Adverse Drug Reactions Flashcards
What is an adverse drug reaction?
Preventable or unpredictable medication event with harm to the patien
Describe the classification of ADRs based on onset.
Acute = < 1 hour Sub-acute = 1-24 hours Latent = > 2 days
Describe the classification of ADRs based on severity of the reaction.
Mild – requires no change in therapy
Moderate – requires change in therapy
Severe – disabling or life-threatening
Define Type A ADR.
Extension of pharmacological effect
This is usually predictable and dose-dependent
This is the most common type of ADR – 2/3
Example: atenolol can slow down heart rate but if you give too much you could cause heart block
Define Type B ADR.
‘Bizarre’ type of ADR
Idiosynchratic or immunologic reactions – includes allergy or pseudoallergy
This is very rare and unpredictable
Example: chloramphenicol and aplastic anaemia
Define Type C ADR.
Associated with long-term use
Involves drug accumulation
E.g. methotrexate and liver toxicity
Define Type D ADR.
Delayed effects – sometimes dose independent
E.g. carcinogenicity and teratogenicity
Define Type E ADR.
Withdrawal reactions
Rebound reactions
Adaptive reactions
Describe and explain clonidine rebound.
Clonidine is an alpha-2 agonist so it suppresses the release of noradrenaline
Long-term use of clonidine leads to an 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 noradrenaline 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 and bronchoconstriction
This occurs because aspirin and NSAIDs inhibit the production of prostanoids, which are bronchodilators
They promote the production of leukotrienes, which are bronchoconstrictors
ACE inhibitors and cough/angioedema
ACE inhibitors prevent the breakdown of kinins
Kinins accumulate in the 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
Why is it difficult to determine the incidence of drug-drug interactions?
There is a lack of availability of comprehensive databases
Difficulty in assessing OTC and herbal drug therapy use
Difficulty in determining contribution of drug interaction in complicated patients
What are the three types of pharmacodynamic drug interaction?
Additive effects
Synergistic effects
Antagonistic effects
What are the different types of pharmacokinetic drug interaction?
Alteration in drug absorption
Protein binding effects
Changes in drug metabolism
Alteration in elimination
What is an example of alteration of absorption?
Chelation
Explain what is meant by protein binding effects.
Competition between drugs for protein or tissue binding sites
It can increase free unbound concentration of a drug thus leading to enhanced pharmacological effects (e.g. warfarin)
Which cytochrome P450 enzymes are responsible for over half ofdrug metabolism?
CYP2D6
CYP3A4
Give a few examples of CYP450 inhibitors.
Cimetidine Erythromycin Ketoconazole Ciprofloxacin Ritonavir Fluoxetine Grapefruit juice
Give a few examples of CYP450 inducers.
Rifampicin Phenytoin Carbamazepine St. John’s Wort (hypericin) Phenobarbitone
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
