Lecture 2

Question 1

Drugs are extracted by liver to different degrees

Question 2

Hepatic ER : The fraction of drug removed during one pass through the liver ; the efficiency of the liver in removing drug from the bloodstream

Question 3

Drugs with a low HER ( ≤ 0.3) tend to be more bioavailable (____________)

Answer 3

low clearance

Question 4

Drugs with a high HER ( ≥ 0.7) tend to be less bioavailable (___________)

Answer 4

high clearance

Question 5

Drugs with 0.3 ≤ HER ≤ 0.7 termed intermediate extraction

Question 6

Hepatic clearance

Mathematical model: To relate hepatic Cl to hepatic physiology

Question 7

_____________:
The liver’s innate ability to clear unbound drug from via metabolism or biliary excretion

Answer 7

Instrinsic clearance

Question 8

Intrinsic Clearance

The total ability of the liver to metabolize a drug in the _____________

Reflects the “ intrinsic” efficiency of the hepatic elimination

Can take any value, i.e., not limited to the blood flow

Answer 8

absence of flow limitation

Question 9

ClT can be used as a monitoring parameter for the function of the ___________

Answer 9

eliminating organ

Question 10

Patients with different degree of eliminating organ dysfunction who are taking the same drug, eliminate
the drug at different rates, and may require different dosage adjustment

Question 11

𝐓𝐨𝐭𝐚𝐥 𝐛𝐨𝐝𝐲 𝐞𝐥𝐢𝐦𝐢𝐧𝐚𝐭𝐢𝐨𝐧=𝐝𝐫𝐮𝐠 𝐞𝐱𝐜𝐫𝐞𝐭𝐞𝐝 ___________ +𝐝𝐫𝐮𝐠 ________________

Answer 11

unchanged+metabolized

Question 12

Cl of some specific markers can be used to determine the function of the eliminating organ e.g.,creatinine is an endogenous byproduct of muscle metabolism that is excreted only by kidney

Question 13

Drugs can be excreted through urine, bile, sweat, expired air, breast milk

Question 14

Renal excretion: drug elimination in the unchanged form (as administered)

Question 15

For drugs primarily excreted in the urine, elimination is dependent on ________________

Answer 15

renal function

Question 16

Renal excretion is the net effect of 3 distinct mechanism within
the kidneys
Renal excretion is the sum of:
________________ (GFR)
Tubular secretion
Tubular reabsorption
Drug excretion may involve one or more of these mechanism

Answer 16

glomerular filtration

Question 17

Factors influencing glomerular filtration:

Molecular size
______________
_______________

Answer 17

Protein binding

Glomerular integrity

Question 18

Renal function: decreased with __________, _____________, shock

Answer 18

age, heart failure

Question 19

____________
Definition: A measure of the flow rate of filtered fluid through the kidneys.

Normal Range: Typically, between 90-125 mL/min, serving as an indicator of renal function

Answer 19

Glomerular Filtration Rate (GFR)

Question 20

___________and __________ in Renal Filtration

Special Property: Both substances are solely filtered in the nephron without being secreted or reabsorbed

Significance: This unique characteristic makes them reliable markers for assessing the filtration rate of the kidneys.

Answer 20

creatinine and inulin

Question 21

Creatinine Clearance (CrCl) = GFR

Determination: CrCl is equivalent to GFR and can be calculated: Directly from the amount of creatinine excreted in __________ over a 24-hour period.

Indirectly from serum creatinine levels using specific formulas.

Answer 21

urine

Question 22

Renal clearance and glomerular filtration rate

For drugs exclusively eliminated renally, where the only renal process is glomerular filtration, GFR is linearly related to drug ______

Answer 22

drug clearance

Question 23

Drugs cleared solely by renal mechanisms will have a y-intercept of _________

Answer 23

zero

Question 24

Drugs with extra-renal routes will have ___________ y-intercepts

Answer 24

larger

Question 25

Drug Distribution and Protein Binding

Factors affecting drug distribution

Characteristics of _______________

Disease states that alter physiology

______________of the drug

Regional differences in physiologic pH

Extent of ____________ of the drug

Answer 25

body tissues

lipid solubility

protein binding

Question 26

Drug Distribution and Protein Binding

Body Tissue Characteristics
Rate of drug delivery from blood to a tissue is highly dependent on _______________

Drugs distribute more rapidly to the areas with higher blood flow ___________, lungs, and kidneys : highly perfused with blood

________,__________ and bone: much Less perfused

Skeletal Muscle :Intermediate perfusion

Answer 26

blood flow

heart

fat, tissue

Question 27

Differences in pH lead to localization of drug in tissues

Excretion of drugs in breast milk: Alkaline drugs , unionized at physiological pH, pass through
lipid membranes into breast tissue

Breast tissue has acidic pH, the alkaline drug becomes_____________-, and trapped in the tissue

Answer 27

ionized