logging in or signing up RENAL EXCRETION shaikhwaji Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 110 Category: Entertainment License: All Rights Reserved Like it (0) Dislike it (0) Added: April 06, 2011 This Presentation is Public Favorites: 0 Presentation Description No description available. Comments Posting comment... By: shaikhwaji (12 month(s) ago) this slides are very good plz upload another slides Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Renal Excretion: Renal Excretion Shaikh. wajhiuddin Dept. of pharmaceutics M.Pharm II sem Govt. college of pharmacy, shaikhwajhi@gmail.comSlide 2: Drug elimination refers to the irreversible removal of drug from all routes of elimination. Elimination is divided into 2 components: Excretion : Is the removal of the intact drug Biotransformation : is the process by which the drug is chemically converted in the body to a metabolite . Excretion is divided into Renal Excretion Non-renal Excretion/extra-renal IntroductionThe Nephron: The Nephron Within the nephron there are: Renal Capsule, Proximal convoluted tubule, Loop of Henle , Distal convoluted tubule and The collecting duct.Slide 4: Biotransformation The kidney, is unable to excrete drugs that are highly lipid soluble. Converting lipid-soluble drugs into more polar (less lipid-soluble) compounds, drug metabolism makes it possible for the kidney to excrete many drugs Principal process 1.Glomerular filtration 2.Active tubular secretion 3.Active or passive tubular reabsorptionGlomerular filtration: Glomerular filtration Is a non selective unidirectional Hydrostatic pressure pushes a portion of blood to be filtered across semi-permeable membrane into the Bowman’s Capsule. Porosity of Glomerular membrane allows only small molecular weight particles to be filtered. GFR can be determined by an agent E.g. Inulin Creatinine Mannitol Sodium thiosulfate: Is a carrier mediated process System is capacity limited and satuarble Drugs with similar structures may compete for the same carrier system E.g. : Probenicid competes with penicillin for the same carrier system Active tubular secretion :Slide 7: Active tubular secretion system for secretion of organic acids /anions E.g. : Penicillin, glucoronides, Salicylates ,Endogenous acid i.e Uric acid system for secretion of organic bases/cations E.g. : Morphine Hexamethonium, Endogenous amines i.e Catecholamines, Histamine Active tubular secretion is dependent on renal plasma flow E.g. : Para amino hippuric acid IodopyracetSlide 8: Tubular reabsorption It occurs after the glomerulus filtration of drugs Reabsorbtion of drugs is indicated when the excretion rate values are less than GFR This reabsorption results in an increase in half life of drug Active tubular reabsorption : Is commonly seen with endogenous substance /nutrients that the body needs to conserve E.g. Electrolytes , glucose , vitamins and Amino acidsSlide 9: Active tubular reabsorption : Is commonly seen with endogenous substance /nutrients that the body needs to conserve Passive tubular reabsorption : Is commonly seen with large number exogenous substance including drugs. Driving force is conc. gradient is estabilished by the reabsorption of water along with sodium and other inorganic ionsSlide 10: Substance Filtered Reabsorbed Excreted % Reabsorbed Sodium ions(mEq) 26,000 25,850 150 99.4 Chloride ions (mEq) 18,000 17,850 150 99.2 Bicorbonate ions (mEq) 4,900 4900 0 100 Urea(mM) 870 460 410 53 Glucose(mM) 800 800 0 100 Water 180,000 179,000 1000 99.4 Renal Excretion ProcessFactors affecting Renal excretion: Factors affecting Renal excretion Physicochemical properties of the drug Molecular size : Below 300 daltons, if water soluble 300-500 daltons can be excreted both in urine and bile pKa : pH dependent excretion for any drug is dependent upon its pKa A polar and ionized drug will be poorly reabsorbed passivelyand excreted rapidly Lipid solubility :Urinary excretion of an unchanged drug is inversely to its lipohilicitySlide 12: Plasma concentration of the drug GF and reabsorption are directly affected by it ,since both are passive process. Distribution and binding characteristics of the drug Clearance is inversly related to Vd. A drug with large