Booklet 8: Routes of Administration

Question 1

What is pharmaceutics?

Answer 1

The science of dosage form design

Question 2

What is a fomulated preparation made out of?

Answer 2

1. Biologically active entity

2. Additives (excipients)

Question 3

What are the advantages of the oral route?

Answer 3

1. Simplest, most convenient and safest
2. For systemic or local effects
3. Drug needs to be able to survive acid conditions of the stomach, resistant to enzymatic attack and absorbed across GIT membrane

Question 4

What are the disadvantages of the oral route?

Answer 4

1. Relatively slow onset of action
2. Irregular absorption due to interaction with food
   Eg. Tetracycline with calcium
3. GI secretions and digestive enzymes (oral insulin)

Question 5

How long is the muscular tube in the gastrointestinal tract?

Answer 5

6cm

Question 6

What are the 4 main anatomical areas in the gastro intestinal tract?

Answer 6

1. Oesophagus
2. Stomach
3. Small Intestine
4. Large intestine or colon

Question 7

How is the surface area for absorption increased?

Answer 7

1. By its surface toughness

2. Majority of epithelium covered by mucus layer

Question 8

The Oesophagus

1. Where
2. pH
3. How is material moved?
4. Transit time
5. Impairment

Answer 8

1. Mouth to stomach
2. pH 5-6
3. Swallowing and peristalic wave of contraction assisted by gravity in an upright position
4. Transit time rapid (5-15s)
5. Swallowing impairment common in elderly

Question 9

The Stomach

1. Where
2. Capacity

Answer 9

1. Temporary reservoir to deliver to duodenum at controlled rate
2. Approx 1.5L (fasting may only be less than 50mL because it is mainly gastric secretions)

Question 10

What are gastric secretions of the stomach?

Answer 10

1. Hormone gastrin
2. Pepsins- secreted from peptic cells in the form of its precursor pepsinogen (peptidase)
3. Mucus (protection to the gastric mucosa)

Question 11

Small intestine

1. How long?
2. Main functions (2)
3. Division (3)
4. Purpose

Answer 11

1. 4-5m long
2. • Digest: complete enzymatic digestion from the stomach
   • Absorb: major site for absorption of most drugs and nutrients
3. • Duodenum (200-300mm)
   • Jejunum (2m)
   • Ileum (3m)
4. Main site of absorption for most drugs and nutrients

Question 12

How is the surface area of the small intestine increased?

Answer 12

1. Folds of Kerchring
2. Villi- approx 0.5-1.5mm long by 0.1mm diameter
3. Microvilli - 600-1000 each villus
   - Provide largest increase in surface area
   - Covered by fibrous substance (glycocalyx)

Question 13

What is in the structure of a villus in the small intestine?

Answer 13

Outer
- Microvilli
- Fats and partially digested fats
- Basement membrane
- Capillaries
- Lymph vessel
Inner

Question 14

What is the transit time of the small intestine?

Answer 14

3. 5-4.5 hours in healthy volunteers

- presence of fat does delay but only modest (30-60 minutes)

Question 15

Colon

1. How long is it?
2. How is the surface area increased?
3. Main functions (3)

Answer 15

1. 1.5m
2. Irregularly folded mucosae: increase 10-15 times that of a simple sylinder (1/30th of small intestine)
3. • Absorption: Na+, Cl-, water
   • Exchange: bicarbonate and K+
   • Storage and compaction of faeces

Question 16

What is the colon colonised by?

Answer 16

A variety of bacteria

Question 17

What is the pH of the Caecum?

Answer 17

6-6.5, increases to 7-7.5

Question 18

What is the transit time of the colon?

Answer 18

24 hours (about) 
- proteolytic activity very low compared to that of the small intestine
(time controlled release formulation, pH dependent release dosage forms)

Question 19

Mechansims of Drug Absorption

2

Answer 19

Transcellular

• accross cells
• passive diffusion
• carrier mediated :active transport, facilitated diffusion
• Endocytosis

Paracellular
- between cells

Question 20

Passive diffusion (driving force, eg)

Answer 20

1. Concentration difference and proceed from high to low concentration
2. Small lipophillic mechanisms, many drugs

Question 21

Active Transport

Answer 21

1. Require energy as driving force and proceed from low concentration to high concentration
2. May become saturated
3. May be competition for same transport system by similar substance

Question 22

Facilitated diffusion

Answer 22

1. Still requires concentration gradient as driving force as in passive diffustion
2. Faster rate than anticipated
3. Saturable and subject to inhibition
4. Very minor route for drug absorption

Question 23

Endocytosis

Answer 23

1. Primary mechanism to absorb macromolecules

Eg. Vaccine (polio) absorption

Question 24

Paracellular drug absorption

Answer 24

1. Via aq pours between cells
2. Small intestine relatively leaky
3. Important for transport of sugars, ions, amino acids, and peptides at concentrations above capacity of their carriers
4. Route for small hydrophilic and charged drugs

Question 25

Efflux of drugs from intestine

Answer 25

1. Efflux proteins expel specific drugs back into GIT | 2. Key counter transport proteins = P-glycoprotein

Question 26

What are some barriers to drug absorption in the lumen?

Answer 26

1. Chemical degradation 2. Enzymatic degradation 3. Complexation 4. Absorption

Question 27

What are some barriers to drug absorption in the unfiltered water layer?

Answer 27

1. Complexion to mucous | 2. Water and mucous diffusion

Question 28

Gastro intestinal membrane barriers

Answer 28

1. Transcellular transport 2. Paracellular transport 3. Efflux