Drug Absorption and Distribution

Question 1

What is pharmacokinetics?

Answer 1

The study of the change in drug and metabolite concentrations in tissues and body fluids
(what the body does to the drug)

Question 2

What is the therapeutic window of a drug?

Answer 2

The concentration range of a drug taken orally between the maximum non-toxic and minimum therapeutic concentration

Question 3

What is the therapeutic ratio/index?

Answer 3

The ratio of the maximum non-toxic dose compared to the minimum therapeutic dose.

Safest drugs have the highest therapeutic ratio

Question 4

What is TD50?

Answer 4

The toxic dose of a drug for 50% of the population

Question 5

What is ED50?

Answer 5

The minimum effective dose for 50% of the population.

Question 6

How can the therapeutic ratio be measured?

Answer 6

TD50/ED50

Question 7

Explain the acronym ADME as a way of thinking about pharmacokinetics?

Answer 7

Absorption: movement of a drug from the point of administration to the plasma
Distribution: from plasma to tissues and organs
Metabolism: of drugs by enzymes in the body
Excretion: of drug/metabolite by the body

Question 8

What is ADME important for understanding?

Answer 8

drug development
understanding toxicity 
Establishing route of administration 
Establishing drug dose
Understanding possible drug interactions

Question 9

what is bioavailability?

Answer 9

fraction of unchanged drug that reaches systemic circulation.
(eg. intravenous drug delivery is 100% bioavailable)

Question 10

How can bioavailability be decreased?

Answer 10

poorer absorption

first pass metabolism

Question 11

what does absorption depend on?

Answer 11

Route of administration: intravenous is fastest

Chemical nature of compound: Lipophilicity (the higher the better), Charge (uncharged is faster), Size (smaller the better)

Formulation: A key area in pharmacy research (eg. liquid, gelatin capsule, etc)

Blood flow rate to the site of delivery

Question 12

What are the different formulations of drugs and what are their relative speeds of absorption?

Answer 12

Liquids - absorb faster than capsules or tablets due to the greater area for exchange

Gelatin-Coating tablets - slow absorption and decreases local peak concentrations

Capsules - containing granules with differently soluble coatings allowing for controlled release

Intramuscular injection of an oily depot of lipophilic drugs - allows for the very slow release. (eg. anti-psychotic drugs in non-compliant patients)

Question 13

What is the fastest and slowest route of administration?

Answer 13

Intravenous (IV) is the fastest

Sublingual (sI; under the tongue) is absorbed relatively quickly but not as fast as IV

Orally(po) / Rectally (pr) are slow routes of administration

Question 14

what is a risk with an intravenous administration?

Answer 14

potential risk of infection

Question 15

What is the issue of a sublingual route of administration?

Answer 15

Only a small amount of the drug can be absorbed and therefore it requires a very potent drug.

Question 16

What is a transcutaneous route of administration of drug?

Answer 16

Only suitable for some drugs, where a lipophilic carrier is needed to cross the skin.
Often given in the form of a patch which when stuck on allows the drug to be absorbed.

Question 17

What is Enteral absorption?

Answer 17

Absorption via the GI tract.

This can be either orally or rectally

Question 18

What should be considered when taking an enteral drug?

Answer 18

Consider its interaction with food
Consider the rate of transit in the gut
For oral delivery, consider the pH sensitivity given the need to pass through the stomach
Consider the first pass metabolism

Question 19

What is first pass metabolism?

Answer 19

Whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. It is the fraction of drug lost during the process of absorption which is generally related to the liver and gut wall

Question 20

What form of a weak base drug is charged?

Answer 20

For a weak base, the protonated form is charged (more alkaline) then there will be more uncharged form present and the drug will cross membranes

Question 21

What form of a weak acid drug is charged?

Answer 21

Protonated form is uncharged, so under more acidic conditions then there will be more uncharged form present. and the drug will cross membranes

Question 22

what are the general principles of pH and the effect on drug movement?

Answer 22

Difference in pH can determine where the drug will accumulate

Drugs tend to accumulate wherever they are ionised, as it is difficult for them to leave such compartments.

Question 23

what is the enterohepatic circulation and how do drugs travel through it?

Answer 23

Some drugs entering the gut are absorbed, enter the portal circulation, pass from liver (with or without conjugation) to bile then back to the intestinal tract.

Question 24

What is the distribution of a drug?

Answer 24

how drugs equilibrate within the body after entering the systemic circulation

Question 25

What are some common fates of drugs to be distributed to?

Answer 25

no distribution

Distribution through extracellular space

Distribute through total body water

Accumulate in cells

Distribute to fat

Question 26

What is the volume of distribution?

Answer 26

The volume of fluid required to contain the total amount of drug in the body at the same concentration as that present in the plasma

Question 27

How do you work out the volume of distribution?

Answer 27

Vd = D / Cp

D - amount of drug
Cp - concentration of drug in plasma

Question 28

What is the purpose of a drug binding to circulating proteins?

Answer 28

Decreases the initial free concentration
Slows distribution
Slows clearance
Prolongs duration of action

Question 29

Give an example of a drug bound by albumin?

Answer 29

Warfarin and salicylates bind to circulating plasma proteins. When more than one of these drugs is present, there can be competition for binding, increasing the free drug concentration.