Adverse Drug Reactions Flashcards
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
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)
What are the most common causes of ADRs
Antineoplastics
Cardiovascular drugs
NSAIDs/analgesics
CNS drugs
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- have same effect on similar receptors
Synergistic effects- potentiates effects of another
Antagonistic effects- decreases effects of another
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- irreversible binding of drugs in GI tract
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
3 ways to classify ADRs
Onset
Severity
Type
Onset classification
Acute <1 hour
Sub-acute 1-24 hours
Latent> 2 days
Severity classification
Mild- no therapy needed
Moderate- requires change in therapy or further treatment
Severe- disabling
What can happen in severe ADR
Congenital abnormalities
Prolonged treatment
Life threatening
What are pseudoallergies
Reactions to drugs that have no immune involvement
Examples of pseudoallergies
ACE inhibitors- cough/ angioedema
Aspirin- bronchospasm
