Adverse drug reactions Flashcards
What is an ADR (5)
- a drug-related event that is noxious and unintended and occurs at doses used in humans for prophylaxis, diagnosis or therapy of disease or for the modification of physiological function
- Overdose, including prescribing and administration errors
- Therapeutic failure
- Drug interactions
- Drug withdrawal
Where do we find information on ADR (2)
- BNF
- EMC
What are the drug factors that predispose to ADRs (7)
- Chemical characteristics
- Chemical similarity
- Bioavailability
- Drug degradation
- Route of administration
- Drug dose and duration of treatment
- Combination of drug and adjuvants
How can you ensure the safety of medicines (5)
- right patient
- right route
- right time
- right dose
- right drug
What patient factors influence ADRs (5)
- Age
- Sex
- Multiple diseases/polypharmacy
- Weight
- Genetics
What social and disease factors affect ADRs (3)
- Affects metabolism
- e.g. smoking and taking theophylline or beta-blockers
- e.g. alcohol and taking paracetamol
What are the PK effects of disease (5)
- Pharmacogenetic variations: fast and slow acetylators
- Hepatic disease: hepatitis or cirrhosis
- Renal disease: accumulation and toxicity
- Cardiac disease: oedema - reduced liver blood flow
- Thyroid disease: thyroid hormone regulates metabolism by CYP450
What are the PD effects of disease (6)
- Hepatic disease:
- reduced blood clotting
- Hepatic encephalopathy - sensitivity to sedatives
- Sodium and water retention
- Altered fluid & electrolyte balance:
- Cardiac glycosides potentiated in hypokalaemia and hypercalcaemia.
What are the classifications of ADRs (4)
- Onset of event
- Type of reaction
- Severity
- Other
What are the subcategories of the onset of event classification of ADRs (3)
- Acute
- Sub-acute
- Latent
What are the subcategories of the type of reaction classification of ADRs (5)
- A - augmented
- B - bizzare
- C - chronic
- D - delayed
- E - end-of-use
What are the subcategories of the severity classification of ADRs (4)
- Minor
- Moderate
- Severe
- Lethal
What are the subcategories of the other classification of ADRs (6)
- SE
- Toxicity
- Intolerance
- Drug allergy
- Drug withdrawal/dependence
- iatrogenic-drug induced disease
What are Type A ADRs (8)
- Augmented
- Occur early in treatment.
- Common- result of PK / PD abnormality
- Response to therapy is exaggerated but otherwise normal pharmacological action, e.g. beta-blockers- bradycardia,
- An example of type A ADR unrelated to therapeutic effects ototoxicity in patients treated with aminoglycoside antibiotics
- Predictable
- Dose-dependent so alleviated by
- Relatively low risk
What are Type B ADRs (5)
- Bizzare
- Not based on the known action of a drug.
- Unpredictable, e.g. allergic reactions
- Inherited abnormalities (genes) and immunological response
- High mortality, e.g. anaphylaxis following penicillin
What is the immunological response to Type B ADRs (6)
- Delay between first exposure & ADR
- No dose-response relationship
- The reaction goes when treatment is stopped.
- The patient may present with a rash, asthma-like symptoms…
- Drugs: penicillins, sulphonamides, protein-based drugs
- Viral disease-associated response
What are the mechanisms of Type B ADRs (4)
- Anaphylaxis: immediate hypersensitivity: IgE
- Cytotoxicity: cell destruction: IgG IgM
- Immune complexes: damaged capillary endothelium
- Delayed hypersensitivity: antigen-specific receptors develop on T-lymphocytes
What are Type C ADRs (4)
- Chronic
- Due to long-term exposure
- This can be due to the accumulation.
- Persist once the drug has been stopped, e.g. bisphosphonate-induced osteonecrosis of the jaw.
What are Type D ADRs (5)
- Delayed
- It may be dose-dependent
- Become apparent some time after the drug has been used.
- This can be due to the accumulation.
- e.g. thalidomide teratogenicity
What are Type E ADRs (4)
- End-of-use
- Occur as a result of drug being stopped.
- It might include withdrawal effects by stopping benzodiazepines/ opioids.
- Reflex hyperacidity stops PPIs
What are pseudo-allergenic reactions (5)
- Occur on first contact with drug
- Allergic reaction mimicked without the same immunological mechanisms occurring
- Histamine released from mast cells
- Genetic & environmental factors
- Itching, bronchospasm, vasodilation
What is a common pharmaceutical predictable ADR (3)
- Example = phenytoin
- Toxicity = Phenytoin toxicity (Ataxia, nystagmus etc)
- Mechanism = Increase in bioavailability as a result of a change in formulation
What is a common pharmacokinetic predictable ADR (3)
- Example = Digoxin
- Toxicity = Digoxin toxicity (Nausea, arrhythmias etc)
- Mechanism = Decreased elimination if renal function impaired
What is a common pharmacodynamic predictable ADR (3)
- Example = Indomethacin
- Toxicity = Left ventricular failure
- Mechanism = Water & sodium retention
What is a common genetically predictable ADR (3)
- Example = Nortriptyline
- Toxicity = Confusion
- Mechanism = Reduced hepatic elimination as a result of deficiency of CYP2D6
What is a common drug-drug interaction predictable ADR (3)
- Example = Lithium + NSAIDs
- Toxicity = Lithium toxicity
- Mechanism = Inhibition of excretion of lithium
When do you report ADRs (4)
- Serious reaction
- Black triangle drug
- The patient is a child.
- Unsure whether to report
