Adverse Drug Reactions Flashcards
What is an adverse drug reaction?
Preventable or unpredictable medication event with harm to 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
Define Type A ADR and give an example
Extension of pharmacological effect
Predictable + dose-dependent
Most common type of ADR
E.g. Atenolol slows HR but excess can cause heart block
Define Type B ADR and give an example
‘Bizarre’ type of ADR
Idiosynchratic or immunologic reactions– includes allergy or pseudoallergy
Rare + unpredictable
E.g. Chloramphenicol + aplastic anaemia
Define Type C ADR and give an example
Associated with long-term use
Involves drug accumulation
E.g. Methotrexate + liver toxicity
Define Type D ADR and give an example
Delayed effects: sometimes dose independent
E.g. immunosuppressants are associated with delayed carcinogenicity
Define Type E ADR and give an example
Withdrawal reactions (sudden cessation) e.g. Opiates Rebound reactions (Stop drug, pathophysiology worsens than pre-drug) e.g. B-blockers Adaptive reactions e.g. Neuroleptics
Describe and explain clonidine rebound.
Clonidine is an A-2 agonist so suppresses release of NA
Long-term use leads to upregulation in adrenergic receptors on the post-synaptic membrane
If dose is missed, it will cause an increase in NA release, which then acts on an increased number of receptors so has a greater effect
Causes a large increase in BP
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 2 examples of pseudoallergies.
Aspirin/NSAIDs + bronchoconstriction
Occurs because aspirin + NSAIDs inhibit production of prostanoids (bronchodilators) + promote production of leukotrienes (bronchoconstrictors)
ACE inhibitors + cough/ angioedema
ACE inhibitors prevent breakdown of kinins
Kinins accumulate in sensory nerves in lungs + trigger cough
What are the 4 most common causes of ADRs?
Antineoplastics
Cardiovascular drugs
NSAIDs/ analgesics
CNS drugs
What is the yellow card scheme?
Voluntary scheme allowing prescribers to report serious adverse drug reactions
Why is it difficult to determine the incidence of drug-drug interactions?
Lack of availability of comprehensive databases
Difficulty in assessing OTC + herbal drug therapy use
Difficulty in determining contribution of drug interaction in complicated patients
What are the three types of pharmacodynamic drug interaction?
Additive: 2 drugs provide similar effects by different MOA
Synergistic: 1 drug potentiates the effect of another
Antagonistic: 1 drug cancels the action of another
What are 4 different types of pharmacokinetic drug interaction?
Alteration in 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 forming insoluble complex which is un-absorbable
Explain what is meant by protein binding interactions. Give an example of a drug in which this is clinically significant
Competition between drugs for protein or tissue binding sites
Can increase free unbound concentration of a drug thus enhancing pharmacological effects (e.g. warfarin)
Which cytochrome P450 enzymes are responsible for over half of drug metabolism?
CYP2D6
CYP3A4
Give 7 examples of CYP450 inhibitors.
Cimetidine Erythromycin + related antibiotics Ketoconazole Ciprofloxacin + related antibiotics Ritonavir + other HIV drugs Fluoxetine + other SSRIs Grapefruit juice
Give 5 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 + thiazides (antihypertensives working in different ways)
Levodopa + Carbidopa (increases efficacy of levodopa in CNS)
What characterises a severe adverse drug reaction/ what are the consequences?
Requires intervention to prevent permanent injury Life threatening Hospitalisation Disability Congenital abnormalities Death
How can type A adverse reactions differ? Explain using the examples of Digoxin and Paracetemol
Digoxin has a linear relationship between adverse reaction + dose
Paracetamol is harmless up to a certain dose, where toxicity sharply increases
Give an example of a serious type B adverse reaction that was totally unexpected
Herceptin in breast cancer treatment caused cardiac toxicity
In which way are most drugs metabolised? What is the consequence of this?
By multiple isozymes
Thus if 1 isozyme is inhibited, others can “pick up slack”
Give 2 drug elimination interactions, one being desired the other unwanted
Good: Probenecid stopped elimination of penicillin, maintained high plasma conc.
Bad: Thiazide diuretics causing increased excretion of Na+, + lithium retention (to toxic levels)
How does number of medications effect frequency of adverse drug reactions?
The more medications, the more adverse reactions
