5 – Excretion

Question 1

Renal excretion

Answer 1

• Most important drug elimination pathway in terrestrial vertebrate animals
• If filtrate is more acidic and drug is a weak acid=more will be non-ionized=more reabsorbed into blood stream

Question 2

3 processes involved in changing blood level of a drug

Answer 2

• Glomerular filtration
• Tubular reabsorption
• Tubular secretion

Question 3

Examples of extrarenal excretion

Answer 3

1. Biliary excretion
2. Pulmonary excretion (exhalation)
3. Lactation
4. Minor routes of excretion

Question 4

Pulmonary excretion (exhalation)

Answer 4

• Important for volatile and gaseous drugs (ex. NO)
• Ex. ethanol is 90% metabolized in liver, but ~2% excreted in expired air=basis for breathalyzer test

Question 4

Biliary excretion

Answer 4

• Important for large drug molecules
• Similar to kidney
  o Facilitated transport (ex. OAT, OCT) and active transport proteins are involved
• We will always have some fraction of drug present in urine and in bile
  o Larger molecules=more in bile

Question 5

Enterohepatic cycling

Answer 5

• Molecules excreted in the bile into intestine can be reabsorbed and distributed back to the liver
  o Can increase half-life or a drug
  o If drugs producing toxic metabolites=exacerbate toxicity to the liver

Question 6

Lactation

Answer 6

• Can be significant route of elimination for lipophilic drugs
• Important consideration for neonatal exposure AND food products

Question 7

Minor routes of excretion

Answer 7

• Saliva
• Sweat
• Hair, nails

Question 8

Summation

Answer 8

• Coadministration of both drugs produces a combined effect
  o Ex. 2+2=4
• Most common

Question 9

Synergism

Answer 9

• Effects of 2 drugs in combination exceeds sum of their individual effects
  o Ex. 2+2=10

Question 10

Potentiation

Answer 10

• Drug with no effect intensifies the effect of a second drug
  o Ex. 2+0=10

Question 11

Antagonism

Answer 11

• Effect of 2 drugs in combination is less than additive
  o Ex. 2+2=1

Question 12

Drug interactions: mechanisms

Answer 12

1. Interactions during biotransformation
   a. Induction or inhibition
2. Interactions during distribution
   a. Competition for binding sites can displace a drug and cause increased free fraction and greater response
3. Interactions during excretion
   a. Decreased clearance due to inhibition of renal excretion
   b. Ex. competition for renal facilitated transport or active transport proteins
4. Interactions during absorption
   a. Substances affecting pH of GI tract can alter absorption