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PharmSci ADME > Elimination > Flashcards

Elimination Flashcards

1
Q

Drug elimination if divided into what major components?

A

excretion

biotransformation

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2
Q

____ is the removal of the intact drug

A

excretion

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3
Q

nonvolatile drugs are excreted by what?

A

renal excretion or other pathways

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4
Q

volatile drugs are excreted by what?

A

lungs

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5
Q

Clearance definition

A

process of drug elimination from body or single organ

- volume of fluid cleared of drug from body

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6
Q

T/F clearance applies to all elimination processes

A

True

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7
Q

The kidney is the main excretory organ for removing ____

A

metabolic waste

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8
Q

Metabolism of a drug occurs via

a. enzymatic
b. nonenzymatic
c. bacterial
d. all of the above

A

all of the above

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9
Q

How can you quantify elimination?

A

clearance rate

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10
Q

GFR

A

120 ml/min

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11
Q

What is GFR controlled by?

A

changes in glomerular capillary hydrostatic pressure

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12
Q

_____ maintains a constant blood flow in the presence of large fluctuations in arterial blood pressure

A

autoregulation

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13
Q

How much fluid is filtered through kidneys a day?

A

180L

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14
Q

_% of fluid volume filtered at the glomerulus is reabsorbed

A

99%

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15
Q

3 major processes of renal drug excretion

A
  • glomerular filtration
  • active tubular secretion
  • tubular reabsorption
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16
Q

Drugs that are nonvolatile, water soluble, low MW or slowly biotransformed by liver are eliminated by what?

A

renal excretion

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17
Q

T/F protein bound drugs get filtered at the glomerulus

A

false!

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18
Q

What is the major driving force in the glomerular capillaries?

A

hydrostatic pressure

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19
Q

How is GFR measured?

A

using a drug that is eliminated primarily by filtration with no reabsorption

clearance is equal to GFR

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20
Q

What is a biomarker of renal function?

A

creatinine

blood levels rise when kidney is deficient

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21
Q

Glomerular filtration of drugs is directly related to what?

A

free drug concentration in plasma

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22
Q

Active tubular secretion

A
  • active transport
  • carrier mediated
  • against concentration gradient
  • capacity limited, may be saturated
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23
Q

What is active tubular secretion dependent on?

A

renal plasma flow

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24
Q

Two carrier systems for active tubular secretion

A
  • organic anion transporter (OAT) for WA

- organic cation transporter (OCT) for WB

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25
Q

What drugs are used to measure active tubular secretion?

A

PAH

iodopyracet

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26
Q

How is PAH secreted?

A

glomerular filtration

active filtration

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27
Q

T/F PAH active secretion is very slow

A

False!

very fast, almost all eliminated in a single pass

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28
Q

T/F active tubular secretion is not affected by protein binding

A

true

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29
Q

When dose tubular reabsorption occur?

A

after the drug is filtered through glomerulus

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30
Q

Tubular reabsorption

A
  • active or passive

- transport back to plasma

31
Q

If a drug is completely reabsorbed the clearance of the drug is what?

A

0

32
Q

For drugs that are partially reabsorbed, clearance is what?

A

less than 120 ml/min

33
Q

The reabsorption of drugs that are acids or weak bases is influenced by what?

A

pH of fluid in renal tubule

pKa of drug

34
Q

_____ affects transit time within renal tubules, where drug reabsorption takes place

A

urine flow

35
Q

HH for WA tubular reabsorption

A

pH = pka + log (I/U)

10^pH-pka/ 1+ 10^pH-pka

36
Q

HH for WB tubular reabsorption

A

pH = pka + log (U/I)

10^pka-pH/1 + 10^pka-pH)

37
Q

Where does the greatest effect of urinary pH on reabsorption occur?

A

WB with aka 7.5 - 10.5

38
Q

T/F for a weak acid drug, the extent of dissociation is more affected by changes in urinary pH if pKa = 3 than if pka = 5

A

False

pKa = 5 than if pKa = 3

39
Q

What is more easily reabsorbed by tubular reabsorption?

A

nonionized acids and bases

40
Q

Urine pH range

A

4.5 -8

41
Q

What can acidify urine?

A

protein rich diet

ascorbic acid

42
Q

What can alkalinize urine?

A 
carbohydrates
fruit
veggies
HCO3-
antacids
43
Q

HH U/P ratio tubular reabsorption for WA

A

U/P

1 + 10^pHurine - pka/ 1 + 10^pHplasma -pka)

44
Q

HH U/P ratio tubular reabsorption for WB

A

P/U

1 + 10^pka - pHurine/ 1 + 10^pka - pHplasma

45
Q

Glomerular filtration transport

A

passive

46
Q

location of active tubular secretion

A

proximal tubule

47
Q

location of tubular reabsorption

A

distal tubule

48
Q

Drug ionization in glomerular filtration

A

either

49
Q

Drug ionization of active tubular secretion

A

mostly WA and WB

50
Q

Drug ionization of tubular reabsorption

A

non-ionized

51
Q

Drug protein binding glomerular filtration

A

only free drug

52
Q

drug protein binding active tubular secretion

A

no effect

53
Q

Glomerular filtration is influenced by…

A

protein binding

54
Q

Active tubular secretion is influenced by…

A

Competitive inhibitors

55
Q

Tubular reabsorption is influenced by…

A

urinary pH and flow

drug pKa

56
Q

Drug clearance definition

A

describe drug elimination from body w/o identifying mechanism of processmL/min

57
Q

T/F drug clearance considers the entire body as a single drug eliminating system

A

True!

58
Q

Clearance equation

A

Clt = elimination rate/CP

59
Q

What rate order is clearance?

A

1st order

60
Q

Physiologic organ clearance model

A
  • based on drug clearance through individual organs

- clearance depends on blood flow and ability of organ to eliminate drug

61
Q

Non-Compartment clearance model

A
  • clearance determined directly from plasma time concentration curve
62
Q

Renal clearance (Clr)

A

volume of plasma cleared through kidney

  • for any drug cleared through kidney, the rate of the drug passing through the kidney must equal the rate of drug excreted in the urine
63
Q

Clr equation

A

filtration rate + secretion rate - reabsorption rate /Cp

64
Q

Clearance <1

A

drug partially reabsorbed

65
Q

Clearance >1

A

drug actively secreted

66
Q

Clearance = 1

A

drug filtered only

67
Q

If glomerular filtration is the sole process for drug excretion and no drug is reabsorbed, then the amount of drug filtered at any time will always be _____

A

Cp x GFR

68
Q

For drugs that are primarily filtered and secreted, with negligible reabsorption, thee overall excretion rate will _____ GFR

A

exceed

69
Q

At low concentrations, active secretion is not saturated and the drug is excreted by _______

A

filtration and active secretion

70
Q

At high concentrations, the % of drug excreted by active secretion ______ due to saturation

A

decreases

71
Q

Explain the extraction ratio

A

fraction of a substance removed from blood flow through organ

E = Cl/blood flow

72
Q

Clearance is limited by what factor?

A

Q (blood flow to organ eliminating drug)

73
Q

What is the max Q value in body?

A

1.5 L/min

74
Q

As Cl increases, what happens to drug’s half life?

A

t1/2 decreases

PharmSci ADME (4 decks)

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