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Biopharm And Pharmacogenomics. > Exam 3 > Flashcards

Exam 3 Flashcards

1
Q

Clearance in the liver is sensitive to

high extraction ratio drugs

A

Changes in blood flow

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2
Q

Normal value for glomerular filtration rate

A

120-125 mL/min

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3
Q

Clearances of drugs and extraction ratios depend upon:

A

Organ perfusion
Plasma protein binding
Inherent characteristics within the cells

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4
Q

Normal renal arterial blood pressure

A

~100 mm Hg

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5
Q

Cells of the tubular epithelium remove certain molecules and ions (Such as______) from blood and secrete them into the filtrate within the tubules

A

(H+ and K+)

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6
Q

Elimination in the liver becomes __

Low extraction rate drugs

A

Rate-limited at a step other than perfusion-

Usually metabolism

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7
Q

Carries blood from general circulation to liver

A

Hepatic artery

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8
Q

Most common and most important phase II reaction

A

Glucuronidation and sulfate conjugation

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9
Q

afferent arterioles

A

blood into the glomerular part of the nephron, Bowman’s capsule

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10
Q

Heme-containing oxidative enzymes

A

Cytochromes P450

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11
Q

Ideal body weight calculation

A

Males=50kg+(2.3* inches more than 5ft)

Females= 45.5 kg + (2.3*inches more than 5ft)

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12
Q

Insensitivity or decreased sensitivity of cells to drugs that ordinarily cause growth inhibition or cell death

A

Drug resistance

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13
Q

Because tubules are very long

A

a lot of water reabsorbed

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14
Q

Carries nutrients to the liver, accounts for 75% of blood flow to the liver

A

Portal vein

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15
Q

pH of urine

A

variable, 4.5 – 8

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16
Q

Drugs that may require carrier-mediated transport and specific transporters for liver drug transport

A

Polar or ionized drugs

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17
Q

_____ transporters → broad substrate specificity; will bind many ionized drugs

A

Tubular

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18
Q

Main mechanism of reabsorption

A

passive transcellular diffusion through the epithelial membrane of tubules

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19
Q

Adjusted body weight calculation

A

IBW+[(actual body weight-IBW)x0.4]

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20
Q

The region between the sinusoids and hepatocytes

A

Space of Disse

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21
Q

By-products of P450 reactions

A

Reactive oxygen species (ROS)

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22
Q

The cycle in which the drug is absorbed, excreted into the bile, and reabsorbed

A

Enterohepatic circulation

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23
Q

Number of P450s encoded in human genome

A

57

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24
Q

Renal clearance corrected for plasma protein binding

A

Extraction ratio

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25
Q

~ 175nm in diameter, 6-8% sinusoidal surface area, no basal lamina→ free passage of large molecules, explains the metabolism of tightly protein-bound xenobiotics

A

Sinusoidal junctions

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26
Q

Are protein bounds drugs filtered?

A

No, Protein-bound drugs are not filtered

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27
Q

Drugs excreted mainly m bile have MW

A

> 500

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28
Q

Renal blood pressure fall to _______ in glomerulus

A

~45-60 mm Hg

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29
Q

Secretion involves _______, since these solutes more concentrated in the filtrate than in plasma

A

active transport

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30
Q

Glomerular filtration rate (GFR)

A

the volume of blood filtered by the kidneys per minute is ~125 ml/min, or ~20% of the RPF

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31
Q

Total ability of the liver to metabolize a drug in the absence of flow limitation

A

Intrinsic clearance

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32
Q

Kidneys receive ~ ____ L of blood per minute

A

1.2

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33
Q

Schwartz equation

Children

A

CrCl (mL/min) = (height in cm) x (0.413) / SCr

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34
Q

Phagocytes tissue macrophages- engulf old red blood cells and foreign material

A

Kupffer cells

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35
Q

As filtrate moves to the collecting tubule, it is progressively _________ in solutes as a results of reabsorption of water

A

Concentrated

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36
Q

Renal blood flow (RBF)

A

volume of blood flowing through the renal vasculature per unit time:
 ~1.2 L/min or 1700 L/day

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37
Q

Because filtration is driven by hydrostatic pressure, the concentration of a drug (or metabolite) in the filtrate is the _____ as in plasma

A

same

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38
Q

Class of P450s that metabolize endogenous compounds: cholesterol and bile acids, steroids, prostaglandins, vitamins AandD, eicosanoids

A

Class 1

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39
Q

Liver lobes secrete

A

Bile acids

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40
Q

Drugs excreted in expelled air

A

Sulfanilamide, sulfapyridine

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41
Q

Clearance ratio =1

A

Drug is filtered only

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42
Q

During __________, drug is progressively removed from the bloodstream and tissues, and thus from the site of action

