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Pharmacokinetics Flashcards

1
Q

The volume of distrubution describes the relationship between the ____ of a dose and the ___

A

Administered
Plasma concentration that results

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2
Q

Volume of distrubution assumes which 2 things?

A

Drug distributes instantaneously (full equilibration occurs at time 0)

The drug is not subject to biotransformation or elimination before it fully distributes

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3
Q

When is a drug in its most concentrated form?

A

BEFORE we administer it. As soon as it gets it the blood stream it becomes dilute.

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4
Q

How many L of water are in a 70 kg man?

A

42

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5
Q

How much of total body water is intracellular and extracellular?

A

I: 28 L
E: 14 L

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6
Q

Of extracellular fluid, how much is interstitial fluid and how much is plasma volume?

A

Interstitial: 10 L
Plasma: 4 L

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7
Q

A drug with a volume of distribution that exceeds total body water is assumed to be hydrophilic or lipophilic.

A

Hydrophillic. It distributes into the total body water as well as into the fat.

Ex: Propofol distributes into the body fat, so it has a large Vd.

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8
Q

A drug with a Vd that is less than TBW is assumed to be hydrophilic or lipohillic?

A

Hydrophilic

It distributes into some or all of the body water, but it does not distribute into fat

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9
Q

Do drugs that are lipophillic with a larger Vd require a higher or lower dose to achieve a given plasma concentration?

A

Higher

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10
Q

Vd equation

A

Administered dose / desired plasma concentration

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11
Q

Loading dose equation

A

Volume of distribution

x

Desired Plasma Concentration /
Bioavailaibility

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12
Q

Is clearance directly or inversely proportional to blood flow to cleaning organ?

A

Directly

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13
Q

Is clearance directly or inversely proportional to the extraction ratio?

A

Directly

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14
Q

Is clearance directly or inversely proportional to the drug dose?

A

Directly

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15
Q

Is clearance directly or inversely proportional to half life?

A

inversely

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16
Q

Is clearance directly or inversely proportional to drug concentration in the central compartment?

A

Inversely

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17
Q

What is the rate constant k12?

A

Drug transfer from the central to the peripheral compartment

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18
Q

What is the rate constant k21?

A

Drug transfer from the peripheral to the central compartment

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19
Q

What is ke?

A

Rate constant for drug elimination from the body

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20
Q

What is elimination half life vs elimination half time?

A

Life: Time it takes for 50% of drug to be removed from the BODY during elimination phase

Time: Time is takes for 50% of drug to be removed from the PLASMA during elimination

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21
Q

What is context sensitive half time?

A

Time it takes for plasma concentration to decline by 50% after an INFUSION is stopped.

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22
Q

What happens to context sensitive half time the longer you have the patient on a an opioid drip?

A

It increases in all of the drugs except for Remifentanil

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23
Q

Most drugs are strong or weak acids or bases?

A

Weak acids or bases

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24
Q

Ionization is dependent on which 2 factors?

