ADRs & Toxicology Flashcards
What are side effects?
Are a consequence of the pharmacological mechanism of action of the drug - usually due to presence of receptors in a number of tissues or lack of receptors specificity. This means that you cannot completely eliminate side-effects they are a natural consequence of using a particular drug
What are some examples of side effects?
Drowsiness with older antihistamines, constipation & nausea with opioids
In some situations a side-effect can be used as a therapeutic effect e.g. older antihistamines for sedation, opioids for diarrhoea
What is an adverse drug reaction?
Is any response to a drug that is noxious (harmful) and unintended that occurs at doses normally used in humans.
An ADR may require immediate treatment or a decrease in dose or may indicate caution in the future (alerts)
What are some examples of adverse drug reactions?
Severe tachycardia or tremor when using normal dose of salbutamol
How are ADRs classidied?
Type A and Type B ADRs: Rawlins-Thompson Classification
What are Type A drug reactions?
Predicted from pharmacological actions (mechanism of action of the drug) and are usually dose-related. The yare common, predictable, dose-dependent, usually associated with low morbidity & morality, usually addressed by dose reduction. Account for majority of ADR 80%
What is an example of a Type A drug reaction?
Bradycardia from beta-blockers, bleeding with anticoagulation
What are some other causes of Type A drug reactions?
Very often, an ADR occurs because the individual patient’s unique circumstances have not been fully considered e.g. impaired hepatic or renal function (reduced metabolism of morphine in hepatic failure)
Could also be due to increased sensitivity of organs (e.g. respiratory centre in COPD may be unduly sensitive to opioids)
What are Type B ADRs?
Often known as idiosyncratic, unpredictable or bizarre ADs. Cannot be predicted from the drugs mechanism of action and are not dose-dependent. Can be very serious and associated with relatively high mortality.
May not be predicted in clinical trials
What are some factors contributing to Type B ADRs?
Genetic factors
Host factors
Hypersensitivity reactions
What are the incidences of ADRs?
ADRs responsible for hospital admissions around 5% (2-12%)
In the community they are 2-40%
Great majority of ADRs are deemed preventable
Are there any patient risk factors that should be taken into account?
Age - young, elderly, renal/hepatic function, Vd differences, increased sensitivity
Disease state: CHF, HIV
Gender: women more susceptible to ADRs
Genetics/Ethnicity: different phenotypes for handling drugs
Immunological factors: some more sensitive
Number of drugs: polypharmacy
Narrow therapeutic index
Route of administration
Formulation/Bioavailability
Additives/Excipients
How do we identify ADRs?
Accurate drug history (including non-prescription/recreational/complementary
A temporal relationship needs to be established (many ADRs can be delayed reactions)
Dechallenge and rechallenge to prove the ADR may not be possible or ethical
What is pharmacovigillance?
The overall process of tracking and monitoring ADRs - Medsafe oversees this
How are ADRs reported in NZ?
Voluntary reporting form for health professionals on Medsafe. The form is sent to the Centre for Adverse Reaction Monitoring