A

Elimination

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43
Q

Drug that may stimulate biliary excretion

A

Phenobarbital

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44
Q

Cells become resistant to drugs with different structures and mechanisms

A

Multiple drug resistance

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45
Q

4 phase II reactions

A

Glucuronide conjugation
Peptide conjunction
Methylation
Acetylation

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46
Q

Vegetable and fruit diets, including citrus fruits (high amounts of alkaline minerals: K, Ca, Mg) →

A

Higher pH

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47
Q
  • Removes waste products from blood
  • Returns water and other essential substances back to blood
  • Removes normal components of blood present at greater than normal concentrations – excess water, Na+, Ca2+, etc.
  • When concentration of normal components lower than normal – reclamation increases
A

Role of Urine

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48
Q

Diets rich in protein: meat, fish, poultry and dairy products (rich in choline, P and S), also grains and cereals →

A

Lower pH

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49
Q

GFR controlled is by

A

Hydrostatic pressure

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50
Q

Consequence of the interaction of the drug, the individual, and the environment

A

Drug dependence

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51
Q

Cenobitic metabolizing P450 class

A

Class 2

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52
Q

Formed by P450 oxidation of various compounds, such as PAHs

A

Epoxides

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53
Q

Liver clearance may be influenced by changes in

Low extraction ratio drugs

A

Plasma protein binding or cellular eliminating activity

54
Q

Major phase II enzymes

A

UDP- glucuronyl transferases (UGTs)

glutathione-S-transferases (GSTs)

55
Q

No barrier for molecules up to

56
Q

Augmentation of a pharmacological action of a drug, dose-dependent, and thus readily reversible on drug withdrawal or dose reduction; account for 80% of all ADRs

A

Type A ADRs

57
Q

Phase I reaction

A

Introduces a reactive group

58
Q

interlobar arteries

A

penetrate within the kidney

59
Q

Carries oxygen to the liver, responsible for 25% of liver blood supply

A

Hepatic artery

60
Q

Transferases

A

Transfer of group between molecules

61
Q

maintenance of a constant blood flow despite large fluctuations in the arterial blood flow
•filtration fraction, GFR/RPF, also constant

A

Autoregulation

62
Q

Processes in the nephron

A

Globular Filtration
Secretion
Reabsorption

63
Q

Tubular secretion of H+:

A

 Important for control of blood pH
 pH of urine vary from 4.5-8.5 to maintain blood pH 7.3-7.4
 Usually, urine more acidic than blood

64
Q

3 phase I reaction examples

A

Oxidation
Reduction
Hydrolysis

65
Q

Elimination in the liver becomes ___

high extraction ratio drugs

A

Rate-limited by perfusion

66
Q

Renal clearance uses what drugs as a reference?

A

Insulin and creatinine

67
Q

progressive decrease in the pharmacological action of drug

A

Consequently of Elimination

68
Q

Liver cells

A

Hepatocyte

69
Q

Idiosyncratic adverse reactions, bizarre, cannot be predicted from the known pharmacology of the drug

A

Type B ADRs

70
Q

Isomerases

A

Rearrangement reactions

71
Q

Catalyze the nucleophilic attack of a water molecule on one of the two electron-deficient C of epoxide ring

A

Epoxide hydrolase

72
Q

Ligases

A

Bond formation

73
Q

The fraction of blood volume containing the drug that flows through the organ and is eliminated of drug per unit time

A

Clearance (any organ)

74
Q

The volume of plasma flowing through the liver that is completely cleared of drug per unit time

A

Hepatic clearance (Clh)

75
Q

Phase II reaction

A

Attaches a polar molecule

76
Q

Basic unit of the liver

A

Liver lobule

77
Q

Class of P450s that contain microsomal enzymes

78
Q

Rate of urine formation:

A

usually 60-120 mL/hr ≈ 1-2 mL/min

79
Q

Clearance ratio >1

A

Drug is actively secreted

80
Q

Mechanism of filtration

A

Hydrostatic pressure

81
Q

Drugs found in sweat

A

Amphetamine, cocaine, morphine, ethanol

82
Q
  • Maintain homeostasis by regulating fluid and electrolyte balance
  • Accomplished by making urine and adjusting its composition as needed by the body
A

Main function of kidneys

83
Q

For drugs with a very high intrinsic clearance, Clh is dependent on ____, and independent of ______

A

Hepatic blood flow,

protein binding

84
Q

balance between the hydrostatic and osmotic pressure

A

Filtration pressure

85
Q

Composition of the filtrate

A

the same as plasma, except proteins and protein-bound solutes, no different from interstitial fluid

86
Q

Liver volume ______ by ______% in the over 60yr

A

Declines by 30%

87
Q

liquid collected in Bowman’s capsule as a result of glomerular filtration; ultrafiltrate of plasma

