3 Medical Mathematics: Pharmacokinetics (not done)

Question 1

Dosage regimen

Answer 1

Dosage
Route of administration
Frequency
Duration of administration

Question 2

Optimum dosage regimen

Answer 2

Effective
Nontoxic
Without prolonged drug residues in tissues of food animals

Question 3

Rate of absorption Measured by what?

Answer 3

Time

Question 4

Extent of absorption Measured by what?

Answer 4

systemic bioavailability (F%)

Question 5

Rate of absorption

Is the time to peak plasma concentration

Answer 5

.

Question 6

What is Systemic bioavailability?

Answer 6

is the fraction of the dose which reaches the systemic circulation intact

Question 7

Systemic bioavailability formula

Answer 7

Systemic bioavailability (F%) = AUC extravascular X 100 / AUC IV

Question 8

What is AUC?

Answer 8

Area under the plasma concentration-time curve

Question 9

Compartment refers to what?

Answer 9

to those tissues and organs for which the rates of uptake and subsequent clearance of a drug are similar.
One-compartment model
All tissues and organs which the drug penetrates behave as if they were in ready equilibrium with the blood.

Question 10

Rate of distribution is Estimated by what?

Answer 10

the distribution phase half-time (t1/2) in the two-compartment model

Question 11

Extent of distribution is Measured by what?

Answer 11

the apparent volume of distribution (Vd)

Question 12

What is Apparent volume of distribution (Vd)?

Answer 12

the volume of fluid which would be required to contain the amount of the drug in the body if it were uniformly distributed, and the concentration in that fluid was equal to the concentration in the plasma

Question 13

Apparent volume of distribution (Vd) formula

Answer 13

Vd (L/kg) = amount of drug in the body (D) / plasma drug concentration (Cp)

Question 14

The amount of drug in the body = the dose IV

For IV the Vd (L/kg) = Dose (D) (mg/kg) / Cp (mg/L)

Answer 14

.

Question 15

For extravascular the Vd (L/kg) = D (mg/kg) X F% / Cp (mg/L)

Answer 15

.

Question 16

Clinically when:

Vd < 1L/kg

Answer 16

The drug has a limited distribution (tends to stay in plasma)

Question 17

Clinically when:

Vd = 1L/kg

Answer 17

The drug has a wide distribution

Question 18

Clinically when:

Vd > 1L/kg

Answer 18

The drug has a very wide distribution

Question 19

Elimination is measure by what?

Answer 19

Measured by half-life (t1/2) or total body clearance (CLB)

Question 20

What is Half-life (t1/2)?

Answer 20

is the time required for the body to eliminate one-half of the drug it contains

Question 21

What is First-order kinetics?

Answer 21

Elimination of most drugs follows first-order kinetics.
First-order kinetics means that the rate of removal of drug from the plasma is proportional to the concentration present at a given time (a constant percent of drug is eliminated per unit time).

Question 22

Few drugs such as aspirin in cats and phenylbutazone in dogs and horses follow what?

Answer 22

zero-order kinetics

Question 23

What is zero-order kinetics?

Answer 23

the rate of elimination remains constant regardless of the amount of drug in the body (a constant amount of drug is eliminated per unit time)

Question 24

The half-life determines what?

Answer 24

the rate at which plasma concentration of a drug rises during constant IV infusion to attain a steady-state concentration

Question 25

What is Steady-state plasma concentration or plateau (Cp (SS))?

Answer 25

Is the plasma concentration of drug when the maintenance rate of drug administration is equal to the rate of elimination

Question 26

After four half-lives, the plasma concentration is what?

Answer 26

93.75% of the eventual steady-state plasma concentration (or 90% of the steady-state concentration is achieved in 3.3 t1/2)

Question 27

Acceptable residue of a pesticide in cow’s milk is 5 ppb. Average concentration of this pesticide in milk from a herd inadvertently exposed to this pesticide is 80 ppb. The half-life of elimination in milk is 5 days. How long would you recommend the milk from this herd to be withheld assuming that elimination follows first-order kinetics? a. 10 days b. 15 days c. 20 days d. 25 days e. 30 days

Answer 27

c. 20 days

Question 28

What is Total body clearance (ClB)?

Answer 28

is the rate of drug elimination from the body, by all routes, relative to the concentration of drug in plasma. CLB = CLr + CLnr

Question 29

What is Plasma clearance (CLp)?

Answer 29

the volume of plasma cleared of the drug per unit time (mL/min.).

