Introduction to Pharmacokinetics 1

Question 1

What is pharmacodynamics?

Answer 1

The action of a drug on the body (physiological to biochemical)

Question 2

What is pharmacokinetics?

Answer 2

Effects of the body on the drug.

Question 3

Compare pharmacokinetics and pharmacodynamics.

Answer 3

Pharmacodynamics:
- Specific to drug or drug class.
- Macromolecular targets
Pharmacokinetics:
- Non specific
- General process

Question 4

Describe the process of drug absorption.

Answer 4

The transfer of drug from site of administration to general circulation via:
- Pores or ion channels
- Passive diffusion (gases, hydrophobes mols, small mols)
- Carrier mediated
- Pinocytosis

(Bioavailability)

Question 5

Describe the process of drug distribution.

Answer 5

The transfer of drug from the general circulation into different organs of the body.
- Apparent volume of distribution (Vd)

Question 6

Describe the process of drug elimination.

Answer 6

The removal of drug from the body – this may involve metabolism or excretion or both.
- Clearance (Cl)
- Plasma Half -Life (t1/2)

Question 7

What are the common routes of administration.

Answer 7

1. Topical: local effect, applied directly where action is desired (epithelial surface)
2. Enteral: systemic, via digestive tract (oral, sublingual, rectal)
3. Parenteral: systemic inhalation or injection (IV, S/C, I/M, Intra-dermal, intrathecal -into CSF subarachnoid space)

Question 8

What determines the route of administration?

Answer 8

• Physical characteristics of the drug
• Speed of absorption
• Need to bypass hepatic metabolism & achieve ^conc. at site.

Question 9

What factors Influence drug absorption from the Gut.

Answer 9

1. Drug structure:
   - ^ polar/ ionised poorly absorbed
   - pH partitioning for weak acids and bases
   - breakdown of peptides by digestive enzymes.
2. Formulation:
   - disintegration of tablet/ capsule
   -modified release formulations e.g enteric aspirin
3. Gastric emptying (GE) can effect rate but not quantity
   - Food slows absorption delays GE & ^secretions
   - Fasting/ malnutrition
4. First-pass metabolism

Question 10

What is first pass metabolism?

Answer 10

The degree of metabolic breakdown of an orally administered drug that occurs in the intestine or liver before it reaches the systemic circulation.

Question 11

Why is first pass metabolism important?

Answer 11

• Results in only a proportion of drug reaching the circulation
• May require alternative ROA (e.g. IV, IM)
• Helps clinicians decide correct route for optimum therapeutic effect.

Question 12

Influence of different drug routes on plasma conc. vs time plots.

Answer 12

Oral: C-max reached after t- max post adminstration.
IV: C-max = T0 immediately post administration. No absorption step.

Question 13

Define onset of action.

Answer 13

• When plasma level reaches minimum effective concentration (MEC).

Question 14

How do we minimise adverse reactions?

Answer 14

Maintain plasma levels below the maximum safe concentration (MSC).

Question 15

Define duration of action.

Answer 15

Time period for which the plasma level is at or above MEC.

Question 16

What is area under the curve?

Answer 16

• A measure of the total amount of drug that enters the body after administration.
• Calculated form plasma conc. vs time plots (mg hr/ L)
• AUC & max plasma conc. are higher with IV than oral

Question 17

What is bioavailability and what is its formula?

Answer 17

The fraction of the administered dose that reaches the systemic circulation as intact drug.
Formula: (multiply by 100 for %)

Question 18

Why is bioavailability important?

Answer 18

• Determines dose needed for different ROA via comparing plasma levels of a drug obtained after administration with different routes (e.g. IM vs IV, IV, vs PO)
• Helps define the true dose which is not dose given, but drug available to exert its effect.