Adverse Drug Reactions (20.02.2020) Flashcards
Epidemiology of adverse drug reaction
- substantial morbidity and mortality
- estimates of incidence vary with study methods, population, and ADR definition
- 4th to 6th leading cause of death among hospitalized patients*
- 6.7% incidence of serious ADRs*
- 0.3% to 7% of all hospital admissions
- annual costs in the billions (?$120 billion in US)
- 30% to 60% are preventable
UK prevelaance 6.5%
What criteria can you use to classify ADRs?
Onset
Severity
Type
Onset of event - classification of ADRs
Acute
- Within 1 hour
Sub-acute
- 1 to 24 hours
Latent
- > 2 days
SEVERITY - classification of ADRs
Mild
- requires no change in therapy
Moderate
- requires change in therapy, additional treatment, hospitalisation
Severe
- disabling or life-threatening
Severe ADRs
- Results in death
- Life-threatening
- Requires or prolongs hospitalisation
- Causes disability
- Causes congenital anomalies
- Requires intervention to prevent permanent injury
- > you might have to stop the drug, give an antidote..
Type A ADR
- extension of pharmacologic effect
- usually predictable and dose dependent
- responsible for at least two-thirds of ADRs
- > 66% of ADRs
- e.g., atenolol and heart block, anticholinergics and dry mouth, NSAIDS and peptic ulcer
Different type A ADRs (examples)
- digoxin: very linear dose dependance
- paracetamol: not a problem at a lower dose when you get above a certain dose you get a sharp increase of toxicity and you may get liver damage.
Type B ADRs
- idiosyncratic (you don’t really know why) or immunologic reactions
- includes allergy and “pseudoallergy”
- rare (even very rare) and unpredictable
- e.g., chloramphenicol and aplastic anemia (=total BM failure, people tend not to survive it; other ABs available so people don’t use it), ACE inhibitors and angioedema (swelling of lips, tongue, breathlessness, rarely HF)
=> Many serious ADRs are totally unexpected eg Herceptin
and cardiac toxicity
Type C ADRs
- associated with long-term use
- involves dose accumulation (how much of the drug has accumulated over time?)
- e.g., methotrexate and liver fibrosis, antimalarials and ocular toxicity
Type D reactions
- delayed effects (sometimes dose independent)
- carcinogenicity (e.g. immunosuppressants)
- teratogenicity (e.g. thalidomide)
Type E reactions
Withdrawal reactions
-> Opiates, benzodiazepines (fitting), corticosteroids (patients collapse if you stop suddenly)
Rebound reactions
-> Clonidine, beta-blockers, corticosteroids (when you stop the drug and then the situation is worse than when you started)
“Adaptive” reactions
-> Neuroleptics (major tranquillisers) ????
Clonidine withdrawl
- after treatment the BP goes up again, higher than it was before treatment
- can cause stroke, death..
- pharmacological explanation of why it happens
ABCDE classification of ADRs
A Augmented pharmacological effect B Bizarre C Chronic D Delayed E End-of-treatment
Types of allergic reactions
Type I - immediate, anaphylactic (IgE)
e.g., anaphylaxis with penicillins
=> this is the most important one in this context because you have to be able to recognise it and treat it right away
Type II - cytotoxic antibody (IgG, IgM)
e.g., methyldopa and hemolytic anemia
(less common)
Type III - serum sickness (IgG, IgM)
antigen-antibody complex
e.g., procainamide-induced lupus
(less common)
Type IV - delayed hypersensitivity (T cell)
e.g., contact dermatitis
Examples of peudoallergies
Aspirin/NSAIDs – bronchospasm
ACE inhibitors – cough in a large number of patients/angioedema
