PHRD5925 Pharmaceutics Lecture 11 - Drug Absorption (Part 1)

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daynuhmay
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271257
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PHRD5925 Pharmaceutics Lecture 11 - Drug Absorption (Part 1)
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2014-04-20 20:17:46
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Drug Absorption
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Drug Absorption
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  1. 5 physiological factors affecting oral drug absorption
    • 1) surface area
    • 2) GI pH
    • 3) gastric emptying
    • 4) effects of food
    • 5) absorption mechanisms
  2. what part of the GI has the highest surface area?
    ileum of the SI
  3. rank GI surface area
    ileum > jejunum > duodenum > stomach
  4. drug form that is more lipid soluble & better (passively) transported
    UN-ionized
  5. 3 parameters involved in the pH-partition theory
    • 1) pKa (dissociation constant)
    • 2) pH
    • 3) lipid solubility (partition)
  6. pH in relation to drug absorption from stomach
    • ABSORBED: weak acidic, neutral 
    • NOT ABSORBED: basic
  7. pH in relation to drug absorption from the intestine
    • ABSORBED: weak basic and neutral
    • NOT ABSORBED: acidic
  8. Henderson-Hasselbalch equation


    • Acid:
    • Base: 
  9. for a given pKa, _____ (increasing/decreasing) pH increases absorption of a weak acid
    decreasing
  10. for a given pKa, _____ (increasing/decreasing) pH increases absorption of a weak base
    increasing
  11. normal low bulk or liquid intake takes ____ min to empty from the stomach
    20-60min
  12. effect of delayed stomach emptying on the rate of drug absorption
    reduced rate of drug absorption
  13. effect of hot contents on gastric emptying rate
    increased emptying rate
  14. effect of aggression on gastric emptying rate
    increased rate
  15. effect of lying on left hand side on gastric emptying rate
    decreased rate
  16. when increased rate of gastric emptying has a favorable effect (2)
    • 1) well soluble drugs
    • 2) drugs degraded in stomach
  17. when decreased gastric emptying rate has a favorable effect (2)
    • 1) poorly soluble drugs
    • 2) drugs transported by carriers
  18. the quicker the stomach emptying, the ____ the plasma concentration
    higher
  19. 3 ways food effects drug absorption
    • 1) delayed gastric emptying
    • 2) pH change 
    • 3) physical/chemical interaction of food w/ drug
  20. - absorption occurs by passing through the intestinal cells
    - most significant route of drug transport
    passive transcellular transport
  21. - absorption occurs by transport  between intestinal cells (aqueous tight junctions)
    - small hydrophilic cations are best candidates
    passive paracellular transport
  22. what happens to tight junctions from the SI to colon?
    junctions become progressively tighter
  23. best candidates for transcellular transport
    small, amphipathic drugs
  24. major example of an efflux transporter
    p-glycoprotein (P-gp)

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