A

The pKa of the drug
The pH of the solution

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25
A drugs pKa equals the pH where 50% of the drug is _ and 50% is _
Ionized Nonionized
26
A weak acid is paired with a + ion such as:
Na, Ca ++, Mg ++ Ex: Sodium thiopental
27
A weak base is paired with a negative ion, such as:
Cl- or Sulfate- Ex: Lidocaine hydrochloride
28
Describe fetal ion trapping using Lidocaine as an example:
pKa of Lidocaine is 7.9 pH of mama is 7.4 Close to 50% of drug can cross the lipid bilayer into the placenta Baby circulation is more acidic therefore when Lidocaine crosses over less drug can get back over to mom
29
Describe how maternal alkalosis would make fetal ion trapping better or worse
Mom's pH is closer to pkA of Lidocaine. More drug can cross the placenta which means more drug cannot cross back over
30
Neuraxial drug that is MOST likely to undergo fetal ion trapping?
Lipdocaine
31
Neuraxial drug that is LEAST likely to undergo fetal ion trapping?
Chloroprocaine Due to a high pKa
32
Where are plasma proteins made?
Liver
33
What is the most plentiful plasma protein?
Albumin
34
What charge does Albumin carry?
-
35
Albumin primarily binds to what type of charged drugs?
+
36
What charge is alpha 1 glycoprotein? What type of charged drugs does it usually bind to?
+ -
37
Which 2 populations have decreased alpha 1 gylcoproteins?
Neonates Pregnancy
38
What is beta-globulin? What do you need to know about it?
A plasma protein Binds with BASIC drugs
39
How does renal failure lead to decreased plasma protein?
Increased protein excretion
40
What is zero order kinetics?
Constant amount of drug is eliminated per time (There is ZERO difference in how much drug is eliminated per time)
41
How can you think about zero order kinetics in relation to a bus?
A bus can only pick up so many people at a time, it can be over saturated if more people are waiting than fit. The people who do not fit will have to wait until it drops off and comes back around.
42
What is first order kinetics?
A constant fraction of the drug is eliminated per time Keep halving the amount of drug (think 1/2 life)
43
Does saturated enzymes represent zero or first order kinetics?
Zero
44
Most drugs follow zero or first order kinetics?
First
45
Which specific drugs follow first order kinetics?
aspirin phenytoin alcohol warfarin heparin theophylline
46
Metabolism of drugs primarily occurs in the liver but can also take place in the blood by which mechanisms?
Hoffman elimination Hydrolysis reactions catalyzed by non-specific plasma esterases and pseudocholinesterases
47
Drugs should be transformed into water soluble or lipid soluble materials to prepare for excretion?
Water and ionized and inactive
48
Is Propofol or Fospropofol a prodrug? Metabolized by? What is the active metabolite?
Fospropofol Alkaline phosphates
49
What are the 3 main phases of metabolism?
1 Modification 2 Conjugation 3 Elimination
50
What happens in the modification phase of metabolism?
Increase polarity of the drug so it may be eliminated in the urine
51
What happens in the conjugation phase of metabolism?
Highly polar water soluble substrate is added to molecule to get it ready for excretion
52
What happens in the elimination phase of metabolism?
ATP is needed for carrier proteins to transport inactive drug across cell membranes. These are in the kidneys, liver, GI tract
53
What are the 3 types of phase 1 reactions?
Oxidation: adds oxygen to a molecule Reduction: adds electrons Hydrolysis: adds water to split compound apart
54
What is enterohepatic circulation?
Conjugated compounds excreted into the bil that become reactivated in the intestine and are reabsorbed into into the blood
55
what is the extraction ratio?
Measure of how much drug is delivered to the clearing organ vs how much drug is eliminated by the organn.
56
What does an extraction ratio of 1.0 mean?
100% of the drug that gets delivered to the clearing organ is removed
57
What does an extraction ratio of 0.5 mean?
50% of the drug that gets delivered to the clearing drug gets removed
58
For a drug with a high hepatic extraction ratio (> 0.7), clearance is dependent on ___
Liver blood flow
59
For a drug with a low hepatic extraction ratio (<0.3), clearance is dependent on__
