Introdcution to Pharmacokinetics & Pharmacodynamics (1)

Question 1

What is meant by the term “biodisposition”

Answer 1

This is just another word for pharmacokinetics

Question 2

What is meant by the term “biotransformation”

Answer 2

This is just another word for metabolism of drugs

Question 3

What are the two routes of administration that are subject to first-pass metabolism by the liver?

Answer 3

Oral and rectal

Question 4

Define “bioavailability”

Answer 4

The fraction of the administered drug which reaches the systemic circulation. It is denoted by “F”.

Question 5

How can you measure bioavailability?

Answer 5

Draw the time-concentration graphs for both the IV drug and the oral or rectal drug. Get the areas under the curve. Divide the Oral/Rectal-AUC by the IV-AUC. Bioavailability: F = Oral-AUC / IV-AUC

Question 6

If you give a drug orally, and you know its bioavailability, how can you figure out how much of it is absorbed?

Answer 6

Mass(absorbed) = Mass(administered) x Bioavailability. e.g. Penicillin G has an oral bioavailability of 25%. If 10mg is administered orally, then 2.5mg will reach the systemic circulation.

Question 7

Why is rectal administration only partially subject to first-pass metabolism by the liver?

Answer 7

Because blood drainage from the inferior rectum goes straight to the IVC, bypassing the liver. However, blood drainage from the superior rectum goes via the portal circulation to the liver. Therefore, approximately 50% of the rectally administered dose is subject to first-pass metabolism.

Question 8

What does Fick’s law describe, in the context of pharmacokinetics?

Answer 8

Fick’s law describes the tendency of a drug to be absorbed more quickly if there is better bloodflow to its site of administration.

Question 9

For the purposes of calculating drug concentrations after a given dose administered, what can you assume is the volume of plasma in a normal 70kg person?

Answer 9

Of Total Body Mass, 60% is fluid. Of this Total Body Water, 1/3 is Extracellular. Of this ECF, 20% is Plasma. Thus, 70 x 0.6 x 1/3 x 0.2 = 2.8 Therfore a 70kg person has approximately 2.8L of plasma.

Question 10

When calculating drug concentrations and distribution, it is important to know the plasma volume and interstitial fluid volume. How much bigger is the interstitial fluid volume than the plasma volume?

Answer 10

TBW = 60% body weight. ECF = 1/3 TBW. Plasma forms 20% of ECF, and Interstitial Fluid forms the remaining 80%. Therefore the interstitial fluid volume is about 4 times the size of the plasma volume. (Some sources say 3-4 times)

Question 11

Give a few examples of drugs that undergo zero-order kinetics at clinically relevant doses?

Answer 11

Ethanol, Phenytoin, Salicylates, Lithium

Question 12

Give a definition of first-order kinetics.

Answer 12

The drug’s rate of elimination is proportional to the drug’s plasma concentration. Metabolism and elimination is flow-dependent. A constant PROPORTION of drug is eliminated per unit of time.

Question 13

In first-order kinetics, after how many half-lives has 95% of the drug been eliminated?

Answer 13

Approx 4.5 half-lives.

Question 14

Give a definition for Clearance, and explain which units are used.

Answer 14

Clearance is the Volume of Plasma that is cleared of a drug per unit time. Units: mL/hr.

Question 15

If a drug has hepatic excretion, how is the drug physically excreted from the body? And if the drug has renal excretion?

Answer 15

Hepatic excretion: in bile. Renal excretion: in urine.

Question 16

If you are plotting a drug’s elimination on a semi-log plot of time vs concentration, and the drug elicits first-order kinetics, what does the curve look like?

Answer 16

It is a straight line.

Question 17

Give a definition for “steady state”.

Answer 17

This is when the infusion rate (the rate in) is equal to the elimination rate (the rate out)

Question 18

If you are giving an IV infusion, how long does it take to reach steady state? Does this depend on the rate of infusion?

Answer 18

It will always take about 4-5 half-lives, REGARDLESS of the infusion rate.

Question 19

What is the purpose of giving a loading dose?

Answer 19

This allows you to reach steady state much more quickly. If you were giving an IV-infusion without a loading dose, it would take 4-5 half-lives to reach steady state.

Question 20

What is a Quantal Dose-Effect Curve, and what is it used for? What is on the x-axis and y-axis?

Answer 20

A Quantal Dose-Effect Curve is used instead of a standard Dose-Response Curve. This is because it is used for a “quantal” pharmacological response, which is an all-or-nothing event such as prevention of seizures. The x-axis is the dose, and the y-axis is the percentage of individuals responding (exhibiting the specified quantal effect)

Question 21

With regard to a quantal pharmacologic response, what is the ED₅₀ ?

Answer 21

The ED₅₀ ​is the dose at which 50% of the population will exhibit the specified quantal effect, e.g. prevention of arrhythmia. It is called the median effective dose.

Question 22

With regard to a quantal pharmacologic response, what is the LD₅₀ ​?

Answer 22

The LD₅₀ ​is the dose at which 50% of the population would be killed; i.e. the lethal dose. It is called the median lethal dose.

Question 23

With regard to a quantal pharmacologic response, What is the TD₅₀ ​?

Answer 23

The TD₅₀ ​is the dose at which 50% of the population would exhibit a specified toxic response, and it is called the median toxic dose.

Question 24

How do you calculate the therapeutic index?

Answer 24

This is the ratio of the TD₅₀ to the ED₅₀. It is therefore calculated as TD₅₀ divided by ED₅₀ (for a given clinical toxic effect and a given therapeutic effect)

Question 25

What is Phase I metabolism? What is Phase II metabolism?

Answer 25

Phase I - oxidation / reduction / hydrolysis. Phase II - conjugation (e.g. glucuronidation, acetylation, sulfation).

Question 26

What is meant by the Volume of Distribution?

Answer 26

This is the measure of the apparent space in the body available to contain the drug, and does not represent an actual anatomical or physical volume. It is the volume required to distribute the drug homogenously at the same concentration found in the blood, plasma, or water.

Question 27

What is the lowest possible Volume of Distribution?

Answer 27

This is equivalent to the volume of plasma. So it would be 2.8L/70kg, or 0.04L/kg.

Question 28

What are some of the highest Volumes of Distribution?

Answer 28

If the unit is per 70kg, some drugs will have a Vd as high as 500, 1000, 4000. If the unit is per kg of body weight, some drugs will have a Vd as high as 7, 15, 60.