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PHAR226 > Elimination > Flashcards

Elimination Flashcards

1
Q

What is elimination?

A

irreversible removal of drug from the body by all drug removal mechanisms

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2
Q

What are the mechanisms of elimination?

A

biotransformation (metabolism)
-irreversible removal of drug by chemical conversion to metabolite
excretion
-irreversible removal of intact (parent) drug

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3
Q

Which organs are involved in biotransformation?

A

liver
GIT wall/microflora
kidney
lung
skin

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4
Q

Which organs or bodily fluids are involved in excretion?

A

kidney
liver
lung
saliva
milk

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5
Q

Are metabolites toxic or active?

A

can be either

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6
Q

What is clearance?

A

measure of the efficiency of mechanism(s) involved in drug removal (elimination) from the body

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7
Q

What is the physiological definition of clearance?

A

clearance is the volume of blood completely cleared of drug per unit time

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8
Q

What is the general definition of clearance?

A

proportionality constant relating rate of elimination to the plasma concentration of drug at time, t

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9
Q

What is systemic clearance?

A

considers whole body as single drug eliminating system
-sums up all simultaneously occurring elimination pathways

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10
Q

Why is important to calculate Cls?

A

allows prediction of Css,ave and the calculation of maintenance doses

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11
Q

What is the equation for Css?

A

Css=dosing rate (MD)/Cls

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12
Q

True or false: oral clearance=systemic clearance

A

false

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13
Q

Differentiate oral clearance from systemic clearance.

A

oral clearance:
-during absorption, drug is lost during events in the GIT (1st pass effect)
-encompasses loss of drug from admin site into systemic circulation
systemic clearance:
-removal of drug that is within systemic circulation

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14
Q

For a given drug, which has a larger value: systemic clearance or oral clearance?

A

oral clearance
-F is always <1

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15
Q

What is the equation for oral clearance (Clo)?

A

Clo=Cls/F
Clo=Dosepo/AUC

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16
Q

What is the equation for systemic clearance (Cls)?

A

Cls=F x Clo
Cls=F x (dosepo/AUC)

17
Q

What are the principal pathways for clearance?

A

hepatic (Clh)
renal (Clr)

18
Q

How is organ clearance linked to Cls?

A

each eliminating organ removes a fraction of drug from the volume of blood perfusing the eliminating organ per unit time
-all these fractions are summed to give total volume of blood completely cleared per unit time

19
Q

What are the major mechanisms of hepatic clearance?

A

biliary excretion (transporters)
biotransformation
-phase 1 enzymes, phase 2 enzymes

20
Q

What are the major mechanisms of renal clearance?

A

glomerular filtration (GFR)
tubular absorption (TR)
tubular secretion (TS)
Clr=Clgfr+Clts-Cltr

21
Q

What is the difference between rate of elimination and elimination rate constant?

A

rate of elimination:
-amount/conc of drug eliminated per unit time
-not a constant
elimination rate:
-fraction of drug eliminated per unit time
-a constant

22
Q

True or false: Cls is not a constant

A

false
Cls is a constant

23
Q

What is the general cardiac output?

A

5ml/min

24
Q

What is the hepatic blood flow?

A

1.5L/min

25
Q

What is the renal blood flow?

A

1.2L/min

26
Q

What is the equation for extraction ratio?

A

E=(Ca-Cv)/Ca

27
Q

What must occur for drug to be eliminated?

A
  1. blood must deliver drug to the eliminating organ (Q)
  2. eliminating organ must extract drug from blood (E)
28
Q

What is the equation for clearance?

A

clearance=QxE

29
Q

What is extraction ratio?

A

fraction of drug entering the eliminating organ that is removed during transit through the organ

30
Q

What are the values for E?

A

0-1
0=no drug removed
1=all drug removed

31
Q

What is Forgan?

A

(1-E)=Forgan
fraction of drug molecules escaping the organ and leaving in the venous blood

32
Q

What is the maximum value of Cl?

A

Q (blood flow to the organ or CO is if considering total body clearance or systemic clearance)

33
Q

What are the factors affecting extraction?

A

drug binding to/partitioning into blood cells
drug binding to plasma proteins
unbound drug diffusion into the hepatocyte
unbound drug excretion into bile
unbound drug enzymatic biotransformation
blood perfusion (Q) to the liver

34
Q

What is a high E?

A

E>0.7
-Q is rate limiting

35
Q

What is an intermediate E?

A

0.3<E>0.7</E>

36
Q

What is a low E?

A

E<0.3
-Q is not rate-limiting, its one of the other ones

37
Q

Differentiate between high E drugs and low E drugs.

A

high E drugs:
-Q is rate limiting
-perfusion rate-limited so Cl changes with Q while E is unaffected
low E drugs:
-changes in Q do not change CL
-most drugs

PHAR226 (12 decks)

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