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Pharmacokinetics Flashcards

1
Q

What is pharmacokinetics?

A

The study of the kinetics of drug absorption and disposition

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2
Q

What is the equation for the concept of distribution (VD) of drugs?

A

Volume of beaker = Amount added/[Drug]

VD = A/[D]P

Where A = amount of drug in body and [D]P = concentration of plasma in blood

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3
Q

If you want to locate a specific drug in the plamsa what value would you use?

A

[D]P(target)

A(target) = VD x [D]P(target)

Where Atarget it the amount of drug in the body required to achieve [D]P(target)

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4
Q

What is the equation for loading dose?

A

LD x B = Atarget

LD = Atarget/B

LD = (VDx [D]P(target))/B

Where B is bioavailability (the fraction od administered dose absorbed from the body)

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5
Q

What is the equation best used for loading dose?

A

LD = (VD x [D]P(target))/B

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6
Q

What determines the rapid target concentration of a drug in the plasma?

A

Concentration of drug in plasma, bioavailability and the volume

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7
Q

Which will be better distributed to the body and large VD or a small VD?

A

Large

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8
Q

As VD goes up, what happens to the [D]P in tissue binding?

A

Goes down

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9
Q

How is VD obtained from the body?

A

Give bolus of drug, measure plasma levels over time, extrapolate to find plasma level at time 0

VD = amount in body at time 0/[D]P0 = DoseIV/[D]P0

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10
Q

What is the differncce between 1 compartment and 2 compartment VD?

A

VD(final) reached in minutes with 1

VD(final) reached only after delay with 2

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11
Q

What equation would you used if the drug exhibited 1-compartment behavior?

A

LD = (VD x [D]P(target))/B

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12
Q

What equation would you use for a drug that inhibits 2-compartment behavior?

A

LD = (V? x [D]P(target))/B

? = VD(aplha) or VD(beta) depending on trade offs

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13
Q

Solve for parameters of Digoxin LD. Given:

[D]P(target) = 1.5 ug/L

VD= 580 L

Oral bioavailability = 0.7

A

Oral LD = (580 L x 1.5 ug/L) /0.7

Oral LD = 1243 ug or 1.2 mg

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14
Q

What is the equation for drug clearance?

A

Cl = Rate of Drug elimination /[D]P

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15
Q

What are the units for Drug Clearance?

A

Volume/Time

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16
Q

Solve for drug clearnace. Given:

Rate of drug elimination = 10 mg/hr

[D]P = 4 mg/L

A

Cl = 10 mg/hr / 4 mg/L

Cl = 2.5 L/hr

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17
Q

How are most drug eliminated by the body?

A

First order kinetics

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18
Q

Drug clearnance is a determinant of [D]P at….

A

Steady state [D]PSS

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19
Q

When is the steady state said to exist?

A

Rate of Drug Administration (R0) = Rate of drug elimination

Input = Output

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20
Q

What is the equation for steady state?

A

[D]PSS = Rate of drug eliminiation stead state/ Cl

R0 = Rate of Drug administration steady state

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21
Q

What is the maintance dose (MD)?

A

AMount of drug taken at regular intervals

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22
Q

What is the dosing interval (DI)?

A

Time between MDs

23
Q

What is bioavailability?

A

Fraction of administered dose that is absorbed into systemic circulation

24
Q

What is the equation for rate of drug administration?

A

R0 = (B x MD) / DI

25
Q

What is the equation for drug clearance steady state?

A

[D]PSS = (B x MD) / (DI x Cl)

26
Q

What is [D]PSS dependent on?

A

The ratios of MD and DI

27
Q

What is [D]PSS a major determinant of?

A

Therapeutic response

Toxicity

28
Q

When the goal is to provide [D]P(target) how is the equation for drug clearance stead state rearranged?

A

MD/DI = ([D]P(target) x Cl) / B

29
Q

The rate of elimination most occurs in the ____ and ___.

A

Liver and kidney

30
Q

What are the rate of renal elimination and the rate of hepatic elimination?

A

ClR and ClH

31
Q

What is the equation for drug clearnance determination of full clearance?

(For liver and renal stuff)

A

Cl = ClR + ClH

32
Q

What is the rate of renal elimination due to?

