2. Pharmacokinetics

Question 1

Pharmacokinetics

Answer 1

= What does the Body do to the drug

Question 2

Pharmacodynamics

Answer 2

= What the drug does to the body

Question 3

Stages of a drug…

Answer 3

absorption

distribution

metabolism

excretion

Question 4

What is absorption

Answer 4

= passage of drug from its site of administration into the plasma

• drug must enter plasma before reaching site of action

Question 5

Where does oral absorption occur?

Answer 5

= through GIT tract

• stomach
• Small intestine (Mainly)
• large intestine

Question 6

Factors affecting oral administration?

Answer 6

• gastric emptying
• GI motility
• Splanchnic blood flow –> decreased splanchnic blood flow decreased absorption
• particle size
• formulation

Question 7

What is distribution?

Answer 7

= distribution around the body occurs when the drug reaches the circulation

–	Drugs are distributed throughout body fluids and fats

Question 8

Factors affecting distrubition?

Answer 8

The distribution pattern between various body compartments depends on
• Characteristics of the drug
o Permeability across tissue barriers
o Binding with compartments
o Oil: water partition coefficient
o Physiochemical properties of drugs

•	Physiological factors 
     o	Regional blood flow 
     o	Cardiac output 
     o	Capillary permeability 
     o	Tissue volume (except the CNS - protected by the BBB)

Question 9

What is metabolism?

Answer 9

Biotransformation of a drug by enzymes

• – Drug is made more polar (hydrophilic) that hastens excretion by the kidneys, because the polar metabolite is not readily reabsorbed in the renal tubules

–	The metabolites are usually less active than parent drug 

–	Liver is primary site of metabolism

Question 10

where does elimination?

Answer 10

• Metabolism (metabolic biotransformation)
o Liver (main source of metabolism)
o Intestine, kidney, lung

•	Excretion 
    o	Renal (urine) 
    o	Biliary (faeces) 
    o	Exhalation 
    o	Other routes (e.g. lactation)

Question 11

Name the phases in Hepatic Metabolism

Answer 11

Phase 1 Metabolism

• biotransformation reactions introduce orr expose functional groups on the dug with the goal of increasing the polarity of the compound
• grouped into three categories, oxidation, reduction, and hydrolysis
• convert a parent drug to be more polar

Phase II metabolism
- o glucuronidation, acetylation, and sulfation reactions
 “conjugation reactions” that increase water solubility of drug with a polar moiety

Question 12

What is half life and why is it important?

Answer 12

Half-life = time taken for plasma concentration or the amount of drug in the body to decrease by 50%

Less half-life = less side effects, therefore longer half-life = more side effects

Describes how long a drug or metabolite
stays in the body

Determines frequenting of dosing

Question 13

What is the CYP450?

Answer 13

= main family of enzymes where drug interactions occur

Most enzyme can metabolise a range of dugs

 Substrate – metabolised by and may compete for metabolic sites
 Inhibitor – competes for and ‘blocks’ metabolic site (not always a substrate)
 Inducer – increases metabolic activity by increasing amount of enzyme
 Ie. drug can be a substrate, inhibitor, or inducer of CYP enzyme system

Question 14

What are pharmacokinetic drug interactions?

Answer 14

• Absorption
o Normally food interactions

• Distribution
o Including protein binding

• Metabolism
o Cytochrome P450

• Renal elimination
o Competition for active efflux/ tubular reabsorption

Question 15

What is volume of distribution?

Answer 15

= the volume of fluid required to contain the total amount of drug in the body at the same concentration as that present in the plasma
Determined by

• Plasma protein binding
• Tissue binding

Question 16

Importance of Volume of distrubition?

Answer 16

Drugs with large volumes of distribution tend to:

• Have longer half lives
• Accumulate in the body with repeated dosing
• Cross the placenta and into breast milk
• Cross the blood brain barrier
• Require loading doses

Drugs with small volumes of distribution tend to:

• Have shorter half lives
• Accumulate less in the body
• Be safer to use in pregnancy and breastfeeding
• Be free of CNS effects

Question 17

What is Bioavailability and why is it important?

Answer 17

• Bioavailability (F) is the fraction of the dose that is absorbed into the systemic circulation
• Values of F may be between 0 and 1 (or 0% to 100%)
• Bioavailability is 100% (F = 1) following an intravenous injection, less following oral administration
• Determining bioavailability is important for calculating drug dosages for non-intravenous routes of administration.

Question 18

What is bioequivalence?

Answer 18

The term bioequivalence is often used to describe that two products have the same rates of absorption and bioavailability

Bioequivalence is important to determine whether different brands of a drug can be interchanged

Question 19

What is first pass metabolism?

Answer 19

= Metabolism of a drug before it reaches the systemic circulation
- Oral route of administration is most affected by first pass

Question 20

What are the three fundamental process of elimination via the kidney?

Answer 20

• Glomerular filtration
• Tubular reabsorption (usually lipophilic drugs)
• Tubular secretion

Question 21

Steps in urine formation?

Answer 21

• Filtration
   Only takes place in renal corpuscle
• Reabsorption
   Occurs when filtered material is moved back into the blood
• Secretion
   Removes selected material from the blood and places it in the filtrate

Question 22

What is the relevance of renal elimination?

Answer 22

• Urinary pH and renal blood flow also affect renal elimination
• In renal impairment, consider dosage reduction of drugs cleared predominantly by kidneys