Mechanisms of adsorption of drugs for pharmacological effectpptx

MECHANISM AND FACTORS AFFECTING ABSORPTION OF DRUGS

1. RENU SAHARAN M. Pharm. (Pharmaceutics) M.M. College of Pharmacy MMDU, Mullana Mechanism of Drug Absorption

2. MMCP VISION “Providing technical and practice oriented pharmacy education to prepare students with attributes to meet the need of industry and society” MMCP MISSION To develop best technically competent pharmacy professionals by inculcating desired attributes in them for meeting industry demands. To make best pharmacists who can practice pharmacy to become effective team member of healthcare system and provide optimum pharmaceutical care solutions. Promotion of useful and innovative research to contribute in development of nation and global society.

3. CONTENTS Mechanism of drug absorption Passive diffusion Pore transport Carrier mediated Ionic diffusion Ion pair transport Endocytosis Factors affecting drug absorption References 3

4. Mechanism of Drug Absorption Passive diffusion Pore transport Carrier- mediated transport a) Facilitated diffusion b) Active transport Ionic or Electrochemical diffusion Ion-pair transport Endocytosis 4

5. Passive Diffusion Also known as non-ionic diffusion. It is defined as the difference in the drug concentration on either side of the membrane. Absorption of 90% of drugs. The driving force for this process is the concentration or electrochemical gradient. 5

6. 6 Cont … Passive diffusion is best expressed by Fick’s first law of diffusion which states that the drug molecules diffuse from a region of higher concentration to one of lower concentration until equilibrium is attained & the rate of diffusion is directly proportional to the concentration gradient across the membrane. dQ = D A K m/w (C GIT – C) dt h Certain characteristic of passive diffusion can be generalized. Down hill transport 6

7. Greater the surface area & lesser the thickness of the membrane, faster the diffusion. Equilibrium is attained when the concentration on either side of the membrane become equal. Greater the membrane/ water partition coefficient of drug, faster the absorption. Passive diffusion process is energy independent but depends more or less on the square root of the molecular size of the drugs. The mol. Wt. of the most drugs lie between 100 to 400 Daltons which can be effectively absorbed passively. 7 Cont …

8. Pore transport Also known as convective transport , bulk flow or filtration . Important in the absorption of low mol. Wt. (less than 100). Low molecular size (smaller than the diameter of the pore) & generally water-soluble drugs through narrow, aqueous filled channels or pores in the membrane structure. e.g. urea, water & sugars. The driving force for the passage of the drugs is the hydrostatic or the osmotic pressure difference across the membrane. 8 drug membrane

9. Cont … The rate of absorption via pore transport depends on the number & size of the pores, & given as follows: dc = N. R 2 . A . ∆C dt ( η ) (h) where, dc = rate of the absorption. dt N = number of pores R = radius of pores ∆C = concentration gradient η = viscosity of fluid in the pores 9

10. Carrier Mediated Transport Mechanism Involves a carrier (a component of the membrane) which binds reversibly with the solute molecules to be transported to yield the carrier solute complex which transverses across the membrane to the other side where it dissociates to yield the solute molecule The carrier then returns to its original site to accept a fresh molecule of solute. There are two types of carrier mediated transport system: a) Facilitated Diffusion b) Active Transport 10

11. a) Facilitated Diffusion This mechanism involves the driving force that is concentration gradient. In this system, no expenditure of energy is involved (down-hill transport), therefore the process is not inhibited by metabolic poisons that interfere with energy production. 11

12. Cont … Limited importance in the absorption of drugs e.g. Such a transport system include entry of glucose into RBCs & intestinal absorption of vitamins B 1 & B 2 . A classical example of passive facilitated diffusion is the gastro-intestinal absorption of vitamin B 12 . An intrinsic factor (IF), a glycoprotein produced by the gastric parietal cells, forms a complex with vitamin B 12 which is then transported across the intestinal membrane by a carrier system . 12

13. b) Active Transport More important process than facilitated diffusion. The driving force is against the concentration gradient or uphill transport . Since the process is uphill, energy is required in the work done by the barrier. As the process requires expenditure of energy, it can be inhibited by metabolic poisons that interfere with energy production . 13

14. Cont … A good example of competitive inhibition of drug absorption via active transport is the impaired absorption of levodopa when ingested with meals rich in proteins. The rate of absorption by active transport can be determined by applying the equation used for Michalies-menten kinetics: dc = [C].(dc/ dt ) max dt Km + [C] Where, (dc/ dt ) max = maximal rate of drug absorption at high drug concentration. [C] = concentration of drug available for absorption Km = affinity constant of drug for the barrier. 14

15. Ionic or Electrochemical Diffusion In t his charge influences the permeation of drugs. Molecular forms of solutes are unaffected by the membrane charge & permeate faster than ionic forms. The permeation of anions & cations is also influenced by pH. Thus, at a given pH, the rate of permeation may be as follows: Unionized molecule > anions > cations 16

16. Cont … The permeation of ionized drugs, particularly the cationic drugs, depend on the potential difference or electrical gradient as the driving force across the membrane. Once inside the membrane, the cations are attached to negatively charged intracellular membrane, thus giving rise to an electrical gradient. If the same drug is moving from a higher to lower concentration, i.e., moving down the electrical gradient , the phenomenon is known as electrochemical diffusion . 17

17. Ion Pair Transport Drugs that ionize at all pH conditions absorbed after complexing with oppositively charged ions. 18

18. Cont … Drugs have low o/w partition coefficient values, such agents penetrate the membrane by forming reversible neutral complexes with endogenous ions. e.g. mucin of GIT. Such neutral complexes have both the required lipophilicity as well as aqueous solubility for passive diffusion. This phenomenon is known as ion-pair transport. 19

19. Endocytosis 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 . 20

20. Cont … In endocytosis, there are two process: A) Phagocytosis ( Cell Eating ) : uptake of solid particles. B) Pinocytosis ( Cell Drinking ) : uptake of fluid solute. 21

21. References Biopharmaceutics & pharmacokinetics by D.M.Brahmankar & Sunil B. Jaiswal . Biopharmaceutics & pharmacokinetics by P.L.Madan . Biopharmaceutics & pharmacokinetics by G.R.Chatwal . Human anatomy & physiology by Tortora . www.google.com.

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