Excretion

Question 1

What is renal excretion?

Answer 1

most important drug elimination pathway in terrestrial vertebrate animals

Question 2

what are the 3 processes involved in changing the blood level of drug?

Answer 2

• glomerular filtration
• tubular reabsorption
• tubular secretion

Question 3

What are extrarenal excretion routes?

Answer 3

1. biliary excretion
2. pulmonary excretion (exhalation)
3. lactation
4. minor routes of excretion

Question 4

What is biliary excretion?

Answer 4

• important for “larger” drug mcs (MW > 300 g/mol)
• similar to kidney, facilitated transport (ex: OAT & OCT) & active transport (ex: MDR, MRP, & BCRP) proteins are involved

Question 5

What is enterohepatic cycling?

Answer 5

• drugs or drug metabolites excreted in the bile into intestine can be reabsorbed & distributed back to liver
• this can increase half-life of a drug, & in the case of drugs producing toxic metabolites, it can exacerbate toxicity to the liver

Question 6

what is pulmonary excretion?

Answer 6

exhalation
- important for volatile & gaseous drugs (ex: nitrous oxide: N2O)
- ex: ethanol is 90% metabolized in liver but approximately 2% excreted in expired air; basis for breathalyzer test

Question 7

What is excretion via lactation?

Answer 7

• can be significant route of elimination for lipophilic drugs, ranging from 0.1-2% of maternal dose
• important consideration for neonatal exposure
• important consideration for food products (ex: milk, cheese)

Question 8

What are the minor routes of excretion?

Answer 8

saliva, sweat, hair, nails

Question 8

What is the coadministration of 2 or more drugs often associated w/?

Answer 8

Altered clearance of 1 (or more) of the drugs

Question 9

What is summation (additivity)?

Answer 9

• coadministration of 2 drugs produces a combined (additive) effect (2 + 2 = 4) (there is no interaction & effects are additive)
• this is most common, but there are exceptions

Question 10

what are 4 terms important for drug interactions?

Answer 10

1. summation (additivity)
2. synergism
3. potentiation
4. antagonism

Question 11

What is synergism?

Answer 11

effect of 2 drugs in combination exceeds the sum of their individual effects (2 +2 = 10)

Question 12

what is potentiation?

Answer 12

drug w/ no effect intensifies (potentiates) the effect of a second drug (2 + 0 = 10)

Question 13

what is antagonism?

Answer 13

effect of 2 drugs in combination is less than additive (2 + 2 =1)
- this is usually due to competitive synergism for a receptor)

Question 14

What kind of drug interactions can occur during biotransformation?

Answer 14

recall: induction or inhibition of phase I & II enzymes

Question 15

What kind of drug interactions can occur during distribution?

Answer 15

• recall: plasma & cellular binding prots
• competition for binding sites can result in displacement of a drug, causing increased free (unbound) fraction & greater response

Question 16

What kind of drug interactions can occur during excretion?

Answer 16

decreased clearance due to inhibition of renal excretion; usually competition for renal facilitated transport or active transport prots

Question 17

What kind of drug interactions can occur during absorption?

Answer 17

substances affecting pH of GI tract can alter absorption (recall: pKa stuff)