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26 Cards in this Set
- Front
- Back
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renal clearance consists of:
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-glomerular filtration
-active secretion -active and passive reabsorption |
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active secretion I
what type of process? |
protein carrier-mediated process
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active secretion I
the kinetics is saturable, for low drug concentrations linear: the rate of secretion (equation) |
Cls= secretion rate/plasma concentration
= e * vm/km * [D] {rate parameter of secretion} |
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active secretion II
clearance of secretion (equation) |
Cls= fu * (e*vm/km)
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active secretion II
some compounds(e.g. p-aminohippuric acid) are secreted during the first pass- used to measure RBF |
true
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tubular reabsorption I: equilibrium
compounds are reabsorbed from the filtrate how? |
actively in PT
passively along entire tubule |
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tubular reabsorption I: equilibrium
for easily transported drugs: |
--nonionized molecules in significant fraction
--optimal lipophilicity (-2 <logP<4) --non amphiphilic |
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tubular reabsorption I: equilibrium
the extent of passive reabsorption is given by: |
the equilibrium urine/plasma ratio
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tubular reabsorption I: equilibrium
pH of urine : |
4.5 to 8
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tubular reabsorption II: equilibrium
to access the equilibrium, we need the total concentrations in urine and plasma, both including: |
- free nonionized molecules.... ca
- free ionized molecules ... ca * qh - protein bound nonionized molecules... ca * K * p - protein bound ionized molecules...ca*K*p*qh |
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tubular reabsorption II: equilibrium
the total concentration is the: |
sum of the concentrations of nonionized and ionized molecules, both free and bound
c=ca + ca + qh + ca * K * p + ca * K * p * qh |
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tubular reabsorption III: equilibrium
the total concentration can be written as: |
c= ca * (1 + qh) * (1 + K * p)
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tubular reabsorption III: equilibrium
ionization is described by: |
the factor qh= the ratio of ionized and nonionized concentrations
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tubular reabsorption III: equilibrium
for both acids and bases (equation) |
qh= 10 ^ sgn * (pKa - pH)
-1 for acids +1 for bases |
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tubular reabsorption IV: equilibrium
for quickly transported drugs the free nonionized concentrations ca in plasma and urine are: |
equal
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tubular reabsorption IV: equilibrium
the urine/plasma concentration ratio is: |
Cur total drug concentration urine
------ = ------------------------------------------- cp total drug concentration plasma |
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tubular reabsorption V: equilibrium
Cur/cp ---> 0 |
reabsorption: very high
excretion: very low pKa : acids |
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tubular reabsorption V: equilibrium
Cur/cp 0-1 |
reabsorption: medium
excretion: medium pKa: acids |
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tubular reabsorption V: equilibrium
Cur/cp --> 1 |
reabsorption: low
excretion: high pKa: acids and bases |
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tubular reabsorption V: equilibrium
Cur/cp >3 |
reabsorption: very low
excretion: very high pKa: bases |
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tubular reabsorption V: equilibrium
Cur/cp >>3 |
reabsorption: neglible
excretion: maximum pKa: bases |
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low tubular reabsorption
the distribution equilibrium is not achieved by: |
hydrophilic drugs (logP <-2)
lipophilic drugs (logP >4) drugs completely ionized in urine (acids pH~4.5 pKa < 2.5) (bases pH ~8 pKa > 10) |
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low tubular reabsorption
consequences: |
equation Cur/cp.... not valid
previously mentioned compounds have low reabsorption and high excretion |
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tubular reabsorption: clearance I
description of clearance complicated because: |
- the input flow is GFR with the drug concentrations given by filtration and secretion (if present)
- the drug concentration changes thanks to: reabsorption of water and reabsorption of drug molecules - the output flow is urine flow rate (UFR) - the plasma drug concentration needed for Cl |
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tubular reabsorption: clearance II
Clr (eq) |
Clr = reabsorption rate/plasma conc
reabsorption rate is rate of input-rate of output Clr= fu * (GFR + e*vm/km) - UFR * Cur/cp |
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renal clearance
Clr can also be described using: |
urine data
Clr= excretion rate/plasma conc Clr= UFR * Cur/cp |
