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Pharm Exam 1 > Drug Elimination > Flashcards

Drug Elimination Flashcards

1
Q

how many doses does it take to reach steady-state?

A

4-6

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2
Q

loading dose

A
  • if a drug takes a long time to reach therapeutic levels, then a higher dose (the loading dose) may be given initially before dropping down to a lower maintenance dose
  • three variables are used to calculate loading dose= (TC*Vd)/F
  • TC= peak desired concentration of drug
  • does not affect the time to reach steady state
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3
Q

maintenance dose

A
  • dosing strategy to maintain a steady state of drug in the body
  • dose is based on replacing the amount of drug cleared from the body since the previous drug administration
  • clearance is the primary determinant for calculating the maintenance dose
  • Maintenance Dose = (CLxTCxT)/F
  • at steady state, maintenance dose replaces drug lost since previous dose
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4
Q

elimination clearance

A

-irreversible drug removal from the plasma through eliminating organs

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5
Q

intercompartmental clearance

A
  • drug distribution between plasma and tissues

- a bidirectional process

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6
Q

maintenance dosing rate is selected baed on the _______

A

expected clearance

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7
Q

steady state concentration (when not IV)

A
  • a function of dosing rate and elimination clearance

- Css= (dosing rate * F)/Clearance

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8
Q

the time to steady-state is independent of _____

A

dosage

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9
Q

fluctuations at steady state

A
  • proportional to dosage interval/half-time

- blunted by slow absorption

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10
Q

Continuous IV infusion and steady state

A
  • attained after about four half times
  • time to steady state is independent of dosage
  • Infusion rate= CL*Css
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11
Q

Clearance and continuous infusion

A

CL=Infusion rate/Css

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12
Q

first order eliminatio

A
  • the elimination rate of the drug is a constant fraction of the drug remaining in the body (and not a constant amount of drug per hour)
  • most drugs used clinically
  • monoexponential decay with a CONSTANT half life of elimination
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13
Q

zero order kinetics

A
  • drugs that are eliminated primarily by metabolism may display zero-order kinetics of elimination
  • when metabolic paths are saturated, metabolism occurs at a fixed rate so it doesn’t change in proportion to drug concentration
  • a fixed amount of drug is metabolized per unit time
  • half life isn’t constant
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14
Q

drugs that exhibit zero-order kinetics of elimination

A
  • aspirin
  • ethanol**
  • heparin
  • phenylbutazone
  • phenytoin**
  • salicylates
  • theophylline
  • tolbutamide
  • warfarin
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15
Q

dose dependent kinetics

A

-when a drug’s elimination is mediated mainly by metabolism, its elimination will tend to follow first order kinetics when concentrations are well below Km of the metabolic enzymes, but will follow zero order kinetics at doses above Km

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16
Q

elimination clearance

A
  • volume of plasma cleared of drug per unit time
  • units are mL/min or L/hr (flow)
  • can occur through the kidneys, liver, lung, etc.
17
Q

total clearance

A

-sum of all the individual and simultaneously occuring organ clearances

18
Q

Dose adjustment in renal insufficiency

A
  • impaired renal function often results in reduced clearance of drugs that are eliminated mainly by the kidney
  • daily drug dose must be reduced by the ratio of measured clearance in renal failure over expected normal average clearance
  • in renal failure, get higher troughs because of decreased clearance and thus higher peaks
19
Q

How to reduce the dosing rate

A
  • reduce the dose
  • increase the dosing interval
  • both
20
Q

Creatinine clearance

A
  • volume of blood plasma that is cleared of creatinine per unit of time and is the most commonly used measure for approximating the GFR
  • not the same as clearance of a drug and is only a measure of the function of the kidneys
21
Q

Determinants of hepatic drug clearance

A
  • hepatic blood flow (rate of drug delivery to the eliminating organ)
  • plasma protein binding (fraction of drug available for clearance)
  • intrinsic clearance (hepatocellular metabolism and/or biliary exctretion)
22
Q

restrictive hepatic clearance

A
  • drugs with low hepatic extraction
  • a change in binding or drug metabolism/excretion activity will have a greater effect on hepatic clearance than changes in liver blood flow
  • capacity limited clearance
  • ex. warfarin, phenytoin
23
Q

non-restrictive hepatic clearance

A
  • drugs with high hepatic extraction
  • hepatic clearance is sensitive to changes in liver blood flow and less sensitive to alterations in binding or intrinsic clearance
  • flow-dependent clearance
  • conditions that reduce hepatic blood flow (congestive heart failure, hypotension) will reduce hepatic clearance
24
Q

factors affecting the pharmacokinetic profile

A
  • individ variability
  • patient compliance
  • disease states
  • pharmacogenetics
  • age and gender
  • medication interactions

Pharm Exam 1 (10 decks)

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