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Pharmacokinetics > Drug Clearance > Flashcards

Drug Clearance Flashcards

1
Q

Drug clearance is measured in what units?

A

volume/time (mL/min)

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2
Q

What is the formula(s) for Cl?

A

Cl = elimination rate (mg/min) / plasma conc (mg/mL)

Cl = Vd x K

Cl = Q x ER

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3
Q

In the formula Cl = Q x ER,

What does Q and ER stand for?

A 
Q = blood flow
ER = extraction ratio
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4
Q

What does Clr stand for?

A

renal clearance

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5
Q

What are the formula(s) for Clr?

A

Clr = Qu x Cu / Cp

Clr = filtration rate + secretion rate - reabsorption rate / Cp

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6
Q

What is the clearance ratio?

A

Cl drug / Cl inulin

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7
Q

If clearance ratio < 1 = ?

A

partially reabsorbed

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8
Q

If clearance ratio = 1 ??

A

filtered only

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9
Q

If clearance ratio > 1 = ??

A

actively secreted

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10
Q

What is happening if the graph is curved?

A

You know that both secretion and filtration are happening

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11
Q

What kind of graph would tell you that only filtration is happening?

A

straight line

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12
Q

What is the formula for free amount of drug (Cpfree)

A

Cpfree = (1-alpha) Cp

free amount = free fraction x total amount

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13
Q

What does (1-alpha) mean?

A

free amount

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14
Q

What does fe stand for?

A

fraction of drug excreted

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15
Q

What does R stand for?

A

infusion rate

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16
Q

What does Css mean?

A

steady state [drug]

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17
Q

What are the formulas for clearance after IV infusion?

A 
Cl = R/Css
Cl = k x Vd
18
Q

What is hepatic clearance affected by?

A
  • blood flow
  • intrinsic Cl
  • protein binding
19
Q

What does Clh mean?

A

hepatic clearance

20
Q

What is the formula for hepatic clearance?

A

Clh = [Q(Ca-Cv)]/Ca = Q x ER

21
Q

What does Ca mean?

A

arterial concentration

22
Q

What does Cv mean?

A

venous concentration

23
Q

What does Clint stand for?

A

intrinsic clearance

24
Q

For some drugs that are ____ extracted, the extraction ratio is greater than 0.7

A

highly

25
Q

What does highly extracted mean?

A

That the liver removes the drug almost as fast as its delivered to it.

26
Q

Highly extracted drugs:

An increase in blood flow will _____ the organ (hepatic) clearance rate.

A

increase

27
Q

Highly extracted drugs:
Are known as _____ ____ limited or ____ ____ sensitive
(same answer for both blanks)

A

blood flow

28
Q

Highly extracted drugs:

For drugs that affect ____ ______ it also decreases organ blood flow and as such will decrease its own clearance rate

A

cardiac output

29
Q

Drugs that are ____ extracted by the organ have an extraction ratio (ER) of about 0.1 to 0.4

A

poorly

30
Q

Poorly extracted drugs:

Does blood flow affect clearance rate?

A

No - a change in organ blood flow doesn’t really affect the clearance rate.

31
Q

Poorly extracted drugs:

Drugs that are poorly extracted are known as ______ limited

A

enzyme

32
Q

Poorly extracted drugs:

If you induce the enzymes that are responsible for metabolizing the drugs, how will hepatic clearance be affected?

A

it will go up significantly.

33
Q

Poorly extracted drugs:

If you induce the enzymes that are responsible for metabolizing the drugs, how will biliary clearance be affected?

A

clearance will also go up for drugs eliminated via the biliary excretion

34
Q

Poorly extracted drugs:

Why do poorly extracted drugs have variable half-lives and clearance rates?

A
  • because patients have much different timers of hepatic enzymes
  • thus, much different extraction ratios occur for the same drug in different people which results in much different clearance rates
35
Q

What is Intrinsic Clearance (Clint) used to describe?

A
  • the ability of the liver to remove the drug in the absence of any flow limitation
  • this reflects the inherent activity of the mixed-function oxidases
36
Q

What does it mean if Q > Clint?

A

blood flow is not the limiting factor

37
Q

What does it mean if Clint > Q ?

A

you have tons of enzymes, they are not the limiting factor

38
Q

Drug protein binding is not a factor in hepatic clearance for drugs that have ___ extraction ratios

A

high

39
Q

Drugs that have low extraction ratios may be affected by plasma ____ _____ depending on the fraction of drug bound to proteins

A

protein binding

40
Q

For drugs that have low extraction ratios and low binding to plasma proteins, _____ changes in protein binding would not produce any significant changes in hepatic clearance

A

small

41
Q

Drugs with low extraction ratios and low binding to plasma proteins are ???

A

capacity-limited, binding insensitive drugs

42
Q

Drugs with low extraction ratios are high binding to plasma proteins are ??

A

capacity-limited binding sensitive drugs
*because a small displacement in the protein binding of these drugs will cause a very large increase in the free drug concentration

Pharmacokinetics (12 decks)

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