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)
