8. Adverse reactions to medicines including contrast media Flashcards
what is an adverse event or experience
untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment
what is an adverse drug reaction
in the preapproval clinical experience with a new medicinal product or its new usages, particularly as the therapeutic doses may not be established and all noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reaction
what is an unexpected adverse drug reaction
an adverse reaction the nature or severity of which is not consistent with the applicable product info
what does the term severe indicate
describes the intensity of a specific event, the event itself may be of relatively minor medical significance
eg severe headache
what does the term serious indicate
not the same as severe, which is based on patient even outcome or action criteria usually associated with events that pose a threat to a patients life or functioning
a serious adverse event/experience or reaction is any untoward medical occurrence that at any dose is what 6 things
results in death
life threatening
requires hospitalization/prolonged hospitalisation
results in persistent/significant disability
is a congenital anomaly/birth defect
is medically important event/reaction
what are mild severity graded adverse events in regard to how bad the symptoms are, how it is observed and what intervention is indicated
symptomatic/mild symptoms
clinical/diagnostic observation only
intervention not indicated
what are moderate severity graded adverse events in regard to what intervention is indicated and what activities are limited
minimal, local or non invasive intervention indicated
limiting age dependent daily living
what are severe/medically significant but not immediately life threatening severity graded adverse events in regard to outcomes
hospitalisation or prolongation of hospitalisation, disabling
what are the 5 common terminology criteria for adverse events severity grades
- mild
- moderate
- severe or medically significant but not immediately life threatening
- life threatening consequences
- death
how are adverse reactions graded in NZ
by letters A-I with A being the least severe and I being error causing death
what is category A adverse reaction
circumstances or events that have the capacity to cause error
what is category B adverse reaction
error occurred but error did not reach the patient
what is category C adverse reaction
error occurred that reached the patient but did not cause patient harm
what is category D adverse reaction
error occurred that reached the patient and required monitoring to confirm that it resulted in no harm to the patient and/or required intervention to preclude harm
the ADR mechanism involve what 2 things
interaction with receptor/enzymes (pharmacological?)
alteration of structural proteins, DNA or lipids (chemical)
what are type 1 or A adverse reactions
predictable dose dependent based on the known pharmacology of the drug
what are type 2 or B adverse reactions
not predictable, no clear dose dependency and not due to the known pharmacology of drug
type 1 or A adverse reactions happen due to what
due to the known pharmacology of the drug and are therefore dose dependent and predictable
what are 3 example situations of type 1/A adverse reaction causes
take too much drug (eg wrong dose/freq/duration)
take 2+ drugs with overlapping pharmacology
take 2+ drugs that have metabolic interaction
what do 2 or more drugs compete for in terms of absorption
reduced uptake, decreased effect
what do 2 or more drugs compete for in terms of metabolism in terms of clearance, inhibition, bioactivation, enzymes
reduced clearance = increased plasma conc
inhibition of one pathway = greater clearance via bioactivation = incr toxicity
induction of enzymes = decr plasma conc
what do 2 or more drugs compete for in terms of distribution
competition for uptake transporters or protein binding = increased plasma conc
what do 2 or more drugs compete for in terms of excretion
competition for efflux transporters = decreased elimination = increased plasma conc
what is a perpertrator drug and victim drug
perpetrator drug can inhibit the enzyme that metabolizes victim drug
this increases drug conc of victim drug
what happens when drug A induces the enzyme responsible for the metabolism of Drug B
plasma conc of drug B is less than expected = less activity = therapeutic failure
what is polypharmacy
taking several medicines at the same time (4 or 5+)
what is hyperpolypharmacy
10 or more medicines
what does lack of metabolism lead to
enhanced plasma conc and exaggerated pharmacological responses
enhanced toxicity due to lack of detoxification pathway
is hypersensitivity conc dependent
no clear dose and conc dependency
anaphylaxis has what effect on peripheral resistance and BP
drop in peripheral resistance leads to drop in blood pressure
what is anaphylactoid reactions or hypersensitivity and what does it involve, does it involve IgE
involve release of mediators such as histamine and may/may not involve specific IgE
what are chemotoxic organ specific ADRs what 6 things is it associated with
