Biopharmaceutics A Specific Aims PDF

[Biopharmaceutics part A - Specific Aims] 1\. Be able to describe the advantages of the oral route of administration. 2\. Be able to describe the mucus of the GI epithelium, including role, main components, and turnover time. 3\. Be able to describe the stomach, including its volumes under fed an...

[Biopharmaceutics part A - Specific Aims] 1\. Be able to describe the advantages of the oral route of administration. 2\. Be able to describe the mucus of the GI epithelium, including role, main components, and turnover time. 3\. Be able to describe the stomach, including its volumes under fed and fasting states, roles, pH, and secretions. Does phase III of the MMC ('housekeeper wave') occur in the fasting stomach or the fed stomach? 4\. Be able to describe characteristics of the small intestine and the colon, such as roles, approximate length, pH, and major factors affecting their ability (or limitation) to absorb drugs. 5\. Be able to explain the patterns of gastric motility in the fasted and fed stomach. What are the 2 major factors that affect the gastric residence time of dosage forms? What are the roles of the pyloric sphincter? 6\. Be able to describe gastric residence times of drugs: What is the connection between the size of the dosage form or the meal, and gastric residence time? Why would the drug probably reach the intestine faster if it is administered with water, in comparison to administration with food or on an empty stomach? 7\. Be able to describe typical transit times of drugs in the small and large intestines. 8\. Be able to describe barriers to drug absorption in the gut lumen and unstirred water layer. How can gastrointestinal pH, food (including grapefruit juice), or disease states affect drug absorption? Which types of luminal enzymes are most likely to affect drugs and dosage forms and how? Which type of excipients can lipases digest? 9\. Be able to describe major characteristics of the GI membrane and mechanisms of drug transport across it. Which mechanism is the most common for drug absorption? 10\. Be able to describe passive diffusion of drugs, including which drugs are most likely to pass through that route \[Answer: small lipophilic molecules\], and factors that affect the rate of transport. In the diffusion process across the GI membrane, when are 'sink conditions' maintained? Is the concentration of the drug in the blood substantial in comparison to the concentration of the drug in the GI fluids at the absorption sites? 11\. Be able to describe active transport of drugs across the GI membrane: Is it mediated by carriers? Does it require investment of energy by the cells, and how does this affect the ability to transport drugs against a concentration gradient? Is it a saturable mechanism? Which molecules (including drugs) can use this mechanism for transport? Can drugs use more than one mechanism of transport for absorption? Transporters for which compounds would be the most relevant for drug absorption, short peptides, sugars, electrolytes, vitamins (B1, B2, B12), or bile salts? Does this mechanism require that the transported molecules will have specific chemical structures? 12\. Be able to describe drug transport by facilitated diffusion. Is this mechanism important for the absorption of many drugs? 13\. Be able to describe the major characteristics of endocytosis, including its 3 major types. 14\. Be able to describe the drug transport mechanism that might enable some drug macromolecules (including oral Sabin polio vaccine) to be absorbed. 15\. be able to describe the paracellular pathway for drug transport. Which types of drugs are anticipated to use this mechanism for transport? 16\. Be able to describe efflux of drugs in the intestine. What is the main protein in the small intestine that is responsible for this phenomenon? Can efflux affect the bioavailability of some drugs? If yes, what would be the effect? 17\. Review questions.