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Mechanism rohit mishra

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Rohit Mishra

This document discusses the various mechanisms of drug absorption from the gastrointestinal tract into systemic circulation, including passive diffusion, pore transport, ion-pair transport, carrier-mediated transport, and endocytosis. Passive diffusion is the major mechanism for over 90% of drugs and involves diffusion of non-ionic drugs down their concentration gradient across membranes. Pore transport involves bulk flow of water and small molecules through aqueous pores or channels. Ion-pair transport allows absorption of ionized drugs that form complexes. Carrier-mediated transport uses integral membrane proteins to facilitate diffusion or actively transport drugs using ATP or ion gradients. Endocytosis absorbs molecules by engulfing them in vesicles.

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ROHIT MISHRA M.PHARM PHARMACEUTICS GLA
The process of movement of unchanged drug from the siteof administration to systemic circulation. What is Drug Absorption
MECHANISMS OF DRUG ABSORPTION
I. PassiveDiffusion Diffusion Movement fromhigh low concentration Major process for absorption of more than 90% of drugs Non ionic diffusion Driving force concentration or electrochemical gradient Difference in the drug concentration on either side of the membrane Drug movement is a result of kinetic energy of molecules
Mechanism rohit mishra
Mathematically(Ficks First law of diffusion) .................I dQ/dt = rate of drug diffusion (amount/time) D = diffusion coefficient of the drug A= surface area of the absorbing membrane for drug diffusion Km/w = partition coefficient of drug between the lipoidal membrane & the aqueous GI fluids (CGIT C) = difference in the concentration of drug in the GI fluids & the plasma (Concentration Gradient) h = thickness of the membrane
Characteristics of Passive diffusion: Energy independent Greater the area & lesser the thickness of the membrane, faster the diffusion The process rapid over for short distances Concentration equal on both the sides of the membrane - Equilibrium is attained Greater the PC of the drug faster the absorption
ii. PoreTransport It is also called as convective transport, bulk flow or filtration. Mechanism through the protein channel present in the cell membrane. Drug permeation through pore transport renal excretion, removal of drug from CSF & entry of drug into the liver
The driving force hydrostatic or osmotic pressure differences across the membrane. Thus, bulk flow of water along with the small solid molecules through aqueous channels. Water flux that promotes such a transport is called as solvent drag The process is important in the absorption of low molecular weight (<100D), low molecular size (smaller than the diameter of the pore) & generally water soluble drugs through narrow, aqueous filled channels or pores e.g. urea, water & sugars. Chain like or linear compounds (upto 400D)- filtration
iii. Ion-PairTransport Responsible for absorption of compounds which ionizes at all pH values. e.g. quaternary ammonium, sulphonic acids Ionized moieties forms neutral complexes with endogenous ions which have both the required lipophilicity & aqueous solubility for passive diffusion. E.g. Propranolol, a basic drug that forms an ion pair with oleic acid & is absorbed by this mechanism
Carrier MediatedTransport Involves a carrier which reversibly binds to the solute molecules and forms a solute-carrier complex. This molecule transverse across the membrane to the other side and dissociates, yielding the solute molecule. The carrier then returns to the original site to accept a new molecule. There are two type of carrier mediated transport system 1) Facilitated diffusion 2) Active transport
FacilitatedDiffusion Facilitated diffusion is a form of carrier transport that does not require the expenditure of cellular energy. Carriers are numerous in number & are found dissolved in cell membrane . The driving force is concentration gradient, particles move from a region of high conc to low conc.
Contd The transport is aided by integral membrane proteins. Facilitated diffusion mediates the absorption of some simple sugars, steroids, amino acids and pyrimidines from the small intestine and their subsequent transfer across cell membranes.
ActiveTransport Requires energy, which is provided by hydrolysis of ATP for transportation. More commonly, metabolic energy is provided by the active transport of Na+, or is dependent on the electrochemical gradient produced by the sodium pump, Na+/K+ ATPase (secondary active transport).
This transport requires energy in the form of ATP
Primary ActiveTransport Direct ATPrequirement The process transfers only one ion or molecule & only in one direction. Hence, called as UNIPORT E.g. absorption of glucose ABC (ATP binding Cassette) transporters
Secondary ActiveTransport No direct requirement ofATP The energy required in transporting an ion aids transport of another ion or molecule (co-transport or coupled transport) either in the same direction or opposite direction. 2 types: Symport (co-transport) Antiport (counter transport)
symportantiport ATP ATP Antiport and Symport
Endocytosis It is a process in which cell absorbs molecules by engulfing them. Also termed as vesicular transport. It occurs by 3 mechanisms: Phagocytosis Pinocytosis Transcytosis
Phagocytosis
Pinocytosis It is a form of endocytosis in which small particles are brought to the cell, forming an invagination. These small particles are suspended in small vesicles. It requires energy in the form ofATP. It works as phagocytosis, the only difference being, it is non specific in the substances it transports. This process is important in the absorption of oil soluble vitamins & in the uptake of nutrients
References D.M Brahmankar and Sunil B. Jaiswal, Biopharmaceutics and Pharmacokinetics: A Treatise 2009 second edition Published by M.K Jain for Vallabh Prakashan New Delhi Page number 1-23
Mechanism rohit mishra

