Adverse drug reactions Flashcards
What is an adverse drug reaction?
Response to a medicinal product which is noxious and unintended- use within and outside terms of the marketing authorisation (overdose, off-label use, misuse, abuse, medication error), occupational exposure
What is a side effect?
Any effect caused by a drug other than the intended therapeutic effect
Less harmful, predictable, may not require discontinuation of medication
What is drug toxicity?
Adverse effects of a drug that occur because the dose or plasma conc has risen above the therapeutic range
How common are adverse drug reactions?
Common, usually early in the course of therapy, many disease presentations as a result of prescription, many are avoidable
Why are ADRs and increasing health problem?
Increase in; elderly population (x4 more likely), polypharmacy, availability of OTC medicines, use of herbal/traditional medicines, medicines available via the internet
Why are ADRs important?
Reduce quality of life for patients and adherence to and therefore efficacy of beneficial treatments, cause diagnostic confusion, undermine the confidence of patients in their health care professionals, consume scarce NHS resources (extra care of patients/ litigation costs)
How are ADRs classified?
Type A (augmented)= predictable from the known pharmacology of the drug and dose-related, common, usually mild (Captopril= hypertension/ renal impairment/ cough) Type B (Bizarre)= unrelated to known pharmacology of the drug and idiosyncratic, rare, severe (Captopril= proteinuria/ leukopenia/ loss of taste)
Describe hypersensitivity reactions
Potentially serious, not dose-related, need for careful drug history (drug allergy/atopy)
Targets skin, lungs, haematopoiesis
Describe reproductive adverse reactions
-Teratogenesis= animal testing of new drugs mandatory, embryo teratogenic effects week 2-8 of intra-uterine life, drugs may affect cell division or protein/DNA synthesis
(thalidomide, alcohol, cytotoxic, warfarin, steroids)
-Altered growth= tetracycline teeth, smoking
-Labour= beta-blockers
-Post-partum effects= respiratory or CVS depressants can cross the placenta (opioids)
What are the key risk factors in ADRs?
- Poor knowledge of drug and clinical pharmacology in prescribers
- Known toxic effects, low therapeutic index, steep dose-response curve in medicines
- Neonates, genetic factors, allergy, disease (hepatic or renal), adherence problems, elderly age (multiple drugs, physiological reserve, poor clearance) in patients
How many patients are exposed in drug development?
Phase 1- healthy volunteers, 20-30
Phase 2- patient group (dose ranging) 50-100
Phase 3- patient group (efficacy) 200-500
(Phase 1-3= 10 years)
Phase 4= marketed drug after drug licenced by MHRA
What is pharmacovigilance?
Detection and evaluation of adverse effects of drugs
How are adverse drug reactions detected?
Voluntary reporting systems- yellow cards
Prescription event monitoring- observational cohort studies
Population statistics/ record linkage
Medical literature
What can the yellow card system detect?
Unrecognised ADRs (signal generation)
Identification of predisposing factors
Comparing ADR profiles of drugs
Continual safety monitoring
What changes might follow yellow card schemes?
Restriction in use
Reduction in dose
Special warning and precautions
Product withdrawn
