Session 9

Question 0

What are the advantages of topical administration?

Answer 0

Concentrates the drug at the site of action, less of it is absorbed by the systemic circulation.

Question 1

Give examples of sites of administration

Answer 1

Oral, inhaling, topical, IV, IM, rectal, transdermal patches

Question 2

Define oral bioavailability

Answer 2

Proportion of drug given orally (or any route except IV) that reaches the circulation unchanged

Question 3

How is oral bioavailability measured?

Answer 3

By area (depends on first pass metabolism and gut absorption) and rate (depends on pharmaceutical factors)

Question 4

How can oral bioavailability be calculated?

Answer 4

AUC oral/AUC injected x 100

Question 5

What is the first pass effect?

Answer 5

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

Question 6

How can you avoid the first pass effect?

Answer 6

Parenteral administration (e.g. IV, IM, subcutaneous)
Rectal (note drainage to both portal and systemic systems)
Sublingual (e.g. use of glyceryl trinitrate in angina)

Question 7

Define volume of distribution.

How is it obtained?

Answer 7

Theoretical volume into which the drug is distributed if this occurred instantaneously.
By extrapolation of plasma levels to zero time

Question 8

When is protein binding interaction important?

Answer 8

When the object drug: is high bound to albumin, has a small volume of distribution and has a low therapeutic ratio

Question 9

What is a class I drug?

Answer 9

An object drug. Used at a dose lower than number of albumin binding sites

Question 10

What is a class II drug?

Answer 10

A drug that is used at doses greater than number of binding sites, and thus displaces the Class I drug.

Question 11

Describe 1st order kinetics

Answer 11

The rate of elimination of the drug is proportional to the drug level. Constant fraction of the drug is eliminated per unit time. There is a definable 1/2 life

Question 12

Describe 0 order kinetics.

Answer 12

The rate of elimination is a constant.

Question 13

Describe the graphs of both 1st and 0 order kinetics against time

Answer 13

1st order –> linear when log y axis plotted against time

0 order –> straight line when linear y axis scale plotted against time

Question 14

When does drug metabolism display 1st order or 0 order kinetics?

Answer 14

High doses –> 0 order

Low doses –> 1st order

Question 15

Describe drug elimination

Answer 15

Mixed function oxidases (liver microsomal enzyme) consists of cytochrome P450 reductase. Main CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 3A4. Low substrate specificity. Inducible and inhibitable.

Question 16

Describe renal excretion

Answer 16

The free fraction of drug is filtered. Drugs can be actively secreted by the tubules (e.g. penicillin secreted by proximal tubule. Passive reabsorption of drug is dependent on pH. Only the non-ionised moiety is lipid soluble and crosses membranes easily.

Question 17

What is the pK value indicative of?

Answer 17

The pK of a drug is the pH at which half of it is ionised and half of it is non-ionised.

Question 18

Describe the treatment of overdose of weak acids (e.g. aspirin).

Answer 18

Forced alkaline diuresis

Question 19

What would you do if you were prescribing to someone with renal failure?

Answer 19

• If drug is excreted by kidneys, half lives of drug are longer. Lower maintenance dose of the drug
  • Longer half lives also means longer time to reach a steady state (remember it takes 5 half lives to reach equilibrium).
  • Loading dose can be altered.
• Protein binding can be altered