Adverse Drug Reactions Flashcards
How many hospital admissions are as a result of an ADR
- 3.6% of hospital admissions are the result of an ADR
How long are patients who suffer an ADR likely to stay in hospital
- patients who suffer an ADR are likely to stay in hospital for over twice as long as those who do not
How much do ADRs cost the NHS
- cost the NHS around 600 million every year
What does rhabdomylsis look like
- rare, acute and potentially fatal muscle condition that results from the destruction of muscle cell membranes and the release of intracellular contents
- muscle swelling, tenderness and wekaness
- urine is grey to brown due to myoglobin
- CK is raised - usually by up to 10-100 times the normal limit
- associated with renal failure because myoglobin precipitates in the renal tubules
- associated with hyperkalemia because potassium is released when muscle cells. break down - this can be fatal
what can cause rhabdomyolysis
- increased age
- female sex
- pre-existing renal impairment
- high dose
- combination of statins with dilitiazem which inhibits the metabolism of statins by inhibiting cytochrome P450 isoenzyme
What is the maximum recommended dose of simvastatin with dilitiazem or amlodipine
20mg per day in order to prevent toxicity
what should you do in rhabdomylosis
- stop the statin
- if renal failure is established consider urgent dialysis
- IV fluids to prevent renal failure
- consider sodium bicarbonate to alkalinize the urine and reduce the precipitation of myoglobin in the renal tubules
- monitor serum potassium concentration and correct if necessary
How do you define an adverse drug reaction
- Use of a medicinal product within the terms of marketing authorisation as well as from use outside the terms of marketing authroisation including overdose, misuse, abuse and medication errors and suspected adverse reactions associated with occupational exposure
What is an adverse event
- is any harmful of unpleasant event that the patient experiences while using a drug whether or not it is related to the drug
What is an adverse drug reaction
- This is an adverse event where it is suspected to be caused by the drug
All ADRs are
All ADRs are adverse events but not all adverse events are ADRs
What is a type A ADR
Reactions that are generally
- dose related
- common, predictable
- related to the pharmacology
- unlikely to be fatal
Give examples of type A ADRs
- digoxin toxicity
- constipation with opioid analgesics
- bruising with warfarin
Give examples of type B ADR
Type B (bizarre) reactions are generally
- not dose related
- uncommon, unpredictable
- not related to the pharmacology
- often fatal
Name some examples of type B ADRs
- penicillin hypersensitivity
- malignant hyperthermia
- hepatitis caused by anaesthetic agents
describe type C ADRs and examples
- uncommon
- related to cumulative dose
- time related
examples
- suppression to the hypothalamic pituitary adrenal axis with long term corticosteroids
Describe type D ADRs and examples
Delayed
- uncommon
- usually dose related
- occurs or becomes apparent some time after use of drugs
Examples
- carcinogensis
Describe type E ADRs and examples
End of Treatment
- uncommon
- occurs soon after withdrawal of the drug
examples
- opiate withdrawal syndrome
Describe type F ADRs and examples
Failure
- common
- dose related
- often caused by drug interactions
Examples
- failure of the oral contraceptive in the presence of an enzyme inducer
- failure of therapeutic effect in patients taken anticoagulants leading to stroke
What is the new system used to look at ADR
DoTS
How does DoTS look at ADRs
- Dose
- Timing
- Susceptibility
What are the types of ADRs divided by dose (DoTS)
- Hyper-susceptibility reactions = occur at doses much lower that therapeutic
- Collateral effects - occur at therapeutic doses
- Toxic effect - occur at doses higher than those used therapeutically
How can ADRs be divided by time (DoTS)
- time dependent = those which are dependent on the time the patient has been taking the drugs
- Time independent = those which can occur at any time during the drug treatment
What are the things that make you susceptible to ADRs (DoTS)
- immunological reactions
- genetics
- age
- sex
- physiology
- exogenous
- disease states affecting the patient e.g. renal dysfunction, liver disease
IGASPED
Are harmful drug interactions adverse drug reactions
True
a suicide that is suspected to have been triggered by the use of a drug may be considered an ADR
True
the older you are the
more prone to an ADR you are
- age related decline in both the metabolism and elimination of drugs from the body is often one reason for their increased susceptibility
children respond to
medications differently to adults
what differences can effect how children cope with a medication
- body composition
- metabolism
- end organ response
- can effect development
describe how neonates are different and how it can effect drugs
- high body water content - this can increase the volume distribution of water soluble drugs
- reduced albumin and total protein - this may cause increased effective concentrations of protein bound drugs
- immature blood brain barrier - can increase sensitivity to drugs such as morphine
give an example of how drugs can affect children’s development
- A classic example of ADR is increased risk of dystonic (extrapyramidal) adverse effects associated with metoclopramide in children and young adults whereas in adults in causes parkinsonian like symptoms
What are the co-morbidities that increase the risk of ADRs
- congestive heart failure
- diabetes mellitus
- chronic pulmonary disease
- rheumatological and malignant disease
What ADRs are more common in women than in men
- psychiatric adverse effects with the anti-malarial mefloquine
- drug induced torsade de pointes (polymorphic ventricular tachycardia) linked to ventricular fibrillation and death, drugs such as erythromycin and sotalol are incriminated, women have an intrinsically longer QT interval than men
- hyponatraemia with diuretics
how does ethnicity effect ARDs
- distribution of cytochrome P450 genotypes involved in drug metabolism different according to ethnicity
What is pharmacogenetics
- this is the study of genetic variations that influence an individuals response to drugs
