gut physiology and fucntion

• Pharmacokinetics (PK)


  What the body does to a drug
• Pharmacodynamics (PD)

  What the drug does to the body
• Key systems relevant for PK processes

  • Absorption (GI tract)
  • Distribution (Circulatory)
  • Metabolism (Liver)
  • Excretion (Kidneys)
• Advantages of oral drug administration

  • It's the most convenient and cost-effective route of administration
  • Non-invasive
  • Long shelf-life - stable
• Functions of the GI system

  • Mechanical (e.g. chewing) and chemical (e.g. enzymes) breakdown of food into small to be absorbed into the circulatory system for distribution throughout the body - similar principles apply for drugs
  • Digestion of food
  • Absorption of nutrients, and drugs
  • Elimination
• Regions of the GI tract

  • Mouth
  • Oesophagus
  • Stomach
  • Small intestine
• Accessory organs of the GI tract

  • Salivary glands
  • Liver
  • Gall bladder
  • Pancreas
• Mouth

  • Breaks up food particles (saliva assists)
  • Saliva has mucin which act as a lubricant
• Oesophagus

  • Transport of food to stomach
  • Entry to stomach via sphincter
• Stomach


  • Secretion of gastric juices for chemical digestion
  • Mechanical break up of the food - (has a muscular wall that moves to help with the break down of food)
  • Mixing of the food and gastric juices - allow for the gastric juices to do its job
• Transmucosal tablets - Sublingual and Buccal mucosa

  They release the drug molecule from mucosal membrane to blood vessels by two mechanisms that is, trans cellular (going through the cell) and paracellular (going around the cell)
• Peristalsis


  Muscular movement of the gut, doesn't need gravity
• Role of the stomach in food and drug absorption

  • Gastric juices - HCl (controlled by vagus nerve and the hormone gastrin) and digestive enzymes
  • Initiates the digestion of proteins through the enzyme pepsin
  • HCl + pepsin → chemical digestion
  • Peristalsis → mechanical digestion
  • Mucus coating - lubricates and protects epithelial surface against pepsin
  • Formation of chyme
  • Moving food to small intestine - gastric emptying
  • Presence of food in the stomach delays gastric emptying and affects the rate of absorption
• The low pH of the stomach allows micro-organisms to be killed
• Gastric emptying

  • Time varies depending on meal properties e.g. volume of meal, Kcal contents, fat content, protein content, liquid/solid state
  • Time also varies depending on population e.g. sex, particular disease states
• Role of small intestine

  • Completes digestion of nutrients in chyme
  • Its a major site of absorption of different nutrients due to: large surface area and high perfusion (lots of blood supply/capillaries), exposure to enzymes and solubilisers, receives secretion from liver and pancreas
  • Its major site of absorption of orally administered drugs
  • The site of first-pass metabolism of drugs (via CYP3A4)
  • Movement of food residues two the large intestine - transit time differs across segments
• Why is surface area of the small intestine so large?

  • Mucosa - epithelium + connective tissue with blood and lymphatic vessels + muscles); submucosa and serosa
  • Villi - extend from the luminal surface of the small intestine
  • Microvilli (brush border) - on the surface of the epithelial
  • Highly convoluted, circular folds + villi + microvilli → increase surface area for absorption
• Why is large SA so important for drug absorption after oral administration?

  • Larger the SA, the more contact the drug will have with the host
  • Dissolved drug is absorbed across the gut wall mainly via the process of passive diffusion, other routes - paracellular and transport-facilitated
  • Drugs can also be pushed out of cells - so cells have systems to push drug out
  • Enterocytes contain metabolic enzymes (intestinal first-pass) - drug going through first pass can make drug lose its effectiveness
  • Blood perfusing intestine goes into liver via hepatic portal vein
  • After passing through the liver, drug goes into systemic circulation
• Coeliac disease is a chronic autoimmune disorder of the small intestine, inflammation process triggered by consumption of gluten-containing food
• Role of liver and pancreas secretions

  • Liver - main site of metabolism of xenobiotics, secretes bile that enters duodenum via hepatic duct - stored in gall bladder between meals, important for digestion of lipids
  • Pancreas - proteolytic enzymes - trypsin and chymotrypsin for protein digestion, lipase for digestion of lipids, HCO3- → stomach acid-neutralising
• Digestion of carbohydrates, proteins, and lipids (fat) occurs in the GI tract
• Absorption of water and minerals occurs in the large intestine
• The gut microbiota plays a role in the gut-brain axis, where the systems in the body are combined and the brain influences GI physiology, motility, mucin production etc, and the GI system influences brain, behaviour and mood