Pharmacokinetics

Question 1

Define Bioavailability

Answer 1

Fraction of the administered dose that reaches the systemic circulation

Question 2

Define Clearance

Answer 2

The amount of plasma cleared of a solute in a given unit of time

Question 3

Define Elimination Rate Constant Ke

Answer 3

Fraction of total amount of drug eliminated per unit time

Question 4

Define fe

Answer 4

Amount of drug that is renally eliminated

Question 5

Define Volume of Distribution

Answer 5

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

Question 6

What is Css?

Answer 6

The concentration of a Drug at steady state

Question 7

How many half lives does it take to get a drug to steady state concentration in the plasma?
• what about time needed to eliminate?

Answer 7

4-5 half lives - to build to steady state and to eliminate

Question 8

What does it mean if a drug has concentration dependent activity?

Answer 8

• 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

Question 9

Why would you want to just SPACE the dosing interval for aminoglycoside therapy rather than reduce dose and administer at the same intervals?

Answer 9

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

Question 10

NOTE: Pay attention to things like nausea and vomiting when trying to figure out why a patient’s drug may not be working

Answer 10

NOTE: Pay attention to things like nausea and vomiting when trying to figure out why a patient’s drug may not be working

Question 11

What should be an important consideration related to protein loss in patients with kidney disease?

Answer 11

Determine if the drug is Protein bound or not

Question 12

How does reduced albumin affect a drug that is protein bound typically?

Answer 12

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

Question 13

Before changing up the dosing on a protein bound drug, what should you do?

Answer 13

• Use something like the Sheiner-Tozer equation to get an estimate of how much of the drug is FREE

Question 14

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?

Answer 14

• Certain drugs like like Moriphine are metabolized by the liver BUT THEN THE METABOLITES are excreted through the kidneys

Question 15

T or F: there is overall less elmination of all protein bound drugs.

Answer 15

FALSE, drugs like Penicillin are protein bound but are still excreted extremely efficiently by the proximal tubules.

Question 16

What happens if you give drug X and Y that are both excreted in the renal tubules but drug X is excreted more efficiently?

Answer 16

You will OD on drug Y because X will be eliminated from the system at the expense of maintaining levels of Y

Question 17

What are inhibitors of the organic Cation and Anion transporters in the Proximal Tubule?

Answer 17

Cation:
• Cimetidine
• Trimethoprim

Anion:
• Probenecid

Question 18

How can pH affect reabsorption?

Answer 18

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.

Question 19

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

Answer 19

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

Question 20

Cockcroft and Gault formula
• what is it?
•what factors are taken into account with it?

Answer 20

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

Question 21

T or F: Formulas used to calculate GFR do so by using lean body wt.

Answer 21

False, these formulas use Body Surface Area

Question 22

When should you look at eGFR rather than just Cockcroft and Gault for dosing?

Answer 22

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.

Question 23

T or F: eGFR is a good determinant of kidney function in acute kidney disease and dialysis patients.

Answer 23

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

Question 24

T or F: in an obese person it is most accurate to use Cockcroft and Gault in evaluation of kidney function.

Answer 24

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

Question 25

T or F: like in Fat people you should use body wt. or body SA adjusted GFR estimates when dealing with old people too.

Answer 25

True

Question 26

When should you do more than just look at serum creatinine to estimate GFR?

Answer 26

• Extremes of age (elderly, children)

* Extremes of body size (obesity, low body mass index, i.e.,