Adverse Drug Reactions Flashcards
What is an adverse drug reaction?
- Preventable or unpredictable medication event with harm to the patient
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
What is the ABCDE classification of adverse drug reactions?
- A – augmented pharmacological action
- B – bizarre
- C – chronic
- D – delayed
- E – end of treatment
Define Type A ADR and give an example (3 answers are given but just get any you can)
- Augmented (extension of) pharmacological effect
- Predictable and dose-dependent
- This is the most common type of ADR – 2/3
- Examples:
- Atenolol can slow down heart rate but if you give too much you could cause heart block
- Anti-cholinergics and dry mouth
- NSAIDs and peptic ulcers
Define Type B ADR and give an example
- ‘Bizarre’ type of ADR
- Idiosynchratic or immunologic reactions – includes allergy or pseudoallergy
- This is very rare and unpredictable
- Example:
- ACEis and angioedema
- Chloramphenicol and aplastic anaemia
Define Type C ADR and give an example (2 answers given but give any of these)
- ‘Chronic’ - associated with long-term use
- Involves drug accumulation
- E.g:
- Methotrexate and liver toxicity
- Anti-malarial drugs and ocular toxicity
Define Type D ADR and give 2 examples
- Delayed effects – sometimes dose independent
- E.g:
- Carcinogenicity (e.g. immunosuppressants)
- Teratogenicity (e.g. thalidomide)
Define Type E ADR and give 3 reactions that constitute this type of ADR
- End-of treatment reactions - WAR acronym
- Withdrawal reactions
- Adaptive reactions
- Rebound reactions
Describe and explain clonidine rebound, starting with what clonidine is and then how it has this ADR rebound effect - also what type of ADR is this?
- 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 - undesired
- This is a type E ADR
Describe the classification of allergies - the various types, what they are otherwise known as, and the main mediators involved
- All types of hypersensitivity reactions
- Type 1 – immediate, anaphylaxis (IgE)
- Type 2 – cytotoxic antibody (IgG + IgM)
- Type 3 – serum sickness (IgG + IgM)
- Type 4 – delayed hypersensitivity (T cell)
What are pseudoallergies and give 2 key examples of pseudoallergies caused by drugs
- Pseudoallergies are when you get conditions where it mimics allergies but it is not actually anything to do with the immune system, i.e. pharmacological not immunological
1. 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 (brady)kinins
- Kinins accumulate and trigger sensory C-fibre nerves in the lungs to cause coughing
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 - cumulative effect
- Synergistic effects - potentiation of each other’s 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
(Basically changes in adme - one to look out for is the protein binding effects - this is a essentially a change in distribution though)
What is an example of alteration of absorption?
Give an example
- Chelation
- Quinolone and tetracyclines may be given and you can also digest ferrous sulfate (Fe2+), antacids (Al3+, Mg2+, Ca2+) and dairy products (Ca2+)
- These interact to form a stable chelate which prevents absorption of both the mineral ions and the antibiotics quinolone and tetracycline
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 of drug metabolism?
- CYP2D6
- CYP3A4
Give a few examples of CYP450 inhibitors
- Erythromycin
- Ketoconazole
- Ritonavir and other HIV drugs
- Cimetidine
- Fluoxetine and other SSRIs
- Ciprofloxacin
- 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 - synergistic interaction, both work to reduce BP
- Penicillin and gentamicin - synergistic interaction, both antibiotics
- Salbutamol and ipatropium - synergistic interaction (salbutamol is a beta-2 antagonist and ipatropium is an anti-cholinergic, therefore both work to treat asthma)
