L30/1 - physiological factors affecting drug absorption after oral administration Flashcards
parameters that effect GI absorption of drugs
- anatomy/histology
- physiology
- pathology
- drug interactions
- food (fed vs fasting)
- GI transit
- metabolism within GI
- first pass effect in liver
- enterohepatic recycling
- active secretion
what is the therapeutic window?
area of concentration you need to be in for efficacy of the drug. most drugs have wide window (e.g 1 paracetamol treats us)
gastric transit & drug absorption
- stomach grinds food and breaks it up by chemical decomposition
- gastric fluid is an acid containing pepsin: which can degrade drugs
- drug absorption across stomach wall does not contribute much to oral absorption of drugs (drugs mostly absorbed in SI)
issue with gastric fluid
- some drugs are degraded by acidic conditions in stomach
- so gastro resistant dosage forms that do not release drug in acidic environment have been made
- polypeptides are completely degraded by pepsin
- so oral route of administration impossible and alternative found (e.g insulin administered by injection)
GI tract motility: gastric emptying
stomach gradually releases its contents into SI
factors affecting gastric emptying and therefore drug absorption
- meal volume: bigger meal = quicker initial emptying rate
- type of meal
- physical state of contents
- chemicals
- drugs
- body position
- disease
- exercise
how does the type of meal affect gastric emptying?
- fatty acid reduces emptying rate (more carbons on chain = more reduce)
- triglycerides reduce emptying rate (occurs in unsaturated more)
- carbs and a.a reduce emptying rate (concentration dependent matter/ osmotic pressure)
how does the physical state of contents affect gastric emptying?
solutions or suspensions of small particles empty quicker than chunks of material
how do chemicals affect gastric emptying?
- acids reduce
- alkalis increase
how do drugs affect gastric emptying?
anticholinergics, narcotics, ethanol reduce emptying rate
how does body position affect gastric emptying?
lying on left side reduces emptying rate
how does disease effect gastric emptying?
ulcers reduce emptying rate
how does excursive affect gastric emptying?
vigorous exercise reduces emptying rate
describe gastric transit and drug absorption when a drug is rapidly released from dosage form into gastric fluid
- drug in solution in stomach
- in fasting subject, the drug leaves stomach rapidly via pylorus
describe gastric transit and drug absorption when there is a gastro resistant dosage form
- it cannot pass pylorus
- only particles of few mm diameter exit
- need to wait for HOUSE KEEPER WAVE: strong contraction
- lag time (as nothing has been dissolved) between the moment at which the drug is taken and its arrival at its absorption site
intestinal transit and drug absorption
- microvilli of intestinal mucous membrane increase SA
- pH of intestinal fluid is neutral / kinda alkaline
- SI is where most drugs absorbed
what is the rate of absorption in the SI affected by?
- rate of disaggregation and dissolution
- GI transit
- transport across GI memb