Drug Elimination & Multiple Dosing Flashcards

1
Q

Define loading dose. How is calculated?

A

large dose given initially to reach therapeutic levels quickly (followed by lower maintenance dose or infusion to sustain target concentration levels)

LD = TC x Vd/F
(depends on Vd)

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2
Q

Define steady-state concept.

A

steady-state is the maintenance of the target concentration (therapeutic range). Loading doses help reach target concentration faster, BUT it will still take 4-6 half-lives to reach steady state independent of dose)

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3
Q

List the primary pharmacokinetic parameters. How are they used to determine loading dose and maintenance dose?

A
  • clearance determines MD

- Vd determines LD

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4
Q

Define maintenance dose.

A
  • based on amount of drug cleared from the body since last administration
  • maintains steady state after target has been reached

MD = CLxTCxT/F
(depends on CL)

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5
Q

Describe the concept of repetitive dosing.

A

Typically, it takes 4-6 half-lives to reach steady state (maintaining target concentration). With continuous infusion, it takes a long time to reach target concentration and then it plateaus off. By giving repetitive doses, you reach target concentration faster.

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6
Q

Compare/Contrast elimination and intercompartmental clearance.

A

EC: irreversible drug removal from the plasma through an eliminating organ; unidirectional

IC: drug distribution between plasma and tissues (bidirectional)

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7
Q

Define first order elimination.

A
  • constant fraction of the drug is being eliminated from the body
  • constant half life
  • ex: lidocaine
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8
Q

Define zero-order elimination.

A
  • drugs eliminated primarily by metabolism
  • constant amount of the drug is being eliminated from the body
  • elimination does not change with dosage b/c metabolic pathways are saturable
  • HALF LIFE DOES NOT APPLY; it is NOT constant
  • ex: phenytoin, ethanol, aspirin, heparin, theophylline, warfarin
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9
Q

Define dose-dependent elimination.

A

For drugs that are eliminated primarily by metabolism…

- concentration > Km = zero order; C/t = Vmax

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10
Q

Define total clearance.

A

sum of clearance by all eliminating organs and tissues

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11
Q

Define elimination half life.

A

T1/2 = 0.69xVd/CL ====> k = CL/Vd

time it takes to eliminate 50% of the drug

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12
Q

What are the 2 primary pharmacokinetic factors?

A
  • Vd

- CL

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13
Q

How do you determine time it takes to reach steady state?

A

t0.90 = 3.3t0.50

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14
Q

Why do you adjust for renal insufficiency? How can you adjust?

A
  • impaired clearance of drugs eliminated by the kidneys
  • daily dose must be reduced to prevent buildup of drug and toxic concentration levels
  • adjust by reduced dose or increased dose intervals or both
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15
Q

Define creatinine clearance rate.

A

CrCL = volume of blood plasma that is cleared of creatinine/time

  • used to approximate GFR
  • measures kidney function
  • used to adjust dosage for renal failure
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16
Q

List determinants of hepatic clearance.

A
  1. hepatic blood flow - rate of drug delivery to liver
  2. plasma protein binding - fraction of drug available for clearance
  3. intrinsic clearance - hepatocellular metabolism and bile excretion
17
Q

Define restrictive hepatic clearance.

A
  • for drugs that are not extracted by the liver
  • blood flow does not matter in the equation (Q&raquo_space; fxCL)
  • CLh = fxCLint
  • aka capacity-limited
  • ex: warfarin, phenytoin
18
Q

Define non-restrictive hepatic clearance.

A
  • drugs are heavily extracted by the liver
  • blood flow matters greatly
  • aka flow-dependent
  • CLh = Q
  • conditions that reduce Q (CHF, hypotension) will reduce CL
  • ex: lidocaine, propanolol