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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
Q

What will inhibit the secretion of penicillin?

A

Probenecid

Both acidic

26
Q

What will inhibit the secretion of procainamide?

A

cimetidine

Both basic

27
Q

Drugs that inhibit tubular secretion will cause….

A

reduced clearance and increased plasma concentrations of the drugs they are inhibiting

28
Q

If Clr of a drug is larger than its filtration clearance then….

A

secretion is involved in the excretion of the drug

29
Q

If a drug is basic, making the urine basic/acidic will cause…

A

basic = drug stays unionized, reabsorb inc, renal Cl dec

acidic = drug ionized, reabsorb dec, renal excretion inc

30
Q

Ways to increase rate of drug elim for overdose/toxicity

A

Changing urine pH

increased urine flow may decrease reabsorption = inc elim

31
Q

If Clr of drug is less than its filtration clearance, then….

A

reabsorption is involved in excretion

32
Q

Most acidic drugs will bind to…

A

plasma albumin

33
Q

Example of acidic drugs

A 
Tolbutamide
Phenytoin
Ibuprofen
Naproxene
Warfarin
34
Q

Liver disease such as cirrhosis will ____ albumin conc

A

reduce

35
Q

Burns, surgery, acute viral hepatitis and renal failure will _____ albumin conc

A

reduce

36
Q

dehydration and neurologic disorders will ____ albumin conc

A

increase

37
Q

Drugs that reduce the affinity of albumin for drugs will…

A

increase the free fractions

38
Q

Mostly basic and neutral drugs will bind to…

A

AAG = Alpha1-Acid Glycoprotein

39
Q

Drugs that bind AAG include….

A 
propranolol
Lidocaine
Verapamil
Disopyramide
Imipramine
40
Q

Live disease such as cirrhosis will ____ plasma AAG

A

reduce

41
Q

Plasma AAG concentrations will increase in…

A 
trauma
inflammatory disease
surgery
burns
acute MI
42
Q

Competitive displacement can ____ the affinity for AAG

A

reduce

43
Q

Lipoproteins will bind….

A

basic and neutral drugs. Lipophilic drugs

Cyclosporine binds extensively

44
Q

Lipoprotein conc will change in several diseases, including….

A

renal failure
DM
Hyperlipoproteinemia
Alcoholism

45
Q

Vt for lipophilic drugs is…

A

total body water - blood water volume

these drugs distribute both in the extracellular and intracellular spaces

46
Q

Vt for hydrophilic drugs is…

A

volume of extraceluarl water - plasma water volume

polar drugs do no penetrate the intracellular space

47
Q

Drugs with very low Vss

A

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
Q

Drugs with very large Vss

A

Vss = (fub/fut)/(Vt), Vb is relatively small

Changes in Fub/Fut affect value of Vss proportionally almost

49
Q

For low E drugs, Cl formula can be written as

A

Fub X Cl’int

50
Q

For high E drugs, Cl formula can be written as

A

Cl ~ Q

51
Q

Change in Fub of low E drugs will affect Cl….

A

directly

52
Q

change in Fub of high E drugs will affect Cl…

A

no effect

53
Q

Examples of Low E drugs

A

Phenytoin
Diazepam
Warfarin
Valproic Acid

54
Q

Examples of High E drugs

A

TCA
Verapamil
Propranolol

55
Q

Drugs with low renal E are…

A

affected most by changes in Fub

56
Q

Drugs with high renal E are…

A

affected least by changes in Fub

57
Q

Example of high renal E drug

A

Penicillins

58
Q

Example of low renal E drug

A

gentamicin

Pharmacokinetics (4 decks)

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