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PHRM 501 > Exam 3: Renal Clearance > Flashcards

Exam 3: Renal Clearance Flashcards

1
Q

Metabolism

A

Chemical conversion of parent drug

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2
Q

Excretion

A

Removal of intact drug

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3
Q

Non-volatile/polar drugs:

A
  • Passage through kidney to bladder and removal via urine

* Other fluids: Bile, sweat, saliva, lactation milk

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4
Q

Volatile drugs:

A

Excretion into expired air

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5
Q

What does the kidney do?

A
  • Removes wastes
  • Controls fluid balance
  • Regulates balance of electrolytes
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6
Q

Which processes are involved in Removal of wastes

A
  • Glomerular filtration

* Tubular secretion

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7
Q

Reuptake of nutrients

A

• Tubular reabsorption

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8
Q

Renal artery

A

takes blood to kidney

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9
Q

Renal Vein

A

carries blood from the kidney

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10
Q

Kidney Processes lots of fluid:

A
  • ~173 L water/day in
  • ~171-172 L water/day returned to body
  • ~1-2 L excreted as urine
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11
Q

Anatomy of the Kidney

A

We have two of them

Urine pools in the collecting duct and leaves via the ureter

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12
Q

Blood enters via

A

afferent arterioles

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13
Q

Blood leaves via

A

efferent arterioles

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14
Q

Functional unit of kindey

A

nephron

~1 million/kidney

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15
Q

Within each nephron is a

A

glomerulus, proximal tubule,

loop of Henle, distal tubule, and collecting duct

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16
Q

Waste collects as urine

A

in the collecting duct

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17
Q

Three important processes relevant to drugs take

place in the kidney:

A
  • Glomerular filtration
  • Tubular secretion
  • Tubular reabsorption
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18
Q

What does glomerular filtration and tubular secretion do

A

they remove drug from circulation

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19
Q

What does tubular reabsorption do

A

returns drug to circulation

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20
Q

Filtration happens in the

A

Glomerulus

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21
Q

Secretion happens in the

A

Proximal tubule

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22
Q

Reabsorption happens in the

A

Distal tubule

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23
Q

Glomerulus

A

Glomeruli have a semi-permeable membrane that separates small ions/molecules from larger constituents of blood

  • Easy for small molecules to pass
  • Not so easy for large and/or negatively charged molecules
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24
Q

Podocytes

A

epithelial cells that cover the outer surfaces of glomerular capillaries

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25
Q

As the diameter of the blood vessels decreases

A

their ability to carry blood decreases

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26
Q

Hydrostatic pressure:

A

Pressure gradient from the arterial end of the capillaries entering the tissue to the venous capillaries leaving the tissue

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27
Q

How much output dose kidney recieve

A

The kidneys receive ~20% of the cardiac output

-e.-Lots of blood flow (~1 L/min)

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28
Q

In the kidney, the diameter of the afferent arterioles is

A

larger than the efferent arterioles

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29
Q

Tubes in kidney

A

The diameter of the tube going in is larger than the tube going out, hence fluid pressure builds up
• These tubes can relax or be constricted to control blood pressure in the glomerulus

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30
Q

Osmotic Pressure

A

Net movement of water due to differences in solute concentration

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31
Q

Water diffuses through semipermeable membrane towards region of

A

higher solute concentration

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32
Q

The higher the solute concentration

A

the greater driving force for water diffusion

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33
Q

Osmolality differences drive

A

water uptake/removal

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34
Q

Water diffuses to areas of

A

higher solute concentration

higher protein conc.

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35
Q

solutes are dissolved in

A

an aqueous solution

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36
Q

Solutes want to diffuse

to areas of

A

lower conc.

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37
Q

Water in the glomerulus

A

Water is freely filtered from the plasma in the glomerulus

• This leaves the remaining plasma proteins and cells more concentrated

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38
Q

colloid osmotic

pressure

A

protein concentration difference

- drives the reabsorption of water

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39
Q

Net Filtration Pressure

A

There is a balance between pressure exerted on the capillaries and opposing pressure from the interstitial fluid

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40
Q

• In the kidneys, the hydrostatic pressure at the glomerulus

A

is ~60 mm Hg

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41
Q

The colloidal osmotic pressure

A

~18 mm Hg

42
Q

The capsular hydrostatic pressure

A

~32 mm Hg

43
Q

Thus, the net outward pressure

A

~10 mm Hg

44
Q

The kidneys receive ~20% of cardiac output

A

~60 L/hr blood flow

45
Q

How much blood entering the glomerulus is filtered

A

~20%

46
Q

Typical glomerular filtration rate (GFR) is

A

120 mL/min

47
Q

Glomerular Filtration

A

• Location: Occurs in the glomerulus
• Function:
- Retention of cellular components and large plasma proteins
- Passage of small molecules/ions
• Limited by size exclusion – driven by hydrostatic pressure
• Impacted primarily by protein-binding and blood flow
- Passive transport

48
Q

The proximal convoluted tubule has

A

lots of surface area

- lots of mitochondria in cells

49
Q

Different regions of the subsequent tubule structure have different
functions

A
  • Reabsorption of water
  • Reabsorption of ions
  • Reabsorption of sugars
  • Secretion of organic acids/bases
  • Excretion of salts/bicarbonate
  • Regulation of pH
  • Formation of ammonia
50
Q

Tubular Secretion

A
  • Occurs mainly in the proximal tubule
  • Active transport (mostly faciliated)
  • Two main secretion processes
  • One for weak acids (organic anions)
  • One for weak bases(organic cations)
  • Impacted primarily by competitive inhibitors
51
Q

Is an organic anion transporter likely to

transport weak acid or weak base drugs?

