Exam Two - Introduction to PK Flashcards
First Pass Metabolism (Effect)
liver breaks down absorbed meds (via portal circulation) BEFORE drug reaches systemic circulation, may significantly REDUCE concentration attainable in body. This may completely prevent some drugs via oral route. Reflected in reduced bioavailability (F)
F
Bioavailability
Bioavailability
fraction of PO reaching systemic circulation when compared to IV standard of 1
PO
oral meds
ADME
absorption
distribution
metabolism
excretion
Absorption factors affecting PK (ADME)
- stomach pH, GI motility, GI blood flow, fed/fasted, drug solubility, drug dissociation, molecule charge, drug-food interactions
Distribution factors affecting PK (ADME)
- patient’s Vd (volume of distribution) - (pregnancy, burns, cachexia), cardiac output, tissue perfusion (diabetics), limb loss
Metabolism factors affecting PK (ADME)
liver function (impacts of cancer, hepatitis), drug interactions, nutritional status, perfusion of liver
Excretion factors affecting PK (ADME)
renal function, some biliary considerations
Actual (total) BW
- scale weight “as is”
Ideal BW
calculation based upon population averages, what we think someone should weigh for a given height/sex
Adjusted BW def
educated WAG. calculation to adjust dosing of some drugs in obese patients. attempt to prevent over and over dosing. often used in patients who are > 30% IBW
formula for adjusted BW
= IBW + 0.4(TBW-IBW)
formula for male ideal body weight
50 + 2.3(each in >60”) = _____kg
formula for female ideal body weight
45.5 + 2.3(each inch >60”) = __________kg
How does losing a limb affect BW?
lose a percentage of weight
How do you adjust IBW for paraplegia?
subtract 5-10%
how do you adjust IBW for quadriplegia?
subtract 10-15% from IBW
Why do we adjust IBW for para/quadriplegia?
loss of muscle tone in limbs
What is the most common reason for LE amputations?
Diabetes
Obesity def
BMI of 30 or higher
What does BMI measure?
measure of an adult’s weight in relation to height
BMI formula
BMI = weight (kg)/ height (m^2)
1 kg = _____ lbs
2.2
1 in = _____ cm
2.54
PK implications of obesity for distribution
-higher % of body fat could make a drug resevoir
- lower % of lean tissue and body water
PK implications of Obesity for metabolism
- higher cardiac output
- enlarged liver with variable effect on metabolic pathways
PK implications of Obesity for excretion
- high renal blood flow
- higher GFR
GFR
glomerular filtration rate
What is GFR important for?
dosing drugs with renal clearance
important in elderly
impacts clearance and excretion
CrCl
creatinine clearance
- typically estimated, need 24 hr urine to measure
compare GFR with CrCl
CrCl usually higher
What formula is used to estimate CrCl?
cockcroft-Gault eq
male cockcroft-gault eq
((140-age in years)weight kg)/(72 x SCr)
female cockcroft eq
male * 0.85
Css
drug concentration in the body at steady state. takes 3-5 drug half-lives to attain steady state
Half-life (T1/2)
time for drug level to decay by half. half life affects dosing interval
peak
css max, or “high point” after infusion
trough
css min, or “low point” just PRIOR to next influsion
AUC
area under curve
- calc or trapezoidal rule! drug exposure
fist order kinetics
amount eliminated over time changes, but fraction eliminated is constant (8,4,2,1mg…)
zero order kinetics
amount of drug eliminated does not change with concentration remain, but fraction eliminated does
pro-drug
administered in inactive form, need the liver to activate it! convert to active form in body via metabolic process, may avoid destruction in GI tract, avert first-pass metabolism, reduce toxicity, etc.
CYP 450 system
inhibition and induction
- major factor in drug-drug interactions.
-leads to sub-therapeutic response or potential toxicity
inhibition CYP 450
enzyme inhibitors block metabolism of substrate which leads to increased concentration of said substrate in body (EX- nirmatrelvir/ritonavir )
Vd
volume of distribution
induction CYP 450
enzyme inducers accelerate metabolism of substrate which leads to decreased concentration of said substrate in body
volume of distribution
fake number
- a volume that would be required to account for all drug in body if it were present in same concentration as plasma
- expressed in L/kg
Drugs with ______ Vd readily distribute in body
large
Drugs with ______ Vd tend to keep significant amounts in circulation and ____ easily distribute in tissues
large, less
MD
maintenance dose
Maintenance dose
ongoing dose required to maintain a given plasma level accounting for drug LOSS.removal from body via metabolism/excretion. Greatly impacted by drug clearance
LD
loading dose
loading dose
dose to rapidly initally achieve a desired plasma concentration
formula for LD
= (concentration desired x Vd)/(F)
LD impacted by ____________, MD impacted by _____________
volume, clearance
