MnR S9 - Pharmokinetics

Question 1

What must be considered if a solid drug formulation is used opposed to liquid?

Answer 1

Solubility and stability

Question 2

What are the different categories of possible sites for drug administration?

Answer 2

Focal - eye, mouth, inhalation

Systemic
Enteral - Sublingual, oral, rectal

Systemic
Parenteral - Subcutaneous, IV, Intramuscular, Inhalation, transdermal

Question 3

What is a potential advantage of focal drug administration?

Answer 3

Less side effects elsewhere in the body

Question 4

What is oral bioavailability?

Answer 4

Proportion of the dose given other than by intravenous injection which reaches the systemic circulation in an unchanged form

Question 5

What are the two possible measurements of bioavailability and what does each depend on?

Answer 5

Amount - Depends on GI absorption and first pass metabolism

Rate of availability - depends on pharmaceutical factors and rate of gut absorption

Question 6

What is the therapeutic ratio?

Answer 6

Maximum tolerated dose/minimum effective dose

Question 7

Define LC50 and EC50

Answer 7

Lethal concentration of drug in 50% population

Effective concentration of drug in 50% population

Question 8

How is first pass metabolism effect avoided?

Answer 8

Parenteral, sublingual or rectal route to avoid liver

Question 9

What is volume of distribution and how is it measured?

Answer 9

Theoretical volume into which a drug has distributed assuming that this occurred instantaneously

Amount given / plasma concentration at time 0

Question 10

When is protein binding interactions particularly important?

Answer 10

• If drug is highly bound to albumin
• If drug has low therapeutic index
• If drug has small volume of distribution

Question 11

How do precipitant drugs increase risk of toxicity?

Answer 11

• Temporarily leads to higher free levels of object drug which may have previously been bound to binding protein
• Concentration of object drug may then exceed the maximum tolerated dose

Question 12

How does the dose of the object drug and precipitant drug differ?

Answer 12

Object - dose lower than number of albumin binding sites

Precipitant - Dose higher than number of albumin binding sites

Question 13

How do first order and zero order kinetics differ?

Answer 13

First order - Rate of decline of plasma drug concentration is proportional to drug level, graph is exponential, Km exceeds drug concentration

Zero order - Rate of decline of plasma drug concentration is constant, graph is linear, drug concentration exceed Km

Question 14

How many half-lives does it take to achieve a steady state?

Answer 14

Five

Question 15

What are two methods of drug elimination?

Answer 15

Metabolism by liver

Excretion by kidneys

Question 16

List an enzyme inducer molecule and the drug affected

Answer 16

Phenobarbitone - warfarin, phenytoin

Rifampicin - oral contraceptive

Cigarettes - theophylline

Question 17

How could administering cimetidine (H2 antagonist) to a patient being treated for DVT result in haemorrhaging?

Answer 17

Enzyme inhibitor - Increase warfarin concentration above the maximum tolerated dose as less is metabolised by the liver

Question 18

List two properties of enzymes of the CYP450 systems

Answer 18

Low specificity, high affinity for lipid soluble drugs

Question 19

Which drugs are filtered by the kidneys and where?

Answer 19

Free unbound drugs in the glomerular tuft

Question 20

Outline how change in urine pH will effect absorption of weak acids and give an example of a drug impacted this way?

Answer 20

Alkaline - Decrease tubular absorption
Acidic - Increase tubular absorption

Aspirin

Question 21

How is drug half-life effected in renal disease and what are the consequences of this?

Answer 21

Half-life is prolonged so maintenance dose must be lowered