Drug Elimination & Multiple Dosing Flashcards
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
MD = CLxTCxT/F
(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