Excretion

Question 1

Kidney Functions (3)

Answer 1

1. Glomerular Filtration
2. Tubular Secretion
3. Tubular Reabsorption

Question 2

Passive Kidney Functions

Answer 2

Glomerular Filtration & Tubular Reasborption

Question 3

Active Kidney Function

Answer 3

Tubular Secretion

Question 4

Rate of Excretion

Answer 4

Rate of Filtration + Rate of Secretion - Rate of Absorption

Question 5

Glomerular Filtration

Answer 5

• Plasma water is filtered at a rate ~125 mL/min and is called GFR
• ONLY unbound drug is filtered

Question 6

Rate of Filtration

Answer 6

=GFR * Cu

=GFR * C * fp

Question 7

Rate of Excretion

Answer 7

If a drug is ONLY filtered and is ALL excreted in urine

=Rate of filtration (GFR * C *fp)

Question 8

Renal Clearance (Clr)

Answer 8

Clr = Rate of Excretion/ C

=GFR * fp

Question 9

Measurement of GFR

Answer 9

• Creatinine (endogenous) and insulin (exogenous)
• not bound, secreted, reabsorbed
• Clr for these compounds approximates GFR (fp = 1)

Question 10

Secretion

Answer 10

• Carrier mediated, active transport

- Similar equation to hepatic metabolism

Question 11

Clr,sec

Answer 11

Qr * [ (fp * Cli,sec) / Qr + fp * Cli,sec)]

Question 12

Clr, total (assuming no reabsorption)

Answer 12

= Clr,filt + Clr,sec (assume NO absorption)

Question 13

Reabsorption depends on…

Answer 13

1. Urine pH (Ionization)
2. Urine flow - increased urine flow will decrease the time for reabsorption, therefore more rapid excretion
3. Lipophilicty/hydrophilicity

Question 14

True Clr,total

Answer 14

= (Clr,filt + Clr,sec)(1-fraction reabsorbed)

Question 15

How do we know if a drug is reabsorbed?

Answer 15

Clr,total < Clr,filt

Question 16

Acidic Drugs + Urine pH

Answer 16

• Polar acids - not reabsorbed, extensive excretion
• Nonpolar, strong acids with pKa < 6- mostly ionized, little reabsorption, extensive excretion
• Nonpolar, weak acids with pKa > 12 - mostly unionized, extensive reabsorption, little excretion
• Nonpolar acids with pKa 6-12 - Varying degress of ionization, reabsorption, and excretion

Question 17

Basic Drugs + Urine pH

Answer 17

• Polar bases - not reabsorbed, extensive excretion
• Nonpolar, strong bases with pKa > 12 - mostly ionized, little reabsorption, extensive excretion
• Nonpolar, weak bases with pKa < 6 - mostly unionized, extensive reabsorption, little excretion
• Nonpolar bases with pKa 6-12 - carying degrees of ionization, reabsorption, and excretion

Question 18

Forced Diuresis

Answer 18

• More rapid elimination is a way of detoxifying a patient with a drug overdose
• Control pH as well as flow change
• Goal is to increase ionization, decrease reabsorption, and increase excretion

Question 19

Criteria for Forced Diuresis

Answer 19

1. Drug is eliminated mainly by renal pathway

2. Drug must be normally extensively reabsorbed from the renal tubules

Question 20

Problems collecting VALID urinary excretion data… (5)

Answer 20

1. Significant fraction of unchanged drug must be excreted in urine
2. Good assay selectivity
3. Frequent sampling
4. Sufficiently long sampling time (5-7 half lives required for 95 and 99% elimination, respectively)
5. If possible, urine flow and urinary pH should be monitored (hard when out patient)

Question 21

K =

Answer 21

ke + knr

Question 22

dXu/dt

Answer 22

= keDose * e^(-Kt)

Question 23

ln(dXu/dt)

Answer 23

= ln(keDose) - Kt

**When plotting, use midpoint for sampling time

Question 24

Xu

Answer 24

= (keDose/K)*(1-e^(-Kt))

Question 25

XuINF

Answer 25

= keDose/K

Question 26

ln(XuINF - Xu)

Answer 26

ln(XuINF) - Kt | -Gives slope of -K

Question 27

XuINF - Xu

Answer 27

-Term commonly called the AMOUNT of drug REMAINING to be EXCRETED (A.R.E)

Question 28

Biliary Excretion

Answer 28

-Important for the excretion of bile and drugs

Question 29

MW + Excretion

Answer 29

- < 300 = excreted almost exclusively in the urine - 300 – 500 = excreted both in the urine and bile - > 500 = excreted mainly in the bile

Question 30

Polarity + Excretion

Answer 30

- Excretion into bile requires a strong polar group | - Many metabolites are excreted in the bile (Glucoronidation – increases polarity and increases molecular weight by 200)

Question 31

Enterohepatic Circulation + Excretion

Answer 31

- Drug (or metabolite) that is secreted into the bile from the liver is expelled into the duodenum with gall bladder contraction via common bile duct - Parent drug may be reabsorbed and become systemically available (or excreted in feces) - Glucoronide conjugates can be hydrolyzed back to the parent compound by intestinal β-glucoronidase enzymes

Question 32

Multiple Doses + Excretion

Answer 32

- More drug is secreted into bile after multiple doses or a large, singular dose - Can affect the elimination and absorption rates

Question 33

Hepatic Excretion Peaks

Answer 33

- Peak 1 - normal oral absorption peak as drug is absorbed from the gut - Peak 2 - biliary reabsorption