CB - Pharmacokinetics II

Question 1

What is required for rapid and extensive drug absorption?

Answer 1

The drug must dissolve, forming a molecular solution.

Increasing the surface area allows for quicker dissolving (FORMULATION)

Question 2

Sustained release formulation vs Conventional formulation

Answer 2

Sustained release formulation is absorbed more slowly meaning you do not need to take the tablet as often

Question 3

What is gastric emptying?

Answer 3

The process by which the contents of the stomach are moved into the duodenum (method of drug absorbtion)

Question 4

What affects gastric emptying? (3)

Answer 4

1. When you have had a meal
2. Contents of the meal
3. Temperature of the meal

Question 5

What is first-pass metabolism?

Answer 5

When the drug is metabolised by the liver before it enters the general bloodstream

Question 6

What is bioavailability (f)?

Answer 6

The fraction of a dose passing from the administration site into the general circulation as the parent compound (intravenous = 1.0)

Question 7

Common reasons for low bioavailability? (5)

Answer 7

1. Decomposition in the gut lumen
2. First-pass metabolism in the gut wall
3. First-pass metabolism in liver
4. Not absorbed from the gut lumen
5. Tablet does not completely dissolve

Question 8

How can we measure the Bioavailability (f)?

Answer 8

Compare the plasma concentration when the same dose is given intravenously and orally

Intravenous

• 100% gets into the general circulation

Area under the curve (oral dose) / Area under the curve (intravenous dose)

Question 9

What are some consequences due to oral administration? (4)

Answer 9

DELAY

• due to gastric emptying
• influenced by food

LESS LIPID SOLUBLE/MORE WATER SOLUBLE DRUGS

• Absorbed slowly

MORE LIPID SOLUBLE DRUGS

• Absorbed rapidly

F = VARIABLE

• first-pass metabolism
• too hydrophilic to be absorbed
• extremely lipid soluble compounds do not form a solution within the gut lumen

Question 10

What is distribution in pharmacology?

Answer 10

The movement of the drug from the blood into tissues and its return into the blood during elimination

Question 11

What affects the distribution of drugs from plasma into cells ?

Answer 11

Unionised forms can cross membranes

Both dosage and elimination influence the amount of free-drug in the plasma

Protein-bound drugs cannot cross the membrane into tissues

Question 12

What is pH partitioning?

Answer 12

If the membrane separates fluids at different pH values the drug will concentrate at the pH at which it is most ionised

Question 13

What are 6 properties of drug-protein binding?

Answer 13

1. In general it is non specific
2. Low affinity
3. High capacity
4. Saturable at high concentrations
5. Not involved in drug mode of action
6. Acts as a depot or reservoir of drug

Question 13

What proteins bind to acidic and basic drugs? (2)

Answer 13

Plasma albumin binds acidic (and basic) drugs

a1-acid glycoprotein binds basic drugs

Question 14

When is competition important for drug vs drug and drug vs endogenous compounds?

Answer 14

WITH OTHER DRUGS:

• IMPORTANT only if the drug is highly protein bound
• A second drug can change the volume of distribution of a drug

WITH ENDOGENOUS COMPOUNDS
IMPORTANT WHEN:

• Endogenous compound is highly bound
• Unbound endogenous compound is active or toxic e.g. bilirubin in neonate

Question 15

How do you measure Volume of Distribution (Vd)?

Answer 15

Vd = Total in TISSUES / Total in PLASMA