The Adverse Drug Reactions (ADRs) are the 4th to 6th leading cause of death among hospitalised patients and it occurs in 0.3% to 7% of all hospital admissions. The incidence of serious ADRs is 6.7%. 30% to 60% of these ADRs are preventable.
Because of a rapid increase in the list of newer drugs launched in the market in the last few decades; adverse drug reaction monitoring of these drugs is of prime importance. Since India is a country which caters the maximum number of human population for the final assessment of drug safety as a part of post marketing surveillance studies, it becomes necessary to report any untoward reaction to any pharmaceutical product. The drugs which are marketed in India are pre-tested on very small population groups of European countries in an optimal environment and the data about the drug safety collected from that population could not be applied straightly in our population because of the climatic and corporal differences.
Definitions of adverse drug reactions
WHO definition of ADRs: Any response to a drug that is noxious and unintended and that occurs at doses used in humans for prophylaxis, diagnosis, or therapy of disease, or for the modification of physiologic function.
FDA definition of serious ADRs: For reporting purposes, FDA categorizes serious adverse event (event related to drug or devices) as one in which "the patient outcome is death, life-threatening (real risk of dying), hospitalisation (initial or prolonged), disability (significant, persistent, or permanent), congenital anomaly, or required intervention to prevent permanent impairment or damage".
Types of ADRs
Type A reactions: Type A (augmented) reactions are normal pharmacologic effects of the drug exaggerated to the point of being undesirable or intolerable for patients. These ADRs are often dose-dependent, and the percentage of patients who might experience these effects is generally predictable. Examples - Warfarin or heparin, which causes bruising; or diphenhydramine, which causes drowsiness. Another form of type A reaction involves a drug's recognized pharmacologic property other than the primary desired one. For example, b-adrenergic blocking agents exert their effect on receptors other than those targeted in the heart and vasculature, leading to the potential of bronchospasm due to b-blockade of certain receptors in the pulmonary tree.
Type B reactions: Type B (bizarre) reactions are often more severe adverse effects unrelated to the known pharmacologic action of the drug and include most immunologic reactions. Unless patients are tested for antibody markers, these reactions are unpredictable and may or may not be dose-dependent. An example of a type B reaction is an anaphylactic reaction to penicillin. The term "idiosyncratic reactions" has also been used in place of type B adverse reactions.
How to monitor and detect ADRs?
Type B ADRs are the most commonly reported ADRs because of there severity and easy detection by the patient/attendant by virtue of the associated skin rashes usually maculo- papular and pruritis. But Type A ADRs arises because of extension of the pharmacological effects, resolves rapidly with treatment of stoppage of the drug and it is perceived by the patient as deterioration of the disease condition and not as drug reaction/effect. So, it is poorly reported. Adverse drug monitoring and detection is essential in the correct estimation of the incidence of Type A ADRs. Adverse drug monitoring and detection could be done by screening the computerized drug order entry or the original prescriptions using the following methods:
Medication order screening
o abrupt medication discontinuation/abrupt dosage reduction
o orders for tracer substances
o orders for special tests or serum drug concentrations
o orders for "high risk drugs" which are likely to cause ADRs are screened and their use is monitored. Examples of high risk drugs - Aminoglycosides, amphotericin, antineoplastics, corticosteroids, digoxin, heparin, lidocaine, phenytoin, theophylline, thrombolytic agents, and Warfarin.
Laboratory tests and checklist
o Standard laboratory tests
o Adverse drug event questionnaire - extensive checklist of symptoms categorized by body system
Grading of severity
Grade1 - ADR occurred but required no change in treatment with suspected drug.
Grade 2 - Drug held discontinued or changed. No antidote or additional treatment needed.
Grade 3 - Drug held, discontinued or changed and/or antidote or additional treatment.
Grade 4 - ADR required patient transfer to an intensive care setting.
Grade 5 - ADR caused permanent harm to the patient.
Grade 6 - ADR either directly or indirectly led to the patient's death.
All the ADRs with a severity level of 5 and 6 are investigated in detail by doing a Root-Cause-Analysis (RCA) including these areas: Patient identification process, Staffing levels, Orientation and training of staff, Competency assessment/credentialing process, Supervision of staff, Communication among staff members, and Availability of information.
Outcome of ADRs monitoring and detection
" Improved patient outcome
" Anticipation of those patients who are at higher risk where high-risk drugs are prescribed or where the patient is a geriatric, pediatric, organ failure (Renal or Hepatic) or multiple drugs receiving patient.
" It could help in the assessment of the ADRs related to recently approved drugs. It could give a correct estimation of the incidence of drug interactions in the hospital and help in differentiating drug-drug interaction from ADRs. The Boston Collaborative Drug Surveillance programme reported a study of 9,900 patients with 83,200 drug exposures and found 3,600 adverse drug reactions, 234 (6.5%) of which were attributable to drug interactions. In a study where the medical charts of 1,800 surgical patients were reviewed, researchers found at least one potential drug interaction in 17% of patients. Other studies determined that 19% of nursing home patients received combinations of drugs with known harmful interactions, and adverse drug reactions on medicine wards in hospitals resulted from drug interactions in 22% of patients.
-- The authors are with Indraprastha Apollo Hospital, New Delhi