Adverse drug reactions Flashcards
What is the definition of an adverse drug reaction?
Preventable or unpredicted medication event with harm to the patient
What are ARDs classified on?
Onset
Severity
Type
How are ARDs classified based on onset?
Acute- within 1 hour
Sub-acute- 1 t o24 hours
Latent- >2 days
How are ARDs classified based on severity?
Mild- requires no change in therapy
Moderate- requires changes in therapy, additional treatment and hospitalisation
Severe- disabling or life threatening
What is a type A ADR?
Extension of the pharmacologic effect
Usually predictable and dose-dependent
What is the most common type of ADR?
Type A- it is responsible for at least 2/3s of ADRs
Give some examples of Type A ADRs
Atenolol will slow the heart down but if you give too much of it, it may cause complete heart block
Chronic use of NSAIDs can cause peptic ulcers
What is a type B ADR?
Idiosyncratic or immunologic reactions
Include allergy and pseudo allergy
Rare and unpredictable
Give some examples of type B ADRs?
Chloramphenicol can cause aplastic anaemia
ACE inhibitors can cause angioedema
What is a type C ADR?
Associated with long-term use
Involves dose accumulation
Give some examples of type C ADRs?
Methotrexate- liver toxicity
Antimalarials- ocular toxicity
What is a type D ADR?
Delayed effects- sometimes dose independent
Give some examples of type D ADRs?
Carcinogenicity- e.g. immunosuppression
Teratogenicity- e.g. thalidomide
What is a type E ADR?
Withdrawal reactions
Rebound reactions
Adaptive reactions
Give some examples of type E ADRs?
Withdrawal- opiates, benzodiazepines and corticosteroids
Rebound reactions- Clonidine, beta blockers and corticosteroids
Neuroleptics
What is clonidine used for and how does it have an effect?
Used as an anti-hypertensive- it is an alpha 2 agonist meaning that it reduces the release of noradrenaline from sympathetic neurones which leads to drop in blood pressure
What can happen if you miss one or two doses of clonidine?
It could lead to a substantial increase in blood pressure
How does the clonidine rebound occur?
Long term use of clonidine causes long term suppression of peripheral noradrenaline production which in turn leads to compensatory upregulation in adrenergic receptors on post-synaptic neurone
This upregulation in receptors means that when the inhibition of NA release by clonidine is removed, NA starts being produced again and has more receptors to act on and can cause a much greater effect > rise in BP
What is the ABCDE classification?
Augmented pharmacological effect Bizarre Chronic Delayed End of treatment
What is the classification of allergies?
Type I- immediate, anaphylactic (IgE) e.g. anaphylaxis with penicillin
Type II- Cytotoxic antibody (IgG and IgM)
e.g. methyldopa and haemolytic anaemia
Type III- serum sickness (IgG and IgM)
e.g. procainamide induced lupus
Type IV- delayed hypersensitivity (T cell)
e.g. contact dermatitis
What can aspirin/NSAIDs cause and how in terms of pseudoallergies?
Bronchospasm- they are inhibiting the production of prostanoids which are generally bronchodilators
Accompanied by increase in leukotriene production- generally bronchoconstrictors
What do ACE inhibitors cause in about 20% of patients?
Cough- they stop the breakdown of kinins- these are present in the sensory nerves of the lungs. If it accumulates it causes coughing
What common causes of ADRs are there?
Antineoplastics Cardiovascular drugs NSAIDs/analgesics CNS drugs (Above 4 account for 2/3 of fatal ADRs) Antibiotics Anticoagulants Hypoglycaemic Anti-hypertensives
How are ADRs detected?
Subjective report- patient complaint Objective report- observation of event Abnormal findings: Physical examination Laboratory test Diagnostic procedure
What is the yellow card scheme?
System for reporting adverse drug reactions
What does additive effect mean in terms of drug interactions?
Two drugs add together
What does synergistic effect mean in terms of drug interactions?
Two drugs potentiate each other’s actions to get a greater effect than expected
Antagonist effects- drugs that antagonise each others’ actions
How can drug interactions alter absorption?
Chelation
Irreversible binding of drugs in the GI tract makes it difficult to absorb
e.g. tetracycline, quinolone, antibiotics, dairy products
How do drug interactions affect protein binding effects?
Competition between drugs for protein or tissue binding sites
Increase in free (unbound) concentration may lead to enhanced pharmacological effects e.g. warfarin
How do drug interactions affect drug metabolism?
It could be inhibited or enhanced by coadministration of other drugs. Some are metabolised by a single isozyme, most are metabolised by multiple isozymes
Why is being metabolised by multiple isozymes useful?
If one of the isozymes is inhibited, the other isozymes could increase their activity to compensate for inhibited isozyme
Which CYP450 isozymes do over half of drug metabolism?
CYP2D6 and CYP3A4
2D6 shows a great degree of variability
Give some examples of CYP450 inhibitors
Cimetidine (H2 antagonist) Erythromycin and related antibiotics Ketoconazole Ciprofloxacin and related antibiotics Ritonavir and the rHIV drugs Fluotexine and other SSRIs Grapefruit juice
Give some examples of CYP450 inducers
Rifampicin
Carbamazepine
St John’s Wort (hypericin)
How does the onset of inhibition and induction differ?
Inhibition- rapid
Induction- takes hours/days (need to produce new gene products/proteins)
How does ADR risk change with increasing number of drugs?
It increases
