W7 32 systemic adverse drug reactions Flashcards
Are drugs safe?
Have to weigh up the harm vs the benefit
Why might there be variation in drug responses - pharmacokinetics?
Individual factors - age, gender, ethnic background, weight, diseases, family history, genome, circadian rhythm, epigenome, microbiome, placebo effect.
Environment - nutrition, drug-drug interactions, chemical exposures, lifestyle, circadian rhythm, epigenome, compliance
What is an adverse drug reaction?
‘Any response to a drug that is noxious and unintended and that occurs at doses used in man for prophylaxis, diagnosis or therapy’
What is an adverse event?
‘An adverse event is any abnormal sign, symptom, lab test, syndromes combination of such abnormalities, untoward or unplanned occurrence (eg an accident or unplanned pregnancy), or any unexpected deterioration in a concurrent illness’
What are the different types of adverse effects and give an example for each?
- Adverse events that are not reactions to medicines, eg fainting at the sight of a needle prior to immunisation
- ADRs (not from errors), eg developing idiosyncratic skin reaction to antibiotic
- ADRs from medication errors, eg anaphylaxis to penicillin in known hypersensitivity
- Medication errors that cause harm that are not ADRs - a cannula penetrates a blood vessel and a haematoma results
- Medication errors that don’t cause adverse events, eg omitted dose of chronic medication with no adverse event
Are ADRs preventable and common?
They are not uncommon. Nearly 75% could have been prevented.
What medications can be given by process of error to produce what adverse outcome?
Penicillin, macrolides - drugs given despite history of allergy or poor documentation of allergy - can result in allergic reaction
Insulin - patient nil by mouth but insulin not adjusted - can cause hypoglycaemia
ACE inhibitors - lack of laboratory monitoring - can cause impaired renal function
Warfarin - lack of therapeutic monitoring - eg haemorrhage, elevated INR
Examples of important ADRs
Erythema multiforme, drug-induced lupus, Torsades de Pointes, gingival hyperplasia
What are the 7 different ways to classify ADRs?
- Seriousness
- Type of drug
- Labelled or unlabelled
- Type of reaction (A-F, Rawlings and Grahame-Smith et al)
- Likelihood (causality)
- Time course
- Combine (dose, time course, susceptibility DoTs)
What is a serious reaction?
Any reaction which results in or prolongs hospitalisation (42%)
Serious reactions can include those that are:
- fatal
- life threatening
- disabling/incapacitating
- cause congenital abnormalities
- medically significant
What is the A,B Rawlings Thompson?
Proposed 2 types of reaction, A as dose related and B as non-dose related
What are Type A Rawlins Thompson reactions?
Dose related, common, predictable, related to pharmacology, low mortality
Eg digitoxin toxicity, bradycardia from a beta blocker, or sedation from a hypnotic. On target effect but more of an effected than is wanted, augmented.
What are type B Rawlins Thompson reactions?
Not dose related, uncommon, unpredictable, not related to pharmacology, high mortality
Eg penicillin hypersensitivity, malignant hyperthermia, hepatitis
Eg ACE inhibitor induced angioedema: life threatening, rare
What is angioedema?
Swelling because of vasodilatation of blood vessels
What are type C reactions?
Dose related and time related
Uncommon
Related to cumulative dose
Eg chronic use of corticosteroids can lead to muscle hypertrophy, can lead to Cushing’s syndrome
What are type D reactions?
Time related, uncommon
Usually dose related
Occurs some time after the use of the drug
Eg renal cancer with Aristolochia, skin cancer, lymphomas and other cancers following topical pimecrolimus and tacrolimus. Usually affect the motor system eg from schizophrenic drugs
Oxytetracycline - pleasing to young palate but can cause dental dysplasia and colour changes
What are type E reactions?
End of use
Withdrawal reactions, uncommon, occur soon after withdrawal
Eg myocardial infarction after beta blocker withdrawal, BZD withdrawal
What are type F reactions?
Failure
Common, dose related
Often caused by drug reactions
Eg oral contraceptives
How might myocardial infarction occur after beta blocker withdrawal?
(Beta blockers slow the heart rate down)
Using beta blockers for a long time means there is probably some receptor downregulation of the beta receptors, tolerance. When taking away beta blockers, there’s fewer receptors but the endogenous adrenaline in the body causes a reflex tachycardia that sometimes causes MI.
What are the important factors in ADRs - DoTS?
Dose, time, susceptibility
When can the ADR occur in relation to dose?
Can occur at:
Doses below therapeutic dose - eg anaphylaxis with penicillin
In the therapeutic dose range - eg nausea with morphine
At high doses - eg liver failure with paracetamol
How is dose considered in ADRs?
All effects can be considered - toxic effects, collateral effects, hypersusceptibility
Describe the dose-response curve (PG337 CURVE)
As dose increases, therapeutic response changes from: hypersusceptibility, collateral effects, toxic effects
What are hypersusceptible, collateral and toxic effects?
Hypersusceptible - low doses will make someone very ill
Collateral effects - normal side effects - occur in the normal dose that we use to produce the intended effect
Toxic effects - occur in too high doses and will produce too high toxic metabolites and negative effects
