Adverse Drug Reactions Flashcards
What is an adverse drug reaction?
What is the most basic form of ADR classification?
Preventable or unpredictable medication event with harm to the patient;
Onset
Severity
Type
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, and requires or prolongs hospitalisation
Describe Type A ADR. Give examples
- Extension of pharmacological effect
- This is usually predictable and dose-dependent
- This is the most common type of ADR
e.g. atenolol and heart block, anticholinergics and dry mouth, NSAIDS and peptic ulcer
Describe Type B ADR.
‘Bizarre’ type of ADR
- Idiosynchratic or immunologic reactions
- Includes allergy or pseudoallergy
- Very rare and unpredictable
e.g. chloramphenicol and aplastic anemia, ACE inhibitors and angioedema
Describe 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
What reactions come under Type E ADRs.
Withdrawal reactions
Rebound reactions
Adaptive reactions
Describe and explain clonidine rebound reaction.
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
Recall 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 (4 types)
Type I - immediate, anaphylactic (IgE) e.g., anaphylaxis with penicillins Type II - cytotoxic antibody (IgG, IgM) e.g., methyldopa and hemolytic anemia Type III - serum sickness (IgG, IgM) antigen-antibody complex e.g., procainamide-induced lupus Type IV - delayed hypersensitivity (T cell) e.g., contact dermatitis
Give examples of pseudoallergies.
Aspirin/NSAIDs – bronchospasm
ACE inhibitors – cough/angioedema
What are the most common types of drugs causing ADRs?
Antineoplastics
Cardiovascular drugs
NSAIDs/analgesics
CNS drugs
What is the yellow card scheme?
A voluntary scheme allowing doctors, dentists, nurses, coroners and pharmacists (and members of the public) to report serious adverse drug reactions
Why is it difficult to determine the incidence of drug-drug interactions?
- Data for drug-related hospital admissions do not separate out drug interactions
- 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
Describe an example of alteration of absorption?
Irreversible binding of drugs in the GI tract
Tetracyclines, quinolone antibiotics
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
How are most drugs metabolised?
Most drugs metabolized by more than one CYP450 isozyme.
If co-administered with CYP450 inhibitor, some isozymes may “pick up slack” for inhibited isozyme
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
Which cytochrome P450 enzymes are responsible for over half of drug metabolism (i.e. the most prevalent)?
CYP2D6
CYP3A4
Give examples of drug elimination interactions (one positive, one negative); Where do they almost always occur?
Drug elimination interactions almost always occur in the renal tubules:
GOOD = Probenecid + penicillin ; Probenecid reduced excretion of penicillin and penicillin used to be expensive.
BAD = Lithium and thiazides ; thiazides lead to toxic accumulations of lithium.
