Exam 3 Flashcards
(132 cards)
1
Q
Clearance in the liver is sensitive to
high extraction ratio drugs
A
Changes in blood flow
2
Q
Normal value for glomerular filtration rate
A
120-125 mL/min
3
Q
Clearances of drugs and extraction ratios depend upon:
A
Organ perfusion
Plasma protein binding
Inherent characteristics within the cells
4
Q
Normal renal arterial blood pressure
A
~100 mm Hg
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+)
6
Q
Elimination in the liver becomes __
Low extraction rate drugs
A
Rate-limited at a step other than perfusion-
Usually metabolism
7
Q
Carries blood from general circulation to liver
A
Hepatic artery
8
Q
Most common and most important phase II reaction
A
Glucuronidation and sulfate conjugation
9
Q
afferent arterioles
A
blood into the glomerular part of the nephron, Bowman’s capsule
10
Q
Heme-containing oxidative enzymes
A
Cytochromes P450
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)
12
Q
Insensitivity or decreased sensitivity of cells to drugs that ordinarily cause growth inhibition or cell death
A
Drug resistance
13
Q
Because tubules are very long
A
a lot of water reabsorbed
14
Q
Carries nutrients to the liver, accounts for 75% of blood flow to the liver
A
Portal vein
15
Q
pH of urine
A
variable, 4.5 – 8
16
Q
Drugs that may require carrier-mediated transport and specific transporters for liver drug transport
A
Polar or ionized drugs
17
Q
_____ transporters → broad substrate specificity; will bind many ionized drugs
A
Tubular
18
Q
Main mechanism of reabsorption
A
passive transcellular diffusion through the epithelial membrane of tubules
19
Q
Adjusted body weight calculation
A
IBW+[(actual body weight-IBW)x0.4]
20
Q
The region between the sinusoids and hepatocytes
A
Space of Disse
21
Q
By-products of P450 reactions
A
Reactive oxygen species (ROS)
22
Q
The cycle in which the drug is absorbed, excreted into the bile, and reabsorbed
A
Enterohepatic circulation
23
Q
Number of P450s encoded in human genome
A
57
24
Q
Renal clearance corrected for plasma protein binding
A
Extraction ratio
25
~ 175nm in diameter, 6-8% sinusoidal surface area, no basal lamina→ free passage of large molecules, explains the metabolism of tightly protein-bound xenobiotics
Sinusoidal junctions
26
Are protein bounds drugs filtered?
No, Protein-bound drugs are not filtered
27
Drugs excreted mainly m bile have MW
>500
28
Renal blood pressure fall to _______ in glomerulus
~45-60 mm Hg
29
Secretion involves _______, since these solutes more concentrated in the filtrate than in plasma
active transport
30
Glomerular filtration rate (GFR)
the volume of blood filtered by the kidneys per minute is ~125 ml/min, or ~20% of the RPF
31
Total ability of the liver to metabolize a drug in the absence of flow limitation
Intrinsic clearance
32
Kidneys receive ~ ____ L of blood per minute
1.2
33
Schwartz equation
| Children
CrCl (mL/min) = (height in cm) x (0.413) / SCr
34
Phagocytes tissue macrophages- engulf old red blood cells and foreign material
Kupffer cells
35
As filtrate moves to the collecting tubule, it is progressively _________ in solutes as a results of reabsorption of water
Concentrated
36
Renal blood flow (RBF)
volume of blood flowing through the renal vasculature per unit time:
~1.2 L/min or 1700 L/day
37
Because filtration is driven by hydrostatic pressure, the concentration of a drug (or metabolite) in the filtrate is the _____ as in plasma
same
38
Class of P450s that metabolize endogenous compounds: cholesterol and bile acids, steroids, prostaglandins, vitamins AandD, eicosanoids
Class 1
39
Liver lobes secrete
Bile acids
40
Drugs excreted in expelled air
Sulfanilamide, sulfapyridine
41
Clearance ratio =1
Drug is filtered only
42
During __________, drug is progressively removed from the bloodstream and tissues, and thus from the site of action
Elimination
43
Drug that may stimulate biliary excretion
Phenobarbital
44