capacity The ability of the liver to extract the drug from the blood
60
What is first pass metabolism?
When a drug is taken orally, after it is absorbed in GI tract it goes to to the liver where a portion of it is metabolized before the biophase *This is why oral doses are higher than IV
61
Which 2 drugs undergo enterohepatic circulation?
Diazepam Warfarin
62
Where are p450 enzymes located?
in the smooth endoplasmic reticulum of the hepatocyte Also located in lung, kidneys, skin, adrenal gland, GI tract
63
What is the most important CYP450 which metabolizes 50% of the drugs we administer?
CYP3A4
64
Is Tobacco smoke an example of an enzyme inducer or inhibitor?
Inducer
65
Is grapefruit juice an example of an enzyme inducer or inhibitor?
Inhibitor
66
Are barbiturates an example of an enzyme inducer or inhibitor?
Inducer
67
Is Cimetidine an example of an enzyme inducer or inhibitor?
Inhibitor
68
Is Alcohol an example of an enzyme inducer or inhibitor?
Inducer
69
Is Omeprazole an example of an enzyme inducer or inhibitor?
Inhibitor
70
Is Phenytoin an example of an enzyme inducer or inhibitor?
Inducer
71
Is Rifampin example of an enzyme inducer or inhibitor?
Inducer
72
Is Carbamazepine an example of an enzyme inducer or inhibitor?
Inducer
73
Is Isoniazid an example of an enzyme inducer or inhibitor?
Inhibitor
74
Are SSRIs an example of an enzyme inducer or inhibitor?
Inhibitor
75
Is Erythromycin an example of an enzyme inducer or inhibitor?
Inhibitor
76
Is Ketoconazole example of an enzyme inducer or inhibitor?
Inhibitor
77
Is St Johns Wort an example of an enzyme inducer or inhibitor?
Inducer
78
Is Tamoxifen an example of an enzyme inducer or inhibitor?
Inducer
79
Are hydrophilic drugs excreted changed or unchanged?
Unchanged because they are already polar so they can get into the urine easily!
80
Acidic urine favors reabsorption of acidic or basic drugs?
Acidic
81
Acidic urine favors excretion of acidic or basic drugs?
Basic
82
Basic urine favors reabsorption of acidic or basic drugs?
Basic drugs
83
Basic urine favors excretion of basic or acidic urine?
Acidic
84
What can you give the pt to alter urine pH and acidify the urine? This helps eliminate basic drugs
Cranberry juice Ammonium chloride
85
What can you give the pt to alter urine pH and alkalize the urine? This helps eliminate acidic drugs
Na bicarb Acetazolamide
86
Hydrolysis uses water to cleave an __ linkage
ester
87
Do plasma enzymes undergo enzyme induction like hepatic enzymes?
No
88
Is Sch metabolized by pseudocholinesterase, nonspecific esterase, alkaline phosphate, or Hofmann elimination?
PChe
89
Is Mivacurium metabolized by pseudocholinesterase, nonspecific esterase, alkaline phosphate, or Hofmann elimination?
PChe
90
Are esters metabolized by pseudocholinesterase, nonspecific esterase, alkaline phosphate, or Hofmann elimination?
PChe
91
Is Remifentanil metabolized by pseudocholinesterase, nonspecific esterase, alkaline phosphate, or Hofmann elimination?
nonspecific esterases
92
Is Remimazolam metabolized by pseudocholinesterase, nonspecific esterase, alkaline phosphate, or Hofmann elimination?
nonspecific esterases
93
Is Esmolol metabolized by pseudocholinesterase, nonspecific esterase, alkaline phosphate, or Hofmann elimination?
nonspecific (RBC)
94
Is Etomidate metabolized by pseudocholinesterase, nonspecific esterase, alkaline phosphate, or Hofmann elimination?
Nonspecific esterases + hepatic
95
Is Atracurium metabolized by pseudocholinesterase, nonspecific esterase, alkaline phosphate, or Hofmann elimination?
Tissue esterases + Hofmann
96
Is Clevidipine metabolized by pseudocholinesterase, nonspecific esterase, alkaline phosphate, or Hofmann elimination?
Nonspecific esterases
97
Is Fospropofol metabolized by pseudocholinesterase, nonspecific esterase, alkaline phosphate, or Hofmann elimination?
alkaline phosphatase
98
Is Cisatracurium metabolized by pseudocholinesterase, nonspecific esterase, alkaline phosphate, or Hofmann elimination?
Hofmann
99
Is Atracurium metabolized by pseudocholinesterase, nonspecific esterase, alkaline phosphate, or Hofmann elimination?
Hofmann + Nonspecific esterases

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