Factors Affecting Absorption

Question 1

List 3 drug properties that affect absorption from the GIT

Answer 1

Solubility - drug form (salts), pH (ionisation), surfactants (e.g. bile salts)
Dissolution - particle size, polymorphism
Diffusion

Question 2

Which form will the molecules of a weak acid be in in the stomach (pH 1.2) and the intestines (pH 6.8)?

Answer 2

Stomach (acidic) = mostly unionised

Intestines (more alkaline) = nearly totally ionised

Question 3

Which form will the molecules of a weak base be in in the stomach (pH 1.2) and the intestines (pH 6.8)?

Answer 3

Stomach (acidic) = mostly ionised

Intestines (more alkaline) = nearly totally unionised

Question 4

What does the pH-partition hypothesis state?

Answer 4

Weakly acidic drugs are likely to be absorbed from the stomach where unionised (however often better absorbed from the intestines)
Bases will be best absorbed in the intestines (mostly unionised here)

Question 5

Why are substances better absorbed in the intestine than in the stomach? (4)

Answer 5

Intestines have:
Larger surface area for absorption
Longer residence time for absorption
Rich blood and lymph supply in walls
Ionised form could interact with other ions in the GI fluid to form a neutral pair = aids lipophilicity

Question 6

List the 4 main regions for absorption of the GIT

Answer 6

Oesophagus
Stomach
Small intestine
Large intestine (colon)

Question 7

How is lubrication provided in the oesophagus?

Answer 7

Epithelial cells with simple mucous glands secrete mucus to lubricate the oesophagus

Question 8

How is food moved down the oesophagus?

Answer 8

Single peristaltic wave moves down oesophagus and also helped by gravity

Question 9

What is Gastrin?

Answer 9

Stimulates acid production
Stimulated by peptides, amino acid and muscle distention
Released from G cells

Question 10

Name the 5 sub-sections of the large intestine/colon

Answer 10

Caecum
Ascending colon
Transverse colon
Descending colon
Rectum

Question 11

How are the contractions of gastric emptying stimulated?

Answer 11

The contractions are electrically stimulated

Question 12

Describe the 4 phases of gastric emptying

Answer 12

I: occasional contractions over 40-60 mins
II: more contractions over 40-60 mins
III: powerful peristalsis, pylorus opens and stomach empties
IV: short transition back to phase I
This repeats every 2 hours until fed

Question 13

What must be in the stomach in order for a drug to reach the small intestine quickly?

Answer 13

No food, only water

Question 14

Why should tetracycline be taken on an empty stomach?

Answer 14

The tetracycline can form an insoluble complex with calcium ions

Question 15

Why should grapefruit juice be avoided when taking statins?

Answer 15

Some statins interact with bergamottin in the juice

Question 16

Why should aspirin and ibuprofen be taken with food?

Answer 16

To avoid irritation of stomach lining

Question 17

List 4 factors that influence colonic transit

Answer 17

Diet
Eating pattern
Disease
Dosage form

Question 18

How is drug absorption different in neonates?

under 4 weeks

Answer 18

Neonates have fewer bile salts which can reduce drug absorption

Question 19

How is drug absorption different in infants?

Answer 19

Intestinal microflora changes can increase some drug absorption

Question 20

How is drug absorption different in the elderly?

Answer 20

Increase in gastric pH and transit times

Decrease in GI fluid volumes and gut wall enzymes

Question 21

List 4 barriers to drug absorption in the GI lumen

Answer 21

Chemical degradation - pH-dependent degradation of some drugs
Enzymatic degradation
Complexation - to dietary components or secretions
Adsorption

Question 22

Which enzymes in the GIT can cause enzymatic degradation of drugs?

Answer 22

Stomach: pepsin
Small intestines: lipases, amylases, proteases
Colon: many bacterial enzymes

Question 23

Name the 4 barriers that a drug molecule must pass through in order to reach the circulation

Answer 23

Lumen
Unstirred water layer
Gastro-intestinal membrane (transcellular or paracellular)
Presystemic metabolism

Question 24

What is the unstirred water layer?

Answer 24

Epithelial cells are covered with this boundary layer
Made up of water, mucus, glycocalyx
Can be a diffusional barrier to drug absorption

Question 25

Describe the transcellular route through the GI membrane (3)

Answer 25

By passive diffusion
Driven by concentration gradient across membrane
Dependent on partition coefficient, MW and binding

Question 26

Describe the paracellular route through the GI membrane (4)

Answer 26

Molecules travel through tight junctions - “controlled gate”
Moderately sized molecules can pass, not particles
Generally passive diffusion but selective for cationic (+ve) drugs, not -ve or neutral drugs
Important route for ions and amino acids

Question 27

Describe the carrier-mediated route through the GI membrane (3)

Answer 27

There are many transporters (proteins) in the apical membrane
Each transporter is substrate-specific
But for drugs with properties similar to a natural substrate, they can bind to the transporter and be carried through the apical membrane against the concentration gradient

Question 28

Describe the endocytosis route through the GI membrane

Answer 28

Plasma membrane forms membrane-bound vesicles

Question 29

Define: Pinocytosis

Answer 29

Fluid containing drug is engulfed into cell

Question 30

Define: Receptor mediated endocytosis

Answer 30

Cell surface receptor binds to molecules and stimulates endocytosis
Vesicle degrades in cell

Question 31

Define: Transcytosis

Answer 31

Vesicle with internalised material is transported through the cell and secreted on opposite (basolateral) side

Question 32

What is pre-systemic metabolism?

Answer 32

1st pass metabolism
Drugs come from GIT and enter hepatic portal vein to liver before reaching systemic circulation
Can radically reduce plasma levels of the drug
Can be avoided by other delivery routes (buccal, sublingual, transdermal, rectal)