Cells become resistant to drugs with different structures and mechanisms
Multiple drug resistance
45
4 phase II reactions
Glucuronide conjugation
Peptide conjunction
Methylation
Acetylation
46
Vegetable and fruit diets, including citrus fruits (high amounts of alkaline minerals: K, Ca, Mg) →
Higher pH
47
* 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
Role of Urine
48
Diets rich in protein: meat, fish, poultry and dairy products (rich in choline, P and S), also grains and cereals →
Lower pH
49
GFR controlled is by
Hydrostatic pressure
50
Consequence of the interaction of the drug, the individual, and the environment
Drug dependence
51
Cenobitic metabolizing P450 class
Class 2
52
Formed by P450 oxidation of various compounds, such as PAHs
Epoxides
53
Liver clearance may be influenced by changes in
| Low extraction ratio drugs
Plasma protein binding or cellular eliminating activity
54
Major phase II enzymes
UDP- glucuronyl transferases (UGTs)
| glutathione-S-transferases (GSTs)
55
No barrier for molecules up to
5000 MW
56
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
Type A ADRs
57
Phase I reaction
Introduces a reactive group
58
interlobar arteries
penetrate within the kidney
59
Carries oxygen to the liver, responsible for 25% of liver blood supply
Hepatic artery
60
Transferases
Transfer of group between molecules
61
maintenance of a constant blood flow despite large fluctuations in the arterial blood flow
•filtration fraction, GFR/RPF, also constant
Autoregulation
62
Processes in the nephron
Globular Filtration
Secretion
Reabsorption
63
Tubular secretion of H+:
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
3 phase I reaction examples
Oxidation
Reduction
Hydrolysis
65
Elimination in the liver becomes ___
| high extraction ratio drugs
Rate-limited by perfusion
66
Renal clearance uses what drugs as a reference?
Insulin and creatinine
67
progressive decrease in the pharmacological action of drug
Consequently of Elimination
68
Liver cells
Hepatocyte
69
Idiosyncratic adverse reactions, bizarre, cannot be predicted from the known pharmacology of the drug
Type B ADRs
70
Isomerases
Rearrangement reactions
71
Catalyze the nucleophilic attack of a water molecule on one of the two electron-deficient C of epoxide ring
Epoxide hydrolase
72
Ligases
Bond formation
73
The fraction of blood volume containing the drug that flows through the organ and is eliminated of drug per unit time
Clearance (any organ)
74
The volume of plasma flowing through the liver that is completely cleared of drug per unit time
Hepatic clearance (Clh)
75
Phase II reaction
Attaches a polar molecule
76
Basic unit of the liver
Liver lobule
77
Class of P450s that contain microsomal enzymes
Class 2
78
Rate of urine formation:
usually 60-120 mL/hr ≈ 1-2 mL/min
79
Clearance ratio >1
Drug is actively secreted
80
Mechanism of filtration
Hydrostatic pressure
81
Drugs found in sweat
Amphetamine, cocaine, morphine, ethanol
82
* Maintain homeostasis by regulating fluid and electrolyte balance
* Accomplished by making urine and adjusting its composition as needed by the body
Main function of kidneys
83
For drugs with a very high intrinsic clearance, Clh is dependent on ____, and independent of ______
Hepatic blood flow,
| protein binding
84
balance between the hydrostatic and osmotic pressure
Filtration pressure
85
Composition of the filtrate
the same as plasma, except proteins and protein-bound solutes, no different from interstitial fluid
86
Liver volume ______ by ______% in the over 60yr
Declines by 30%
87
liquid collected in Bowman’s capsule as a result of glomerular filtration; ultrafiltrate of plasma
Glomerular filtrate
88
Blood leaves the liver via
hepatic vein
89
Drugs that are readily transported from blood into hepatocytes by transcellular diffusion
Lipophillic drugs
90
Renal clearance depends upon 3 processes
1. Filtration rate
2. Secretion rate
3. Reabsorbtion rate
