L10 - Absorption and distribution of drugs

Question 1

Describe the fate of an orally transmitted drug

Answer 1

1. Not dissolved - total oral dose
2. Dissolved in GIT
   - Broken down in stomach (acid) or intestine
   - Not absorbed
   - Secreted into bile
3. Absorbed
4. In liver
   - Secreted into bile
   - Metabolised = first pass metabolism
5. General circulation
   - Bound to plasma proteins (to tissues)
6. In tissues
   - Metabolised/ excreted
   - Tissue bound (to site of action)
7. At site of action

Question 2

Where can metabolism occur?

Answer 2

1. Liver
   - First pass metabolism
2. Kidney
3. Skin, lungs
4. Microbiome
5. Basically anywhere in body
   - Conjugation to small soluble molcs (e.g. sulfation pathways)

Question 3

What happens in phase 1 of biotransformation?

Answer 3

• Oxidation via cytochrome P450 enzymes
• Intro of hydroxyl groups
• Compounds get more hydrophilic
• Occurs simultaneously as phase 2

Question 4

What happens in phase 2 of biotransformation?

Answer 4

• Conjugation reactions
• Charged groups are conjugated (linked) to compounds
• Compounds get even more hydrophilic
  Groups to be linked:
• Sulfate
• Glucuronidate
• Occurs simultaneously as phase 1

Question 5

What is the definition of absorption?

Answer 5

Movement of a drug from its site of administration into the plasma
- Tends to involve passage through layers of cells (epithelia)

Question 6

What is the definition of distribution?

Answer 6

Reversible transfer of a drug from one location to another within the body
- Tends to involve passage through layers of cells (epithelia)

Question 7

What does lipophilicity strongly depend on?

Answer 7

Whether a compound can pass through membranes

Question 8

What is the relationship between ionised and unionised forms of a drug?

Answer 8

Many drugs exist in equilibrium between ionised and unionised forms

• Only the unionised form is sufficiently lipid-soluble to diffuse through membranes

Question 9

Where will drugs tend to accumulate?

Answer 9

Drugs will tend to accumulate in areas where ionisation is favoured

Question 10

Many drugs are weak acids or weak bases, what will this mean?

Answer 10

• Their pKa values are in the physiological pH range

- The degree of ionisation depends on local pH

Question 11

What does absorption depend on?

Answer 11

1. Route of administration
2. Blood flow at site of administration
3. Dose of drug
4. Active v passive diffusion through a membrane
5. Drug solubility
6. Bioavailability

Question 12

What is bioavailability?

Answer 12

The fraction of the total dose administered that reaches the plasma

Question 13

What are the different routes of drug administration?

Answer 13

1. Enteral routes
   - Oral
   - Rectal
2. Parenteral routes
   - Subcutaneous
   - Intra-muscular
   - Intra-venous
   - Intra-arterial
   - Intra-thecal
   - Intra-peritoneal
3. Percutaneous (by way of skin)
   - Inhalation
   - Sublingual
   - Topical/ transdermal
   - Through mucous membranes (e.g. intranasal)

Question 14

What are the different pharmaceutical interventions that can influence absorption?

Answer 14

1. Particle size
2. Dry-powder inhaler
3. Enteric coated tablets (slow release)
4. Slow/ delayed release preparations

Question 15

What factors can affect transdermal absorption?

Answer 15

1. Lipid solubility
2. Formulation
3. Skin thickness
   - Area
   - Age
   - Damage
4. Hydration
   - Occlusive dressings
5. Blood flow

Question 16

What does distribution depend on?

Answer 16

1. Ability of the drug to pass through …?
   - Blood brain barrier
   - Placenta
2. Tissue binding
3. Blood flow
   4.

Question 17

What is the definition of apparent volume of distribution (AVD)

Answer 17

The notional volume of fluid required to dilute the absorbed dose to the concentration found in plasma

Question 18

What is the formula of AVD?

Answer 18

AVD (vol) = dose (unit of mass) / [plasma] (mass/vol)

Question 19

What does an AVD=6 litres say about a drug?

Answer 19

Drug is heavily plasma-protein bound

Question 20

What does an AVD > 70 litres say about a drug?

Answer 20

Drug is heavily tissue bound

Question 21

What are the different ways that a drug can be eliminated?

Answer 21

1. Urine
2. Faeces
3. Milk, sweat
4. Expired air

Question 22

What is ion trapping?

Answer 22

The build up of a higher conc of a chemical across a cell membrane due to the pKa value of the chemical and difference of pH across the cell membrane
- Does not require any enzyme of energy

Question 23

How is ion trapping similar to osmosis?

Answer 23

They both involve the semi-permeable nature of the cell membrane

Question 24

Where will weak acids tend to be well absorbed?

Answer 24

Weak acids tend to be well absorbed from acid environments and accumulate in basic environments

Question 25

Where will weak bases tend to be well absorbed?

Answer 25

Weak bases will tend to be well absorbed from basic (alkaline) environments and accumulate in acidic environments

Question 26

Why are basic (alkaline) drugs secreted into the stomach

Answer 26

Due to ion trapping | - pH is acidic in the stomach, therefore alkaline drugs are secreted into the stomach

Question 27

Where can acidic drugs excreted?

Answer 27

Acidic drugs are excreted in urine when it is alkaline

Question 28

What factors affect the abs of drugs from the GIT?

Answer 28

1. Dispersal/ solubility of drug in gut contents - Formulation 2. Stability of the drug - Acid/ alkali and digestive enzymes 3. Lipid solubility of the drug 4. Time available for abs - Transit time - Diarrhoea and vomiting 5. Conc of drug 6. Blood flow 7. Interaction with food 8. Effect of drug on GIT (irritant etc) 9. Effect of meals 10. First pass metabolism?