Exam Two - Introduction to PK

Question 1

First Pass Metabolism (Effect)

Answer 1

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)

Question 2

F

Answer 2

Bioavailability

Question 3

Bioavailability

Answer 3

fraction of PO reaching systemic circulation when compared to IV standard of 1

Question 4

PO

Answer 4

oral meds

Question 5

ADME

Answer 5

absorption
distribution
metabolism
excretion

Question 6

Absorption factors affecting PK (ADME)

Answer 6

• stomach pH, GI motility, GI blood flow, fed/fasted, drug solubility, drug dissociation, molecule charge, drug-food interactions

Question 7

Distribution factors affecting PK (ADME)

Answer 7

• patient’s Vd (volume of distribution) - (pregnancy, burns, cachexia), cardiac output, tissue perfusion (diabetics), limb loss

Question 8

Metabolism factors affecting PK (ADME)

Answer 8

liver function (impacts of cancer, hepatitis), drug interactions, nutritional status, perfusion of liver

Question 9

Excretion factors affecting PK (ADME)

Answer 9

renal function, some biliary considerations

Question 10

Actual (total) BW

Answer 10

• scale weight “as is”

Question 11

Ideal BW

Answer 11

calculation based upon population averages, what we think someone should weigh for a given height/sex

Question 12

Adjusted BW def

Answer 12

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

Question 13

formula for adjusted BW

Answer 13

= IBW + 0.4(TBW-IBW)

Question 14

formula for male ideal body weight

Answer 14

50 + 2.3(each in >60”) = _____kg

Question 15

formula for female ideal body weight

Answer 15

45.5 + 2.3(each inch >60”) = __________kg

Question 16

How does losing a limb affect BW?

Answer 16

lose a percentage of weight

Question 17

How do you adjust IBW for paraplegia?

Answer 17

subtract 5-10%

Question 18

how do you adjust IBW for quadriplegia?

Answer 18

subtract 10-15% from IBW

Question 19

Why do we adjust IBW for para/quadriplegia?

Answer 19

loss of muscle tone in limbs

Question 20

What is the most common reason for LE amputations?

Answer 20

Diabetes

Question 21

Obesity def

Answer 21

BMI of 30 or higher

Question 22

What does BMI measure?

Answer 22

measure of an adult’s weight in relation to height

Question 23

BMI formula

Answer 23

BMI = weight (kg)/ height (m^2)

Question 24

1 kg = _____ lbs

Answer 24

2.2

Question 25

1 in = _____ cm

Answer 25

2.54

Question 26

PK implications of obesity for distribution

Answer 26

-higher % of body fat could make a drug resevoir - lower % of lean tissue and body water

Question 27

PK implications of Obesity for metabolism

Answer 27

- higher cardiac output - enlarged liver with variable effect on metabolic pathways

Question 28

PK implications of Obesity for excretion

Answer 28

- high renal blood flow - higher GFR

Question 29

GFR

Answer 29

glomerular filtration rate

Question 30

What is GFR important for?

Answer 30

dosing drugs with renal clearance important in elderly impacts clearance and excretion

Question 31

CrCl

Answer 31

creatinine clearance - typically estimated, need 24 hr urine to measure

Question 32

compare GFR with CrCl

Answer 32

CrCl usually higher

Question 33

What formula is used to estimate CrCl?

Answer 33

cockcroft-Gault eq

Question 34

male cockcroft-gault eq

Answer 34

((140-age in years)weight kg)/(72 x SCr)

Question 35

female cockcroft eq

Answer 35

male * 0.85

Question 36

Css

Answer 36

drug concentration in the body at steady state. takes 3-5 drug half-lives to attain steady state

Question 37

Half-life (T1/2)

Answer 37

time for drug level to decay by half. half life affects dosing interval

Question 38

peak

Answer 38

css max, or "high point" after infusion

Question 39

trough

Answer 39

css min, or "low point" just PRIOR to next influsion

Question 40

AUC

Answer 40

area under curve - calc or trapezoidal rule! drug exposure

Question 41

fist order kinetics

Answer 41

amount eliminated over time changes, but fraction eliminated is constant (8,4,2,1mg...)

Question 42

zero order kinetics

Answer 42

amount of drug eliminated does not change with concentration remain, but fraction eliminated does

Question 43

pro-drug

Answer 43

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.

Question 43

CYP 450 system

Answer 43

inhibition and induction - major factor in drug-drug interactions. -leads to sub-therapeutic response or potential toxicity

Question 43

inhibition CYP 450

Answer 43

enzyme inhibitors block metabolism of substrate which leads to increased concentration of said substrate in body (EX- nirmatrelvir/ritonavir )

Question 43

Vd

Answer 43

volume of distribution

Question 43

induction CYP 450

Answer 43

enzyme inducers accelerate metabolism of substrate which leads to decreased concentration of said substrate in body

Question 44

volume of distribution

Answer 44

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

Question 45

Drugs with ______ Vd readily distribute in body

Answer 45

large

Question 46

Drugs with ______ Vd tend to keep significant amounts in circulation and ____ easily distribute in tissues

Answer 46

large, less

Question 47

MD

Answer 47

maintenance dose

Question 48

Maintenance dose

Answer 48

ongoing dose required to maintain a given plasma level accounting for drug LOSS.removal from body via metabolism/excretion. Greatly impacted by drug clearance

Question 49

LD

Answer 49

loading dose

Question 50

loading dose

Answer 50

dose to rapidly initally achieve a desired plasma concentration

Question 51

formula for LD

Answer 51

= (concentration desired x Vd)/(F)

Question 52

LD impacted by ____________, MD impacted by _____________

Answer 52

volume, clearance