Vd is poorly excreted in urine. Only unbound or free drug appear in the GF Fu = Cu c where, Fu= fraction of unbound drug in plasma Cu = conc.of unbound c = Total plasma concSlide 13: E.g. Cl R of oxytetracycline is 99 ml /min (66% unbound) Cl R of Doxycycline is 16 ml/min(7%) Blood flow to the kidneys Renal blood flow is imp. in case of drug excreted by GF and those that are actively secreted . But in 2 nd case increased perfusion increases the contact of drug with the secretary site and enhance the elimination. Hence Cl R in such case perfusion rate limitedSlide 14: Biological factor Age ,sex ,species ,difference in genetic , carcadian rhythm etc alter drug excretion . 10% lower in female , in old age ,GFR is reduced and tubular function is altered Drug interaction Any Drug interaction results in alteration of binding characteristics ,renal blood flow ,active secretion , would alter clearance E.g.. Urinary excretion of Digoxin is reduced by diazepam Gentamicin induced nephrotoxicity by furesemideSlide 15: Disease states Renal dysfunction : It greatly impairs the elimination of drugs especially those that are primarily excreted by the kidneys. Some of the cause of renal failure are Diabetes, hypertension and nephrotoxic Uremia : characterized by impaired glomerulus filtrationSlide 16: Non-renal routes of excretion Bile E.g. vit. B 12 , folic acid ,cardiac glycosides Lungs E.g. Halothane Sweat E.g. Benzoic acid, salicylic acid ,antipyrine and heavy metals Saliva E.g. Caffiene , phenytoin ,carbamazepine Bitter after taste in the mouth of a patient on medication is an indicate Black hairy tongueSlide 17: Breast milk E.g. Discoloration of teeth with tetracycline Jaundice by interaction of bilirubin and sulphonamide Gastrointestinal Excretion Genital ExcretionSlide 18: REFERENCE: L. shargel, S. wu –pong , A.B Yu “Applied Biopharmaceutis and Pharmacokinetics “ 5 th edition Mc Graw Hill publication , Page no 136 2. www. google.com 3. D.M. Bramankar, S.B jaiswal “Biopharmaceutis and Pharmacokinetics “ 1 st edition ,2007 Vallabah prakashan ,page no 178Slide 19: THANKYOU You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.
RENAL EXCRETION shaikhwaji Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 110 Category: Entertainment License: All Rights Reserved Like it (0) Dislike it (0) Added: April 06, 2011 This Presentation is Public Favorites: 0 Presentation Description No description available. Comments Posting comment... By: shaikhwaji (12 month(s) ago) this slides are very good plz upload another slides Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Renal Excretion: Renal Excretion Shaikh. wajhiuddin Dept. of pharmaceutics M.Pharm II sem Govt. college of pharmacy, shaikhwajhi@gmail.comSlide 2: Drug elimination refers to the irreversible removal of drug from all routes of elimination. Elimination is divided into 2 components: Excretion : Is the removal of the intact drug Biotransformation : is the process by which the drug is chemically converted in the body to a metabolite . Excretion is divided into Renal Excretion Non-renal Excretion/extra-renal IntroductionThe Nephron: The Nephron Within the nephron there are: Renal Capsule, Proximal convoluted tubule, Loop of Henle , Distal convoluted tubule and The collecting duct.Slide 4: Biotransformation The kidney, is unable to excrete drugs that are highly lipid soluble. Converting lipid-soluble drugs into more polar (less lipid-soluble) compounds, drug metabolism makes it possible for the kidney to excrete many drugs Principal process 1.Glomerular filtration 2.Active tubular secretion 3.Active or passive tubular reabsorptionGlomerular filtration: Glomerular filtration Is a non selective unidirectional Hydrostatic pressure pushes a portion of blood to be filtered across semi-permeable membrane into the Bowman’s Capsule. Porosity of Glomerular membrane allows only small molecular weight particles to be filtered. GFR can be determined by an agent E.g. Inulin Creatinine Mannitol Sodium thiosulfate: Is a carrier mediated process System is capacity limited and satuarble Drugs with similar structures may compete for the same carrier system E.g. : Probenicid competes with penicillin for the same carrier system