Key Definitions & Adverse Drug Reactions Classification
Adverse drug reaction (ADR)—The World Health Organization defines an ADR as “any response to a drug which is noxious and unintended, and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function.”1 In other words, an ADR is harm directly caused by the medicine at normal doses, during normal use. An unexpected ADR refers to a reaction, the nature or severity of which is not consistent with domestic labeling or market authorization, or is unexpected from characteristics of the medicine.
The term adverse drug effect is interchangeable with adverse drug reaction. Side Effect—Any unintended effect of a pharmaceutical product occurring at doses normally used in humans which is related to the pharmacological properties of the medicine. Such effect may be either positive or negative. Such effects may be well-known and even expected and may require little or no change in patient management.
Serious Adverse Effect— Any untoward medical occurrence that at any dose and results in death, requires hospital admission or prolongation of existing hospital stay, results in persistent or significant disability or incapacity, or is life threatening.
Adverse Drug Event—Any untoward medical occurrence that may be present during treatment with a medicine but does not necessarily have a causal relationship with this treatment, that is, an adverse outcome that occurs while the patient is taking the medicine but is not, or not necessarily, attributable to it.
Causality—The probability that a particular medicine or substance is responsible for an isolated effect or ADR.
Signal—Reported information on a possible causal relationship between and adverse event and a medicine, the relationship being previously unknown or incompletely documented. Usually more than one signal report is required to generate a signal, depending on the seriousness of the event and the quality of the information.
Prescribing error—Incorrect medicine ordering by a prescriber.
Medication error—Administration of a medicine or dose that differs from the written order. Negligence—Medical decision making or care below accepted standards of practice.
Adverse Drug Reactions Classification
ADRs are unexpected, unintended, undesirable, or excessive responses to a medicine, and they may be harmful to the patient. By contrast, side effects are known reactions to a medicine and are typically listed in the medicine’s labeling. The American Society of Health-System Pharmacists2 provides another definition of ADR. It describes an ADR as any unexpected, unintended, undesirable, or excessive response to a medicine that—
- Requires discontinuing the medicine (therapeutic or diagnostic)
- Requires changing the pharmaceutical therapy
- Requires modifying the dose (except for minor dosage adjustments)
- Necessitates admission to a hospital
- Prolongs the patient’s stay in a health care facility
- Necessitates supportive treatment
- Significantly complicates diagnosis
- Negatively affects prognosis
- Results in temporary or permanent harm or disability, or in death ADRs can be classified into six types—
- Type A reactions (dose-related)—These reactions are an exaggerated, but otherwise normal pharmacological responses to the effects of the medicines given in therapeutic dose, cause significant morbidity but are rarely severe. The reaction is treated by reducing the dose or withholding the medicine and considering alternative therapy. Examples of such reactions include⎯ ο Pharmacodynamic (e.g., bronchospasm from beta-blocker administration) ο Toxic (e.g., deafness from overdosing of aminoglycosides)
- Type B reactions (non-dose related)—These reactions are bizarre and unpredictable with no relation to dose or pharmacological action of the medicine and are often allergic in nature. They are uncommon but are often severe and cause high mortality. The reaction is treated by stopping the medicine and avoiding it in the future. Examples of such reactions include⎯ ο Medicine-induced diseases (e.g., antibiotic-associated colitis) ο Allergic reactions (e.g., anaphylactic reaction to penicillin administration) ο Idiosyncratic reactions (e.g., irreversible aplastic anemia caused by chloramphenicol)
- Type C reactions (dose-related and time-related)—These reactions are chronic (long term) and related to cumulative dose. The reaction is treated by reducing the dose or withholding the medicine, which may have to be withheld for a long time. Examples of such a reaction include— o Osteoporosis with oral steroids o Hypothalamic-pituitary-adrenal axis suppression by corticosteroids
- Type D reactions (time related)—These reactions are delayed (i.e., have a lag time) after the use of a drug. They are uncommon but their treatment is often intractable. Examples of such reactions include— o Teratogenic effects with anticonvulsants or lisinopril o Carcinogenesis o Tardive dyskinesia
- Type E reactions (withdrawal)—These reactions occur soon after the end of use (i.e., withdrawal) and are uncommon. The reaction is treated by reintroducing the medicine and then withdrawing it slowly. Examples of this reaction include— o Withdrawal syndrome with benzodiazepines o Opiate withdrawal syndrome o Myocardial ischemia after beta-blocker withdrawal
- Type F reactions (unexpected failure of efficacy)—These reactions occur when there is a failure of efficacy. Such reactions are common, may be dose-related and are often caused by drug interactions. The reaction is treated by increasing the dose and considering the effects of concomitant therapy. Examples include— o Resistance to antimicrobials o Inadequate dosage or oral contraceptives, particularly when used with specific enzyme inducers
MCQ on Pharmacovigilance given at the end of Lecture (see above lecture)
Pharmacovigilance Lectures Playlist
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