Pharmacokinetics Flashcards
Define Bioavailability
Fraction of the administered dose that reaches the systemic circulation
Define Clearance
The amount of plasma cleared of a solute in a given unit of time
Define Elimination Rate Constant Ke
Fraction of total amount of drug eliminated per unit time
Define fe
Amount of drug that is renally eliminated
Define Volume of Distribution
Theoretical volume necessary to account for the total amount of drug if it were present throughout the body at the same concentration as the plasma
What is Css?
The concentration of a Drug at steady state
How many half lives does it take to get a drug to steady state concentration in the plasma?
• what about time needed to eliminate?
4-5 half lives - to build to steady state and to eliminate
What does it mean if a drug has concentration dependent activity?
• It means we need to achieve a target concentration for the drug to be effective, but it doesn’t have to stay there for prolonged periods of time e.g. AMINOGLYCOSIDES
Why would you want to just SPACE the dosing interval for aminoglycoside therapy rather than reduce dose and administer at the same intervals?
SPACE:
• if you space wider the Troughs you fall below the dangerous plasma concentration
LOWER DOSE:
• if you lower dose then you will either fall below the effective concentration (bad when you’re using a concentration dependent drug)
OR
• you will persistently stay close to the toxic concentration
NOTE: Pay attention to things like nausea and vomiting when trying to figure out why a patient’s drug may not be working
NOTE: Pay attention to things like nausea and vomiting when trying to figure out why a patient’s drug may not be working
What should be an important consideration related to protein loss in patients with kidney disease?
Determine if the drug is Protein bound or not
How does reduced albumin affect a drug that is protein bound typically?
Reduce Albumin:
• Drugs that are protein bound will INCREASE their free/ACTIVE concentration in the serum => this may lead to increased activity
• Unless drug is reliant on protein for appropriate delivery to tissue
Before changing up the dosing on a protein bound drug, what should you do?
• Use something like the Sheiner-Tozer equation to get an estimate of how much of the drug is FREE
Suppose you start administering a drug that is Hepatically eliminated with low fe (kidney excretion) to a patient with good liver function, but days later the patient starts to show signs of toxicity. What is a possible explanation?
• Certain drugs like like Moriphine are metabolized by the liver BUT THEN THE METABOLITES are excreted through the kidneys
T or F: there is overall less elmination of all protein bound drugs.
FALSE, drugs like Penicillin are protein bound but are still excreted extremely efficiently by the proximal tubules.
What happens if you give drug X and Y that are both excreted in the renal tubules but drug X is excreted more efficiently?
You will OD on drug Y because X will be eliminated from the system at the expense of maintaining levels of Y
What are inhibitors of the organic Cation and Anion transporters in the Proximal Tubule?
Cation:
• Cimetidine
• Trimethoprim
Anion:
• Probenecid
How can pH affect reabsorption?
Reabsorption of most drugs is passive, thus Uncharged, Lipophilic molecules are the most readily absorbed
• Changing pH can have huge effects on ADME - SOOOO watch out for acidotic/alkalotic pts. etc.
What would the following values for clearance tell you about absorption and secretion of the drug?
• CL = 1.0
•CL greater than 1.0
• CL less than 1.0
CL = 1.0 => reabsorption = secretion, or there is neither
CL greater than 1.0 => drug is SECRETED more than absorbed
CL less than 1.0 => drug is ABSORBED more than secreted
Cockcroft and Gault formula
• what is it?
•what factors are taken into account with it?
C and G
• tells you creatinine clearance
• this is the most frequently used measure of GFR
• takes into account Age, Serum, Creatinine, Gender, and Weight
T or F: Formulas used to calculate GFR do so by using lean body wt.
False, these formulas use Body Surface Area
When should you look at eGFR rather than just Cockcroft and Gault for dosing?
Where precision is required for dosing (due to narrow therapeutic or toxic range) and/or estimates may be unreliable (e.g., due to low muscle mass), recommend methods based upon cystatin C or direct measurement of GFR.
T or F: eGFR is a good determinant of kidney function in acute kidney disease and dialysis patients.
FALSE, use of eGFR in pts. with ACUTE kidney disease and dialysis pts. represents the misuse of eGFR
***DO NOT USE eGFR in pts. with unstable kidney function
T or F: in an obese person it is most accurate to use Cockcroft and Gault in evaluation of kidney function.
FALSE, function will be false elevate because what you really need to be considering is lean body mass towards inc. creatinine
YOU SHOULD USE WT. or BSA adjusted formulas instead
T or F: like in Fat people you should use body wt. or body SA adjusted GFR estimates when dealing with old people too.
True
When should you do more than just look at serum creatinine to estimate GFR?
- Extremes of age (elderly, children)
* Extremes of body size (obesity, low body mass index, i.e.,