A

Glomerular filtrate

88
Q

Blood leaves the liver via

A

hepatic vein

89
Q

Drugs that are readily transported from blood into hepatocytes by transcellular diffusion

A

Lipophillic drugs

90
Q

Renal clearance depends upon 3 processes

A
  1. Filtration rate
  2. Secretion rate
  3. Reabsorbtion rate
91
Q

Drugs that are non restrictively extracted by the liver regardless of bound to protein or free

A

Propranolol, morphine, verapamil

92
Q

Oxidoreductases

A

Oxidation or reduction

93
Q

Renal plasma flow (RPF)

A

renal blood flow minus the volume of red blood cells; important in the rate of drug filtration at the glomerulus

94
Q

Blood flow to an organ is _____ proportional to the arteriovenous pressure difference (perfusion pressure)

95
Q

Hydrolases

A

Hydrolysis of substrate

96
Q

Cockcroft and Gault equation

A

CrCl (mL/min) = (140-age) x IBW (0.85 if female) / SCr x 72

97
Q

Principal site of metabolism

98
Q

Only ________ can diffuse through the epithelial membrane

A

lipophilic, uncharged molecules

99
Q

Class of P450s that contain mitochondrial enzymes

100
Q

Lyases

A

Elimination and addition reaction

101
Q

Drug transported to saliva from blood by

A

Passive trancellular diffusion of free (unbound) drug

102
Q

Tubular secretion involves ____ of drugs from plasma to filtrate, against a concentration gradient

A

Active transport

103
Q

The kidneys readily excrete drugs that are _____ and _____ in the filtrate

A

Water-soluble and ionized

104
Q

Blood flow or an organ is _____ proportional to the vascular resistance

A

Indirectly

105
Q

Drains bile + biliary excretion products from both lobes into the gall bladder

106
Q

Endocrine functions

A

 Secretion of renin, which regulates blood pressure

 Secretion of erythropoietin, which stimulates red blood cell production

107
Q

For drugs with high ER, increase in intrinsic clearance →

A

Only moderate increase in ER and Cl, half-life not affected

108
Q

In alkaline urine - _____ drugs excreted

109
Q

Diffusion of weak acids or weak bases depends on:

A

 filtrate pH → effect on drug ionization

 partition coefficient of unionized drug

110
Q

filtration fraction

A

Ratio of GFR/RPF

111
Q

Fraction of the drug removed from the blood by the liver in one pass

A

Hepatic extraction ratio ( ERh)

112
Q

network of capillaries in the Bowman’s capsule formed from branching of renal artery

A

Glomerulus

113
Q

Half-life of lipophilic drugs ____ with age

114
Q

Indicates the efficiency with which a drug is removed from the plasma

A

Clearance (CL)

115
Q

For drugs with low ER, increase in intrinsic clearance →

A

Increase in ER and Cl, significant decrease in half-life

116
Q

As glomerular filtrate travels down the capillaries → many ______________ back into blood using ATP

A

nutrients and ions actively reabsorbed

117
Q

In acidic – _______ drugs excreted

118
Q

the build-up of a higher concentration of a chemical across a cell membrane due to the pKa of the chemical and difference of pH across the cell membrane

A

Ion trapping

119
Q

Drugs that appear in saliva

A

Phenytoin, lithium, digoxin, salicylate

120
Q

Major effect of tubular secretion

A

PH of plasma and pka of the drug

121
Q

When cells become resistant to drugs that are chemically related or have the same mechanism of action

A

Cross-resistance

122
Q

Terminal branches of the hepatic artery and portal vein fuse within the liver to form ____

123
Q

Any undesirable effect of a drug beyond its anticipated therapeutic effects occurring during clinical use

A

Adverse drug reactions (ADRs)

124
Q

Factors affecting hepatic clearance

A

Extraction ratio of the drug

Blood flow to the liver

125
Q

From glomerulus, blood flows via the _____________ and into the second network of capillaries around the tubules (peritubule capillaries and vasa recti)

A

efferent arterioles

126
Q

A few fruits, such as cranberries, plums, and blueberries, are slightly acid-forming →

A

Lower urine pH

127
Q

After drug administration, drug concentration in plasma _ ____ due to drug elimination and removal

128
Q

Carnies blood from liver to general circulation

A

Hepatic vein

129
Q

Pathways of drug elimination from the body

A

 Excretion

 Metabolism

130
Q

Clearance ratio <1

A

Drug is partially reabsorbed

131
Q

Urinary drug excretion rate

A

Renal clearance, CLR

132
Q

As filtrate travels through the tubules, water reabsorption ______ concentration of drug in filtrate compared to blood

Biopharm And Pharmacogenomics. (1 decks)

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