A

weak acid

52
Q

Tubular Reabsorption

A
  • Occurs mainly in the distal tubule
  • Re-uptake of lipid soluble drugs
  • Passive transport
  • Impacted primarily by urine pH and flow
53
Q

If urine flow rate increases, how do you think

reabsorption will be impacted?

A

Reabsorption will decrease because there is less residence time/ contact time making the plasma dug conc. lower as well

54
Q

Hydrophilic molecules are more soluble

A

in urine and are likely to be excreted

55
Q

Hydrophobic molecules are less soluble in urine

A

and are likely to be reabsorbed

56
Q

Metabolism reduces

A

reabsorption

57
Q

The metabolites are typically more

A

hydrophilic than the parent drug

58
Q

Most pharmaceutical compounds are

A

weak acids or bases

59
Q

Weak acids are predominantly ______ charged at pH values above their pKa

A

negative

60
Q

Weak bases are predominantly ______ charged at pH values above their pKa

A

positive

61
Q

If a drug is uncharged, we can change

A

urine pH to prevent reabsorption

62
Q

increasing the urine pH makes weak acids

A

negatively charged

63
Q

Decreasing the urine pH makes weak bases

A

positively charged

64
Q

Making a molecule charged makes it

A

more water soluble and less likely to pass a lipid membrane

-Thus, urinary excretion is increased

65
Q

Whats the pH or urine

A

6.0

66
Q

If the pH of the urine were to become more basic,

A

a weak acid drug will be more readily excreted

67
Q

Making a molecule charged makes it

A

more water soluble and less likely to pass a lipid membrane

68
Q

urinary excretion can be increased/decreased by

A

changing pH

69
Q

‘Ion-trapping’

A
  • Neutral molecules can pass cell membranes
  • Weak acids will become (-) in a basic compartment
  • Weak bases will become (+) in an acidic compartment
  • Once charged, they can’t escape!
70
Q

Weak acids will accumulate

A

in a basic compartment

- become negative

71
Q

Weak bases will accumulate

A

in an acidic compartment

- become positive

72
Q

The charged drug will accumulate

A

in urine and be unable to be reabsorbed

73
Q

Which renal processes are saturable?

A

Facilitated and Active Transport

- Tubular secretion

74
Q

As drug concentrations increase

A

tubular secretion processes become saturated

75
Q

• Renal excretion is primarily is a

A

first order process

The rate is dependent on concentration

76
Q

Glomerular Filtration and Protein Binding

A

Drugs that are plasma protein-bound do not undergo glomerular filtration
- Only free drug, not protein-bound, drug is available to be
‘extracted’

77
Q

More protein-binding

A

less extraction of drug!

78
Q

Total drug =

A

free drug + protein bound drug

79
Q

• Fraction unbound (fu) =

A

unbound/total

80
Q

What is the unit-less parameter that describes the efficiency of an organ in terms of removal of
drug from circulation?

A

Extraction ratio

81
Q

Extraction Ratio (E)

A

Efficacy of an organ to remove a drug from the bloodstream

• Includes both metabolism and excretion

82
Q

Typical glomerular filtration rate (GFR) is

A

~120 mL/min. (7.2 L/hr)

83
Q

Renal clearance is the

A

sum of clearances from filtration and secretion, less

reabsorption

84
Q

If renal clearance is ~fu*GFR

A

then filtration is assumed to be the predominant mechanism

85
Q

If renal clearance is >fu*GFR

A

then tubular secretion is contributing

86
Q

If renal clearance is

A

then tubular reabsorption is contributing

87
Q

In renal disease, the GFR can be

A

reduced

Less blood flow through the glomerulus, less clearance

88
Q

Creatine

A
  • Endogenous molecule generated in the liver
  • Used by muscles as energy source
  • Broken down into creatinine
89
Q

Creatinine removed primarily by

A

glomerular filtration

90
Q

If glomerular filtration is impaired, the plasma

concentrations of creatinine will increase/decrease?

A

increase

91
Q

Creatinine levels are used to assess

A

renal function

We can monitor the concentration of creatinine in both plasma and urine

92
Q

If a high concentration of creatinine is found in the

urine relative to plasma

A

, it is being effectively cleared

If a low concentration of creatinine is found in the
urine relative to plasma, it is not being effectively
cleared

93
Q

Creatine is

A

It is endogenous
• It is already at a steady state concentration in the blood
• The amount produced = the amount removed in a given time
• It is freely filtered and not secreted or reabsorbed
• Usually all the creatinine that is generated in a day is found in the urine
• The creatinine clearance (CrCl) is approximately equal to the GFR
• Clcreatinine~120 mL/min.
• 120 mL blood is cleared of creatinine each minute

94
Q

How Do We Assess Renal Clearance?

A
  • Collect urine over 24 hours
  • Determine urine volume
  • Determine concentration of creatinine in urine
  • Determine concentration of creatinine in plasma
95
Q

CrCl=

A

(Urine concentration of creatinine)(urine volume/time)/(plasma concentration of creatinine)
• CrCl=(mg/mL)(mL/min.)/(mg/mL)
• CrCl=mL/min

96
Q

Cockcroft-Gault Equation

A

A common equation used to estimate creatinine clearance based on plasma concentrations

97
Q

Creating clearance for females

A

(140- age[years]) x weight [kg] / serum conc. [ umol/L]

98
Q

Creating clearance for males

A

(140- age[years]) x weight [kg]* 1.2 / serum conc. [ umol/L]

99
Q

• In patients with kidney disease, the GFR is

A

reduced

100
Q

Conditions that affect blood flow can affect renal function such as

A

Examples include congestive heart failure and high blood pressure

PHRM 501 (21 decks)

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