biotransformation - pt 2

Question 1

how does molecular weight affect biliary excretion of drugs

Answer 1

• <300 daltons - excreted in urine
• 300-500 saltons - excreted in urine and bile
• > 500 daltons - excreted in bile

Question 2

excretioninto bile requires a:

Answer 2

strong polar group

counterintuitive

Question 3

active transport

Answer 3

• ABC family
• large, hydrophilic, may be charged
• pumped against conc. gradient
• requires ATP

Question 4

passive transport - passive diffusion

Answer 4

• small, uncharged
• diffuse according to conc gradient
• no protein assistance needed

Question 5

passive transport - facilitated diffusion

Answer 5

• performed by SLC family members
• larger, charged
• diffuse according to conc and electrochemical gradients
• does not require ATP

Question 6

SLC transporters in liver

Answer 6

transport drugs into hepatocytes

Question 7

ABC trasnsporters in liver

Answer 7

pump drugs and metabolites out of hepatocytes

Question 8

small Vd

Answer 8

hydrophilic/acidic/large

Question 9

large Vd

Answer 9

lipophilic/basic/small

Question 10

what is the equation for Vd

Answer 10

dose/Cplasma

Question 11

what is the extraction ratio

Answer 11

(Cin - Cout)/Cin

Question 12

what is extraction

Answer 12

a reflection of all enzyme activities

Question 13

what are the 3 parameters extraction is dependent on

Answer 13

• blood flow (Q)
• intrinsic clearance (Cli)
• free fraction (fp)

Question 14

what is intrinsic clearance

Answer 14

the max ability of the liver to irreversibly remove the unbound drug by all pathways in the absence of any flow limitation

Question 15

what is the free fraction

Answer 15

unbound plasma proteins

Question 16

what is the fraction metabolized

Answer 16

% of drug metabolized by the body - takes into consideration all metabolites

Question 17

drugs given orally are normally absorbed in the upper intestine and transported:

Answer 17

directly to the liver via the portal vein

Question 18

drugs that are highly metabolized (E->1) demonstrates low systemic availability and:

Answer 18

have a high “first pass effect”

Question 19

enterohepatic recycling

Answer 19

• drug that is secreted into the bile from liver is expelled into the duodenum with gall bladder contraction via common bile duct
• parent drug may be reabsorbed and become systemicallt available

Question 20

glucoronide conjugates can be hydrolyzed back to the parent compound by microbial and/or intestinal:

Answer 20

B-glucuronidase enzymes