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Mechanism rohit mishra

  • 2. The process of movement of unchanged drug from the siteof administration to systemic circulation. What is Drug Absorption
  • 4. I. PassiveDiffusion Diffusion Movement fromhigh low concentration Major process for absorption of more than 90% of drugs Non ionic diffusion Driving force concentration or electrochemical gradient Difference in the drug concentration on either side of the membrane Drug movement is a result of kinetic energy of molecules
  • 6. Mathematically(Ficks First law of diffusion) .................I dQ/dt = rate of drug diffusion (amount/time) D = diffusion coefficient of the drug A= surface area of the absorbing membrane for drug diffusion Km/w = partition coefficient of drug between the lipoidal membrane & the aqueous GI fluids (CGIT C) = difference in the concentration of drug in the GI fluids & the plasma (Concentration Gradient) h = thickness of the membrane
  • 7. Characteristics of Passive diffusion: Energy independent Greater the area & lesser the thickness of the membrane, faster the diffusion The process rapid over for short distances Concentration equal on both the sides of the membrane - Equilibrium is attained Greater the PC of the drug faster the absorption
  • 8. ii. PoreTransport It is also called as convective transport, bulk flow or filtration. Mechanism through the protein channel present in the cell membrane. Drug permeation through pore transport renal excretion, removal of drug from CSF & entry of drug into the liver
  • 9. The driving force hydrostatic or osmotic pressure differences across the membrane. Thus, bulk flow of water along with the small solid molecules through aqueous channels. Water flux that promotes such a transport is called as solvent drag The process is important in the absorption of low molecular weight (<100D), low molecular size (smaller than the diameter of the pore) & generally water soluble drugs through narrow, aqueous filled channels or pores e.g. urea, water & sugars. Chain like or linear compounds (upto 400D)- filtration
  • 10. iii. Ion-PairTransport Responsible for absorption of compounds which ionizes at all pH values. e.g. quaternary ammonium, sulphonic acids Ionized moieties forms neutral complexes with endogenous ions which have both the required lipophilicity & aqueous solubility for passive diffusion. E.g. Propranolol, a basic drug that forms an ion pair with oleic acid & is absorbed by this mechanism
  • 11. Carrier MediatedTransport Involves a carrier which reversibly binds to the solute molecules and forms a solute-carrier complex. This molecule transverse across the membrane to the other side and dissociates, yielding the solute molecule. The carrier then returns to the original site to accept a new molecule. There are two type of carrier mediated transport system 1) Facilitated diffusion 2) Active transport
  • 12. FacilitatedDiffusion Facilitated diffusion is a form of carrier transport that does not require the expenditure of cellular energy. Carriers are numerous in number & are found dissolved in cell membrane . The driving force is concentration gradient, particles move from a region of high conc to low conc.
  • 13. Contd The transport is aided by integral membrane proteins. Facilitated diffusion mediates the absorption of some simple sugars, steroids, amino acids and pyrimidines from the small intestine and their subsequent transfer across cell membranes.
  • 14. ActiveTransport Requires energy, which is provided by hydrolysis of ATP for transportation. More commonly, metabolic energy is provided by the active transport of Na+, or is dependent on the electrochemical gradient produced by the sodium pump, Na+/K+ ATPase (secondary active transport).
  • 15. This transport requires energy in the form of ATP
  • 16. Primary ActiveTransport Direct ATPrequirement The process transfers only one ion or molecule & only in one direction. Hence, called as UNIPORT E.g. absorption of glucose ABC (ATP binding Cassette) transporters
  • 17. Secondary ActiveTransport No direct requirement ofATP The energy required in transporting an ion aids transport of another ion or molecule (co-transport or coupled transport) either in the same direction or opposite direction. 2 types: Symport (co-transport) Antiport (counter transport)
  • 19. Endocytosis It is a process in which cell absorbs molecules by engulfing them. Also termed as vesicular transport. It occurs by 3 mechanisms: Phagocytosis Pinocytosis Transcytosis
  • 21. Pinocytosis It is a form of endocytosis in which small particles are brought to the cell, forming an invagination. These small particles are suspended in small vesicles. It requires energy in the form ofATP. It works as phagocytosis, the only difference being, it is non specific in the substances it transports. This process is important in the absorption of oil soluble vitamins & in the uptake of nutrients
  • 22. References D.M Brahmankar and Sunil B. Jaiswal, Biopharmaceutics and Pharmacokinetics: A Treatise 2009 second edition Published by M.K Jain for Vallabh Prakashan New Delhi Page number 1-23