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MCM Test 4 > B2.070 Pharmacokinetics: Relationships Among Dose, Exposure, and Effects > Flashcards

B2.070 Pharmacokinetics: Relationships Among Dose, Exposure, and Effects Flashcards

1
Q

therapeutic index

A

difference between therapeutic and toxic ranges

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2
Q

pharmacodynamics

A

effects of the administered drug
desired = efficacy
undesired = toxicity

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3
Q

pharmacokinetics

A

getting the drug to the right place in the right amount

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4
Q

components of pharmacokinetics

A

absorption
distribution
metabolism
excretion

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5
Q

absorption

A

how a drug gains entry into systemic circulation

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6
Q

passive diffusion

A

direct passage through lipid bilayers of cell membrane
driven by concentration gradient
most common way for drugs to cross cell membranes
smaller, less polar molecules

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7
Q

carrier mediated transport

A

transporters facilitate movement
structural selectivity
competition by similar molecules
saturable

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8
Q

facilitated diffusion

A

a type of carrier mediated transport
facilitates passage of polar or charged molecules
does NOT require energy
moves DOWN gradient

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9
Q

active transport

A

energy dependent carrier mediated transport
transport coupled to ATP hydrolysis (primary) or co transport substrate down a gradient (secondary)
can move AGAINST gradient
most rapid

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10
Q

important sites of active transport

A 
enterocytes
hepatocytes
neuronal membranes
renal tubular cells
blood brain barrier
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11
Q

absorption of APAP

A

passive diffusion
max plasma concentrations at 0.5-1 hr
F = 0.7-0.9

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12
Q

blood

A

very large molecules

highly charged molecules

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13
Q

extracellular water

A

large
very polar
water soluble

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14
Q

total body water

A

smaller
water soluble
*acetaminophen

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15
Q

adipose tissue

A

lipid soluble

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16
Q

bone and teeth

A

ions

chelators

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17
Q

other tissues

A

specific uptake mechanisms or binding proteins lead to drug accumulation

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18
Q

apparent volume of distribution

A

the compartment where a drug appears to distribute

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19
Q

C0

A

extrapolated concentration of drug in plasma at time 0 after equilibration

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20
Q

Vd

A

amount of drug/C0

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21
Q

list in order of smallest to largest Vd: ECF, total body water, plasma water, tissue conc

A

plasma
ECF
total body water
tissue concentration

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22
Q

what factors influence distributions

A

gender
age
body fat
edema

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23
Q

what does Vd really represent?

A

relative distribution between plasma and the rest of the body
Amt = Vd * C0
Amt = (VpCp)+(VaCa)+(Vb*Cb)

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24
Q

what does a large Vd indicate?

A

high drug concentrations in one or more tissues

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25
Q

why is Vd qualitatively important in clinical use?

A

indicates ration of plasma concentrations to concentrations in tissues

26
Q

why is Vd quantitatively important in clinical use?

A

allows calculations of total amount of drug in body
supports dose determination to achieve a target concentration
key determinant of half life
*more useful than qualitative

27
Q

primary parameters

A

clearance and Vd

inherent properties

28
Q

clearance

A

primary parameter for elimination (metabolism + excretion)

29
Q

secondary parameters

A

half life

elimination rate constant

30
Q

Kel

A

CL/Vd

31
Q

t0.5

A

0.693*Vd/CL

32
Q

amt of drug in body at any time

A

Vd*plasma concentration

33
Q

APAP Vd

A

0.7 L/kg

total body water

34
Q

metabolism (biotransformation)

A

many drugs are hydrophobic, but efficient excretion requires water solubility
metabolism increases water solubility and excretion

35
Q

phase 1 metabolism

A

introduce/unmask a functional group
relatively few atoms involved
oxidation, reduction, or hydrolysis

36
Q

phase 2 metabolism

A

synthetic reactions
addition of molecules
require specific functional groups

37
Q

do drugs always undergo both phase 1 & 2 metabolism?

A

no, can do either, both, or neither

38
Q

what are 2 different outcomes of phase 1 metabolism?

A
  1. drug metabolite w modified activity produced

2. inactive drug metabolite produced

39
Q

types of phase 2 metabolism

A 
water soluble:
-glucuronidation
-sulfate conjugation
-glycine conjugation
lipid soluble:
-acetylation
-methylation
detoxification:
-glutathione conjugation
40
Q

dominant phase 1 metabolic enzymes

A 
CYP family (cytochrome p450)
high activities in enterocytes and liver contribute to first-pass effect
41
Q

dominant phase 2 metabolic enzymes

A

UGTs
SULTs
NATs

42
Q

what are the 3 metabolic pathways of APAP

A

sulfation catalyzed by SULTs
glucuronidation catalyzed by UGTs
oxidation catalyzed by CYP2E1 + conjugation of oxidation product catalyzed by GSTs

43
Q

what transporters are involved in APAP metabolism

A

no transporters for APAP
no transporters for glutathione conjugate and metabolites of glutathione conjugate
ATP driven active transport for secretion of glucuronide and sulfate conjugates from hepatocyte into bile or blood

44
Q

excretion

A

how xenobiotics or their metabolites are eliminated from the body

45
Q

amount excreted by any process per unit time is proportional to…

A

rate of elimination for that process

concentration of drug in plasma

46
Q

drug concentration in plasma is inversely proportional to….

A

volume of distribution

  • larger volumes eliminated slower
  • lower volumes eliminated faster
47
Q

renal excretion

A

generally smaller MW
favored by high aqueous solubility
excretion by active and passive processes

48
Q

hepatic/biliary excretion

A

generally larger MW
less polar environment
excretion by active and passive processes

49
Q

excretion of APAP

A

APAP excreted in urine
glutathione conjugate is metabolized and excreted in urine
glucuronide and sulfate conjugates mostly excreted in urine, with lesser amount in feces

50
Q

elimination rate (mg/hr)

A

CL (L/hr) * C (mg/L)

51
Q

what is one way to think about clearance?

A

all drug being taken out of a set amount of plasma in a set amount of time
-volume of plasma cleared of drug per unit time

52
Q

total body clearance…

A

sum of hepatic and renal clearance

53
Q

first order kinetics

A 
absorption rate= kabs[drug]
distribution rate=kdis [drug]
metabolism rate=kmet [drug]
excretion rate=kexc [drug]
-parameters proportional to concentration of drug
54
Q

zero order kinetics

A

elimination rate = k

no proportionality, constant over all concentrations

55
Q

rate limiting part of first order kinetics

A

drug concentrations

56
Q

how do drug concentrations change in first order kinetics?

A

by some constant fraction per unit time

57
Q

half life of first order kinetics

A

constant (independent of dose)
dose-independent pharmacokinetics
log plasma conc. vs. time is straight line

58
Q

catalyzed or facilitated processes are….

A

saturable

59
Q

at low concentrations or a catalyzed/facilitated process

A 
first order kinetics
rates proportional to dose
Vd constant
clearance constant
half life constant
60
Q

at saturating drug concentrations of a catalyzed/facilitated process

A 
zero order kinetics
rates are constant regardless of dose
Vd may vary
clearance may vary
half life varies

MCM Test 4 (19 decks)

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