Adverse drug reactions Flashcards
Incidence of ADRs and burden of cost
- ARDs cause substantial morbidity and mortality
- Estimates of incidence vary with study methods, populations and ADR definitions
- ARDs are the 4th to 6th leading cause of death amongst hospitalised patients
- There is a very high percentage of serious, adverse drug reactions (6.7% are serious
- ADRs are responsible for many hospital admissions (0.3% to 7%), and therefore cost a lot of money
- 30-60% of these events are preventable
How are ADRs classified?
Onset, severity and type
What are the categories of onset of ADRs?
Acute: Within 1 hour
Sub-acute: 1 to 24 hours
Latent: more than 2 days
What are the categories of severity of ARDs?
Mild: requires no change in therapy
Moderate: requires a change in therapy, may require additional treatment, and possibly hospitalisation
Severe: disabling, life-threatening, or ones that cause damage to the foetus
- Results in death/ may be life-threatening
- Requires or prolongs hospitalisation
- May cause disability and congenital anomalies
- Requires intervention to prevent permanent injury to the person
What are the different types of ADR reactions?
Type A: Augmented pharmacological effect
Type B: Bizarre
Type C: Chronic
Type D: Delayed
Type E: End-of-treatment
What is a type A reaction?
Examples?
- Most ADRs are type A effects
- This reaction is often an extension of the pharmacologic effect of the drug that we already know about
- It is therefore usually predictable and often dose dependent
- E.g. atenolol and heart block, anticholinergics and dry mouth, NSAIDS and peptic ulcer
- These ADRs are understandable because we know that they are related to the pharmacology of the drug
………….
The green rectangle represents the area where we achieve therapeutic effects. Paracetamol can be given up to a certain dose with very few side effects. Once we go above this, toxicity increases to lethal levels. Digoxin toxicity gradually increases at any dose. There is no dose that you can give without causing some degree of toxicity.
What are type B reactions?
Examples?
- Type B reactions tend to be more dramatic
- They are idiosyncratic (particular to given individuals) or immunologic reactions
- These reactions include allergy and “pseudo-allergy”
- They are rare and unpredictable
- E.g. chloramphenicol and aplastic anemia, ACE inhibitors and angioedema (pseudo-allergy)
What are type C reactions?
Examples?
- Type C reactions are associated with long-term use of drugs
- These reactions involve dose accumulation (total dose someone’s exposed to over a period of time)
- There is a cumulative dose of these drugs
- E.g. methotrexate (used in chemotherapy and as an immunosuppressant) and liver fibrosis
Anti-malarial drugs and ocular toxicity (damage to the retina)
What are type D reactions?
Examples?
- Type D reactions often have delayed effects (sometimes dose independent)
- This is not strongly linked to dose, it may happen at very low doses
- Carcinogenicity (e.g. immunosuppressants)
- Teratogenicity (affects fetus/embryo e.g. thalidomide)
What are type E reactions?
Examples?
Withdrawal reactions: Opiates, benzodiazepines, corticosteroids
Rebound reactions: Clonidine, beta-blockers, corticosteroids
Adaptive reactions: Neuroleptics (major tranquillisers)
Example of a rebound reaction - clonidine withdrawal
- Clonidine used to be used as an anti-hypertensive
- It is an alpha 2 agonist, so it reduces the release of noradrenaline from sympathetic neurones
- This reduction in sympathetic outflow leads to a drop in blood pressure
- If you miss one or two doses of clonidine, it could lead to a substantial rise in blood pressure
- This is because long-term use of clonidine causes long-term suppression of peripheral noradrenaline production, which, in turn, leads to a compensatory upregulation in adrenergic receptors on the post-synaptic neurone
- This upregulation in receptors means that when the inhibition of NA release by clonidine is removed, NA starts being produced again and has more receptors to act on and can cause a much great effect
How are allergies classified?
Type I – immediate, anaphylactic (IgE): e.g. anaphylaxis with penicillin
Type II – cytotoxic antibody (IgG, IgM) e.g. methyldopa and hemolytic anemia
Type III – serum sickness (IgG, IgM) – antigen-antibody complex e.g. procainamide-induced lupus
Type IV – delayed hypersensitivity (T cell) e.g. contact dermatitis
What are pseudoallergies?
Pseudoallergies have nothing to do with the immune system, they are mediated pharmacologically
Pseudoallergy - example of aspirin/NSAIDs and bronchospasm
- 5% of people who take these drugs get bronchospasm
- The reason for this is because these drugs inhibit COX enzymes
- Blocking COX results in a reduction in prostanoid/prostaglandin synthesis (bronchodilators)
- Instead, the body makes more leukotrienes (pro-inflammatory, and bronchoconstrictors)