Question 30

Plasma clearance (CLp) formula

Answer 30

Plasma clearance (CLp) = rate of elimination (mg/min) / plasma drug concentration (mg/mL) The rate of elimination (mg/min) = urine flow (mL/min) X concentration of drug in urine (mg/mL)

Question 31

Calculation of half-life

Answer 31

``` CLB = Vd X (k) / T1/2 CLB = 0.693 X Vd / T1/2 T1/2 = 0.693 X Vd / CLB ```

Question 32

What is the Extraction ratio?

Answer 32

``` Is the fraction of the drug removed from the perfusing blood by an organ Extraction ratio (E) = CA - CV / CA CA = the concentration of drug in arterial blood entering the organ CV = the concentration of drug in venous blood leaving the organ Clorgan = Q X E Q = blood flow to the organ E = Extraction ratio ```

Question 33

examples of drugs that have high hepatic extraction ratio

Answer 33

Lidocaine, propranolol, diazepam and nitroglycerin

Question 34

Calculating Dosage Regimen

Answer 34

Maintenance dose | Loading dose

Question 35

``` Maintenance dose (Best to see notes for all formulas) (pgs ~152) ```

Answer 35

Dosing rate = Clearance X desired steady-state concentration The daily dosing intervaldose = dose/min X 60 min per hour X 24 hours Dose X F / dosing interval = CLB X Cp (ss) CLB = total body clearance Cp(ss)= steady-state plasma concentration

Question 36

The ClB of an antibiotic in a dog is 80 mL/min and Vd is 40 L. What maintenance dose must be administered intravenously every 6 hours to eventually obtain average steady-state plasma concentrations of 4 mg/L? a. 0.32 mg b. 115 mg c. 160 mg d. 230 mg e. none of the above

Answer 36

b. 115 mg

Question 37

Loading dose

Answer 37

Loading dose = Vd X desired serum drug concentration

Question 38

If you wish to give this dog a loading dose to achieve the therapeutic plasma concentration of 4 mg/L rapidly, how much should be given? a. 0.1 mg b. 10mg c. 115.2 mg d. 160 mg e. none of the above

Answer 38

d. 160 mg

Question 39

Dosage adjustment in renal disease

Answer 39

For drugs that depend on renal clearance | Adjustment of either the dose or the dose interval relative to renal function

Question 40

Dosage adjustment in renal disease formulas

Answer 40

Adjusted dose = Normal dose X Patient’s renal clearance / Normal renal clearance Adjusted dose interval = Normal dose interval X Normal renal clearance / Patient’s renal clearance Renal clearance is usually estimated by creatinine clearance

Question 41

Soon after the IV injection of 2 grams of a drug, the concentration in the plasma is 10 mg/100 mL. The calculated apparent volume of distribution would be a. 0.50 liters b. 2.00 liters c. 5.00 liters d. 20.00 liters e. 200.00 liters

Answer 41

d. 20.00 liters

Question 42

Following the IV injection of 100 mg of a drug and before a significant amount is metabolized or excreted, the plasma concentration reaches the constant level. The apparent volume of distribution is found to be 20 liters. The plasma concentration therefore is found to be: a. 1 mg/liter b. 2 mg/liter c. 3 mg/liter d. 4 mg/liter e. 5 mg/liter

Answer 42

e. 5 mg/liter

Question 43

If the apparent volume of distribution of a drug in an animal were 7 liters, what would be the predicted initial plasma concentration of the drug following IV injection of 70 mg? a. 7 mg/mL b. 0.7 mg/mL c. 10.0 mg/mL d. 0.01 mg/mL e. 0.001 mg/mlL

Answer 43

d. 0.01 mg/mL

Question 44

5. The concentration of a drug in urine is 100 mg/mL and in plasma 10 mg/mL, the urine flow is 10 mL/min. What is the renal clearance of the drug? a. 100 mL/min b. 30 mL/min c. 10 mL/min d. 3 mL/min e. 1 mL/min

Answer 44

a. 100 mL/min

Question 45

6. The concentration of drug X “free” in plasma is 1 mg/mL and in urine is 5 mg/mL. Urine flow is 10 mL/min. What is the plasma clearance of drug X? a. 5 mL/min b. 50 mL/min c. 100 mL/min d. 150 mL/min e. 500 mL/min

Answer 45

b. 50 mL/min

Question 46

7. The concentration of a drug in urine is 10 mg/mL and in plasma is 1 mg/mL. The urine flow is 10 mL/min. What is the renal clearance of the drug? a. 100 mL/min b. 30 mL/min c. 10 mL/min d. 3 mL/min e. 1 mL/min

Answer 46

a. 100 mL/min

Question 47

The ClB of an antibiotic in a dog is 80 mL/min and Vd is 40 L. What maintenance dose must be administered intravenously every 6 hours to eventually obtain average steady- state plasma concentrations of 4 mg/L? a. 0.32 mg b. 115 mg c. 160 mg d. 230 mg e. none of the above

Answer 47

b. 115 mg

Question 48

If you wish to give this dog a loading dose to achieve the therapeutic plasma concentration of 4 mg/L rapidly, how much should be given? a. 0.1 mg b. 10mg c. 115.2 mg d. 160 mg e. none of the above

Answer 48

d. 160 mg

Question 49

Which of the following MOST closely describes the clearance rate of a drug that is infused at a rate of 4 mg/min and produces a steady-state concentration of 6 mg/L in the plasma? a. 67 mL/min b. 132 mL/min c. 300 mL/min d. 667 mL/min e. 1,200 mL/min

Answer 49

d. 667 mL/min

Question 50

What is Pharmacokinetics?

Answer 50

Is the mathematical description of the plasma concentration-time course