91
Drugs that are non restrictively extracted by the liver regardless of bound to protein or free
Propranolol, morphine, verapamil
92
Oxidoreductases
Oxidation or reduction
93
Renal plasma flow (RPF)
renal blood flow minus the volume of red blood cells; important in the rate of drug filtration at the glomerulus
94
Blood flow to an organ is _____ proportional to the arteriovenous pressure difference (perfusion pressure)
directly
95
Hydrolases
Hydrolysis of substrate
96
Cockcroft and Gault equation
CrCl (mL/min) = (140-age) x IBW (0.85 if female) / SCr x 72
97
Principal site of metabolism
Liver
98
Only ________ can diffuse through the epithelial membrane
lipophilic, uncharged molecules
99
Class of P450s that contain mitochondrial enzymes
Class 1
100
Lyases
Elimination and addition reaction
101
Drug transported to saliva from blood by
Passive trancellular diffusion of free (unbound) drug
102
Tubular secretion involves ____ of drugs from plasma to filtrate, against a concentration gradient
Active transport
103
The kidneys readily excrete drugs that are _____ and _____ in the filtrate
Water-soluble and ionized
104
Blood flow or an organ is _____ proportional to the vascular resistance
Indirectly
105
Drains bile + biliary excretion products from both lobes into the gall bladder
Bile duct
106
Endocrine functions
Secretion of renin, which regulates blood pressure
| Secretion of erythropoietin, which stimulates red blood cell production
107
For drugs with high ER, increase in intrinsic clearance →
Only moderate increase in ER and Cl, half-life not affected
108
In alkaline urine - _____ drugs excreted
Acidic
109
Diffusion of weak acids or weak bases depends on:
filtrate pH → effect on drug ionization
| partition coefficient of unionized drug
110
filtration fraction
Ratio of GFR/RPF
111
Fraction of the drug removed from the blood by the liver in one pass
Hepatic extraction ratio ( ERh)
112
network of capillaries in the Bowman’s capsule formed from branching of renal artery
Glomerulus
113
Half-life of lipophilic drugs ____ with age
Increases
114
Indicates the efficiency with which a drug is removed from the plasma
Clearance (CL)
115
For drugs with low ER, increase in intrinsic clearance →
Increase in ER and Cl, significant decrease in half-life
116
As glomerular filtrate travels down the capillaries → many ______________ back into blood using ATP
nutrients and ions actively reabsorbed
117
In acidic – _______ drugs excreted
alkaline
118
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
Ion trapping
119
Drugs that appear in saliva
Phenytoin, lithium, digoxin, salicylate
120
Major effect of tubular secretion
PH of plasma and pka of the drug
121
When cells become resistant to drugs that are chemically related or have the same mechanism of action
Cross-resistance
122
Terminal branches of the hepatic artery and portal vein fuse within the liver to form ____
Sinusoids
123
Any undesirable effect of a drug beyond its anticipated therapeutic effects occurring during clinical use
Adverse drug reactions (ADRs)
124
Factors affecting hepatic clearance
Extraction ratio of the drug
| Blood flow to the liver
125
From glomerulus, blood flows via the _____________ and into the second network of capillaries around the tubules (peritubule capillaries and vasa recti)
efferent arterioles
126
A few fruits, such as cranberries, plums, and blueberries, are slightly acid-forming →
Lower urine pH
127
After drug administration, drug concentration in plasma _ ____ due to drug elimination and removal
declines
128
Carnies blood from liver to general circulation
Hepatic vein
129
Pathways of drug elimination from the body
Excretion
| Metabolism
130
Clearance ratio <1
Drug is partially reabsorbed
131
Urinary drug excretion rate
Renal clearance, CLR
132
As filtrate travels through the tubules, water reabsorption ______ concentration of drug in filtrate compared to blood
increases
