Adverse reactions and Yellow Card Flashcards
What is an adverse drug reaction (ADR)?
“An adverse drug reaction (ADR) is a response to a medicinal product which is noxious and unintended, where a causal relationship between the medicinal product and adverse event is either known or strongly suspected.”
What is a side effect ?
Side effect - any unintended effect of a pharmaceutical product occurring at doses normally used in man which is related to the pharmacological properties of the drug.
E.g. diarrhoea after antibiotic or doxazosin for prostatism lowering BP
What is an allergy ?
True allergy is immunologically mediated, not related to usual pharmacology
Often a delay between first exposure and subsequent ADR/Allergy
Very small doses may cause allergic reactions once established
Disappears on drug withdrawal
Is this an ADR, allergy or side effect?
Mr Albatross, 68 yrs, known CKD, develops hearing loss following a course of gentamicin for sepsis
Is this an ADR, allergy or side effect?
Miss Robin, 10 yrs, develops angio-oedema and shortness of breath following administration of cefotaxime for suspected meningitis.
Is this an ADR, allergy or side effect?
Mrs Swift, 55 yrs, develops myalgia after starting atorvastatin for secondary prevention of MI
How common are ADR ?
6–7% of hospital admissions in the UK are due to ADRs.(1)
So about 400,000 admissions due to ADRs
500 million extra days a year spent in hospital (2)
Based on 6 million admissions / year between 16/17 & 19/20 (3)
In what circumstances can ADR occur?
within its licence
off-label
overdose
misuse
abuse
medication errors
occupational exposure
Factors that can influence the chance of a patient experiencing an ADR
Impaired Renal function – accumulation, NTI eg gent, digoxin dose depends on renal function, nephrotoxicty with ACEi, NSAIDs, methotrexate.
Impaired Liver function – metabolism eg terfenadine-induced arrhythmia, hepatotoxicity with tolcapone,
Extremes of age - The elderly
Drug interactions eg excess drowsiness with sedative drugs, bleeding with warfarin and antiplatelets, liver toxicity with triple therapy for TB
Gender - Females more at risk, more susceptible to QT prolongation, hormonal, 1.5 x risk
HIV more at risk of skin reactions with co-trimoxazole and antivirals, rash with amoxicillin and infectious mononucleosis.
Glucose-6-phosphate-dehydrogenase deficiency higher in males and is highly prevalent in Africa (1 in 5) and Asia and Southern Europe. Some drugs eg dapsone, nitrofurantoin, Chinese herbal meds can cause haemolytic anaemia. See BNF
Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) also known as favism (after the fava bean) is an X-linked recessive genetic condition that predisposes to hemolysis (spontaneous destruction of red blood cells) and resultant jaundice in response to a number of triggers, such as certain foods, illness, or medication. It is particularly common in people of Mediterranean and African origin. The condition is characterized by abnormally low levels of glucose-6-phosphate dehydrogenase, an enzyme involved in the pentose phosphate pathway that is especially important in the red blood cell. G6PD deficiency is the most common human enzyme defect.[1] There is no specific treatment, other than avoiding known triggers.
Carriers of the G6PD allele appear to be protected to some extent against malaria, and in some cases affected males have shown complete immunity to the disease. This accounts for the persistence of the allele in certain populations in that it confers a selective advantage.[2] G6PD deficiency resulted in 4,100 deaths in 2013 and 3,400 deaths in 1990
Categories of ADR
Type A reactions – ‘Augmented’
Type B reactions – ‘Bizaare’
Type C – ‘Chronic’
Type D – ‘Delayed Effects’
Explain Type A ADR reactions – ‘Augmented’
80% of all ADRs
an exaggeration of a drug’s normal pharmacological actions
dose-dependent
readily reversible on reducing the dose or stopping drug
Often recognised before marketing
Concomitant use of anti-hypertensives leading to hypotension
E.g. ACE Inhibitor and diuretic for hypertension
NSAIDs and opioid analgesia for pain control
Increased potency when used together
Bradycardia with beta adrenergic blockers (BB)
Headache with glyceryl trinitrate (GTN)
Explain Type B ADR reactions – ‘Bizaare’
unusual and can’t be predicted from the drug’s pharmacology
Immunological or pharmaco-genetic mechanisms
Often unrelated to dose
More serious
Comparatively rare
Not often seen prior to marketing
Examples include
Anaphylaxis with penicillin
Agranulocytosis with clozapine
Aplastic anaemia with chloramphenicol
Malignant hyperthermia with anaesthetics
Myositis, myalgia, myopathy with statins
Explain Type C – ‘Chronic’ ADR
Result from long term drug use
Usually associated with treatment for chronic disease
Examples
Hypothalamic-pituitary-adrenal axis suppression with long term corticosteroid use
Tolerance to nicotine
Explain Type D – ‘Delayed Effects’ ADR
Can occur many years after therapy has stopped
Example
Stilboestrol and vaginal cancer
Explain Type E – ‘End of Use Effects’ ADR
Occur as a result of abrupt cessation of some therapies
Examples
Abrupt withdrawal of systemic corticosteroids can lead to acute adrenal insufficiency, hypotension or death.
Withdrawal effects when stopping some anti-depressants or Alcohol
