Drug excretion

Question 1

What drugs are filtered in the kidney?

Answer 1

All drugs regardless of lipid-solubility or charge, excluding protein bound drugs

Question 2

What kind of drugs will be reabsorbed from the urine?

Answer 2

lipid soluble and uncharged, depends on pH which determines % unionized

Question 3

Drugs that are substrates for endogenous secretory systems can be eliminated at a rate of _____, this is dependent on transporter activity

Answer 3

RPF - renal plasma flow (600 ml/min)

Question 4

What is the GFR and rate of urine output?

Answer 4

GFR = 120 ml/min
Urine output = 1ml/min

Question 5

Describe the pathway of biliary fecal excretion

Answer 5

Drug is absorbed from intestines into hepatic circulation—> liver —> bile duct —-> back to intestine and excreted via feces

**Enterohepatic recycling - drug would be reabsorbed into hepatic blood flow instead of being excreted

Question 6

What enzyme causes enterohepatic recycling of drugs?

Answer 6

Intestinal bacterial enzymes - b-glucuronidase

Question 7

What interrupts enterohepatic cycling?

Answer 7

Antibiotics eliminate bacterial enzymes in the intestines resulting in increased fecal elimination of estrogen-glucuronide BC (example used) reducing plasma levels

Question 8

Do drugs cross into breast milk?

Answer 8

Most drugs do at low levels, infant plasma level is substantially below therapeutic level (<5% of maternal plasma levels), adverse reactions do occur but death is extremely rare

Question 9

How can you limit infant exposure to maternal drugs?

Answer 9

desynchronize breast feeding and peak milk-drug concentrations:

feed at end of dosing interval
administer drug immediately after nursing
dose prior to infants longest sleep time
shorter nursing periods because fat content (and drug content) of milk increases during feeding time

Question 10

The rate of excretion for highly soluble gases is dependent on what?

Answer 10

respiratory rate

Question 11

The rate of excretion for poorly soluble gases is dependent on what?

Answer 11

blood flow (N20)

Question 12

Gases, alcohol, and volatile substances are excreted via _____ excretion and _____ diffusion.

Answer 12

pulmonary, simple

Question 13

What is responsible for certain skin reactions to ingested drugs?

Answer 13

excretion via sweat

Question 14

What accounts for patients tasting a drug after IV administration?

Answer 14

excretion via saliva, if swallowed then same fate as oral administration

Question 15

T/F drug assays can be performed on samples from all routes of excretion?

Answer 15

True

Question 16

What causes chemotherapy induced hair loss?

Answer 16

Excretion via hair

Question 17

What is the best documented and quantitatively most clinically important mechanism by which drug-drug interactions occur?

Answer 17

inhibition or induction of the metabolism of the drug

Question 18

________ ________ act primarily to move drugs out of the cell, effect varies with location

Answer 18

P-glycoprotein transporters

Question 19

What do P-glycoprotein transporters do in the GI tract?

Answer 19

decrease oral absorption of drugs

Question 20

What do P-glycoprotein transporters do in the liver-kidney?

Answer 20

enhance biliary and renal excretion of drugs

Question 21

What do P-glycoprotein transporters do at the blood brain barrier?

Answer 21

limit distribution of drugs to the brain

Question 22

Polymorphic variations in coding genes have potential to cause what two drug interactions?

Answer 22

2nd drug causing competitive inhibition of transport of 1st drug leading to toxicity
or
2nd drug inducing p-glycoprotein enhancing transport of the 1st drug and lessening therapeutic effect