Active tubular secretion :Slide 7: Active tubular secretion system for secretion of organic acids /anions E.g. : Penicillin, glucoronides, Salicylates ,Endogenous acid i.e Uric acid system for secretion of organic bases/cations E.g. : Morphine Hexamethonium, Endogenous amines i.e Catecholamines, Histamine Active tubular secretion is dependent on renal plasma flow E.g. : Para amino hippuric acid IodopyracetSlide 8: Tubular reabsorption It occurs after the glomerulus filtration of drugs Reabsorbtion of drugs is indicated when the excretion rate values are less than GFR This reabsorption results in an increase in half life of drug Active tubular reabsorption : Is commonly seen with endogenous substance /nutrients that the body needs to conserve E.g. Electrolytes , glucose , vitamins and Amino acidsSlide 9: Active tubular reabsorption : Is commonly seen with endogenous substance /nutrients that the body needs to conserve Passive tubular reabsorption : Is commonly seen with large number exogenous substance including drugs. Driving force is conc. gradient is estabilished by the reabsorption of water along with sodium and other inorganic ionsSlide 10: Substance Filtered Reabsorbed Excreted % Reabsorbed Sodium ions(mEq) 26,000 25,850 150 99.4 Chloride ions (mEq) 18,000 17,850 150 99.2 Bicorbonate ions (mEq) 4,900 4900 0 100 Urea(mM) 870 460 410 53 Glucose(mM) 800 800 0 100 Water 180,000 179,000 1000 99.4 Renal Excretion ProcessFactors affecting Renal excretion: Factors affecting Renal excretion Physicochemical properties of the drug Molecular size : Below 300 daltons, if water soluble 300-500 daltons can be excreted both in urine and bile pKa : pH dependent excretion for any drug is dependent upon its pKa A polar and ionized drug will be poorly reabsorbed passivelyand excreted rapidly Lipid solubility :Urinary excretion of an unchanged drug is inversely to its lipohilicitySlide 12: Plasma concentration of the drug GF and reabsorption are directly affected by it ,since both are passive process. Distribution and binding characteristics of the drug Clearance is inversly related to Vd. A drug with large Vd is poorly excreted in urine. Only unbound or free drug appear in the GF Fu = Cu c where, Fu= fraction of unbound drug in plasma Cu = conc.of unbound c = Total plasma concSlide 13: E.g. Cl R of oxytetracycline is 99 ml /min (66% unbound) Cl R of Doxycycline is 16 ml/min(7%) Blood flow to the kidneys Renal blood flow is imp. in case of drug excreted by GF and those that are actively secreted . But in 2 nd case increased perfusion increases the contact of drug with the secretary site and enhance the elimination. Hence Cl R in such case perfusion rate limitedSlide 14: Biological factor Age ,sex ,species ,difference in genetic , carcadian rhythm etc alter drug excretion . 10% lower in female , in old age ,GFR is reduced and tubular function is altered Drug interaction Any Drug interaction results in alteration of binding characteristics ,renal blood flow ,active secretion , would alter clearance E.g.. Urinary excretion of Digoxin is reduced by diazepam Gentamicin induced nephrotoxicity by furesemideSlide 15: Disease states Renal dysfunction : It greatly impairs the elimination of drugs especially those that are primarily excreted by the kidneys. Some of the cause of renal failure are Diabetes, hypertension and nephrotoxic Uremia : characterized by impaired glomerulus filtrationSlide 16: Non-renal routes of excretion Bile E.g. vit. B 12 , folic acid ,cardiac glycosides Lungs E.g. Halothane Sweat E.g. Benzoic acid, salicylic acid ,antipyrine and heavy metals Saliva E.g. Caffiene , phenytoin ,carbamazepine Bitter after taste in the mouth of a patient on medication is an indicate Black hairy tongueSlide 17: Breast milk E.g. Discoloration of teeth with tetracycline Jaundice by interaction of bilirubin and sulphonamide Gastrointestinal Excretion Genital ExcretionSlide 18: REFERENCE: L. shargel, S. wu –pong , A.B Yu “Applied Biopharmaceutis and Pharmacokinetics “ 5 th edition Mc Graw Hill publication , Page no 136 2. www. google.com 3. D.M. Bramankar, S.B jaiswal “Biopharmaceutis and Pharmacokinetics “ 1 st edition ,2007 Vallabah prakashan ,page no 178Slide 19: THANKYOU