describe examples of pharmacogenetics
Abacavir - this is an antiretroviral that causes severe hypersensitivity reactions in 5-8% of patients who have HLA-B5701 allele
- this allele has reduced hypersensitivity reactions and has therefore helped to improve compliance and reduce the incidence of a life-threatening condition
- Stevens-johnson syndrome and toxic epidermal necrolysis are rare ADRs associated with numerous drugs and associated with substantial morbidity and mortality, the presence of the allele HLAB1502 indicates increased skin reactions with carbamazepine, phenytoin, oxcarbazepine and lamotrigine
What is G6PD deficiency
- this is an inherited enzyme deficiency hat causes increased susceptibility to drug induced haemolytic anaemia
What are drugs that are considered to increase the risk of hameolysis when taking with a G6PD deficiency
- Anti-malarials
- nitrofurantoin
- quinolone antimicrobials
- rasburicase
- sulphonamides
What is acute porphyrias
- this is an inherited disorder of haem biosynthesis
- many drugs can trigger acute and life-threatening porphyric crises with severe abdominal pain and neuropsychiatric disturbances
- differs depending on the patient
Herbal treatments…
increase susceptibility to ADRs - they react with other drugs for example St Johns wort interacts with a wide variety of drugs including antiretrovirals and Warfarin
What are factors that may confirm your suspicion of a drug event
- the time relationship between drug exposure and subsequent event
- clinical and pathological characteristics known to be related to drug use but not the disease process
- pharmacological plausibility
- drug is known to cause suspected ADR
- Concomitant medication which could be an alternate cause or could interact
- underlying and concurrent illness which could cause the event
- symptoms improve after reducing or stopping treatment
- the symptoms return on reintroducing treatment
- patient had a similar experience in the past
How should you monitor drugs
Standard blood tests
- be vigilant in those with morbidities especially renal failure
- monitor electrolytes carefully in those taking more than one medicine that can alter renal excretion of sodium and potassium
Plasma drug concentrations
- can reduce harm in some medications such as serum-lithium levels which are taken every 3 months to avoid toxicity and ensure therapeutic levels are maintained
- serum concentrations of amino-glycoside antimicrobials such as gentamicin are closely monitored to ensure efficacy and avoid toxicity
How do you monitor clozapine
- antipsychotic clozapine is associated with a significant risk of agranulocytosis - mandatory monitoring of white blood cells, platelets and neutrophils has led to over 90% of fatal agranulocytosis cases being prevented
How do you monitor methotrexate
- full blood count
- renal function test
- liver function tests
- done weekly until stabilization and then every 2-3 months later
- reduce risk of blood dycrasias
How do you monitor warfarin
- monitor the INR
- ensures that an appropriate level of anticoagulation is maintained and the risk of bleeding is reduced
What should you always consider to prevent an ADR
- susceptibility
- drug history
- harm/benefit
- cautions and contraindications
- documentation
- patient information
- monitoring
- suspicion
what does the yellow card scheme in the UK do
- the yellow card scheme in the UK collects spontaneous reports of suspected ADRs
How does the yellow card scheme pick out the important new reactions
- uses the proportional reporting ratios (PRR)
How does proportional reporting ratios work
- for example in ACE the database of adverse reaction reports had many reports of cough
- there were proportionally far more reports of cough with ACE inhibitors than all other drugs in the database
- this disproportionate number of reports represents a signal of possible ADR
What is a drug safety signal
- this is the hypothesis of a risk associated with a medicine that arises from one or more data sources
What type of medications does the yellow card scheme collect information on
- prescription medicines
- vaccines
- over the counter medicines
- herbal remedies
what pieces of information do you need to provide on the yellow card scheme
- An identified patient
- suspected reaction
- suspected drug
- a reporter
What should you do if you suspect an ADR
- report all serious reactions on a yellow card even if the reaction is well known as it helps build up a profile of the reactions to the medicine
- report all unusual reactions on a yellow card especially if they are not listed in the BNF
What does a black triangle do
- focuses attention on newly licensed drugs
- MHRA are interested in reports concerning these drugs
What medicines have a black triangle
- all medicines with a new active substance and all new biologicals
- medicines which require further information after authorization
- medicines given conditional approval
- medicines marketed where the company has been asked to carry out additional studies e.g. on long term effects, rare adverse effects seen in clinical trials
if the ADR is serious…
if the ADR is serious and has caused hospital admission you file a report with the yellow card scheme regardless if th reaction is well known
What do interactive drug analysis profiles do
These summarise the reports received via the yellow card scheme
what are the downsides to interactive drug analysis profiles
- they only contain reported reactions (95% of ADRs are not reported)
- there is no data on the number of prescriptions issued so incidence cannot be calculated
- there are suspected reactions so no causality can be implied
- comparison of different drugs is not possible due to biases in reporting rates
What are the four major sources of information for current information on ADRs
- The BNF
- The MHRA
- The electronic medicines compendium
- the united kingdom medicines information service
ADRs are common in
- more than 10% of patients
ADRs that are uncommon occur in
- more than 0.1% but less than 1% of patients
ADRs that are rare occur in
- more than 0.01% but less than 0.1% of patients
ADRs that are very rare occur in
- less than 0.01% of patients
