Adverse Drug Reactions Flashcards
What is the difference between a side effect, a harmful effect and a toxic effect?
Side effect = undesirable secondary effect that occurs in addition to the desired effect under normal dose.
Adverse effect = harmful reaction when drug is given under normal conditions & dose.
Toxic effect = deleterious, undesired effect following administration of a higher dose of the drug
What percentage of admissions of older patients are due to ADRs?
Which medication is most related to these admissions?
10%
NSAIDs
What is the prescribing cascade?
When a drug is prescribed as Tx, but then causes ADRs which need to be treated with other drugs etc.
The more drugs you prescribe, the more drug-drug interactions you get.
What is the difference between an adverse drug reaction and an adverse drug event?
ADR = harmful reaction suspected to be caused by the drug at normal dose.
ADE = any undesirable event experienced by the patient when taking a drug, not necessarily caused by the drug.
What is the Rawlins-Thompson classification system?
Classification of adverse reactions.
A - Augmented reactions
B - Bizarre
C - Continuing
D - Delayed
E - End of use
F - (Unexpected) Failure
G - Genetics
What are augmented reactions?
Augmentation / exaggeration of medicine’s normal effect given at usual dose e.g. hypotension with anti-hypertensives
OR
Unwanted reactions form the drug’s pharmacology.
What are pre-disposing factors for an augmented reaction?
Genetics
Age
Polypharmacy
Concurrent disease states
What are bizarre reactions?
Ones that are not pharmacologically predictable - uncommon and unpredictable.
Usually severe - e.g. anaphylaxis with β-lactam ABx
What are continuing / chronic reactions?
Ones which persist for a relatively long time
What are delayed reactions?
Ones that become apparent some time after use of the medicine e.g. teratogenic effects
What are end of use reactions?
Reactions that become apparent some time after the use of a medicine.
What type of reactions are the following:
Anaphylaxis with penicillin = Type B
Bradycardia with β blockers = Type A
Constipation with Ca Channel Blockers = Type A
Skin rash with fluoxicillin = A
Dose-dependent - Type A
Genetic predisposition - Type A or B
Higher mortality - Type B
Unpredictable - Type B
How can you avoid ADRs?
How can you avoid -
- Immediate reactions?
- First dose reactions?
- Early reactions?
- Intermediate reactions
- Late reactions
- Delayed reactions
How are ADRs reported?
Via the Yellow Card Scheme
In the BNF how can you identify clinically significant potential drug interactions?
They are shown in bold against a pink background or a black dot
What are the efflux pumps which remove drugs from cells?
P-glycoprotein pumps
What is a potential adverse drug reaction of rifampicin?
TB drug that can give you orange tears / sweat / urine
Which drugs have a narrow therapeutic range? (WILDCAT)
When are clinically significant drug interactions likely to occur?
When prescribing to Ps with
- liver enzyme or PGP inhibitors or inducers
- seriously ill
- impaired liver or renal function
- drugs with a narrow therapeutic range
- elderly Ps
A 60yo P has been prescibed a calcium channel blocker. They later report having ankle swelling and want to stop the medication. How would you classify this ADR?
- Type A
- Type B
- Type C
- Type E
- Type F
Type A - predictable ADR from the pharmacology of the drug
A research team is investigating the interaction between warfarin and phenytoin. At first, it looks like phenytoin is able to displace other drugs from binding to albumin.
What could be the potential effect?
- Decreased INR
- Decreased Warfarin excretion
- Decreased Warfarin levels
- Increased INR
- Increased warfarin metabolism rate
Option d increased INR. Warfarin is displaced form proteins so plasma levels increase – this might lead eventually to an increased excretion, but certainly not a decreased one. If more warfarin is available, this will potentiate its action and can lead to an increased INR.
A research team continues to investigate the interaction between warfarin and phenytoin. Long term it looks like phenytoin is able induce CP450.
What could be the potential effect?
- Decreased INR
- Decreased Warfarin excretion
- Decreased Warfarin levels
- Increased INR
- Increased warfarin metabolism rate
Option a – with metabolism induced then there is a higher metabolism rate of warfarin and more warfarin will be metabolised – the levels will decrease (i.e., lower than expected) leading to a decreased INR.
What are the principles of safe prescribing?
Maximise effectiveness
Minimise risks
Minimise costs
Respect patient choices
Which drugs commonly need monitoring?
What is medicines optimisation?
What is the true prevalence of penicillin allergy?
1-2% - although 10% of general pop report having a penicillin allergy
What is an adverse drug reaction?
A response to a drug which is noxious and unintended
What is the difference between toxicity and ADR?
Toxicity occurs when a drug is used in toxic levels (i.e. more than normal levels) causing an unwanted effect.
ADR = happens at normal dose levels
What are Type A (Augmented) ADRs?
A stronger than expected or exaggerated manifestation of the normal effects of a drug - predictable as based on the mechanism of action of the drug.
What are Type B (Bizarre) ADRs?
Dose unrelated, idiosyncratic and unexpected reactions given its MOA.
Are more likely to cause death - are often severe. E.g. Hypersensitive reactions
10-15% of ADRs
What are the four types of hypersensitivity reactions?
Type I - Immediate / Anaphylactic
Type II - AB-Dependent Cytotoxic
Type III - Complex Mediated
Type IV - Cell-Mediated / Delayed
How can you remember the four types of hypersensitivity reactions?
ACID
A -Allergic/Anaphylactic/Atopic (Type I);
C – Cytotoxic (Type II);
I – Immune complex deposition (Type III);
D – Delayed (Type IV).
What is Type I hypersensitivity caused by?
IgE mediated reaction
What grading scale is used to grade anaphylactic reactions (Type I hypersensitivity reactions)?
Ring & Messemer 4-Step Grading Scale
Which drugs are linked to causing anaphylactic reactions?
Opiates
Muscle relaxants
Radiocontrast media
Vaccines
NSAIDs
ACEIs
What reaction can NSAIDs cause?
N-SAID Exacerbated Respiratory Disease (N-ERD)
= nasal congestion, rhinorrhoea, wheeze, cough and SOB within 30-180 mins of dose
Related to COX-1 inhibition (not COX-2)
What reaction can ACEIs cause?
Angioedema - due to inhibition of bradykin degradation.
What is the time course of Type I reactions?
How do Type II - IV reactions differ in course to Type I?
How can Type IV sensitivity reactions affect the skin?
Maculo-papular rash can appear 3-8 days after commencing drug
What skin condition can be caused by sulphonamides, tetracyclines, amoxicillin, ampicillin, NSAIDs and anticonvulsants?
What is erythema multiforme major also known as?
Stevens-Johnson Syndrome
What red flags should you be concerned about with drug hypersensitivity?
Rapid onset, rapid improvement with Tx - betware protracted, refractory and biphasic anaphylaxis.
Which medications are high risk for drug hypersensitivity reactions?
ABx
NSAIDs
Taxane chemotherapy
Why can cutaneous signs of a DHR lack initially?
If there is poor cardiac output due to the anaphylaxis.
What does Ring and Messemer Grade IV reactions often present with?
PEA - Pulseless Electrical Activity arrest
How are immediate drug hypersensitivity reactions managed?
Adrenaline - 1:1000!
Which drugs are the most common causes of SCARs? Severe Cutaneous Adverse Reactions
Which criteria predicts mortality in DHRs?
Where should you refer Ps who have a new case of anaphylaxis?
The allergy clinic
What can the allergy clinic do if a P suspects that they have a penicillin allergy?
Challenge test - but only detects Type I reactions - not II - IV
What should happen if Ps have a proven drug allergy?
