18 Adverse Drug Reaction Reporting Flashcards
What is an ADR?
A response to a medicinal product which is noxious and unintended
Are they important?
- Major cause of hospital admissions ~6.5%
- Affect quality of life
- Cost to the NHS in £ hundreds of millions
- Many are preventable
- Several hundred deaths per year
Classifications
- Rawlins and Thompson
* DoTS
Rawlins and Thompson – Type A
- Dose related
- Common, predictable
- Related to the pharmacology
- Low mortality
- e.g. Digoxin toxicity, constipation from morphine, or sedation from a hypnotic
Rawlins and Thompson - Type B
- Not dose related
- Uncommon, unpredictable
- Not related to pharmacology
- High mortality
- e.g. Penicillin hypersensitivity, malignant hyperthermia, hepatitis
ACE-inhibitor induced
angioedema
- Life threatening
- Rare
- Unlikely to be picked up in clinical trials
- Biggest cause of angioedema presenting to A&E
- 0.2%incidence
Rawlins and Thompson - Type C, D, E and F
Classification became complicated • Type C – long term • Type D – delayed • Type E – end of use (withdrawal) • Type F – failure of treatment
New simplified classification DoTS
DoTS stands for
Dose, Time and Susceptibility
DoTS
Dose (response)
The ADR can occur – at doses below therapeutic doses • anaphylaxis with penicillin – in the therapeutic dose range • nausea with morphine – at high doses • liver failure with paracetamol
DoTS
Time (course) can be
characteristic
– with the first dose
– early, or after a time, or with long-term treatment – on stopping treatment (withdrawal)
– delayed
DoTS
Time (course)
- Easily observed in the patient
- Relevant to monitoring and prevention in a patient
- Relevant to pharmacovigilance and drug development
DoTS
Time – independent
- E.g. Increased risk of haemorrhage with change in effective dose of warfarin
• NSAID-induced GI bleeding
• so monitor closely throughout
DoTS
Time - immediate
- Immediate, due to rapid administration
- e.g. red man syndrome from vancomycin
- So infuse slowly
DoTS
Time – first dose
- After the first-dose
- e.g. Hypotension from ACE inhibitors
- Anaphylaxis (type I hypersensitivity)
- So take special precautions for first dose
DoTS
Time – early
- Early (risk falls with time)
- e.g. Nitrate-induced headache
- so advise and monitor
DoTS
Time – intermediate
-Intermediate - risk maximal after a few
days or weeks
– e.g. Ampicillin rash, delayed hypersensitivity
– Quinine and thrombocytopenia (type II)
– Pencillin and interstitial nephritis (type III)
– Cutaneous reactions to antihistamines (type IV)
DoTS
Time – late
- Late (risk increases with time)
- e.g. Osteoporosis (corticosteroids)
- Withdrawal reactions
- So prevent; monitor those on long term treatment
DoTS
Time – delayed
– e.g. Carcinogenesis (ciclosporin, diethylstilbestrol)
– Teratogenesis (thalidomide phocomelia) • so avoid
DoTS
Time – after withdrawal
- e.g. Withdrawal syndromes (e.g. opiates, benzodiazepines)
- Myocardial infarction (beta-blockers)
- so withdraw slowly
DoTS
Susceptibility
• Increased risk can be due to: – genetic variation, – age, – sex, – physiological variation, – exogenous factors, – disease
• More than one factor can be present
Susceptibility examples
Genetic - Porphyria, Malignant hyperthermia
Age - Neonates (chloramphenicol), Elderly (hypnotics)
Sex - Mefloquine and psychiatric effects
Exogenous factors - Drug interactions
Interactions with food
Disease - Renal insufficiency (e.g. lithium)
Examples of DoTS
Osteoporosis
Osteoporosis due to corticosteroids
Dose—collateral effect
Time—late
Susceptibility—older people; women
Examples of DoTS
Anaphylaxis
Anaphylaxis due to penicillin
Dose—hypersusceptibility Time—first dose of a course Susceptibility—not understood;
needs previous sensitisation
Examples of DoTS
Hepatotoxicity
Hepatotoxicity due to isoniazid:
Dose—collateral effect
Time—intermediate
Susceptibility—genetics (drug metabolism),age,
exogenous (alcohol), disease (malnutrition)
Yellow Card scheme
MHRA-run ADR reporting scheme
Complete a yellow card online, telephone, by paper, app
Black triangle drugs
means ‘intensive monitoring’
Who may report?
1964 Doctors, dentists, coroners 1997 Hospital pharmacists 1999 Community pharmacists 2002 Nurses, midwives and health visitors (2005 Pilot patient scheme) 2008 Patients Pharmaceutical companies must report
