Course Hero Logo

Factors which influence drug absorption from the

Course Hero uses AI to attempt to automatically extract content from documents to surface to you and others so you can study better, e.g., in search results, to enrich docs, and more. This preview shows page 23 - 26 out of 114 pages.

Factors which Influence Drug Absorption from the Gastrointestinal TractDrug factors:ConcentrationA large drug dose will be absorbed more rapidlybecause of the high concentration gradientMolecule sizeSmall molecules diffuse more easilypKaWeak acids are better absorbed; lipophilic drugsare better absorbedTablet disintegrationStability of the tablet determines the dispersionrate of the drug, and therefore the rate ofabsorption. This is manipulated intentionally inslow release formulationsParticle sizeThe smaller the particles, the greater the surfacearea from which the drug will be elutedGastrointestinal factorsGastric motilityGastric emptying is the major determinant ofabsorptionIntestinal motilityIntestinal motility can increase or decreaseabsorption (eg. slow gut transit can ensurecomplete absorption of a drug bezoar)Splanchnic perfusionGut perfusion is a rate-limiting step in drugabsorption only for rapidly absorbed drugs, but as
perfusion slows it also becomes more importantfor all other drugs.Surface areaSurface area of the small intestine is massive(usually, tens of square metres) and this increasesabsorption. Factors which decrease intestinalsurface area (eg. denuded villi due togastroenteritis, or surgacal short gut) will decreasedrug absorptionMode of transportDrugs can be transported by passive diffusion(either paracellular or transcellular); some areactively transported out of the gut lumen, andothers may be actively excreted back into it byefflux pumps.Intestinal contentInteraction with other drugs and food substances(eg. tetracycline chelating intestinal calcium frommilk, thereby forming an insoluble complex whichdefeats absorption)Bile and bile saltsThe emulsifying effect of bile is critical to theabsorption of fat-soluble vitamins and steroidsEnterohepaticrecirculationSome drugs may be eliminated in the bile only tobe reabsorbed in the jejunumGut bacteriaGut bacteria may either deactivate drugs (bymetabolisng them) or activate drugs (bymetabolism of an inactive precursor).Metabolism in theintestinal wallEnterocytes may metabolise drugs before theyundergo first-pass metabolism. Injured enterocytes(eg. after ischaemia) may lose their metabolicfunction.
The most common mechanism of absorption for drugs ispassive diffusion. This process can be explainedthrough the Fick law of diffusion, in which the drug molecule moves according to the concentrationgradient from a higher drug concentration to a lower concentration until equilibrium is reached.Distribution (2 parameters of drug distribution, protein binding, volume of distribution, distributionphase)• reversible transfer of a drug from the systemic circulation to the site of action and to the othercompartments• goal is to reach the biological site of actionFactors Affecting Distribution:1. Cardiac Output - volume of blood pumped by the heart per minute is directly related to the extent ofdistribution. (normal: 2.2-3.5 L/min/sqm) higher CO, better distribution2. Regional Blood Flow - fraction of thecardiac output that reaches a specificorgan or tissue (direct with D.)• 100% lungs• 25% liver• 25% kidney• <1% bones and adipose tissue2 PHARMACOKINETIC PARAMETERS:1. Volume of Distribution (Vd)- is a hypothetical value of body fluid required to dissolve a given amount ofdrug to a concentration equal to that of plasma concentration. unit = Liters

Upload your study docs or become a

Course Hero member to access this document

Upload your study docs or become a

Course Hero member to access this document

End of preview. Want to read all 114 pages?

Upload your study docs or become a

Course Hero member to access this document

Term
Fall
Professor
N/A
Tags
Pharmacology, amiodarone, The Grave,

Newly uploaded documents

Show More

Newly uploaded documents

Show More

  • Left Quote Icon

    Student Picture

  • Left Quote Icon

    Student Picture

  • Left Quote Icon

    Student Picture