Predisposing factors High risk of developing ADRs

Polypharmacy Interactions or by Synergistic effect

Multiple and Intercurrent diseases : Renal or Hepatic problems
Age : Elderly, pediatrics
Drug characteristics : Highly toxic drugs, narrow therapeutic index drugs.
Gender : Women are more susceptible.
Race and Genetics : Genetics defects; accounts for alterations in handling of drugs.
Mechanisms of Type A ADRs
1. Pharmaceutical causes:
Drug quantity present in a particular product.
Changes in the drug release properties.
Salt forms of the drug used.
2. Pharmacokinetic causes:
Alterations in absorption, distribution, metabolism, and elimination.
3. Pharmacodynamic causes:
Increased sensitivity of target tissues or organs may predispose a person to ADRs.
Drug receptors
Homeostatic mechanism
Disease conditions unmask the ADRs
Mechanisms of Type B ADRs
Decomposition of the active ingredients.
Excipients (additives, preservatives, colouring and solubilising agents).
Synthetic by products of active ingredients.
Severity of ADR
Minor: Therapy, antidote or hospitalization are not required.
Moderate: Requires drug change, specific treatment, or hospitalization.

Severe: Potentially life threatening; permanent damage, and prolonged

hospitalization.
Lethal: Directly can lead to death.
Prevention of ADR
Can not be totally avoided.
It can only be minimized.
Steps taken include:
Avoid inappropriate drugs in the context of clinical condition.
Use appropriate dose, route, frequency based on the patient variables (age, sex,
other drugs, other disease conditions, etc.,)
Elicit medication history; considered untoward incidents; rule out drug interactions.
Elicit history of allergies.
Carryout appropriate monitoring.
Adverse drug reaction management
1. Assess the nature and severity of the reaction:
Whether an urgent action is required or can be managed by primary care. Eg:
whether a anaphylactic shock or something minor.
2. Review on the presenting symptoms:
Timing: Time of start of the reaction after giving the drug; Time taken to abate after
the stopping of drug or reducing the dose.
Relationship to dose: Whether reaction minimized with reducing the dose;
symptoms resolve when the medicine withdrawn and recur when reintroduced.
Other possible causes: Possibility of underlying illness or other disease; other
medications (including OTC and Herbals); drug interactions (including diet).
3. Take complete drug history - Review any History of Allergy or previous ADR:
When the drug was started, dose, other drugs, OTC and herbal.
Past ADRs.
Long duration of action or long term use effect can be expected for some drugs.
Review the adverse effect profile of the drugs, and check how common it is.

4. Further Examination and Investigations if required:

Specific investigations and laboratory tests required.
Eg; Liver and Renal Function Tests.
Further complications of ADR.
Drug monitoring.
In a nutshell
Assess the reaction: Emergency care/admission if ADR is Serious or life threatening;
primary care; or seeks specialist advice.
Review the treatment: Either withdraw the suspected drug or reduce the dose.
Manage the symptoms of ADR and provide supportive therapy.
Record the ADR in the individuals health record.
Consider the submission of an ADR report (Yellow Card) if appropriate.
Documentation for the future purpose.
Detection and Monitoring of ADR
1. Premarketing Studies:
Preclinical studies done in animals (can not extrapolate data with the human)
Clinical trials prior marketing done in small number of patients, long duration effects
not in study, special populations not considered, co morbidities not considered and
polypharmacy not considered.
Type A reactions are mostly the known ones.
Infrequent ADRs are not known.
2. Post Marketing Surveillance:
Information from the healthcare system
Spontaneous adverse reaction reporting.
Record linkage.
Epidemiology methods: Cohort study and Case- Control study
Assessing causality

Causality assessment is the method by which the extent of relationship between a

drug and a suspected reaction is established.
It takes on factors such as:
Time relationship
Exclusion of other causes
Dechallenge
Rechallenge
Serum plasma concentration of the drug
Under-reporting
Factors:
Reporting higher for the new drugs than for old.
Serious reactions gets reported to a higher degree.
Type B reaction reported more.
Reporting affected by the promotional claims of the drug sponsor.
Publicity of a specific drug related problem triggers further reporting, not
necessarily related to the real frequency.
Reporting is affected by general publicity around the adverse reaction reporting
scheme.
Reasons of health professional not reporting ADR
Lack of time.
Lack of information on what, how or where to report.
Uncertain drug reaction.
The reaction already well known.
Fear of legal involvement.
Tips that can increase the ADR Reporting
Convenient method of reporting of ADRs.
Providing feedback through articles in journals and bulletins.

Conducting awareness and educational meetings.

Collaboration with professional associations.
Involve other medical staffs, nurses and patients in the reporting of suspected ADR.