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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
What drugs are used to measure active tubular secretion?
PAH | iodopyracet
26
How is PAH secreted?
glomerular filtration | active filtration
27
T/F PAH active secretion is very slow
False! | very fast, almost all eliminated in a single pass
28
T/F active tubular secretion is not affected by protein binding
true
29
When dose tubular reabsorption occur?
after the drug is filtered through glomerulus
30
Tubular reabsorption
- active or passive | - transport back to plasma
31
If a drug is completely reabsorbed the clearance of the drug is what?
0
32
For drugs that are partially reabsorbed, clearance is what?
less than 120 ml/min
33
The reabsorption of drugs that are acids or weak bases is influenced by what?
pH of fluid in renal tubule | pKa of drug
34
_____ affects transit time within renal tubules, where drug reabsorption takes place
urine flow
35
HH for WA tubular reabsorption
pH = pka + log (I/U) 10^pH-pka/ 1+ 10^pH-pka
36
HH for WB tubular reabsorption
pH = pka + log (U/I) 10^pka-pH/1 + 10^pka-pH)
37
Where does the greatest effect of urinary pH on reabsorption occur?
WB with aka 7.5 - 10.5
38
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
False pKa = 5 than if pKa = 3
39
What is more easily reabsorbed by tubular reabsorption?
nonionized acids and bases
40
Urine pH range
4.5 -8
41
What can acidify urine?
protein rich diet | ascorbic acid
42
What can alkalinize urine?
``` carbohydrates fruit veggies HCO3- antacids ```
43
HH U/P ratio tubular reabsorption for WA
U/P | 1 + 10^pHurine - pka/ 1 + 10^pHplasma -pka)
44
HH U/P ratio tubular reabsorption for WB
P/U | 1 + 10^pka - pHurine/ 1 + 10^pka - pHplasma
45
Glomerular filtration transport
passive
46
location of active tubular secretion
proximal tubule
47
location of tubular reabsorption
distal tubule
48
Drug ionization in glomerular filtration
either
49
Drug ionization of active tubular secretion
mostly WA and WB
50
Drug ionization of tubular reabsorption
non-ionized
51
Drug protein binding glomerular filtration
only free drug
52
drug protein binding active tubular secretion
no effect
53
Glomerular filtration is influenced by...
protein binding
54
Active tubular secretion is influenced by...
Competitive inhibitors
55
Tubular reabsorption is influenced by...
urinary pH and flow | drug pKa
56
Drug clearance definition
describe drug elimination from body w/o identifying mechanism of processmL/min
57
T/F drug clearance considers the entire body as a single drug eliminating system
True!
58
Clearance equation
Clt = elimination rate/CP
59
What rate order is clearance?
1st order
60
Physiologic organ clearance model
- based on drug clearance through individual organs | - clearance depends on blood flow and ability of organ to eliminate drug
61
Non-Compartment clearance model
- clearance determined directly from plasma time concentration curve
62
Renal clearance (Clr)
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
Clr equation
filtration rate + secretion rate - reabsorption rate /Cp
64
Clearance <1
drug partially reabsorbed
65
Clearance >1
drug actively secreted
66
Clearance = 1
drug filtered only
67
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 _____
Cp x GFR
68
For drugs that are primarily filtered and secreted, with negligible reabsorption, thee overall excretion rate will _____ GFR
exceed
69
At low concentrations, active secretion is not saturated and the drug is excreted by _______
filtration and active secretion
70
At high concentrations, the % of drug excreted by active secretion ______ due to saturation
decreases
71
Explain the extraction ratio
fraction of a substance removed from blood flow through organ E = Cl/blood flow
72
Clearance is limited by what factor?
Q (blood flow to organ eliminating drug)
73
What is the max Q value in body?
1.5 L/min
74
As Cl increases, what happens to drug's half life?
t1/2 decreases

PharmSci ADME (4 decks)

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