Adverse Drug Reactions Flashcards
What are adverse drug events?
preventable or unpredicted medication events with harm to the patient
*Medication errors AND adverse drug reactions
How are ADRs classified based on onset?
Acute <1 hour
Sub-acute 1-24 hours
Latent >2 days
How are ADRs classified based on severity?
Mild - no change in therapy required
Moderate - change in therapy required, additional treatment and hospitalisation
Severe - disabling, life-threatening, prolongs hospitalisation, causes congenital abnormalities,
requires intervention to prevent further injury
How are ADRs classified based on type?
Type A: Augment/extend the pharmacological effect
- Usually predictable and dose-dependent, represents 2/3rds of ADRs
- Paracetamol has a threshold below which it has minimal side effects (and then exceeding this, side effects rapidly increase). Digoxin just has a dose-dependent line with constant increasing SEs
- E.G. Atenolol + heart block, NSAIDs + peptic ulcers
Type B: Bizarre – Idiosyncratic or Immunologic reactions
- Unpredictable, rare, and include allergy and “pseudo-allergy”
- E.G. Chloramphenicol + aplastic anaemia, ACE inhibitors + angioedema
Type C: Chronic – Long-term use side effects
- Involves dose accumulation
- E.G. Methotrexate + liver fibrosis
Type D: Delayed – Delayed effects
- Carcinogenicity – e.g. immunosuppressants
- Teratogenicity – e.g. thalidomide
Type E: End of treatment side effects - BDP = benzodiazepines
- Withdrawal reactions – patient cannot make endogenous supply – opiates, corticosteroids, BDPs
- Rebound reactions – disease gets worse when drugs stopped – clonidine, b-blockers, corticosteroids
- “Adaptive” reactions – adapted body reactions to drugs – neuroleptics (tranquilisers)
What are the different types of allergic reaction?
What are their mediators and examples?
Type 1 – immediate, anaphylactic - IgE
- E.G. anaphylaxes with penicillin
Type 2 – cytotoxic antibody - IgG, IgM
- E.G. methyldopa and HA
Type 3 – serum sickness (antibody-antigen complex) - IgG, IgM
- E.G. procainamide-induced lupus
Type 4 – delayed-type hypersensitivity - T-Cell
- E.G. contact dermatitis
What are examples of type B ADRs?
Aspirin/NSAIDs -> bronchospasm:
- Aspirin/NSAIDs inhibit COX so less prostaglandin synthesis and more leukotrienes made
ACE inhibitors -> cough/angioedema:
- ACEi inhibit production of AngII and stop the breakdown of inflammatory mediators such as bradykinin which stimulate the cough receptors in the lungs
What are common causes of ADRs?
- Antineoplastics – cytotoxic drugs
- Cardiovascular drugs
- NSAIDs/analgesics
- CNS drugs
*^^ These 4 account for 2/3rds of fatal ADRs
- Antibiotics. Note that ADR frequency increases with increased individual drug use
- Anticoagulants
- Hypoglycaemics
- Antihypertensives
How do you detect ADRs?
Subjective reports:
- Patient complaints – yellow-card system
Objective reports:
- Direct observations of events
- Abnormal findings – physical examination, lab tests, diagnostic procedures
What is the yellow card scheme?
This was a scheme introduced after the 1964 incident with thalidomide and is run by the Committee on Safety of Medicines (branch of medicines control agency)
Voluntary, can be used by any healthcare professional, and includes blood products, vaccines and contrast media
Established drugs -> only report serious adverse reactions
“Black triangle” drugs (newly licensed) -> report ANY suspected adverse reactions
Why is incidence difficult to ascertain?
- Data for drug-related hospital admissions do not differentiate out drug interactions, only ADRs
- There is a lack of available comprehensive databases
- Difficulty in assessing OTC drug use
- Difficulty in determining drug contribution to interactions in complicated patients
- Sometimes the principal causes of ADRs is with specific drugs – e.g. statins
What are the pharmacodynamics of drug interactions?
drug’s effects on the body – e.g. receptor site dynamics
Additive, synergistic, or antagonistic effects from co-administration
- Synergistic actions of antibiotics – use of two ABs will increase the effect more than their separate contributions (i.e. 2+2=5) OR they antagonise each other
- Overlapping toxicity – ethanol and benzodiazepines
- Antagonistic effects – anticholinergic medications
What are the pharmacokinetics of drug interactions?
body’s effects on the drug – e.g. absorption, distribution, metabolism, excretion
Alteration in absorption – CHELATION:
- Irreversible binding in the GI-tract, for example, antibiotics to metal ions or calcium to form chelates that prevent absorption of the antibiotic
Protein-binding interactions – not usually clinically significant but some are (e.g. warfarin)
- Warfarin is 99% albumin-bound so anything to decrease that will increase the free warfarin so there is more anti-coagulative effects
Drug metabolism and excretion:
- Drugs can either be (1) directly excreted, (2) undergo Ph1 metabolism and be excreted, (3) undergo Ph1 and Ph2 and then be excreted or (4) only undergo Ph2 and then be excreted
What are the pharmaceuticals of drug interactions?
drug interactions outside the body – e.g. in IV infusions
What are phase 1 metabolic reactions?
oxidation, reduction, hydrolysis
What are phase 2 metabolic reactions?
conjugation (glutathione, amino-acid), glucuronidation, sulphation, acetylation and methylation
