Routes Of Admin Lec 2 PDB

Question 1

List three reasons what we prefer oral administration

Answer 1

1) Convenient
2) Well accepted by patients
3) Cheap

Question 2

Where does drug and nutrient absorption take place?

Answer 2

Small intestine

Question 3

The stomach secretes what two substances?

What happens to these two substances?

Answer 3

1) Hydrochloric acid
2) Pepsinogen

The hydrochloric acid stimulates the conversion of pepsinogen to pepsin by acidic hydrolysis.
Pepsin is a potent proteolytic enzyme

Question 4

What happens to polypeptides and short peptides in the stomach?

Answer 4

Polypeptides are broken down by pepsin whereas small peptides can pass through unchanged

Question 5

The small intestine has a huge surface area due to 3 things… what are they?

Answer 5

1) Folds of Kerckring
2) Villi
3) Microvilli

Question 6

The large intestine is also known as the what?

Answer 6

Colon

Question 7

The colon contains WHAT that can metabolise certain drugs?

Answer 7

Anaerobic and aerobic bacteria

Can metabolise drugs such as L-dopa

Question 8

Strongs acids (pKa 10) are…

WELL or POORLY absorbed?

Answer 8

POORLY absorbed as a high percentage of molecules are ionised at pH of 6.5

Question 9

What happens if movement of a drug through the GI tract is too fast?

Answer 9

The drug may pass through the system without being absorbed

Question 10

What happens if movement of a drug through the GI tract is too slow?

Answer 10

The drug may be degraded or the epithelium may be irritated

Question 11

The larger the meal, the __ the initial emptying rate

Answer 11

quicker

Question 12

First pass effect results in a net __ of drug which reaches systemic circulation

Answer 12

loss

Question 13

Amount of drug reaching systemic circulation depends on:

3 things…

Answer 13

1) Release from dosage form
2) Stomach, intestinal and hepatic 1st pass effects
3) Absorption across GI membrane

Question 14

What is enterohepatic recycling?

Answer 14

• Drug eliminated by biliary secretion into small intestine

- Reabsorbed and reaches systemic circulation

Question 15

Presence of food can have a complex effect on the abs and BA or drugs.
It can reduce, ___, ___ or have __ ____ on abs rate depending on drug

Answer 15

delay, increase or have no effect

Question 16

Food can have complex effects on abs and BA of drugs by many mechanisms. List 8

Answer 16

1) Delayed gastric emptying time
- damage to protein or acid labile drugs
2) Stim bile secretion
- inc solubilisation and abs of lipophilic drugs
3) Inc viscosity of luminal contents
4) Stim hepatic blood flow
- effects on first pass metab
5) pH changes in GO tract
- decreased pH may aid dissolution of basic drugs - ionise
6) Change in luminal metab
- some foods activate/inhibit enzymes in GI
7) Interaction of drug and food
- e.g chelation
8) Competition for uptake transporter
- e.g L-Dopa, abs by AA transporter so compete protein

Question 17

Statins cannot be taken with grapefruit juice for what reason?

Answer 17

Grapefruit juice inhibits CYP3A enzymes increasing BA of statin (reduces degradation) and can lead to muscle toxicity

Question 18

What is P-gp and where is it found?

Answer 18

An efflux pump found in the apical membrane of cells in the small and large intestine (also BBB and liver etc…)

Question 19

P-gp is known as an MDR protein. What does this stand for?

Answer 19

Multi drug resistance protein

Question 20

List 4 advantages to oral drug delivery…

Answer 20

1) Convenient (accessible, good compliance)
2) Large surface area and rich blood supply
3) Prolonged retention and potential for 0 order release
4) Cheap

Question 21

List 7 disadvantages to oral drug delivery…

Answer 21

1) Highly variable
2) Adverse reactions (gastro-toxicity)
3) High metabolic activity and hepatic 1st pass effect
4) pH extremes
5) Efflux pumps e.g P-gp
6) Intestinal motility
7) Impermeability of epithelium e.g large, hydrophobic peptides

Question 22

Name 5 strategies for improving oral drug delivery…

Answer 22

1) Increasing drug lipophilicity - prodrugs
2) P-gp inhibitors
3) Cytoadhesion - target drugs to specific areas or cells in GI tract
4) Mucoadhesive patches
5) New delivery systems e.g protective coatings, micro and nanoparticles (micelles, vesicles etc)

Question 23

How can membrane permeability be improved e.g in Ampicillin?

Answer 23

• Ampicillin is chemically modified to make more fatty prodrug
• Increases drug absorption as can cross lipid membrane
• Metabolised by esterase’s, cleaving the ester bond
• Leaves the parent drug

Question 24

P-gp inhibitors are extremely useful at increasing bioavailability by preventing the efflux of which group of oral agents?

Answer 24

• Chemetherapeutics