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PT 1 > L3 Pharmacokinetics II: Drug Elimination and Multiple Dosing > Flashcards

L3 Pharmacokinetics II: Drug Elimination and Multiple Dosing Flashcards

1
Q

Vd (volume of distribution) = ?

A

Dose/C0 (initial concentration)

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2
Q

For all drugs that obey first-order kinetics, it takes ___ half-lives to reach steady state.

A

4-6

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3
Q

Loading dose = ?

A

[Cp (peak desired) * Vd]/F

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4
Q

Why do we use loading doses?

A

They more rapidly achieve a therapeutic drug level.

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5
Q

True or false - the time to reach steady state is reduced by the loading dose.

A

False - it is not reduced.

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6
Q

Maintenance dose = ?

A

[CL * Cp * T (dosing interval)] / F

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7
Q

What is the maintenance dose?

A

The dosing strategy used to maintain a steady state of drug in the body

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8
Q

What is the primary determinant for calculating the maintenance dose?

A

Clearance

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9
Q

What is the target concentration for a maintenance dose?

A

The middle of the steady-state

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10
Q

What is irreversible drug removal from the plasma through an eliminating organ?

A

Elimination clearance

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11
Q

What is intercompartmental clearance?

A

Drug distribution between plasma and tissues (bidirectional process)

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12
Q

Maintenance dosing rate = ?

A

Rate of elimination = CLe * Cp

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13
Q

Css (steady-state concentration) = ?

A

[Dosing Rate * F]/CL

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14
Q

In steady state, the rate of drug administration = ?

A

Rate of drug elimination

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15
Q

True or false - the time to steady-state is independent of dosage.

A

True

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16
Q

Fluctuations in steady-state are proportional to ___.

A

Dosage interval/half-time

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17
Q

What blunts fluctuations in steady-state?

A

Slow absorption

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18
Q

Steady state concentration is proportional to ___.

A

Dose/dosage interval

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19
Q

Steady-state concentration is inversely related to ___.

A

CL/F

20
Q

When using a continuous infusion, steady state concentration is proportional to ___ and inversely related to ___.

A

Infusion rate; CL

21
Q

I (infusion rate) = ?

A

CL * Css

22
Q

CL (when drug administered by continuous infusion) = ?

A

I / Css

23
Q

Describe the elimination rate of the drug in first-order kinetics.

A

It is a constant fraction of the drug remaining in the body per unit time.

24
Q

First-order elimination rate = ?

A

-kC

25
Q

Most drug obey what type of kinetics?

A

First-order

26
Q

C (first-order) = ?

A

C0*e^-kt

27
Q

Drugs that are eliminated primarily by ___ may display zero-order kinetics.

A

Metabolism

28
Q

Describe the elimination rate of the drug in zero-order kinetics.

A

A fixed amount is metabolized per unit time

29
Q

Zero-order elimination rate = ?

A

dC/dt = -k

30
Q

What two main drugs display zero-order kinetics?

A

Phenytoin, ethanol

31
Q

C (zero-order) = ?

A

C0 - kt

32
Q

Describe the general principle of dose-dependent kinetics.

A

When a drug’s elimination is mediated predominantly by metabolism, its elimination will tend to follow first-order kinetics when C &laquo_space;Km of the metabolic enzymes, but will follow zero-order kinetics when C&raquo_space; Km of the metabolic enzymes.

33
Q

dC/dt = ? (no adjustments)

A

-[Vmax * C]/[Km + C]

34
Q

dC/dt = ? (first-order, C &laquo_space;Km)

A

-[Vmax * C]/Km

35
Q

dC/dt = ? (zero-order, C&raquo_space; Km)

A

-Vmax

36
Q

What is the volume of plasma cleared of drug per unit time?

A

Elimination clearance (units of flow - mL/min)

37
Q

CL total = ?

A

CL renal + CL hepatic + CL other

38
Q

Elimination half-life = ?

A

Time to eliminate 50% of the body content of the drug = (0.69Vd)/CL

39
Q

t 0.90 = ?

A

Time to reach steady state = 3.3(t 1/2)

40
Q

What is the dosing rate equation when renal failure is present?

A

Normal dosing rate * [CL renal failure/CL normal]

41
Q

How can a dosing rate by reduced in renal insufficiency?

A
  1. Reduce the dose
  2. Increase the dosing interval
  3. Both
42
Q

What is creatinine clearance rate (CrCL)?

A

The volume of blood plasma that is cleared of creatinine per unit time; approximates GFR

43
Q

CrCL = ?

A

[(140-age)(body wt. in kg)]/(72*serum [Cr] in mg/dL)

Reduce estimates by 15% in females

44
Q

What are the three determinants of hepatic drug clearance?

A
  1. Hepatic blood flow (rate of drug delivery to eliminating organ)
  2. Plasma protein binding (fraction of drug available for clearance)
  3. Intrinsic clearance (hepatocellular metabolism/biliary excretion)
45
Q

CL (hepatic) = ?

A

Q[(fCL intrinsic)/(Q + [fCL intrinsic])]

Q = liver blood flow
f = free fraction (unbound)
46
Q

CL (hepatic) when drugs have low hepatic extraction = ?

A

f * CL intrinsic

(Q&raquo_space; f* CL intrinsic)

Examples: warfarin and phenytoin

47
Q

CL (hepatic) when drugs have high hepatic extraction = ?

A

Q

Q &laquo_space;f* CLint

PT 1 (34 decks)

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