Adverse Drug Reactions Flashcards
What is an adverse drug event?
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
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
Define Type B ADR.
‘Bizarre’ type of ADR Idiosynchratic or immunologic reactions includes allergy or pseudoallergy This is very rare and unpredictable
Define Type C ADR.
Associated with long-term use Involves drug accumulation
Define Type D ADR.
Delayed effects – sometimes dose independent
Define Type E ADR.
Withdrawal reactions Rebound reactions Adaptive reactions
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 promotes the production of leukotrienes, which are bronchoconstrictors 2. 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 anyone to report serious adverse drug reactions New “black triangle” drugs - report any adverse reactions Older drugs - only report serious adverse 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 - 2+2 = 4 Synergistic effects - 2+2=5 each is more powerful together than alone 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
What is an example of alteration of absorption?
Chelation - Irreversible binding of drugs 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)
Which cytochrome P450 enzymes are responsible for over half of drug metabolism?
CYP2D6 CYP3A4
Give a few examples of CYP450 inhibitors.
Cimetidine Erythromycin and related antibiotics Ketoconazole Ciprofloxacin and related antibiotics Ritonavir and other HIV drugs Fluoxetine and other SSRIs 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
What are the 3 features of ADR classification?
Onset Severity Type
Give 3 examples of type A ADRs.
atenolol can slow down heart rate but if you give too much you could cause heart block anticholinergics and dry mouth, NSAIDS and peptic ulcer
What is the ADR dose relationship for digoxin and paracetamol?
Type A Digoxin: ADR’s and dose positive linear relationship
Paracetamol: Low ADR to dose linear ratio until the end of the therapeutic window when the ratio shoots up
Give 2 examples of type B ADRs
Example: chloramphenicol and aplastic anaemia ACE inhibitors and angioedema Common in cancer treatments
Give 2 examples of type C ADRs
methotrexate and liver fibrosis, antimalarials and ocular toxicity
Give 2 examples of type D ADRs
carcinogenicity (e.g. immunosuppressants) teratogenicity (e.g. thalidomide)
Give 3 examples of type E withdrawal ADRs
Opiates, benzodiazepines, corticosteroids
Give 3 examples of type E rebound ADRs
Clonidine, beta-blockers, corticosteroids
Give an example of a type E adaptive ADRs
Neuroleptics (major tranquillisers)
Give an example of each kind of hypersensitivity reaction
Type I - anaphylaxis with penicillins Type II - methyldopa and hemolytic anemia Type III - procainamide-induced lupus Type IV - contact dermatitis
What are the 3 categories of drug interaction
Pharmacodynamic Related to the drug’s effects in the body Pharmacokinetic Related to the body’s effects on the drug Pharmaceutical drugs interacting outside the body
What does inhibiting one CYP 450 not always increase the level of the drug it metabolises?
Other CYP 450 isoenzymes “pick up the slack” and metabolise the drug.
Give a good and bad example of drug elimination reactions
probenecid and penicillin (good) lithium and thiazides (bad): thiazides increase sodium excretion and retain lithium which is very toxic at high levels.
