Lecture 5

Question 1

What is drug excretion?

Answer 1

• removal of the parent drug and drug metabolites from the body

Question 2

Primary sites of drug excretion

Answer 2

• Kidney (most important)
• Bile (most common with kidney)
• Lung
• Breast Milk

Question 3

What is renal drug excretion?

Answer 3

• kidney excretion
• serves to limit the duration and intensity of drug effects
• decreased kidney function = prolonged duration of action and intensity of drug

Question 4

What is the Nephron?

Answer 4

• basic structural and functional unit of the kidney
• regulates water, electrolyte and drug excretion
• controls blood volume, blood pressure, blood pH, and solute excretion

Question 5

What factors affect renal drug excretion?

Answer 5

• Glomerular filtration
• tubular secretion
• tubular reabsorption

Question 6

glomerular filtration

Answer 6

• drugs enter kidney from renal artery
• hydrostatic pressure within glomerular capillaries forces low molec weight drugs and small ions into renal tubules
• filtration rate ~ 20% of total renal plasma flow
• lipid solubility and pH do not affect filtration here, only size
• proteins not filtered

Question 7

Tubular secretion

Answer 7

• secretion is a rapid and high capacity process
• drugs not filtered by glomerulus leave by the efferent arteriole which divide to form capillaries that surround the proximal tubule
• drugs can be secreted from capillaries into the lumen of the proximal tubule
• drug secretion primarily occurs by two transport systems, one for weak acids and one for weak bases

Question 8

Tubular reabsorption

Answer 8

• as drugs move toward the distal tubule, their concentration increases due to the actions of the loop of henle which concentrates tubular solutes
• once in distal tubule the drug conc > drug conc in the blood that immediately surrounds it (creates concentration gradient)
• if drug is uncharged or lipid soluble its able to be reabsorbed back into the blood

Question 9

What is the effect of Age on renal function?

Answer 9

• low in newborn infants
• reaches that of a healthy adult by age 2
• starts to decrease again as we age resulting in decreased drug excretion

Question 10

What is biliary drug excretion?

Answer 10

when drugs are eliminated to the bile, released into the intestine during the digestive process and excreted in the feces or under enterohepatic recycling

Question 11

Characteristics of drugs eliminated into the bile:

Answer 11

• molecular weight > 300 Da (larger drugs)
• have both polar and lipophilic groups (amphipathic molecules)
• are glucuronidated

Question 12

What transports things into the bile?

Answer 12

• transporters on the canalicular membrane of hepatocytes transports drugs and metabolites from the liver into the bile
• P-GP transports a variety of amphipathic drugs into bile
• MRP2 transports glucuronidated metabolites into bile

Question 13

What is Enterohepatic recycling?

Answer 13

• drugs & conjugates that get excreted into bile enter the intestinal lumen where intestinal bacteria can cleave conjugate metabolites leaving the parent drug
• parent can then be reabsorbed in the intestine to re-enter the body
• drugs that undergo this persist in the body for much longer

Question 14

What is pulmonary drug excretion?

Answer 14

• drugs eliminated this way are usually gaseous and/or highly volatile
• ex general anesthetics
• not heavily reliant on drug metabolism

Question 15

What factors affect pulmonary drug excretion?

Answer 15

1. rate of respiration
2. cardiac output
3. solubility of drug in blood
   - high drug solubility = low pulmonary excretion
   - low blood drug solubility = high pulmonary excretion

Question 16

Characteristics of drugs excreted in the breast milk

Answer 16

1. low protein binding
2. ow molecular weight
3. high lipophilicity

Question 17

How are drugs excreted in the breast milk?

Answer 17

• breast cancer resistance protein (BCRP) transports drugs into breast milk
• bm has a lower pH and higher lipid content than plasma
• relatively few drugs pose a clinically relevant risk to infants

Question 18

Other routes of drug excretion

Answer 18

• hair
• saliva
• sweat

Question 19

Drug excretion via hair

Answer 19

• excreted into hair follicles

- hair grows ~1cm / month, so can be checked for exposure

Question 20

drug excretion via saliva

Answer 20

-drugs excreted here are usually swallowed and then subject to intestinal absorption or fecal excretion

Question 21

sweat

Answer 21

• mostly washed away

- minor dermal reabsorption may occur