Adverse drug reactions Flashcards
what is an adverse drug reaction?
- preventable or unpredicted medication event with harm to the patient
what can ARDs be classified based on?
- onset
- severity
- type
explain the classification based on ONSET
- acute: within 1 hour
- sub-acute: 1 to 24 hours
- latent: >2 days
describe the classification based on severity
- mild: required no change in therapy
- moderate: requires changes in therapy, additional therapy
- severe: disabling or life threatening, result in death, requires hospitalisation
in classification based on type, what is type A?
- extension of pharmacologic effect
- usually predictable and dose dependent
- responsible for 2/3rds ARDs
give 2 examples of type A
- atenolol: slow heart down, give too much may cause complete heart block
- NSAIDs: chronic use = peptic ulcers
why is paracetamol a type A?
- up to certain dose, paracetamol is pretty harmless
- beyond certain point, get serious toxicity that affects liver
describe type B ARDs
- idiosynchratic or immunologic reactions
- allergy and pseudoallergy
- rare and unpredictable
give 2 examples of type B
- Chloramphenicol: can cause aplastic anaemia
- ACE inhibitor can cause angioedema
describe type C ADRs
- associated w/ long term use
- involves dose accumulation
give 2 examples of type C
- methotrexate: liver toxicity
- antimalarials: ocular toxicity
what is type D ADR?
- delayed effects: sometimes dose independent
- carcinogenicity: e.g. immunosuppression
- teratogenicity: e.g. thalidomide
What is type E ADR?
- withdrawal reactions: e.g. opiates, benzodiazepines, corticosteroids
- rebound reactions e.g. clonidine, beta blockers, corticosteroids
- adaptive reactions neuroleptics (major tranquilisers)
what is clonidine rebound?
- alpha 2 agonist
- reduces release of NA from sympathetic neurones
- reduction in symp outflow = drop in BP
- if miss one or 2 doses, can lead to substantial RISE in BP
explain why missing a couple of doses causes a rise
- long term use causes long term suppression of peripheral NA production
- leads to compensatory upregulation in adrenergic receptors on post-synaptic neurone
- upregulation in receptors means that when inhibition of NA release by clonidine is removed, NA produces again
- has more receptors to act on = much greater effect
what is the ABCDE classification of ADR?
- augmented pharm effect
- bizarre
- chronic
- delayed
- end of treatment
what are 4 classifications of allergies?
- Type 1: immediate, anaphylactic (IgE)
- type 2: cytotoxic antibody (IgG and IgM)
- type 3: serum sickness (IgM and IgG): antigen-antibody complex
- type 4: delayed hypersensitivity (T cell)
give an example of type 1
anaphylaxis with penicillins
give an example of type 2
methyldopa and HA
give an example of type 3
procainamide-induced lupus
give an example of type 4
contact dermatitis
what pseudoallergy can aspirin/NSAIDs cause?
- bronchospasm
- inhibit production of prostanoids (bronchodilators)
- accompanied by inc. leukotriene production (bronchoconstrictors)
what pseudoallergy can ACE inhibitors cause?
- cough/angioedema
- stops breakdown of kinins
- if kinin accumulates, triggers coughing
- angioedema similar to anaphylaxis but not allergic
what are common causes of ARDs?
- antineoplastics
- CV drugs
- NSAIDs
- CNS drugs
- antibiotics
- anticoagulants
- hypoglycaemia
- anti-hypertensives
what are the ways in which ADRs are detected?
- subjective report: pt complaint
- objective report: direct observation for event, abnormal findings
- yellow card scheme: system for reporting ADR
what does pharmacodynamic mean?
related to drugs effect in body
what does pharmacokinetic mean?
related to body’s effect on drugs
what does pharmaceutical mean?
drugs interacting outside body
what are additive effects and examples?
- 2 drugs add together
- overlapping toxicities of ethanol and benzodiazepines
what are synergistic effects and an example?
- 2 drugs potentiate each others actions to get a greater effect than expected
- e.g. synergistic actions of antibiotics
what are antagonist effects and an example?
- drugs that antagonize each other’s actions
- e.g. amitriptyline and acetylcholinesterase inhibitors
in pharmacokinetic drug interactions, what is alteration in absorption?
- chelation
- irreversible binding of drugs in GIT that makes it difficult to absorb
e. g. tetracyclines, quinolone
in pharmacokinetic drug interactions, describe the protein binding effects
- competition b/ drugs for protein or tissue binding sites
- inc. in free conc = enhances pharmacological effects
- PB interactions not usually clinical significant but few are
give an example where PB interactions are significant
warfarin
very heavily protein bound, small inc. in unbound warfarin = big difference
in pharmacokinetic drug interactions, describe drug metabolism
- drug metabolism can be inhibited or enhanced by coadmin of other drugs
- some drugs metabolized by single isozyme
- most metabolised by multiple isozymes
why is being metabolized by more than one enzyme useful?
if one of the isozymes is inhibited, other isozymes could inc. their activity to compensate for inhibited ioszyme
what family of enzymes are involved in drug metabolism?
CYP450
give examples of CYP450 inhibitors?
- cimetidine (H2 antagonist)
- erythomycin
- ketoconazole
- ritonavir
- fluxetine
- grapefruit juice
give examples of CYP450 inducers
- rifampicin
- carbamazepine
give examples of 4 deliberate interactions
- levodopa and carbidopa
- ACE inhibitors and thiazides
- penicillins and gentamycin
- salbutamol and ipratropium
