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Flashcards in Drug Elimination & Multiple Dosing Deck (18):

Define loading dose. How is calculated?

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)


Define steady-state concept.

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)


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

- clearance determines MD
- Vd determines LD


Define maintenance dose.

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

(depends on CL)


Describe the concept of repetitive dosing.

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.


Compare/Contrast elimination and intercompartmental clearance.

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

IC: drug distribution between plasma and tissues (bidirectional)


Define first order elimination.

- constant fraction of the drug is being eliminated from the body
- constant half life
- ex: lidocaine


Define zero-order elimination.

- 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


Define dose-dependent elimination.

For drugs that are eliminated primarily by metabolism...
- concentration > Km = zero order; C/t = Vmax


Define total clearance.

sum of clearance by all eliminating organs and tissues


Define elimination half life.

T1/2 = 0.69xVd/CL ====> k = CL/Vd
time it takes to eliminate 50% of the drug


What are the 2 primary pharmacokinetic factors?

- Vd
- CL


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

t0.90 = 3.3t0.50


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

- 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


Define creatinine clearance rate.

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


List determinants of hepatic clearance.

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


Define restrictive hepatic clearance.

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


Define non-restrictive hepatic clearance.

- 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