Drug Availiability

Question 1

What is a partition coefficient?

Answer 1

A way of calculating how well a drug is dissolved in oil or water

Question 2

Which compound crosses the phospholipid bilayer most easily - a polar or a nonpolar compound?

Answer 2

A nonpolar compound

- small polar compounds can also cross the phospholipid bilayer, having a molecular weight of 1000 or less

Question 3

How do we determine the partition coefficient?

Answer 3

1. add drug to a flask containing half oil and half water and shake it
2. siphon water, measure the drug content in the the water, then do the same for the oil
   - the partition coefficient measures how hydrophobic or lipophobic a compound is

Question 4

What extra steps do pharmacologists have to take into account when considering enteral drugs?

Answer 4

They have to take into account the pH of the stomach (1 pH or 2 pH) as well as the pH of the intestines (pH 5- 6.5)

Question 5

What is physiological pH?

Answer 5

The human pH level (around 7.4)

Question 6

What is a pKa?

Answer 6

a calculation that represents the pH at which the drug is 50% water soluble and 50% fat soluble
- it is the pH of the solution from which we calculate the partition coefficient

Question 7

What does how well a drug will be polarized determine?

Answer 7

How well it will react in different pH environments

Question 8

What is the first rule to remember about the polarity of a weak acid (exam question)?

Answer 8

A weak acid will become LESS ionized in an ACIDIC environment (it will become more fat soluble in an acidic environment)

Question 9

What is the second rule to remember about the polarity of a weak base (exam question)?

Answer 9

A weak base will be less ionized in an alkaline environment (it will become more water soluble in an acidic environment)

Question 10

What determines how well a drug will be absorbed in a specific environment?

Answer 10

The drug’s pKa (the pKa is the standard for the relativity of the pH of the environment)

Question 11

What does amphoteric mean?

Answer 11

A compound that has 2 pKa’s (one at an extreme acid and one at an extreme base)

Question 12

What other factors determine the absorption of a drug?

Answer 12

1. body size (the bigger the body, the higher the fat percentage, and the fat to water ratio is different)
2. gender (females have a higher percentage of fat and a lower percentage of water)
3. Age (children are smaller but have a faster metabolism)

Question 13

What is corticosteroid binding globulin?

Answer 13

A transporter protein for cortisol (which is unionized)

Question 14

What is adipose tissue?

Answer 14

Body fat

Question 15

What happens when a particle is more ionized?

Answer 15

It stays in the blood longer (because it is hydrophilic)

Question 16

What is one way that a drug gets distributed in the body?

Answer 16

Via transporter proteins

Question 17

What is one example of a transporter protein?

Answer 17

Albumin (mostly for unionized compounds)

Question 18

What is depot binding?

Answer 18

When the drug gets stuck in carrier proteins and adipose tissue

Question 19

What are fenestra?

Answer 19

Gaps in a capillary that allow for crossing of particles

Question 20

What do the capillaries of the blood-brain barrier lack?

Answer 20

Fenestra

Question 21

What are the only three ways a particle can cross the blood-brain barrier?

Answer 21

1. having a transporter (like L-Dopa, the precursor to dopamine)
2. being a nonpolar compound
3. being a small compound

Question 22

What is biotransformation?

Answer 22

Biologically changing the compound (aka metabolic clearance)

Question 23

Where does most metabolism take place?

Answer 23

In the liver

Question 24

What is the goal of metabolism (exam question)?

Answer 24

The goal of metabolism is to make the compound more ionized (therefore making it more abundant in the blood, and not leaking to other membranes…this makes it easier to eliminate)
- metabolism also deactivates (or sometimes activate) the compound, but this is really incidental

Question 25

What is the area postrema?

Answer 25

One of the few regions of the brain not protected by the blood-brain barrier (is the vomiting centre of the brain)
- detects toxic substances in the bloodstream

Question 26

What are some ways that we eliminate a drug?

Answer 26

• defication
• urination
• perspiration
• respiration
• through breastmilk

Question 27

What is one example of the body metabolizing a drug to activate it?

Answer 27

Aspirin is inactive until the body breaks it down into salicylic acid

Question 28

Describe a phase I reaction in metabolism?

Answer 28

• is non-synthetic
• has three processes
  
  1. oxidation (removes electrons)
  2. reduction (adds electrons)
  3. hydrolysis (adds H2O, an ion)
• goal is to make it more ionized*

Question 29

Describe a phase II reaction in metabolism?

Answer 29

• is a synthetic process
• has four processes:
  
  1. methylation (adds a methyl group)
  2. acetylation (adds an acetyl group)
  3. glutathione
  4. glucurinidation

Question 30

What is the difference between a synthetic and a non-synthetic process?

Answer 30

A synthetic process adds a compound to make it more polarized, while a non-synthetic process manipulates the ions already present in the compound

Question 31

What is a p450 enzyme?

Answer 31

A group of enzymes that are mostly responsible for biotransformation

Question 32

What is a metabolite?

Answer 32

A product of metabolism