22. Adverse drug reactions Flashcards
why are adverse drug reactions an issue?
- they cause substantial morbidity and mortality
- they are one of the leading causes of death amongst hospitalised patients
- they are responsible for many hospital admissions and cost a lot of money
- 30-60% of events are preventable
how is the onset of adverse drug reactions classified?
ACUTE: within 1hr
SUB-ACUTE: 1-24hrs
LATENT: more than 2 days
how is the severity of adverse drug reactions classified?
MILD: requires no change in therapy
MODERATE: requires a change in therapy, may require additional treatment and possibly hospitalisation
SEVERE: disabling, life-threatening, requires prolonged hospitalisation
how is the type of reaction of adverse drug reactions classified?
TYPE A: Augmented pharmacological effect TYPE B: Bizarre TYPE C: Chronic TYPE D: Delayed TYPE E: End-of-treatment
what are the characteristics of type A reactions?
- an extension of the pharmacologic effect of the drug that we already know about
- usually predictable and dose dependent
- responsible for at least 2/3 ADRs
give some examples of type A reactions
- atenolol and heart block
- anticholinergics and dry mouth
- NSAIDS and peptic ulcer
what are the characteristics of type B reactions?
- more dramatic
- particular to given individuals/immunological reactions (e.g. allergy and “pseudo-allergy”)
- rare and unpredictable
give some examples of type B reactions
- chloramphenicol and aplastic anemia
- ACE inhibitors and angioedema (pseudo-allergy)
what are the characteristics of type C reactions?
- associated with long-term drug use
- involve dose accumulation (total dose someone is exposed to over a period of time)
give some examples of type C reactions
- methotrexate and liver fibrosis
- anti-malarial drugs and ocular toxicity
what are the characteristics of type D reactions?
- delayed effects
- not strongly linked to dose - may happen at very low doses
give some examples of type D reactions
- carcinogenicity (e.g. immunosuppressants)
- teratogenicity (e.g. thalidomide)
what are the characteristics of type E reactions?
- withdrawal reactions: opiates, benzodiazepines, corticosteroids
- rebound reactions: clonidine, beta-blockers, corticosteroids
- “adaptive” reactions: neuroleptics (major tranquillisers)
what is clonidine?
- an alpha 2 agonist which reduces the release of noradrenaline from sympathetic neurones
- the reduction in sympathetic outflow leads to a drop in blood pressure
- clonidine used to be an anti-hypertensive
why does clonidine withdrawal occur and what does it result in?
- long-term use of clonidine causes long-term suppression of peripheral noradrenaline production which leads to compensatory upregulation in adrenergic receptors on post-synaptic neurones
- the 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 so causes a greater effect –> substantial rise in blood pressure
how are allergies classified?
TYPE 1: immediate, anaphylactic (IgE) e.g. anaphylaxis with penicillin
TYPE 2: cytotoxic antibody (IgG, IgM) e.g. methyldopa and hemolytic anaemia
TYPE 3: serum sickness (IgG, IgM) antigen-antibody complexes e.g. procainamide-induced lupus
TYPE 4: delayed hypersensitivity (T cell) e.g. contact dermatitis
describe the example of aspirin/NSAIDS and bronchospasm as a pseudoallergy
- 5% of people that take the drug get bronchospasm
- this is because these drugs inhibit COX enzymes
- blocking COX results in reduced prostanoid/prostaglandin synthesis (bronchodilators)
- instead the body makes more leukotrienes (pro-inflammatory and bronchoconstrictors)
what are pseudoallergies?
pseudoallergies have nothing to do with the immune system
describe the example of ACE inhibitors and cough/angioedema as a pseudoallergy
- 10-20% of people taking ACE inhibitors suffer from chronic, dry cough
- this is due to the accumulation of inflammatory peptides in the lung
- bradykinin triggers cough through sensory receptors in the lung
- less than 1% of patients may suffer from angioedema (many of the same signs and symptoms of anaphylaxis but less severe)
what are common causes of ADRs?
- antibiotics
- antineoplastic drugs
- anticoagulants
- cardiovascular drugs
- hypoglycemic drugs
- antihypertensive drugs
- NAID/analgesics
- CNS drugs
how are ADRs detected?
- subjective report (complaint)
- objective report (observation and abnormal findings) –> physical examination, lab testing, diagnostic procedure
what is the yellow card system?
- a public way of detecting adverse reactions
- it can be used by doctors, dentists, nurses, coroners, pharmacists and members of the public
- includes blood products, vaccines, contrast media
- for established drugs only report SERIOUS ADRs (fatal disabling)
- for “black triangle” drugs (newly licensed) report ANY SUSPECTED ADRs
- ADR suspected –> ADR confirmed –> frequency estimated –> prescribers informed
what is the problem with drug-drug interactions?
- there are no proper databases to find this out
- people take over-the-counter medicines
- difficulty assessing herbal drug therapy use
- difficulty determining the contribution of drug interaction in complicated patients
what are the 3 varieties of drug interactions?
PHARMACODYNAMIC INTERACTIONS: related to the drug’s effects in the body (receptor site occupancy)
PHARMACOKINETIC INTERACTIONS: related to the body’s effects on the drug (absorption, distribution, metabolism, elimination)
PHARMACEUTICAL INTERACTIONS: drugs interacting outside the body (mostly IV infusions)
