22) Adverse Drug Reactions Flashcards
What is an adverse drug reaction?
Preventable or unpredictable medication event with harm to the patient
Describe severe ADRs
Results in death Life-threatening Requires or prolongs hospitalisation Causes disability Causes congenital anomalies Requires intervention to prevent permanent injury
ABCDE CLASSIFICATION OF
ADVERSE DRUG REACTIONS
A Augmented pharmacological effect B Bizarre C Chronic D Delayed E End-of-treatment
Define Type A ADR.
Extension of pharmacological effect Predictable Dose-dependent Most common type of ADR (2/3) Example: atenolol --> heart block NSAIDS --> peptic ulcer Anticholinergics --> dry mouth
Define Type B ADR.
‘Bizarre’ type of ADR
Idiosynchratic or immunologic reactions – Includes allergy or pseudoallergy
Rare
Unpredictable
e.g. chloramphenicol –> aplastic anaemia
ACE inhibitors –> angioedema
Define Type C ADR.
Associated with long-term use
Involves drug accumulation
E.g. methotrexate –> liver toxicity
antimalarials –> ocular toxicity
Define Type D ADR.
Delayed effects – sometimes dose independent
E.g. immunosuppressants –> carcinogenicity thalidomide –> teratogenicity
Define Type E ADR.
Withdrawal reactions
(opiates, corticosteroids, benzodiazepines)
Rebound reactions
(Clonidine, beta-blockers, corticosteroids)
Adaptive reactions
(Neuroleptics (major tranquillisers))
Describe and explain clonidine rebound.
Clonidine = alpha-2 agonist = suppresses NA release
Long-term Clonidine use –> upregulation in adrenergic receptors on the post-synaptic membrane
If the dose of clonidine is missed once or twice, it will cause an increase in NA release, which then acts on an increased number of receptors so has a greater effect
This causes a large increase in blood pressure
What is the ABCDE classification of adverse drug reactions?
A – augmented pharmacological action B – bizarre C – chronic D – delayed E – end of treatment
Describe the classification of allergies.
Type 1 – immediate, anaphylaxis (IgE)
Type 2 – cytotoxic antibody (IgG + IgM)
Type 3 – serum sickness (IgG + IgM)
Type 4 – delayed hypersensitivity (T cell)
Give examples of pseudoallergies.
Aspirin/NSAIDs –> bronchoconstriction
Aspirin + NSAIDs inhibit prostanoid (bronchodilators) production & promote leukotrienes (bronchoconstriction) production
ACE inhibitors –> cough/angioedema
ACEI prevent kinin breakdown–> Kinins accumulate in sensory nerves in the lungs and trigger cough
What are the most common causes of ADRs
Antineoplastics
Cardiovascular drugs
NSAIDs/analgesics
CNS drugs
What is the yellow card scheme?
A voluntary scheme allowing doctors, dentists, nurses, coroners and pharmacists to report SERIOUS adverse drug reactions
pharmacodynamic drug interaction?
Additive effects
Synergistic effects (antibiotics)
Antagonistic effects
What are the different types of pharmacokinetic drug interaction?
Alteration in drug absorption + metabolism _ excretion
+ Protein binding effects
What is an example of alteration of absorption?
Chelation
Which cytochrome P450 enzymes are responsible for over half of drug metabolism?
CYP2D6
CYP3A4
Describe the difference in the speed of inhibition and the speed of induction of CYP450 enzymes.
Inhibition is RAPID
Induction takes hours/days
Give an example of a deliberate drug interaction.
ACE inhibitors and thiazides
classification of ADRs
--------onset Acute = < 1 hour Sub-acute = 1-24 hours Latent = > 2 days --------severity Mild – requires no change in therapy Moderate – requires change in therapy Severe – disabling or life-threatening --------type ABCDE
drug elimination interactions
almost always in renal tubule
- lithium and thiazides = bad
- probenecid and penicillin = good
genetic differences influence individual response to drugs
polypharmacy, age, diet and renal function can effect drug reactions
genetic differences influence individual response to drugs
polypharmacy, age, diet and renal function can effect drug reactions
