Introduction to Clinical Pharmacology

Question 1

What is Clinical Pharmacology

Answer 1

Study of drugs in humans

Variable response of patients to drugs

Thus different doses needed

Overall response of patients due to
Pharmacodynamic effects
Pharmacokinetic effects

Question 2

What is pharmacodynamics?

Answer 2

The relationship between the unbound drug concentration at the receptor and the drug response
i.e what the drug does to the body

Question 3

List the 5 pharmacodynamis effects

Answer 3

• Usually quite specific to a class of drug
• Chemical structure will define biological activity
• Dependent on concentration of free drug at its target
• Associated with response at site of action and desired clinical response
• Mechanism of action and localisation of the site of drug action
• May also give rise to unwanted side effects and toxicity

Question 4

What is pharmacokinetics?

Answer 4

• Science of the relationship between the movement of the drug through the body and the processes affecting it

Question 5

What is the role of pharmacokinetic effects

Answer 5

• Govern the concentration of a free drug delivered to site of action
• is the relationship between the dose given/taken, the unbound drug concentration at its site of action and how long the effect is maintained

Pharmacokinetic effects will determine how long and the intensity of the pharmacological action

Question 6

What process occur when a drug is ingested

Answer 6

absorption, distribution, metabolism and excretion.

Question 7

Chemical and biochemical knowledge of drug absorption and metabolism can be used to understand and prevent what?

Answer 7

• Side effects,
• Toxicity
• Drug interactions.

Question 8

what does absorption, distribution and metabolism depend on?

Answer 8

• Route of administration of drug

- Physico-chemical properties of drug

Question 9

Elimincation occurs via?

Answer 9

• Renal excretion
• Liver metabolism
• Chemical transformation.

Question 10

What the extent of metabolism vary with?

Answer 10

-varies with the physico-chemical properties of the drug.

Question 11

The parameters ADME determine what?

Answer 11

the drug concentration in the body when drugs are prescribed

Question 12

The effectiveness of a dosage regimen is determined by what?

Answer 12

the conc of drug in the body

Ideally drug conc measured at site of action (receptor)

Question 13

Ideally drug concentration is measured at the site of action but receptor is typically inaccessible . So what should be done instead?

Answer 13

-measure drug conc in blood* (proportional to conc at receptor)

Question 14

What is convention?

Answer 14

to measure drug concentrations in plasma

Question 15

Why is measuring blood concentrations more difficult?

Answer 15

due to interference from other compounds

Question 16

What is absorption?

Answer 16

The process by which unchanged drug proceeds from the site of administration to the site of action

Question 17

What is distribution?

Answer 17

The reversible transfer of drug between the blood and the tissues

Question 18

what is metabolism?

Answer 18

Metabolism into active and inactive metabolites which are then excreted

Question 19

What is excretion?

Answer 19

The irreversible loss of drug (&/or metabolites) from the site of measurement (i.e. systemic circulation)

Question 20

Why don’t drugs administered by IV not require absorption?

Answer 20

Drugs administered IV are injected directly into the site of measurement (systemic circulation), therefore absorption is not required

Question 21

Drugs administered via other routes must be ……

Answer 21

transported through membranes to reach the intravascular circulation.

Question 22

What happens to drugs administered via other routes other than IV during absoprtion

Answer 22

• A proportion of the dose may not be delivered or be eliminated during the absorption process (so unabsorbed)
• i.e. <100% of the drug reaches the systemic circulation
• Fraction of dose that reaches systemic circulation is termed bioavailability, F.

Question 23

Rate & extent of distribution is dependent upon

Answer 23

• Perfusion of tissue with blood
• Permeability of membrane
• Plasma protein binding
• Tissue protein binding
• Physicochemical nature of drug

Question 24

What is distribution represented by?

Answer 24

Represented by the drugs Volume of Distribution (V)

Question 25

If the membrane between blood and tissue offers no resistance to the passage of drug:

Answer 25

• Drug in blood leaving the tissue is in virtual equilibrium with that within the tissue
• Movement of drug is limited by blood flow

Question 26

What is a major determinant of drug distribution?

Answer 26

plasma protein binding

Question 27

What is a limitation in perfusion-rate?

Answer 27

-Movement of drug is limited by blood flow

Question 28

Perfusion-rate limitation occur if membrane between blood and tissue offers no resistance to the passage of the the drug. Drug in the blood leaving the tissue is in virtual equilibrium with what?

Answer 28

Drug in blood leaving the tissue is in virtual equilibrium with that within the tissue

Question 29

When does permeability-rate limitation exist?

Answer 29

exists if membrane resistance to drug movement becomes high

Question 30

What happens to drug movement during permeability rate limitation?

Answer 30

Movement is slow and insensitive to changes in blood flow.

Question 31

How is equilibrium affected when permeability-rate limitation occurs

Answer 31

Equilibrium is not achieved by the time blood leaves the tissue.

Question 32

When permeability-rate limitation exists, what is blood and tissue viewed as?

Answer 32

Blood and tissue must now be viewed as separate compartments.

Question 33

Name the proteins in blood that drugs bind to.

Answer 33

albumin; α1 acid glycoprotein; lipoproteins; cortisol binding globulin

Question 34

Is the level of protein binding the same for each drug?

Answer 34

Yes

Question 35

At equilibrium what does the distribution of the drug depend on?

Answer 35

At equilibrium distribution of drug in body depends on binding to plasma proteins & tissue components

Question 36

Only what is capable or leaving plasma and tissues?

Answer 36

Only unbound drug is capable of leaving plasma or tissues