Factors Affecting Absorption Flashcards Preview

PM2B Spring Amy L > Factors Affecting Absorption > Flashcards

Flashcards in Factors Affecting Absorption Deck (32):
1

List 3 drug properties that affect absorption from the GIT

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

2

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

Stomach (acidic) = mostly unionised
Intestines (more alkaline) = nearly totally ionised

3

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

Stomach (acidic) = mostly ionised
Intestines (more alkaline) = nearly totally unionised

4

What does the pH-partition hypothesis state?

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)

5

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

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

6

List the 4 main regions for absorption of the GIT

Oesophagus
Stomach
Small intestine
Large intestine (colon)

7

How is lubrication provided in the oesophagus?

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

8

How is food moved down the oesophagus?

Single peristaltic wave moves down oesophagus and also helped by gravity

9

What is Gastrin?

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

10

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

Caecum
Ascending colon
Transverse colon
Descending colon
Rectum

11

How are the contractions of gastric emptying stimulated?

The contractions are electrically stimulated

12

Describe the 4 phases of gastric emptying

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

13

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

No food, only water

14

Why should tetracycline be taken on an empty stomach?

The tetracycline can form an insoluble complex with calcium ions

15

Why should grapefruit juice be avoided when taking statins?

Some statins interact with bergamottin in the juice

16

Why should aspirin and ibuprofen be taken with food?

To avoid irritation of stomach lining

17

List 4 factors that influence colonic transit

Diet
Eating pattern
Disease
Dosage form

18

How is drug absorption different in neonates?
(under 4 weeks)

Neonates have fewer bile salts which can reduce drug absorption

19

How is drug absorption different in infants?

Intestinal microflora changes can increase some drug absorption

20

How is drug absorption different in the elderly?

Increase in gastric pH and transit times
Decrease in GI fluid volumes and gut wall enzymes

21

List 4 barriers to drug absorption in the GI lumen

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

22

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

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

23

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

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

24

What is the unstirred water layer?

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

25

Describe the transcellular route through the GI membrane (3)

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

26

Describe the paracellular route through the GI membrane (4)

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

27

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

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

28

Describe the endocytosis route through the GI membrane

Plasma membrane forms membrane-bound vesicles

29

Define: Pinocytosis

Fluid containing drug is engulfed into cell

30

Define: Receptor mediated endocytosis

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

31

Define: Transcytosis

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

32

What is pre-systemic metabolism?

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)