Pharmacokinetics

Question 1

What is the diffference between clearance and elimination half-life?

Answer 1

Clearance - Body’s Efficiency of drug removal

Elimination Half-life - Rate of Drug Removal

Question 2

What is the difference between Bioavailability and Volume of Distribution?

Answer 2

Bioavailability - Fraction of Drug Absorbed

Volume of Distribution - Apparent Space the Drug Resides in

Question 3

• **What is the most important concept to be considered when designing a regimen for long-term drug administration?
• Define this term.
• **How can this be calculated?
• Define the variables

Answer 3

Clearance

Clearance - theoretical Volume of Fluid from which the drug is removed per unit of time

CL = Rate of Elimination/Concentration
CL = Q [(Ca-Cv)/Ca] = QE

Q = Blood Flow to the organ 
Ca = Arterial Concentration of Drug
Cv = Venous Concentration of Drug
E = [(Ca-Cv)/Ca] - Extraction ratio

Question 4

How do you ensure that you maintain steady-state concentrations of a drug within the therapeutic window?

Answer 4

• Administer the Drug at the same rate that it is eliminated

Question 5

What is the Rate Limiting Variable in Clearance of a drug?

Answer 5

Blood Flow to the Organ

Question 6

What are the two methods by which all drugs are eliminated?

- which is most common?

Answer 6

0 order and 1st order kinetics

• 1st order is by far the most common

Question 7

Between 0 order and 1st order kinetics, which eliminates a constant fraction of the remaining concentration per unit of time?

Answer 7

1st order - specific fraction of the drug is elminated from the remaining concentration per unit time

Question 8

What is Ke?

- how is it obtained

Answer 8

Elimination Rate constant obtained by taking the log of [Drug] and graphing it against time

Question 9

What is the volume of distribution?

- What is the formula?

Answer 9

The fluid volume that would be required to contain all of the dose at the same concentration as exists in the blood plasma

Vd = Dose / Cb

Cb = Blood concentration

Question 10

How do you find the elimination constant for a drug eliminated by 1st order kinetics?

Answer 10

Ke= Q [(Ca-Cv)/Ca] / Vd

also,

Ke = CL/Vd

Question 11

What is the relationship of half life to dosing interval?

Answer 11

A drug is often given at half-life intervals

Question 12

What are the 4 main factors that make 1/2 life a clinically important thing?

Answer 12

1. Determination of Dosing Interval
2. A factor in Determining Dose
3. May Determine Route
4. Good indicator of the time required to reach steady-state after a dosage regimen is initiated

Question 13

What is the one compartment pharmacokinetic Model?

• how accurate is it?
• Kinetics?

Answer 13

*Assumes the Body is One Compartment

***ONLY WORKS FOR DRUGS THAT ARE DISTRIBUTED UNIFORMLY THROUGHOUT THE BODY

• Not a very adequate model
• 1st order Elimination

Question 14

What is the two compartment model?

- how does the graph of the two compartment model differ from that of the one compartment model?

Answer 14

Two Compartment Model - assumes drug is injected into the blood then must equilibrate between two compartments

• Graphically you’ll see in initial large drop in concentration that corresponds to equilibration between the two compartments

Question 15

How do you find clearance rate for a multicompartment model?

Answer 15

Clearance Rate = Dose / AUC

AUC = area under the curve

Question 16

How do you determine dosing while taking into account bioavailability?

Answer 16

F(Dosing Rate) = CL/Css

F Dose/T = CL/Css

Dose = (CssCLT) / F

Where:

• T = Dosing Interval
• CL = clearance
• Css = Steady State Concentration (in plasma)

Question 17

How many half-lives does it typically take to reach steady state?
- what is the time to steady state strictly dependent on?

Answer 17

FIVE

***SINCE it takes 5 half lives then time to steady state is DEPENDENT ONLY ON T(1/2)

Question 18

When determining what drug to give a patient, what are the only two factors that the physician can control?

Answer 18

• Dose and Dosing Interval

PHYSICIANS CAN ONLY CONTROL STEADY STATE MAX AND MIN*

Question 19

T or F: for IV administration the time to steady state is still 5 half lives

Answer 19

True

Question 20

How do you determine how fast to administer a drug intravenously to get to a given concentration?

Answer 20

Css = Infusion Rate / Total Body Clearance

Question 21

When would you administer a loading dose?

Answer 21

• Heart Attacks
• Serious Heart Failure
• Overwhelming Bacterial Infections

Question 22

What is the formula for Loading dose?

Answer 22

LD = (Css * Vd) / F

where: 
LD - Loading Dose
Css - Steady State Concentration (DESIRED) 
Vd - volume of distribution 
F - Bioavailability

Question 23

What are patients given following a loading dose?

- what is the formula for calculating this?

Answer 23

Dosing Rate

Dosing Rate = (Target Css * CL) / F

Question 24

What are some drugs that exibit zero order kinetics?

Answer 24

Ethanol
Heparin
Aspirin
Tetracycline

(Phenytoin, Amobarbital)

Question 25

When do drugs display zero order kinetics?

Answer 25

When the enzyme is overloaded with drug

Question 26

What is the formula for loading dose in zero order kinetics?

Answer 26

LD = (Vd x Css)/F

Question 27

What is the formula for steady state concentration for zero order kinetics?

Answer 27

Css = (Km*DR)/(Vm-DR) Km = CONCENTRATION/dose for 50% max Rate

Question 28

What is the formula for Dosing rate for zero order kinetics?

Answer 28

DR = (Css*(Vm-DR))/Km ``` Km = CONCENTRATION/dose for 50% max rate Vm = Max Rate ```