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
Explain Type F – ‘Effect Failure ADR
Failure of a drug to achieve therapeutic effect
Example
Inadequate dose of contraceptive when used with rifampicin
What are the Steps to determine whether a drug is responsible for an ADR
Timing - anaphylaxis with penicillins, Long after – hepatitis with fluclox
Dose
Nature of problem
Experience
De-challenge / rechallenge - Check SPC; background incidence of the ADR eg headache is common but blood dyscrasias or acute dystonias are frequently associated with medicines.
Lack of alternative aetiologies
The patient
How to avoid an ADR
Use as few concurrent drugs as possible.
Use the lowest effective dose.
Check if the patient is pregnant or breastfeeding.
Is the patient at either extreme of age?
Do you know of all the drugs used by the patient?
Check for OTC drugs.
Check for contra-indications such as renal or hepatic impairment.
Check for previous ADR.
What next if ADR is spotted ?
Admit if serious or life threatening.
Seek advice from your GP/Consultant & Pharmacist as to likelihood & best management
Report what’s happened on the yellow card system
Explain Yellow card reporting scheme
The Medicines and Healthcare Products Regulatory Agency (MHRA) are responsible for monitoring the safety of all medicines in the UK
Yellow Card Scheme is an important source of information for them.
It supports the process of pharmacovigilance
What is Pharmacovigilance?
The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem”
(WHO, 2002)
the process of:
monitoring the use of medicines in everyday practice to identify previously unrecognised adverse effects or changes in the patterns of adverse effects;
assessing the risks and benefits of medicines in order to determine what action, if any, is necessary to improve their safe use;
providing information to healthcare professionals and patients to optimise safe and effective use of medicines; and
monitoring the impact of any action taken.
When to use yellow card scheme ?
For all suspectedserious, significant or harmful ADRs
In Black Triangle products
including suspected ADRs considered not to be serious
Established products
Report all unusual, unknown or serious ADRs
Serious ADRs include Fatal; Life-threatening; Disabling; and Incapacitating; ADRs resulting in or prolonging hospitalisation
All Paediatric reactions
What is a black triangle drug?
Any drug or vaccine which is:
a new active substance or a biosimilar medicine
a new combination of medicines or active substances
a new route of administration
a new drug-delivery system
an established medicine which is to be used in a new patient population
Eg Cozaar▼(losartan), for it’s new indication of heart failure
What medicines could I make a yellow card report for?
Any medicine,vaccines,complementary medicine
A medical device
A medicine or device of poor quality
Fakes or counterfeit, medicine or devices
Nicotine e-cigarettes
Especially for those involving
children or elderly,
biological medicines
vaccines
delayed drug effects & interactions.
complementary remedies.
