Absorption from GIT 1 Flashcards
The oral cavity contains the greatest variety of micro-organisms present within the human body.
Why can’t these organisms enter the body further from the oral cavity?
Entry of the microorganisms + potential toxic waste is limited by the oral epithelium (not a highly permeable membrane)
What should the drug do before it can be absorbed from oral cavity?
The drug should first dissolve in saliva.
- Poorly water-soluble compounds will not dissolve well + likely to be swallowed intact.*
- Even if drug is dissolved in oral cavity, the saliva is constantly being swallowed + process competes vith absorption across oral mucosa*
What are the advantages of oral mucosa drug delivery?
Oral cavity is rich in blood vessels + lymphatics therefore a rapid onset of action + high blood levels are obtained quickly
Drugs absorbed through the oral mucosa enter bloodstream directly via jugular vein + avoid metabolism in the liver before systemic circulation
What are the disadvantages of oral mucosal drug delivery?
Only small moderately lipophilic molecules can be absorbed
- very lipophilic molecules will not solubilise in saliva = will be poorly absorbed in the mouth
- polar molecules (ionised in saliva pH 6.7 - 7.4) will not penetrate the oral mucosa and will be poorly absorbed
Dosage form must be kept in place during absorption process
A significant amount of drug must be swallowed
Total area for absorption is low
Taste of drug must be bland
Drug must be non-irritant
What is the main function of the stomach?
Processing food
- Stomach is a processing organ not absorptive.*
- Therefore, most drugs will be absorbed in the small intestine + not stomach*
Why is there little absorption in stomach for most drugs?
Stomach = total absorptive are of 1m2, perfusion 150ml/min, low permeability of membranes
Small intestine = total absorptive area 200m2, perfusion 1L/min, high permeability of membranes
There is little absorption in the stomach…but why is the stomach important for absorption of drugs after oral administration?
Environment: The human stomach secretes 1-1.5L of gastric juice per day – highly acidic and reach in enzymes. The pH ranges from 1.5-2(fasting) to 3-6 (fed).
This environment affects solubility, ionisation and stability of drugs
Motility: Gastric emptying time is highly variable (transit time 0-2h).
Presence of food, size of the meal, as well as food or formulation components will greatly affect gastric emptying time, and therefore the rate of absorption of drugs
Which part of the body is the main absorption site?
Small intestine
Primary function = digestion + absorption
Large SA available for absorption (due to folding into microvilli + villi)
Highly perfused: blood capillary + lymphatic lacteals
Transit time = 3-4 hours
Describe the absorption mechanism of the small intestines
For the drug to enter membrane of the enterocyte, the drug molecule should overcome barriers:
-
Solubility in the aqueous environment of GIT lumen
- a drug must solubilise in the GIT lumen before it can be absorbed
- solubility depends on hydrophobicity + pKA of the drug + environment in the GIT
-
Prescence of unstirred water layer + mucus
- due to the layer being static, drug movement is by diffusion whcih is slow
- Chemical + enzymatic stability in the GIT lumen
What properties should the drug molecule have to pass enterocyte membrane (intestines)?
Small
Stable
Hydrophilic
Ionised
- These molecules will arrive easily*
- Solubility is very important*
Why does the small intestines have a higher absorptive layer than the stomach epithelium?
Stomach epithelium does not have microvilli
There are tight junctions imbetween intestinal epithelial cells = form intercellular barrier between epithelial cells
Although some hydrophilic drugs can be absorbed through the intercellular route, the transport route is not as important as transcellular.
Passive diffusion is the main mechanism of absorption when transporting drugs across cell membranes.
How do we describe Passive diffusion?
D (diffusion coefficient) is drug molecule specific
Physicochemical properties that determine diffusion coefficient = partition coefficient + molecular weight
What is partition coefficient?
How we measure lipophilicity of a drug (how the drug distributes itself between a pair of solvents when it is in un-ionised form)
- Hydrophobic drugs dissolve mainly in the oil + have high partition coefficent
- Hydrophilic drugs dissolve mainly in the water + have low partition coefficient
- `For a drug to be absorbed, it must have some solubility in water + in oily membrane
- Drugs with a low partition coefficient are poorly absorbed because they cannot dissolve in the oily cell membrane
- Drugs with a high partition coefficient will not be absorbed as they cannot dissolve in the intestinal lumen + reach membrane
