ADME

Question 1

What are the TWO main important factors for ADME ?

Answer 1

lipophilicity and hydrophilicity

Question 2

what is logP ?

Answer 2

it is the measure of the lipophilic / hydrophilic nature of a molecule

Question 3

what are the characteristics of lipophilic and hydrophilic molecules ?

Answer 3

lipophilic
1. insoluble in aqueous environment
2. Binds strongly on plasma proteins

hydrophilic
1. soluble in aqueous environment
2. Inability to cross plasma membrane

Question 4

what biopharmaceutical factors affect lipophilicity and hydrophilicity ?

Answer 4

1. Permeability and solubility
2. Size matters
   
   • Use of diffusion, aqueous channels and carriers.
3. Ionisation and pH trapping
   
   • if an ion is thrown on a membrane, it will repel. Therefore we need ion channels
   • unionised form of drugs will pass membrane while ionised will not
   • acidic drug can exist in unionised state thereby more likely to pass plasma membrane
   • basic drugs are less acidic, therefore more like to dissociate to ionised form .

Question 5

What is oral bioavailability

Answer 5

Extent and rate at which a drug enters systemic circulation and reaches the target area

Question 6

List FOUR factors affecting absorption

Answer 6

• 1st pass metabolism
• Gastric emptying
• modified release formula
• Food : eating can change the pH of the stomach which can then impact absorption

Question 7

what is volume of distribution (Vd). State its formula and units

Answer 7

Is a pharmacokinetic parameter that relates the total amount of drug in the body to the concentration in the bloodstream

Vd = Amount of drug in body (D)
————————————
Plasma concentration (Cp)

Units = Litres /kg

Question 8

Discuss FOUR factors that affect distribution

Answer 8

1. Physiochemical properties of drug
   - size of drug molecules
   Larger molecules do not easily cross membrane. For example heparin

• pKa of drug
  pka difference between plasma and tissue can lead to accumulation
• hydrophobic substances tend to become enrich in fat tissue (obesity can influence distribution of drugs

2. Barriers of organ or tissue

• lipid soluble drugs can pass readily from mother to fetus
• presence of blood brain barrier

Question 9

Name 5 characteristics of a perfect drug

Answer 9

1. passes into the body
2. Reaches its biological target
3. Stays in the body long enough to achieve its therapeutic end
4. Does not produce harm while in the body
5. Exits the body when its job is done

Question 10

Drug metabolism occurs at TWO sites. For each site state the organs it occurs at.

Answer 10

1. At tissue level

• liver, kidney and lungs

2. At intracellular level

• smooth endoplasmic reticulum

Question 11

Outline phase 1 metabolism

Answer 11

In phase 1, the reaction changes the structure of the drug molecule.
So from drug to derivative.

e.g oxidation, reduction and hydrolysis

Drug ———— Derivative

Question 12

What is 1st pass metabolism

Answer 12

When some of the drug gets metabolised before it reaches its site of action

Question 13

Describe the role of conjugation in relation to phase II metabolism

Answer 13

• Form covalent bonds
• Increase water solubility
• Form an inactive product

Question 14

Describe TWO factors that affect metabolism

Answer 14

1. Genetic factors
2. External factors

e.g consumption of grape fruits can lead to increased concentration of drug in blood due to inhibition of the enzyme CYP3A4 . Which is dangerous for drugs with low therapeutic index such as immunodepressant, statins, CCB

Explanation: Grapefruit juice can block the action of intestinal CYP3A4, so instead of being metabolised, more of the drug enters the blood and stays in the body longer