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POM Exam 2 > Pharmacokinetics > Flashcards

Pharmacokinetics Flashcards

1
Q

pharmacokinetics

A
  • how a drug molecule moves through your body from administration to elimination
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2
Q

pharmacodynamics

A
  • how a drug molecule affects its target to produce the desired physiological effect
  • also includes toxic side effects
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3
Q

4 subprocesses of pharmacokinetics

A
  • drug absorption
  • drug distribution
  • drug metabolism
  • drug clearance
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4
Q

absorption

A
  • how does a drug get into the body
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5
Q

distribution

A
  • how does a drug get to the target site
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6
Q

metabolism

A
  • how is a drug molecule chemically altered by the body
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7
Q

clearance/elmination

A
  • how is a drug molecule removed from the body
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8
Q

how do drugs enter the body

A
  • must cross epithelial or endothelial cell layers
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9
Q

how drugs cross plasma membranes

A
  • passive diffusion
  • facilitated diffusion
  • or active transport
  • based on physical properties
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10
Q

charge of drug molecules

A
  • must be neutrally charged to cross plasma membrane by diffusion
  • hydrophobic
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11
Q

pH of environment

A
  • affects the charge state of a drug molecule

- alters its absorption

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12
Q

bioavailability

A
  • how much of the drug is absorbed
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13
Q

how drugs are distributed effectively

A
  • most reach the blood

- topical drugs are an exception

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14
Q

how oral drugs enter the body

A
  • enter GI tract and cross epithelium to interstitial space

- cross endothelium of capillaries to enter plasma (intravenous space)

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15
Q

how inhalation drugs enter the body

A
  • cross epithelial layers at alveoli
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16
Q

how topical drugs enter the body

A
  • only cross epidermis
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17
Q

how IM/SC drugs enter the body

A
  • skip through epithelial layer
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18
Q

how IV drugs enter the body

A
  • direct injection into bloodstream
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19
Q

absorption properties of the patient

A
  • surface area
  • drug transit time
  • pH of lumen
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20
Q

which has the most surface area for the most absorption

A
  • small intestine

- 25-40 m^2

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21
Q

surface area of mouth, esophageal, stomach

A

1 m^2

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22
Q

surface area of large intestine

A

2 m^2

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23
Q

drug transit time of mouth/esophagus

A
  • rapid
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24
Q

drug transit time of stomach

A
  • variable, but less rapid

- food slows transit

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25
Q

drug transit time of small intestine

A
  • slow
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26
Q

pH of mouth

A

neutral

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27
Q

pH of stomach

A

acidic

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28
Q

pH of large intestine

A

neutral

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29
Q

pH of small intestine

A

neutral

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30
Q

best place for acidic drugs

A
  • stomach
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31
Q

best place for drugs overall

A
  • small intestine
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32
Q

non-saturable processes

A
  • diffusion
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33
Q

saturable processes

A
  • facilitated diffusion

- active transport

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34
Q

what does it mean to be a saturable process?

A
  • limited by amount of transport protein present
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35
Q

weak acid drugs absorbed well in stomach

A
  • aspirin

- furosemide

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36
Q

weak base drugs absorbed well in small intestine

A
  • imipramine

- metoprolol

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37
Q

which drugs reach the general circulation at 100%

A
  • IV drugs
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38
Q

bioavailability

A
  • the fraction of a drug dose that reaches the systemic circulation
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39
Q

bioavailability of other drugs

A
  • lower than IV
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40
Q

area under curve

A
  • a measure of total drug exposure that you get by administration
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41
Q

how to calculate bioavailability

A

area under curve (drug)
___________________
area under curve (IV)

42
Q

first pass effect

A
  • drugs need to pass through liver before they pass through general circulation
    • generally concentration is reduced
  • this is due to portal circulation
43
Q

when is bioavailability of drugs measured

A
  • after the first pass effect
44
Q

oral drugs and intestinal bacteria

A
  • decrease absorption and bioavailability
45
Q

drug binding to serum proteins

A
  • affects both distribution and clearance
46
Q

volume of distribution

A
  • the distribution of a drug across the three body water compartments
  • crucial when calculating rate of drug clearance
47
Q

xenobiotics

A
  • molecule that is alien to your body

- like a drug

48
Q

where are drugs metabolized

A
  • lungs
  • liver
  • small intestines
  • kidneys
49
Q

why are drugs metabolized?

A
  • to inactivate them

- facilitate elimination via urine or feces

50
Q

ways of drug elmination

A
  • phase I then phase II
  • phase I only
  • phase II only
  • NEVER PHASE II THEN PHASE I
51
Q

Phase I

A
  • functionalization phase
  • drug converted to functionalized metabolite
  • possibly still active
  • makes easier to conjugate to in next week
52
Q

Phase II

A
  • conjugation phase
  • chemically inactivate the drug
  • increase chemical polarity (hydrophobicity) of the molecule
  • facilitate renal and hepatic clearance
53
Q

acetominophen phase I reactions

A
  • oxidation
54
Q

acetaminophen phase II reaction

A
  • glutathionation - addition of glutathione group
55
Q

types of phase I reactions

A
  • oxidation
  • reduction
  • hydrolysis
56
Q

most common phase I reaction

A
  • oxidation
57
Q

phase II reactions

A
  • glucuronidation
  • glutathione-conjugation
  • glycine-conjugation
  • sulfation
  • acetylation
  • methylation
58
Q

most common phase II reaction

A
  • glucuronidation
59
Q

oxidation/reduction catalyzed by

A
  • cytochrome P450 families
60
Q

hydrolyses catalyzed by

A
  • epoxide hydrolase families
61
Q

glucuronidation catalyzed by

A
  • UDP-glucouronosyltransferase families
62
Q

glutathione conjugation catalyzed by

A
  • glutathione-s-transferase families
63
Q

sulfation catalyzed by

A
  • sulfotransferases
64
Q

acetylation catalyzed by

A
  • N-acetyltransferases
65
Q

methylation catalyzed by

A
  • methyltransferases
66
Q

which families are responsible for Phase I metabolism of xenobiotics

A
  • CYP families 1-3
67
Q

drug metabolized via multiple mechanisms

A
  • Acetaminophen
  • APAP
  • Phase I creates the toxic intermediate
68
Q

pro-drug activated by phase I reaction

A
  • clopidogrel

- plavix (anticoagulant)

