Lecture 7.1 & 7.2: Pharmacokinetics of Drug Administration

Question 1

What is Pharmacology?

Answer 1

Science of drug action on biological systems

Question 2

What is Pharmacokinetics?

Answer 2

It is the study of what the body does to a drug

Question 3

What is Pharmacodynamics?

Answer 3

It is the study of what a drug does to the body

Question 4

ADME in Drug Metabolism

Answer 4

Absorption
Distribution
Metabolism
Elimination

Question 5

What is Pharmacogenetics?

Answer 5

• Genetically determined variations in
  responses to drugs
• Role of inheritance in individual
  variations in drug responses

Question 6

What are the 4 questions to be asked when prescribing drugs?

Answer 6

• Is the drug getting into patient
  (Pharmaceutical Process)
• Is the drug getting to site of action?
  (Pharmacokinetic Process)
• Is the drug producing desired effect?
  (Pharmacodynamic Process)
• Is this translated to a therapeutic
  effect? (Therapeutic Process)

Question 7

Sites/Types of Administration of Drugs (7)

Answer 7

• Oral
• IV
• Sublingual
• Inhalation
• Transdermal Patch
• Topical
• Rectal

Question 8

What is the oral bioavailability of a drug?

Answer 8

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

Question 9

What is the Therapeutic Window of a Drug?

Answer 9

Maximum tolerated dose/minimum effective dose

Question 10

What is the Therapeutic Index/Ratio?

Answer 10

It the range of doses at which a medication is effective without unacceptable adverse events

Question 11

Why do oral drugs often have less effect than IV drugs at similar doses?

Answer 11

Drugs administered orally are first exposed to the liver and thus may be extensively metabolised before reaching the rest of the body whereas IV drugs directly enter systemic circulation and reach the rest of the body

Question 12

How can first pass metabolism be avoided? (4)

Answer 12

• Parenteral (iv, im, sc)
• Rectal (note drainage to both portal and systemic
  systems)
• Sublingual (e.g. use of glyceryl trinitrate in angina
• Topical (eg transdermal cannabinoids/CBD)

Question 13

What is First Pass Metabolism?

Answer 13

The first pass effect is a phenomenon of drug metabolism at a specific location in the body which leads to a reduction in the concentration of the active drug, specifically when administered orally, before it reaches the site of action or systemic circulation

Question 14

What is Volume of distribution (Vd)?

Answer 14

• A pharmacokinetic parameter that relates the total
  amount of drug in the body to the concentration in
  the bloodstream
• Vd is defined as the total amount of drug in the body
  divided by its concentration in plasma

Question 15

What does it mean for a drug to have a high volume of distribution?

Answer 15

A drug with a high Vd has a propensity to leave the plasma and enter the extravascular compartments of the body, meaning that a higher dose of a drug is required to achieve a given plasma concentration

Question 16

What does it mean for a drug to have a low volume of distribution?

Answer 16

A drug with a low Vd has a propensity to remain in the plasma meaning a lower dose of a drug is required to achieve a given plasma concentration

Question 17

What factors influences Vd?

Answer 17

• Drug properties which affect protein binding and
  tissue binding
• Molecule Size
• Charge
• pKa
• Lipid/Water Partition Coefficient

Question 18

Protein binding interactions are important when object drug…? (3)

Answer 18

• Is highly bound to albumin (>90%)
• Has a small volume of distribution
• Has a low therapeutic ratio

Question 19

Drug Binding to Proteins: Class I

Answer 19

It is used at dose lower than number of albumin binding
sites

Question 20

Drug Binding to Proteins: Class II

Answer 20

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

Question 21

What organ predominantly metabolises drugs?

Answer 21

Liver

Question 22

What organ predominantly excretes drugs?

Answer 22

Renal System

Question 23

Drug Pharmacokinetics: 1st order kinetics

Answer 23

• Rate of elimination is proportional to drug level
• Constant fraction of drug eliminated in unit time
• Half life can be defined

Question 24

Drug Pharmacokinetics: Zero order kinetics

Answer 24

Rate of elimination is a constant

Question 25

During repeated drug administration, a new
steady state is achieved in….?

Answer 25

5 half lives

Question 26

Renal Excretion of Drugs

Question 27

Liver Enzyme: CYP450

Answer 27

• Enzyme family
• Involved in toxin/drug metabolism
• Highly polymorphic: over 100 allelic variants and
  subvariants described

Question 28

CYP Allele

Answer 28

• Normal
• Decreased
• No function
• Increased
• Unknown function
• Uncertain function

Question 29

What Chromosome is CYP2D6 on?

Answer 29

Chromosome 22

Question 30

What does CYP2D6 Metabolise?

Answer 30

• Tamoxifen
• Antidepressants
• Fluoxetine (Prozac)
• Pain management
• Codeine (CPIC Guidelines)
• Antipsychotics
• Inhibitors such as: Bupropion (Wellbutrin), Fluoxetine
  (Prozac), Paroxetine (Paxil)

Question 31

What does CYP2D6 metabolise Codeine into?

Answer 31

Morphine

Question 32

What is Volume of Distribution?

Answer 32

• Theoretical volume into which drug is distributed if
  this occurred instantaneously
• Obtained by extrapolation of plasma levels to zero
  time
• Is the volume of plasma that would be necessary to
  account for the total amount of drug in the patient’s
  body
• If that drug were present throughout the body at the
  same concentration as found in the plasma

Question 33

How to calculate Vd?

Answer 33

D/C0
(amount of drug injected)/(blood concentration extrapolated at t = 0)