A

Glomerular filtration of drug not bound to plasma proteins

Secretion into renal tubulesof acidic and basic drugs by transport systems in proximal tubule

33
Q

What is the rate of renal elimination reduced by?

A

Reabsoprtion of lipophilic drugs from renal tubule

Renal diseases that dec glomerular filtration and tubular secretion of drug

Competition between drugs for secretion by transport systems in the proximal tubule

34
Q

What is hepatic elimination due to?

A

Metabolism of drugs by liver enzymes

Secretion of drugs into bile by transport systems in the hepatocytes

35
Q

What is hepatic elimination reduced by?

A

Ionization of drugs which limits penetration of drug into hepatocytes

Competition between drigs for metabolism and/ or transport into bile

Liver disease

Genetic variation in drug metabolizing enzyme

36
Q

What is heptic elimination increased by?

A

Induction of liver enzymes by same drug, other drug and/or environmental chemicals

Genetic variation in drug metabolizing enzymes

37
Q

What equation tells the rate of drug administration?

A

MD/DI = ([D]P(target) x Cl) / B

38
Q

What is the equation for the therapeuric window?

A

TW = highest [D]P that is safe/ lowest [D]P that is therapeutically effective

39
Q

What is the maximum dosing interval (DImax)?

A

The longest dosing interval that still provides non-toxic peak plasma levels of drug while providing therapeutically effective trough plasma levels of the drug

40
Q

What is elimination t1/2?

A

Time required for drug elimination process to decrease by the amount of drug in the body by 50%

41
Q

What is the equation for maximum dosing interval?

A

DImax = 1.44 x t1/2 x ln (TW)

42
Q

Solve for the oral MD/DI for digoxin. Given:

[D]P(target) = 1.5 ug/L

Cl = 6.6 L/hr

Oral bioavailability = 0.7

A

Oral MD/DI = ([D]P(target) x Cl) / B

=(1.5 ug/L x 6.6 L/hr) / 0.7

= 14.1 ug/L

43
Q

Calculate DImax for Digoxin: Given:

DP(effect) > 0.8 ug/L

DP(toxic) > 2.5 ug/L

t1/2 = 39 hrs

A

DImax = 1.44 x t1/2 ln (TW)

= 1.44 x 39 hrs x ln (2.5/0.8)

= 64 hrs

44
Q

Calculate the convenience use for DI of 24 hours (<64)

Oral MD/DI = 14.1 ug/L

A

Oral MD/24 hrs = 14.1 ug/L

Oral MD = 14.1 ug/L x 24 hrs

= 338.4 ug

=.34 mg

45
Q

What is the equation for half life?

A

t1/2 = (0.693 x VD) / Cl

46
Q

If there is 2 compartment behavior for half life, what value should be used for distribution volume?

47
Q

What is time to steady state (tss)?

A

Time required to reach [D]PSS if the dosing regimen only involves the repeated adminstration of drug using a specific MD/DI ratio

48
Q

If you have one compartment behavior, four elimination half lives:

A

Provide 94% of [D]PSS when treatment is started

Reduce [D]P to 6% of [D]PSS when treatment stopped

49
Q

If 2-compartment behavior, four elimination half-lives:

A

Provide > or = 94% of [D]PSS when treatment is started

Reduce [D]P to < or = 6% of [D]PSS when treatment stopped

50
Q

What is the equaiton for tSS for 1 and 2 compartment behaviors?

A

tSS = 4 x t1/2

51
Q

Calculate the tSS for Digoxin. Given:

t1/2 = 39 hrs

A

tSS = 4 x t1/2

= 4 x 39

= 156 hrs

(loading doses often prescribed)

52
Q

What are the steps to designing a dose regimen?

A
  1. Decide whether LD is required (if so calculate)
  2. Determine MD/DI ratio
  3. Determine DI
53
Q

If a patient has renal disease how would you adjust the drug?

A

If eliminated by the liver don’t worry about it

  • Re-evaluate need for drug; discontinue if possible
  • Reduce dose
  • Inc dose interval
  • Switch to drug eliminated by liver
54
Q

If a pt has liver disease how would you adjust the drug?

A

If eliminated by the kidneys don’t worry about it

  • Re-evaluate need for drug; discontinue if possible
  • Reduce dose
  • Inc dose interval
  • Switch to drug eliminated by kidney

CMBM exam 4 (27 decks)

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