ADME (l4-8)

Question 1

How do drugs move around the body?

Answer 1

a- by bulk flow (bloodstreamm, lymphatics, cerebrospinal fluid). Chemical nature has no effect
b- by diffusion across barriers (gastrointestinal mucosa, BB barrier etc.). Chemical nature has big effect.

Question 2

What are the 3 methods of injection?

Answer 2

Intravenous (IV), intramuscular (muscle) and subcutaneous (in skin, below the muscle)

Question 3

What does the term ‘depot’ refer to?

Answer 3

When drugs are manufactured using an oil base which retards the movement of the formulation out of the muscle and into the bloodstream. The injected dose is stored in the musle and diffuses over time

Question 4

Outline oral administration

Answer 4

Usually enteral/ GI. Has a large, high permeable surface area with excellent blood supply (vascularised). Enterocytes of epithelium contain metabolic enzymes and transporters.

Question 5

What is the issue with the enteral route?

Answer 5

It is the most unpredictable as many drugs go through firrst pass metabolism and may need to cross many barriers to get to site of action. Thus most drugs are taken by mouth and swallowed. Mainly weak acids/bases are absorbed if not hydrolysed by the stomach

Question 6

Where are drugs broken down?

Answer 6

In the liver. What’s left is the bioavailable drug which enters the bile and entral hepatic circulation.
Drugs eliminated in the bile can be reabsorbed in the GI tract, where its secreted into the bile. Then it’s stored in the gall bladder and released into the duodenum

Question 7

Name other enteric (GI) routes of administration

Answer 7

• Sublingual e.g. films and sprays, avoids first pass metabolism –> fast action
• Rectal e.g. suppositories and enemas, avoids 2/3 first pass metabolism

Question 8

Outline the process of an orally given drug

Answer 8

1. Moves through gut
2. Absorption into blood
3. Enters hepatic portal vein
4. Transported to liver
5. Transferred to gall bladder in bile
6. Secreted into small intestine, then the process starts again

Question 9

Give 2 examples of a pareneral route

Answer 9

1- Inhalation e.g. powder, gases and suspensions. Excelnt network of capillaries = bypasses first pass metabolism = rapid action e.g. anaesthetics

2- Topical; drugs administered to site needed to reduce systemic absorption= reduced side effects. As they don’t need to cross barriers there’s a higher [drug] at site

Question 10

What factors affect absorption?

Answer 10

Solubility and permeability
- Increased water solubility= increased dissolution in GI= increased concentration in GI.
- Many drugs exist as either ionised= not lipid soluble or unionised= lipid soluble so can diffuse readily through layers
High solubility= easily broken down & high permeability= easily transported= rapid response
The pH of the environment will also affect how well the molecule will transport through the membrane

Question 11

How much of an orally given drug is usually absorbed in 1-3 hours?

Answer 11

75%

Question 12

What factors can affect absorption?

Answer 12

• Blood flow
• Surface area
• Gastric motility (may be altered by disorder e.g. drug treatment, migraine)
• With food (splanchnic blood flow)
• particle size
• Capsules/ coatings delaying dissolution

Question 13

How is absorption quantified

Answer 13

By the fraction of the drug administerde that is absorbed and therefore available to have an effect in the body = bioavailability (f)

Question 14

How is bioavailability calculated?

Answer 14

(AUC oral/ AUC iv) * (Dose iv/ Dose oral)

Question 15

Define the following terms:

• Cmax
• Tmax
• Cp
• AUC

Answer 15

Cmax is the max concentration of compound after dosing
Tmax is the time taken to reach max [drug]
Cp is plasma drug concentratiin
AUC is area under curve, a measure of total systemic exposure. It is calculated by measuring the area under the concentration time curve