wk 6- ADR Flashcards
types of adverse reactions
type A- augumented reactions
type B- hypersensitivity/bizzare
type C- chronic
type. D- delayed
type E - end of use
top 4 meds associated with Es
opioids
nsaids
aspirin
beta blockers
define ADR
any reaction to a drug that is harmful to a patient
things that contribute to ADRs (outside of patient factors)
-failing of clinical trials- not enough subjects to detect ADRs until in population
-medication errors (at the level of prescribing, dispensing, taking, adherence, monitoring)
-small therapeutic window
examples of low therapeutic index drugs
anticoagulants
insulin
cardiac glycosides
antiarrhythmics
TCA
anti cancer
immunosuppressants
ED50
effective dose required to produce 50% of max desired effect
LD50
lethal dose required to kill 50% of animals that receive it
What predisposes people to a TYPE A ADR
- very young or old- metabolism and excretion not as efficient
- distribution - affected by changes in body comp and availability of plasma protein for binding
- disease - liver, kidney, GI motility, plasma protein concentrations
- genetics- differences in enzyme activity which changes how the drugs are metabolised
- drug to drug interactions
- one drug can increase or decrease the other
- drugs that have opposite actions can cancel eachother out
- drugs with same actions can potentiate one another
type B ADRs
-rare but unpredictable and not dose related
can be due to allergy or other causes
type B - idiosyncrasy
an effect unrelated to the action of the drug
type B - insensitivity and intolerance
outliers that respond differently to the vast majority
hypersensitivity reactions
immunological reaction to drugs
type 1 -
- type 4 hypersensitvity reactions
type 1 hypersensitvity reaction
anaphylaxis
allergen- IgE
antibodies attach to mast cells - release mediators (eg histamine)
local effects- hayfever, asthma, urticaria
systemic effects- swelling/anaphylaxis
occurs, minutes to hours after exposure
type 2
cytotoxic reaction
drug bind to blood cell membranes
IgG and IgM antibodies activate complement system and autolysis of RBCS
type 3 hypersensitivity reaction
immune complex reaction
drugs for immune complexes with antibodies which circulate in blood and can be deposited in particular areas of the body
occurs 1-3 weeks after exposure
type 4 hypersensitvity
drugs combine with proteins in the skin to form antigen
t cells activitated and cause damage to skin cells (rashes, lumps, itchy, weeping)
occurs 2-7 days after drug exposure
teratogenesis
drugs causing abnormal foetal development
carcinogenesis
drug induced tumours
risk of a drug to drug interaction for patients taking 2-5 drugs
19%
risk of drug to drug interactions for patients taking 6 drugs
80%
drug enzyme induction
drugs that increase the metabolism enzyme activity
increase removal of drug and decrease effectiveness
drug enzyme inhibition
drugs that inhibit and cause accumulation of other drugs in the body
not removing the drug and therefore increases risk of side effects
what do cyp450 enzymes do
found in liver and also small intestine, lungs, placenta nd kidneys and are responsible for metabolising 90% of drugs
what do you need to be mindful of drugs that inhibit or induce cyp450
changes the removal/metabolism of drugs and can lead to ineffectiveness or side effects/toxicity
review inducer/inhibitor table
people at risk of ADRs
older people
children
chronic conditions
HF, DM, anaemia, asthma
changes in renal/hepatic function
genetic predisposition
difference between women and men with ADRs
women are more likely to experience ADRs
polypharmacy
increase in adverse drug reactions when more than 5 drugs are taken
what age related changes occur in distribution in elderly
Distribution
body comp: more fat, less body water
plasma protein concentration: less with age
blood flow: after 30, CO, renal and hepatic blood flow fall
what age related changes occur in metabolism in elderly
- decreased size and cells of liver
-decreased metabolism of drugs (1st pass metabolism reduced by 40%)
other age related changes
-decreased renal clearance of drugs
-renal blood flow, GFR, active tubular secretory processes decline
-drugs excreted by kidneys are more likely to accumulate
pharmacodynamic age related changes in elderly
increased sensitivity to drug receptors with age
renal/hepatic disease can affect drug response
unclear
NSAIDs and the elderly
more likely induce gastric ulceration in older patients
due to:
1. reduced gastric mucosal prostaglandins
2. drug induced inhibition
differences in ADME in infants and children
- reduced gastric pH
- delayed gastric emptying
- irregular GI motility
- more body water and less body fat
- reduced plasma proteins
- lower liver capacity to metabolise drugs
- delayed renal clearance
how can drugs be transferred to the foetus in pregnancy
by diffusion
biggest risk of malformation is up to
8 weeks post conception, avoid drugs during this time
pregnancy category
category A- no risk
B- no risk in animal studies, women not studied
C- fetal harm in animals, no studies in women
D- evidence of human fetal risk but benefits > risk in life threatening situations
X- contraindicated in pregnant women
what drugs can harm feotus
- Male hormones
- Female hormones
- Iron preparations
- Aspirin-like drugs
- Alcohol
- Barbiturates
NSAID and pregnancy
-associated with spontaneous abortion
-not dose dependent, may be time/ duration dependent
-non aspirin NSAID (prescription and OTC)
ADR risk factors
- polypharmacy
- Multiple comorbid conditions
- Drug dose and duration of exposure
- Extremes of age (neonates, children, elderly)
- Female sex
- Genetic predisposition
- Prior history of drug reactions and hypersensitivity
- End organ dysfunction
- Altered physiology
- Inappropriate medication prescribing, use or monitoring
- Lack of patient education and other system failures
who do you report ADR to
TGA
on OTC, prescription, complementary
elderly and adrs
polypharmacy
aging process (renal/hepatic function decreased)
adherence/cognitive impairment
multimorbidity
what is the gold standard for offloading a diabetic forefoot lesion?
contact cast
-shouldnt use with infection
-shouildnt use in neuropathy
non pharamcological magement for a dibaetic wound
-wound care/debridement
-dressing (antimicrobial, absorbant, etc)
-offloading (donut pads, insoles, rockers)
when is clindamycin indicated
when theres an allergy to penicillin and cepholosporin
what pharmacological options do you have for pain
non drug-
immobilise, othroses, footwear, exercises
drug-
NSAID (oral or topical)
opioid
corticosteroid (inject/topical)
antidepressents - chronic neuropathic pain or depression.
