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Pharmacokinetics > Exam 4 > Flashcards

Exam 4 Flashcards

1
Q

Blood supply to liver

A

~75% comes from hepatic vein
~25% from artery

Most others get blood from artery, liver is exception

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2
Q

Physiological factors that are used to predict drug kinetics?

A

Blood flow rate
Extent of plasma-protein binding
Metabolism by liver

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3
Q

If drugs are not eliminated or extracted by the liver, then the hepatic E value is…

A

hepatic E is 0

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4
Q

Drugs that are excreted or eliminated during a single pass through the liver, hepatic E is…

A

Hepatic E is close to 1

Propranolol, lidocaine, propoxyphene - high E but no drug has E of 1

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5
Q

Drugs with Low E but still has high fraction metabolized (100%)

A

Warfarin and tolbutamide, E is <0.01

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6
Q

E and Hepatic Cl are _____ of Drug concentration

A

Independent

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7
Q

F’ is fraction of drug that is…

A

escaping extraction by the liver

fraction of drug that exists the liver in intact form

F cant be > than F’

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8
Q

Increased Fub will….

A

increase E and Hepatic Cl

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9
Q

Increased Q will…

A

increase Hepatic Cl but less than proportionally

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10
Q

An increase in Intrinsic Clearance (Cl’int) will…

A

increase both E and Hepatic Cl

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11
Q

Low E drugs, the Hepatic clearance is limited by…

A

intrinsic Clearance (Cl’int)

Cl’int is much lower than Q

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12
Q

High E drugs, the Hepatic clearance is limited by…

A

the perfusion (Q)

Cl’int is much higher than Q

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13
Q

Hepatic Clearance of very low E drugs….

A

does not depend on Q

is the same as their intrinsic clearance

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14
Q

What is considered a low E drug?

A

E < 0.3

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15
Q

Examples of low E drugs…

A 
Antipyrine
Warfarin
Theophylline
Tolbutamide
Procainamide
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16
Q

Examples of high E drugs…

A 
Propranolol
Verapamil
Lidocaine
Propoxyphene
Morphine
Nitroglycerine
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17
Q

What is considered a high E drug?

A

E > 0.7

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18
Q

Hepatic Clearance of Very high E drugs…..

A

does not depend on intrinsic clearance

same as the liver blood flow

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19
Q

Drugs that have an E between 0.3-0.7 then….

A

considered intermediate extraction drugs with hepatic clearance that depends on both blood flow and intrinsic clearance

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20
Q

Three major mechanisms involved in urinary excretion…

A
  1. Glomerular Filtration
  2. Active tubular secretion
  3. Tubular reabsorption
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21
Q

Glomerular filtration and tubular secretion….

A

remove drugs from the blood for excretion into the urine/

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22
Q

Tubular Reabsorption takes….

A

excreted and/or filtered drug from the urine into the blood

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23
Q

Markers of GFR in clinical settings?

A

Creatine and inulin

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24
Q

How to use Nomogram to estimate Clcr

A
  1. Draw line connecting pt weight to pt age
  2. Draw 2nd line, connecting point where 1st line meets the “R” line and the patients serum creatine. Extrapolate line to the clearance line
  3. Clearance = intersection of 2nd line and clearance line
25
What will inhibit the secretion of penicillin?
Probenecid Both acidic
26
What will inhibit the secretion of procainamide?
cimetidine Both basic
27
Drugs that inhibit tubular secretion will cause....
reduced clearance and increased plasma concentrations of the drugs they are inhibiting
28
If Clr of a drug is larger than its filtration clearance then....
secretion is involved in the excretion of the drug
29
If a drug is basic, making the urine basic/acidic will cause...
basic = drug stays unionized, reabsorb inc, renal Cl dec acidic = drug ionized, reabsorb dec, renal excretion inc
30
Ways to increase rate of drug elim for overdose/toxicity
Changing urine pH increased urine flow may decrease reabsorption = inc elim
31
If Clr of drug is less than its filtration clearance, then....
reabsorption is involved in excretion
32
Most acidic drugs will bind to...
plasma albumin
33
Example of acidic drugs
``` Tolbutamide Phenytoin Ibuprofen Naproxene Warfarin ```
34
Liver disease such as cirrhosis will ____ albumin conc
reduce
35
Burns, surgery, acute viral hepatitis and renal failure will _____ albumin conc
reduce
36
dehydration and neurologic disorders will ____ albumin conc
increase
37
Drugs that reduce the affinity of albumin for drugs will...
increase the free fractions
38
Mostly basic and neutral drugs will bind to...
AAG = Alpha1-Acid Glycoprotein
39
Drugs that bind AAG include....
``` propranolol Lidocaine Verapamil Disopyramide Imipramine ```
40
Live disease such as cirrhosis will ____ plasma AAG
reduce
41
Plasma AAG concentrations will increase in...
``` trauma inflammatory disease surgery burns acute MI ```
42
Competitive displacement can ____ the affinity for AAG
reduce
43
Lipoproteins will bind....
basic and neutral drugs. **Lipophilic drugs** Cyclosporine binds extensively
44
Lipoprotein conc will change in several diseases, including....
renal failure DM Hyperlipoproteinemia Alcoholism
45
Vt for lipophilic drugs is...
total body water - blood water volume these drugs distribute both in the extracellular and intracellular spaces
46
Vt for hydrophilic drugs is...
volume of extraceluarl water - plasma water volume polar drugs do no penetrate the intracellular space
47
Drugs with very low Vss
Vss almost equal to Vb drugs don't distribute much out of the blood Can use Vss ~Vb Changes in blood or tissue binding went affect Vss significantly of these drugs
48
Drugs with very large Vss
Vss = (fub/fut)/(Vt), Vb is relatively small Changes in Fub/Fut affect value of Vss proportionally almost
49
For low E drugs, Cl formula can be written as
Fub X Cl'int
50
For high E drugs, Cl formula can be written as
Cl ~ Q
51
Change in Fub of low E drugs will affect Cl....
directly
52
change in Fub of high E drugs will affect Cl...
no effect
53
Examples of Low E drugs
Phenytoin Diazepam Warfarin Valproic Acid
54
Examples of High E drugs
TCA Verapamil Propranolol
55
Drugs with low renal E are...
affected most by changes in Fub
56
Drugs with high renal E are...
affected least by changes in Fub
57
Example of high renal E drug
Penicillins
58
Example of low renal E drug
gentamicin

Pharmacokinetics (4 decks)

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