Factors Affecting Absorption Flashcards
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
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
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
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)
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
List the 4 main regions for absorption of the GIT
Oesophagus
Stomach
Small intestine
Large intestine (colon)
How is lubrication provided in the oesophagus?
Epithelial cells with simple mucous glands secrete mucus to lubricate the oesophagus
How is food moved down the oesophagus?
Single peristaltic wave moves down oesophagus and also helped by gravity
What is Gastrin?
Stimulates acid production
Stimulated by peptides, amino acid and muscle distention
Released from G cells
Name the 5 sub-sections of the large intestine/colon
Caecum Ascending colon Transverse colon Descending colon Rectum
How are the contractions of gastric emptying stimulated?
The contractions are electrically stimulated
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
What must be in the stomach in order for a drug to reach the small intestine quickly?
No food, only water
Why should tetracycline be taken on an empty stomach?
The tetracycline can form an insoluble complex with calcium ions
Why should grapefruit juice be avoided when taking statins?
Some statins interact with bergamottin in the juice
Why should aspirin and ibuprofen be taken with food?
To avoid irritation of stomach lining
List 4 factors that influence colonic transit
Diet
Eating pattern
Disease
Dosage form
How is drug absorption different in neonates?
under 4 weeks
Neonates have fewer bile salts which can reduce drug absorption
How is drug absorption different in infants?
Intestinal microflora changes can increase some drug absorption
How is drug absorption different in the elderly?
Increase in gastric pH and transit times
Decrease in GI fluid volumes and gut wall enzymes
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
Which enzymes in the GIT can cause enzymatic degradation of drugs?
Stomach: pepsin
Small intestines: lipases, amylases, proteases
Colon: many bacterial enzymes
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
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
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
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
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
Describe the endocytosis route through the GI membrane
Plasma membrane forms membrane-bound vesicles
Define: Pinocytosis
Fluid containing drug is engulfed into cell
Define: Receptor mediated endocytosis
Cell surface receptor binds to molecules and stimulates endocytosis
Vesicle degrades in cell
Define: Transcytosis
Vesicle with internalised material is transported through the cell and secreted on opposite (basolateral) side
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)