assocaited with ionicity, iodine conc, viscosity, osmolality, dose and injection rate
what 2 things can vasovagal ADRs manifest as
bradycardia and hypotension
what is hypersensitivity
reproducible symptoms or signs initiated by exposure to a defined stimulus at a dose tolerated by normal people
what is an allergy
hypersensitivity reaction initiated by specific immunological mechanisms
what are the 2 ways that allergies are mediated by
antibody or cell mediated
what is anaphylaxis
severe life threatening generalized or systemic hypersensitivity reaction involving IgE mediated release of mediators from tissue mast cells and peripheral basophils
what is anaphylactoid
immediate systemic reactions not involving an IgE immune response
what do immediate reactions involve for hypersensitivity in terms of immune system
involve histamine and tryptase release from basophils and mast cells
does hypersensitivity involve IgE antibodies
no
when is hypersensitivity likely to be a true allergic reaction
the more serious and severe the reaction the more likely it is a true allergic reaction
are hypersentivity ADR more likely to be anaphylactoid or anaphylactic
anaphylactoid
anaphylactoid reactions tend to be what related and what are the characteristics and prevalence
tends to be more conc related, unpredictable and happens in more people
what test can be done to confirm CM hypersensitivity in terms of whether it involves cell mediated hypersensitivity
skin test can confirm with CD4+ T cell infiltrates
what are the 5 acute kidney injury
stage 1 = risk stage 2 = injury stage 3 = failure loss of kidney function end stage kidney disease
what is loss of kidney function defined as
complete loss of kidney function >4wks
what is end stage kidney disease defined as
complete loss of kidney function >3months
what is the SCr and GFR changes in stage 1 acute kidney injury /risk
increase SCr by 1.5 and GFR decreases more than 25%
what is the SCr and GFR changes in stage 2 acute kidney injury /injury
increase SCr x 2 and GFR decreases more than 50%
what is the SCr and GFR changes in stage 3 acute kidney injury /failure
increase SCr x 3 and GFR decreases more than 75%
how does kidney function rely on blood vessels
relies on blood vessels around glomerulus
under pressure, liquid is forved out and with that liquid goes unboudn endogenous metabolites and drugs
how is osmolality and viscosity a risk factor for CI AKI
high osmolality unacceptable risk
CM not reabsorbed so gets conc in tubules leading to increases of osmolality and viscosity and increases water reabsorption
increased viscosity decreases flow rate and increases exposure of distal nephron
CM isnt getting reabsorbed so the conc gets greater of CM as water is resorbed and this pulls water back in to the tubes and ruins renal flow and urinary output
how is volume administered a risk factor for CI AKI
ideally CM volume <3 x eGFR
how is intra arterial administration a risk factor for CI AKI
larger volume of CM administered and the potential for renal emoblisation
the risk of CM induced AKI is greatest with people of what GFR
greatest in those with estimated GFR less <30mL/min/1.73m^2
several medications are contradicted with ICM because why
may crystalize and form precipitates
caution should be exercised when using ICM in patients medicated with what drugs
name 3 examples
what levels need to be assessed before using CT CM in these patients
medicated with known nephrotoxic drugs
ACE inhibitors, metformin, NSAIDs
creatinine level need to be assessed
what is hypervolaemia
lose alot of blood and reduced blood volume so kidneys dont get alot of liquid to do its normal function
how do you mitigate the risk of kidney failure in hypervolemia
2 ways
encourage oral hydration or can stop taking ACE inhibitors so your BP may go up but preserves kidney function which is the greater good
ICM has what effects in CM drug interactions
ICM have some anti-coagulant effects so potentiate effects of some medications like heparin, warfarin and aspirin
B blockers do what to the risk and severity of anaphylactoid reactions
increase risk
calcium channel blockers can do what to the effects of ICM
potentiate antihypertensive effects of ICM
diuretics can do what to nephrotoxicity
increase risk
free Gd3+ is toxic why
as it inhibits Ca2+ at calcium channels
will accumulate in carious tissues such as brain
what happens when Gd ions inhibits Calcium channels
interferes with muscle contraction and can interfere with force of cardiac contraction
is the reaction profile of Gd CM dependent on ionicity, viscosity and osmolality of ICM
no
is gadolinium CM considered nephrotoxic and why
no
it is similar to serum and so tissues remain isotonic
what ADR is related to Gd based CM
nephrogenic systemic fibrosis
Gd CM induced NSF involves what mechanism
involves Gd dependent release of cytokines, stimulation of skin macrophages or blood monocytes and subsequent activation of fibroblasts with deposition of collagen
what is a physical effect of Gd CM NSF
thickening and hardening of skin associated with pain, muscle weakness, bone pain, joint contractures
