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 (take away a drug that you have been giving for a long time) Rebound reactions (if you miss a few dose of eg clonidine, your BP suddenly spikes) Adaptive reactions ( i dont know what this is)
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
This diverts the synthesis pathway to lead to 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 (1+1=2) Synergistic effects (1+1=3) Antagonistic effects (effect of 1 cancels the other out)
What are the different types of pharmacokinetic drug interaction?
Alteration in drug absorption Protein binding effects Changes in drug metabolism Alteration in elimination ADME
What is an example of alteration of absorption?
Chelation
eg Tetracyclines, quinolone antibiotics – these drugs can bind to ferrous sulfate (Fe+2), antacids (Al+3, Ca+2, Mg+2), dairy products (Ca+2) when taken together. If bound, they cannot be absorbed in the 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)
Give a few examples of CYP450 inhibitors.
Drug metabolism inhibited or enhanced by coadministration of other drugs. The following 2 will inhibit drug metabolism enzymes:
Erythromycin
Grapefruit juice
Give a few examples of CYP450 inducers.
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 (causing the production of new CYP450 enzymes) takes hours/days
Give an example of a deliberate drug interaction.
ACE inhibitors and thiazides = antihypertensive combo
In summary, what three parameters can be used to classify ADR
Can be classified in terms of their:
Onset (acute/subacute etc)
Severity (mild/moderate/severe)
Type (ABCDE)
In general, are drugs metabolised by one specific subtype of the CYP450 family or can it be metabolised by multiple different isozymes?
Most drugs are metabolized by more than one isozyme of the family
If drug is co-administered with a CYP450 inhibitor, some other isozymes may “pick up the slack” for the inhibited isozyme and metabolise the drug instead of the inhibited enzyme
Give an example of a ‘good’ drug elimination interaction (pharmacokinetic interaction)
Happens Almost always in renal tubule. Some drug elimination interactions are good and some are bad
- probenecid and penicillin (good): probenecid reduces rate of penicillin excretion. This allowed a lower dose of penicillin to be used in the patient
Give an example of a ‘bad’ drug elimination interaction (pharmacokinetic interaction)
- lithium (mood stabiliser) and thiazides (bad): thiazides also increase lithium circulation in the body but this can cause lethal effects on the patient
