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810 > Excretion > Flashcards

Excretion Flashcards

1
Q

Kidney Functions (3)

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

Passive Kidney Functions

A

Glomerular Filtration & Tubular Reasborption

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3
Q

Active Kidney Function

A

Tubular Secretion

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4
Q

Rate of Excretion

A

Rate of Filtration + Rate of Secretion - Rate of Absorption

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5
Q

Glomerular Filtration

A
  • Plasma water is filtered at a rate ~125 mL/min and is called GFR
  • ONLY unbound drug is filtered
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6
Q

Rate of Filtration

A

=GFR * Cu

=GFR * C * fp

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7
Q

Rate of Excretion

A

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

=Rate of filtration (GFR * C *fp)

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8
Q

Renal Clearance (Clr)

A

Clr = Rate of Excretion/ C

=GFR * fp

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9
Q

Measurement of GFR

A
  • Creatinine (endogenous) and insulin (exogenous)
  • not bound, secreted, reabsorbed
  • Clr for these compounds approximates GFR (fp = 1)
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10
Q

Secretion

A
  • Carrier mediated, active transport

- Similar equation to hepatic metabolism

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11
Q

Clr,sec

A

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

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12
Q

Clr, total (assuming no reabsorption)

A

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

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13
Q

Reabsorption depends on…

A
  1. Urine pH (Ionization)
  2. Urine flow - increased urine flow will decrease the time for reabsorption, therefore more rapid excretion
  3. Lipophilicty/hydrophilicity
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14
Q

True Clr,total

A

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

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15
Q

How do we know if a drug is reabsorbed?

A

Clr,total < Clr,filt

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16
Q

Acidic Drugs + Urine pH

A
  • 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
17
Q

Basic Drugs + Urine pH

A
  • 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
18
Q

Forced Diuresis

A
  • 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
19
Q

Criteria for Forced Diuresis

A
  1. Drug is eliminated mainly by renal pathway

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

20
Q

Problems collecting VALID urinary excretion data… (5)

A
  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)
21
Q

K =

A

ke + knr

22
Q

dXu/dt

A

= keDose * e^(-Kt)

23
Q

ln(dXu/dt)

A

= ln(keDose) - Kt

**When plotting, use midpoint for sampling time

24
Q

Xu

A

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

25
Q

XuINF

A

= keDose/K

26
Q

ln(XuINF - Xu)

A

ln(XuINF) - Kt

-Gives slope of -K

27
Q

XuINF - Xu

A

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

28
Q

Biliary Excretion

A

-Important for the excretion of bile and drugs

29
Q

MW + Excretion

A
  • < 300 = excreted almost exclusively in the urine
  • 300 – 500 = excreted both in the urine and bile
  • > 500 = excreted mainly in the bile
30
Q

Polarity + Excretion

A
  • Excretion into bile requires a strong polar group

- Many metabolites are excreted in the bile (Glucoronidation – increases polarity and increases molecular weight by 200)

31
Q

Enterohepatic Circulation + Excretion

A
  • 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
32
Q

Multiple Doses + Excretion

A
  • More drug is secreted into bile after multiple doses or a large, singular dose
  • Can affect the elimination and absorption rates
33
Q

Hepatic Excretion Peaks

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

810 (22 decks)

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