Week 1 - Pharmacokinetics

Question 1

Define Pharmacokinetics

Answer 1

The study of the passage of a drug through the body.
- ‘What the body does to the drug’

Question 2

What are the processes of Pharmacokinetics

Answer 2

• Absorption
• Distribution
• Metabolism
• Excretion

Question 3

What is Absorption

Answer 3

The process by which an unchanged drug proceeds from the site of administration into the blood.

Question 4

Why is drug formulation important

Answer 4

The drug formulation is important because the faster the rate of dissolution, the more rapidly the drug can be absorbed.

Question 5

What type of oral drug is absorbed the fastest

Answer 5

Liquids

Question 6

How does a drug get absorbed

Answer 6

A drug needs to cross a membrane and enter the blood vessels to reach the target site

Question 7

What are the two main processes for the drug to cross membranes

Answer 7

1. Passive diffusion
2. Carrier-medicated transport

Question 8

Explain the structure of membranes which facilitates passive diffusion

Answer 8

• The membrane typically consists of a lipid bilayer
• E.g lipid soluble drugs can easily pass through the lipid membrane
• While Ionised (charged) drugs have difficulty passing the membrane.

Question 9

Define solubility in drugs

Answer 9

• The more soluble the drug is, the more rapidly it is absorbed
• E.g high lipid solubility increase drug absorption

Question 10

Define the difference between Ionised and Un-ionised

Answer 10

• Ionised (charged polar) are water-soluble, it’s lipid-insoluble which means it does not diffuse readily through the cell membranes of the body
• Un-ionised (non-polar) are more lipid-soluble and can easily cross membranes

Question 11

What drugs can easily pass the ‘blood-brain barrier’

Answer 11

Lipid-soluble drugs can easily pass the BBB, while water-soluble drugs are ionised and cannot enter the brain

Question 12

Explain how the surface area affect drug absorption

Answer 12

• A larger absorbing surface area results in a greater drug absorption and the more rapid effects.
• E.g Small Intestine - Large surface area which means drugs are efficiently absorbed

Question 13

Provide an example where the surface area affect the drug absorption

Answer 13

• Sublingual route has a rich blood supply which enhances absorption
• Subcutaneous route has poor vascular sites which delays absorption

Question 14

Explain how the drug formulation affect drug absorption

Answer 14

• Drug formulation can be manipulated to achieve absorption characteristics
• E.g Enteric coated drugs allows sustained release which are useful for drugs that have shorter elimination half-life

Question 15

Explain how the route of administration affect drug absorption

Answer 15

It affects both the rate of onset of action and the magnitude of the therapeutic response

Question 16

Explain why medication are administered on an empty stomach

Answer 16

• The stomach is not a major site for drug absorption
• Ensure dissolution of the drug and rapid passage into the small intestines

Question 17

Define the first-pass effect

Answer 17

Metabolisation of the drug (mostly by the liver), resulting in a reduced concentration of the active drug

Question 18

Define Bioavailability

Answer 18

The proportion of the administered does that reaches the systemic circulation intact

Question 19

Explain the first-pass metabolism

Answer 19

• Orally administered drugs are absorbed in the small intestine.
• Then travel through the portal vein to the liver.
• The liver metabolizes a portion of the drug (first-pass metabolism)
• The remaining amount enters systemic circulation.

Question 20

Provide an example of the first pass metabolism

Answer 20

• You take a drug that contains 100mg
• 80mg of the drug reaches the liver as 20mg isn’t absorbed
• 60mg is extracted in the first pass through the liver

The bioavailability of the drug:
- 20% - As only 20mg is available for distribution and to produce an pharmacological effect

Question 21

Define Distribution

Answer 21

The process of reversible transfer of a drug between one location and another (one of which is usually blood) in the body

Question 22

Explain Plasma Protein Binding

Answer 22

1. When the drug enters the systemic circulation, a proportion of the free drug molecules binds to proteins which is the ‘drug-protein complex’
2. The free drug then enters the tissues to exert a pharmacological effect.
3. Drug-protein complex acts a reservoir, slowly releasing more free drug as needed.

Question 23

Explain the Plasma Protein Binding of Warfarin

Answer 23

• Warfarin has the highly protein bound drug (99%)
• 99% is bound to plasma proteins while 1% of free drug is for distribution

Question 24

Why can low levels of albumin in the blood be dangerous when administering protein-bound drugs

Answer 24

• Low albumin levels increase free drug concentration, leading to stronger effects and a higher risk of toxicity.
• Dose adjustments may be needed (e.g., for phenytoin, warfarin).

Question 25

What is tissue binding in lipid-soluble drugs, and how does it affect their duration of action?

Answer 25

Tissue binding occurs when lipid-soluble drugs bind to adipose tissue because it is stable and has low blood flow. This leads to the drugs being stored in the fat, which results in a longer duration of action due to the drug being released slowly over time.

Question 26

Explain the structure of Blood-brain barrier

Answer 26

- Comprises the endothelial cells of brain capillaries, which are joined to each other by tight junctions - It provide further protection to the brain - The lipid-soluble drugs does penetrate into the brain and cerebrospinal fluid

Question 27

In what situations can other drugs cross the blood-brain barrier

Answer 27

- In meningitis, the blood–brain barrier can become ‘leaky’ (inflammatory process) - Allowing access of drugs such as penicillin (that would not normally) > allow treatment of meningitis

Question 28

What is Drug metabolism

Answer 28

The process of chemical modification of a drug, mostly by enzymes - The liver is the primary site of drug metabolism

Question 29

What is the difference between pro drug and active drug

Answer 29

Active Drug - Drug takes effect directly Pro drugs - Most drugs are less active after drug metabolism. - However, pro drug require activation (in the liver) in order to elicit a therapeutic action - E.g. Anti-rheumatic- leflunomide

Question 30

What is excretion

Answer 30

- The loss of a parent molecule or a metabolite* in, for example, urine or bile. - The kidneys> the main organs of excretion. - Once in the hepatocyte, the drug becomes available for metabolism by enzymes or for excretion into bile

Question 31

Define metabolites in hepatocyte

Answer 31

1. Diffuse 2. Be transported across back into blood for excretion in urine 3. Be transported into the bile> passed into the duodenum > excreted in faeces

Question 32

Define half life

Answer 32

The time required for the concentration of a drug in the body to reduce by half.

Question 33

What are two processes that influence half life

Answer 33

- The smaller volume of distribution (degree of a drug distributing in the body) > shorter half-life - The higher clearance > shorter half-life