

 

TYPE-B REACTIONS

•        Usually due to “Hypersensitivity” & “Idiosyncratic”, mechanism

•        Bizarre effects that are unpredictable on the basis of drug’s known pharmacology

•        Unrelated to dose

•        Although rare, but cause serious illness and death

•        Account for many drug withdrawals from the market e.g. Lipobay, has recently been withdrawn

•        Thin line between side effects & ADRs

•        The clinical trials evaluate most common ADRs i.e. Type-A Reactions

•         Many type-B reactions are evaluated after a   drug is available for widespread use

•        Continuous post marketing surveillance is often required before many type-B reactions can be identified

Classification Based on the Intensity

•        Mild: Do not require an antidote, therapy, or prolongation of hospitalization

•        Moderate: Require change in but not necessarily cessation of the drug or may require prolong hospitalization or require special treatment

•        Severe: Potentially life threatening, requiring discontinuation of drug, specific treatment of the adverse reaction.

•        Lethal: Directly or indirectly contribute to the death.

Incidence

•        ADRs are very common in everyday medical practice.

•        USA—account for 3—7% of all hospitalization

•        Prospective Study—ADRs occurred during 10—20% of hospitalizations (10—20% were severe)

•        Incidence of deaths: 0.5—0.9%

Incidence

•        Australian study (2003)

2067 Adults 20—67 years = 14.7% systemic adverse reactions to one or more drugs

•        Pakistan—unfortunately no data available

Causes of ADRs

•        Drug overdose

•        Drug side effects

•        Drug interactions

Reactions Occurring in Susceptible Subjects

•        Drug Intolerance (a low threshold to normal pharmacological action)

•        Drug Idiosyncrasy (genetically determined, qualitatively abnormal drug reaction related to metabolite or enzyme deficiency)

•        Drug Allergy (hypersensitivity recurrence on re-exposure)

•        Pseudoallergic Reaction (as a result of histamine—lacking immunologic specificity)

 

 

Medication Errors

Medication error is a mistake in prescribing, dispensing and administration of drugs.

•        Types of Medication

•        Prescribing errors

•        Omission errors

•        Wrong time errors

•        Unauthorized drug errors

•        Improper dose errors

•        Wrong dosage form errors

•        Improper dose errors

•        Wrong drug preparation errors

•        Wrong administration technique errors

•        Compliance errors

•        Self medication.

Assessment of Likelihood of ADRs

When an ADR is suspected following factors should be taken into account

•        Full history of patient

•        Past drug history (OTC, herbal, homeopathic or any other drugs)

•        Nature of the reaction

•        Timing of symptoms or events

    It is relatively easy to recognize an ADR that occurs soon after drug administration

IDENTIFICATION OF ADRs

•        Causal relationship between a specific drug and a clinical event

•        Recognition of ADR features

•        Patient should be informed about possible ADRs and how to recognize them

•        Patient should be asked to report any unexpected symptoms, which may develop while taking that drug or within a month or so of its discontinuation

•        Assessment whether ADRs are definite, probable or possible due to the drug

 

CONCLUSION

•        ADRs are inevitable risk associated with use of modern medicines

•        Careful attention to dosage & factors like age, sex, renal and hepatic functions will minimize the risk of Type A Reactions

•        The Pharmacist is well placed to assist in prevention, detection and monitoring of ADRs

 

 

•        Responsibility of every health professional to evaluate the appropriateness of a particular opinion or therapy in the context of the actual clinical situation & with due consideration for any new development in the field.

 

•        Strengthening the professional interaction between Physicians, Pharmacists, Nurses & other allied health professionals.

Detection & Monitoring of ADRs

•               Methods most commonly adopted in post marketing surveillance

l              Case Reports

l              Cohort Studies

l              Case-control Studies

l              Spontaneous Reporting Schemes

MOH Initiative ADR- Reporting

•        In October 2000, Ministry of Health Pakistan, developed & distributed a comprehensive ADR reporting form to all the health care institutions

•        MAIN AIM

–     To Centralize

–     Regularize the mechanism of reporting ADRs

Expectations

•        Valuable Database

•        Resource for implementation of corrective actions

•        With “Yellow Card System”, in place staff can be regularly updated on compliance.

CASE REPORTS

   Detection of new and serious reactions, particularly Type-B reactions

•        This involves publication of single case reports, or case series of ADRs in medical literature.

•        Case reports, in the past have been vital in alerting the professionals to several adverse reactions, such as, “Halothane induced Hepatitis”.

COHORT STUDIES

•             Study the fate of a large group of patients taking a particular drug

•             Compare adverse event rates in group of patients taking drug of intent, with a comparative group

•             Cohort studies include:

l            Ad hoc investigations to investigate specific problems

l            Sponsorship by pharmaceutical companies

l            Prescription Event Monitoring (PEM)

l            Variety of record linkage schemes

 

CASE- CONTROL STUDIES

   Valuable information on the incidence of Type B reactions & association between drug & disease

•        Comparison of drug usage between a group of patients with a particular disease and control group who are similar in confounding factors but don’t have the disease

•        Confirms whether or not a drug causes a given reaction once suspicion has been raised.

 

SPONTANEOUS REPORTING SCHEMES

–     Many countries have established a scheme for adverse drug reaction reporting called as, “Committee on Safety of Medicines,” (CSM)

–     The physicians are asked to report all suspected serious reactions to newer products

–     CSM reporting scheme provides valuable early warnings & enables the study of factors associated with them

–     CSM has introduced a “Yellow Card Scheme,”

 

•        Yellow card scheme is capable of detecting both rare and common reactions

•         Inexpensive to operate

•        It should be available to all the physicians in every health care facility

•        It is unfortunate that in Pakistan there is considerable under reporting of such reactions

•        Less than 5% of serious adverse reactions are notified

Role of Pharmacist in ADR Monitoring

•        Leadership in the development, maintenance and ongoing evaluation of ADR programs

•        Approval of such programs through appropriate committees as, P&TC and organization's administration

Pharmacist should facilitate

•        Analysis of each reported ADRs

•        Identification of drugs and patients at risk

•        Development of policies & procedures for ADR monitoring

•        Interaction between physicians, nurses and paramedics

•        Educational purposes

•        Publication of reports

 

PHARMACIST’S OBLIGATION

•        Its Pharmacist’s responsibility and professional obligation to report any suspected ADR.

•        Pharmacist in an organized health care system should develop comprehensive, ongoing programs for reporting & monitoring of ADRs.

ADR Monitoring & Reporting Program

This program should encourage:

•        ADR surveillance

•        Facilitate ADR documentation

•        Promote reporting of ADRs.

•        Monitor the safety of drug use in high risk patients

•        Stimulate the education of health professionals.

 

ADR programs should focus on:

 

•        Identifying problems leading to ADRs.

•        Planning for positive changes.

•        Measuring the results of these changes.

Courtesy:

Compiled and Shared By: Habib Anwar 

habib.anwar@hotmail.com