69
Q

zero-order kinetics

A
  • drug in excess. have maxed out enzymes
  • clearance rate independent of drug concentration
  • constant mg/hr
  • T1/2 decreases as concentration decreases
  • linear decrease
  • Rx rate = Vmax
70
Q

first order kinetics

A
  • enzymes in excess
  • clearance rate dependent on drug concentration
  • constant % per hour (half life curve)
  • T1/2 constant
  • most drugs eliminated at this rate
  • Rx rate < Vmax
71
Q

where do you see first order kinetics on MM curve?

A
  • on the left side before you reach Vmax
72
Q

where do you see zero order kinetics on MM curve

A
  • on right side when you’ve reached Vmax
73
Q

enterohepatic circulation

A
  • bacteria in intestines chemically reverse phase I and phase II metabolic changes of drug and turn it back to its original form
  • instead of being eliminated, drug is reabsorbed back into blood stream
  • increases biological half life of drugs
    • estradiol
    • valproic acid (anti-epileptic)
74
Q

antibiotics on enterohepatic circulation

A
  • may disrupt glut flora and block effect of EHC
75
Q

antibiotics and oral contraceptives

A
  • may increase the elimination of oral contraceptives by inhibiting EHC
  • increase rate at which birth control is metabolized and reduce efficacy of drug
  • recommend to be on a different birth control
76
Q

antibiotics that block EHC

A
  • amoxicillin
  • ampicillin
  • sulfamethoxazole
  • trimethoprin
  • tetracyline
  • metronidazole

T MASTA

77
Q

drug doses for elderly patients

A
  • reduced due to reduced Vd

- reduced hepatic and renal function

78
Q

best source for changes in dosing of drugs to elderly patients

A
  • Beers criteria for potentially inappropriate medication use in older adults
79
Q

importance of genetic polymorphisms

A
  • affect activities of various proteins involved in pharmacokinetics for a large part of the variability in drug response among individuals
80
Q

drug interactions that affect absorption of each other

A
  • Omeprazole and Cefpodoxime

- Digoxin and antibiotics

81
Q

Cefpodoxime

A
  • antibiotic

- becomes more absorbable in stomach

82
Q

Omeprazole

A
  • proton pump inhibitor to reduce stomach acid
  • increases pH of stomach
  • makes Cefpodoxime less absorbable
83
Q

Digoxin and antibiotics

A
  • antibiotics prevent degradation of digoxin by gut microflora
  • more digoxin absorbed into blood can lead to overdose and toxicity
84
Q

drug interactions that affect distribution

A
  • NSAIDS and warfarin
85
Q

warfarin use

A
  • anticoagulant

- prevent thrombotic and embolic strokes and MI

86
Q

NSAIDs use

A
  • prevent clotting

- used as analgesics

87
Q

NSAIDS and warfarin

A
  • albumin binds warfarin because it is acidic
  • NSAIDs also bind albumin at some site
  • outcompete warfarin and cause it to be free in active form in body
  • can cause serious bleeding
88
Q

drugs and CYP systems

A
  • drugs interact with each other through CYP systems

- can cause each other to be active or inactive

89
Q

omeprazole and clopidogrel

A
  • omeprazole inhibits CYP2C19 that converts clopidogrel to active form
  • reduces efficacy and increases clotting risk
90
Q

verapamil use

A
  • used for hypertension, cardiac arrhythmia, and angina
91
Q

digoxin use

A
  • used for Afib and heart failure
92
Q

verapamil and digoxin use

A
  • P-gp eliminates digoxin (transporter protein that pumps out drug molecules into urine to be eliminated)
  • Verapamil inhibits P-gp
  • too much digoxin is in the blood and you have to worry about associated toxicities
93
Q

pharmacokinetics affected by

A
  • age
  • body composition
  • health status
  • genetic profile
94
Q

how age affects absorption

A
  • reduce small intestine surface area
  • increased gastric pH
  • increase dosing?
95
Q

how age affects distribution

A
  • reduced body water content
  • increased body fat content
  • decrease dosing
96
Q

how age affects metabolism

A
  • reduce liver function

- decrease dosing

97
Q

how age affects clearance

A
  • reduce renal function

- decrease dosing

98
Q

drug transporters that are affected by genetic variation

A
  • p-glycoprotein (ABCB1)
99
Q

drug distribution affected by genetic variation

A
  • serum proteins
100
Q

drug metabolism affected by genetic variation

A
  • phase I/II enzymes
  • CYP2D6
  • CYP2C9
  • CYP2C19
101
Q

clearance transporters affected by genetic variation

A

p-glycoprotein (ABCB1)

102
Q

role of p-glycoprotein

A
  • transmembrane protein that pumps drugs out of cells
  • absorption/clearance of many drugs
  • clearance via bile
  • absorption from Gi tract
  • clearance via urine

POM Exam 2 (21 decks)

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