Chapter 6 – Individual Variation in Drug Responses
Factors that can cause patients to respond to drugs differently
o body weight and composition
o age
o pathophysiology
kidney disease
Liver disease
Acid base imbalance
Altered electrolyte status
o Tolerance
pharmaco dynamic tolerance
metabolic tolerance
tachyphylaxis
o placebo effect
o variability in absorption
bioavailability
other causes of variable absorption
o genetics and pharmacogenomics
o gender and race related variations
Body weight and composition
The intensity of drug response is mostly determined by concentration of the drug at
its site of action; high concentration equals more intense response
When giving the same dose to a small and large person, the drug will have higher
concentration in the small person and produce more intense effect which could lead
to toxicity and under treat the larger person
therefore the size of the patient should be considered when prescribing drug dose
AKA in pediatric patients
dose adjustments are typically based on body surface area because this accounts for
the persons weight and relative amount of body fat
body fat can change drug distribution which can change concentration of the drug at
its site of action
so dose based on body surface area lends precise control of drug response versus
weight based alone
Age
infants and older adults are more sensitive to drugs
in young patients drug sensitivity is higher due to organ immaturity
an older patients drug sensitivity is heightened from decline in organ function,
presence of multiple comorbidities and polypharmacy
Pathophysiology
Kidney disease
o reduces drug excretion causing drug accumulation
o requires lower dosages to avoid accumulation
o Reduced renal function requires reduce dosing if eliminated by the kidneys
liver disease
o reduced drug metabolism causes drug accumulation
Factors that can cause patients to respond to drugs differently
o body weight and composition
o age
o pathophysiology
kidney disease
Liver disease
Acid base imbalance
Altered electrolyte status
o Tolerance
pharmaco dynamic tolerance
metabolic tolerance
tachyphylaxis
o placebo effect
o variability in absorption
bioavailability
other causes of variable absorption
o genetics and pharmacogenomics
o gender and race related variations
Body weight and composition
The intensity of drug response is mostly determined by concentration of the drug at
its site of action; high concentration equals more intense response
When giving the same dose to a small and large person, the drug will have higher
concentration in the small person and produce more intense effect which could lead
to toxicity and under treat the larger person
therefore the size of the patient should be considered when prescribing drug dose
AKA in pediatric patients
dose adjustments are typically based on body surface area because this accounts for
the persons weight and relative amount of body fat
body fat can change drug distribution which can change concentration of the drug at
its site of action
so dose based on body surface area lends precise control of drug response versus
weight based alone
Age
infants and older adults are more sensitive to drugs
in young patients drug sensitivity is higher due to organ immaturity
an older patients drug sensitivity is heightened from decline in organ function,
presence of multiple comorbidities and polypharmacy
Pathophysiology
Kidney disease
o reduces drug excretion causing drug accumulation
o requires lower dosages to avoid accumulation
o Reduced renal function requires reduce dosing if eliminated by the kidneys
liver disease
o reduced drug metabolism causes drug accumulation
