Absorption (VK)


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  • G-I Tract - מערכת העיכול
  • Drugs can be ionised in an aqueous environment.
    Non-ionised drug is more lipid soluble than ionised species.
    Non-ionised species diffuse across cell membranes more easily than ionised species.
  • Absorption (VK)

    1. 1.  Absorption is the process by which a drug enters the bloodstream without being chemically altered or  The of movement of a drug from its site application into lymphatic system the blood or
    2. 2. Mechanism of drug absorption 1. Passive diffusion 2. Carrier- mediated transport: a) Active diffusion b) Facilitated diffusion 3. Endocytosis a) Pinocytosis b) Phagocytosis 4. Exocytosis 5. Pore Transport (Filtration)
    3. 3. Passive Diffusion water soluble drug (ionized or polar) is readily absorbed via aqueous channels or pores in cell membrane. Lipid soluble drug (non ionized or non polar) is readily absorbed via cell membrane itself.
    4. 4. Passive Diffusion Characters  Common.  Occurs along concentration gradient. Non selective  Not saturable  Requires no energy  No carrier is needed  Depends on lipid solubility.  Depends on pka of drug - pH of medium.
    5. 5. “The drug molecules diffuse from a region of higher concentration to lower concentration until equilibrium is attained & the rate of diffusion is directly proportional to the concentration gradient across the membrane”.
    6. 6. Active Absorption  Relatively unusual.  Occurs against concentration gradient.  Requires carrier and energy.  Specific  Saturable.  Iron absorption.  Uptake of levodopa by brain.
    7. 7. Passive transport Along concentration gradient (From high to low) No carriers Active transport Against concentration gradient (From low to high) Needs carriers Not selective Not saturable Selective, saturable No energy Energy is required
    8. 8. Facilitated Diffusion  Occurs along concentration gradient.  Requires carriers  Selective.  Saturable.  No energy is required.
    9. 9. Active transport Against concentration gradient (From low to high) Carrier-mediated facilitated diffusion Along concentration gradient (From high to low) Needs carriers Needs carriers Selective, saturable Selective, saturable Energy is required No energy is required
    10. 10. It involves engulfing extracellular materials within a segment of the cell membrane to form a saccule or a vesicle (hence also called as corpuscular or vesicular transport) which is then pinched off intracellularly.
    11. 11. Endocytosis - surrounding a substance with some of the cell membrane and then, bringing it into the cell, within a vacuole. a) Pinocytosis- bringing in liquids; “cellular drinking” b) Phagocytosis- bringing in solid-like food; “cellular eating” Exocytosis -opposite to the pinocytosis
    12. 12. This process is important in the absorption of fat soluble vitamins & in the uptake of nutrients.
    13. 13. Phagocytosis (“cellular eating”) a cell engulfs a particle and packages it within a food vacuole Pseudopod of amoeba Food being ingested
    14. 14. 3. Exocytosis - opposite of endocytosis. a) This is a way to rid cell of wastes. b) Restores the membrane, so the cell doesn’t shrink.
    15. 15. Outside cell Plasma membrane Cytoplasm (a) Exocytosis
    16. 16. Exocytosis and Endocytosis: Traffic of Large Molecules Exocytosis Endocytosis Visual Summary 5.3
    17. 17. 1. Also known as convective transport, bulk flow or filtration. 2. Important in the absorption of low mol. Wt. (less than 100). Low molecular size (smaller than the diameter of the pore) & generally watersoluble drugs through narrow, aqueous filled channels or pores in the membrane structure. e.g. urea, water & sugars. 3. The driving force for the passage of the drugs is the hydrostatic or the osmotic pressure difference across the membrane. Rate of absorption via pore Transport depends on the number & size of the pores,
    18. 18.  Most drugs are absorbed in the small intestine, because  It is the portal for absorption of nutrients into blood  It is surrounded by a very thin with a large surface area membrane
    19. 19.  Rate - How rapidly does the drug get from its site of administration, to the general circulation  Extent - How much of the administered dose enters the general circulation
    20. 20.  Bioavailability of a drug is defined as the amount / percentage /fraction of drug that is absorbed from a given dosage form and reaches the systemic circulation in unchanged form following nonvascular administration.
    21. 21. PRINCIPLE For drugs taken by routes other than the i.v. route, the extent of absorption and the bioavailability must be understood in order to determine what dose will induce the desired therapeutic effect. It will also explain why the same dose may cause a therapeutic effect by one route but a toxic or no effect by another.
    22. 22.  DRUG RELATED FACTORS  Physical properties of the drug. 1. 2. 3.  1. 2. 3.  Physical state Lipid /Water solubility Concentration Nature of the dosage form . Particle size Disintegration & Dissolution Time Formulations Route of drug administation .
    23. 23.  1. 2. 3. 4. 5. 6. 7. 8. Physiological factors Ionization PH of GIT GI transit time Metabolism of drug Presence of other agents Enterohepatic cycling Area of absorbing surface Plasma protein binding  Pharmacogenetic factors  Disease state
    24. 24.  Physical state Liquids are absorbed better than solids. Crystalloids are absorbed better than colloids  Lipid and water solubility Drugs in aqueous solution mix more readily than those in oily solution with the aqueous phase. At cell surface-lipid soluble drug penetrate more rapidly. Example –bile salts assist the absorption of fat soluble vitamins in SI.  Concentration Passive transport depends upon conc. i.e drug given in concentrated form is absorbed faster.
    25. 25.  Particle size  Larger the particle slower the absorption and vice versa. (EX.Antihelminthic-Bephenium)  Smaller size is imp. for absorption of chloramphenicol,Griseofulvin, oral coagulants, tolbutamide, spironolactone.  Dosage of the active drug can be reduced.  Disintegration & Dissolution Time  Rate of brake up of drug into granules is DI time  Rate at which drug goes into solution is DS time  DI is poor measure as Other factors- solvation, particle size, form, saturation solubility can modify bioavailability.
    26. 26.  Formulations Role of inert diluents –calcium,lactose, starch,lactate. Method of formulation  Route of drug administation. I.V Drug Immediately completely Oral Drug Delayed incomplete
    27. 27. 70 Plasma concentration 60 Bioavailability 50 (AUC)o (AUC)iv i.v. route 40 30 oral route 20 10 Time (hours) 0 0 2 4 6 8 10
    28. 28.  Ionization
    29. 29. Non-ionised drug More lipid soluble drug Diffuse across cell membranes more easily
    30. 30.  The first-pass effect is the term used for the hepatic metabolism of a pharmacological agent when it is absorbed from the gut and delivered to the liver via the portal circulation. The greater the firstpass effect, the less the agent will reach the systemic circulation when the agent is administered orally
    31. 31.  Presence of other agents Vitamin C enhances the absorption of iron. Calcium retards absorption of tetracyclines. Fat soluble vitamins absorption is delayed by liquid paraffin.  Enterohepatic cycling Morphine…..  Area of absorbing surface
    32. 32.  Many drugs bind to plasma proteins in the blood steam  Plasma protein binding limits distribution.  A drug that binds plasma protein diffuses less efficiently, than a drug that doesn’t.
    33. 33.  Change in gastrointestinal pH ◦ Ketoconazole needs acidic conditions in gut  Drug binding in GI tract ◦ E.g. tetracycline and calcium  Change in gastrointestinal flora ◦ Antibiotics with OCs  Change in gastrointestinal motility ◦ Metoclopramide and digoxin  Malabsorption caused by other drugs ◦ Orlistat (Xenical) and fat soluble vitamins