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1. : ………………………………………….…………………… 1 2. Diuretics) - Carbonic anhydrase inhibitors…………………………………….……………… 11 - Osmotic diuretics…………………………………………………………….………….. 19 -...

1. : ………………………………………….…………………… 1 2. Diuretics) - Carbonic anhydrase inhibitors…………………………………….……………… 11 - Osmotic diuretics…………………………………………………………….………….. 19 - Loop diuretics……………………………………………………………………………… 28 - Thiazide diuretics…………………………………………………..……………….…… 40 - Potassium-sparing diuretics……………………………………..…………….…… 48 3. ………………………………………………………………… 59 4. - - Urine acidifers) …………………………………………………..…………… 62 - Urine alkalinisers) …………………………………………..…….………… 67 5. ……………………………………………….……………… 70 6. …………………………………………………………………..……… 74 7. Antidiuretics)………………………………………………………………..……………. 86 8. ……………………………………………………………………………………..…… 90 9. 5-alpha reductase inhibitor………………………………………………………….………………… 94  1 : kidneys) ureter) urinary bladder) urethra) : Reece, W.O. 2009. 2 % - calcitriol 1. 2. - 3. erythropoietin) 4. form) nephron renal corpuscle renal tubule renal corpuscle Borman’s capsule tubule  3 ultrafiltrate tubule % 1% Proximal tubule Bowman’s capsule isotonic loop Na+ 25% Na+ thick ascending limb thick ascending limb afferent arteriole columnar epithelial cell macula densa NaCl mucula densa afferent arteriole macula densa renin juxtaglomerular cell afferent ateriole macula densa Distal thick ascending limb 4 : https://global.britannica.com/science/Bowmans-capsule 3 : https://www.pinterest.com/hokiern69/ems-renal/  5 1. Proximal tubule proximal tubule 65 % filtrate glomerulus isotonic Na+, 3 - , glucose, phosphate, lactate, K+ - 3 4 4 carbonic anhydrase : http://www.uky.edu/~mtp/Diuretic_Drugs.htm 2. Loop of Henle Thin descending limb, thin ascending limb thick ascending limb thick ascending limb Na+ Na+-K+-2Cl cotransport 6 Ca2+, Mg2+ K+ Ca2+ Mg2+ paracellular pathway 5) 5 Na+-2Cl--K+ cotransporter thick ascending limb : http://www.uky.edu/~mtp/Diuretic_Drugs.htm 3. Distal convoluted tubule Na+ Na+-Cl – co-transport Ca2+ Ca2+ parathyroid hormone) 6)  7 6 Na+-Cl- cotransporter distal : http://www.uky.edu/~mtp/Diuretic_Drugs.htm 4. Collecting duct collecting duct Na+ + Na+ + K+ lumen Na+/K+ hormone aldosterone 7) 7 collecting tubule : http://www.uky.edu/~mtp/Diuretic_Drugs.htm 8 1. 2. - 3. 4. 5. 6. 2 - - Diuretics) edema) cerebrum  9 o carbonic anhydrase o Osmotic diuretics) o Na+- K+-- 2CL-symport membrane + transport protein - K+-- 2CL-symport) loop diuretics o Na+-2CL-symport membrane transport + - 2CL-symport) Thiazide diuretics o -sparing diuretics) - renal epithelial Na+ channels - Aldosterone antagonist 10 8 : ter Maaten et al., 2015.  11 Carbonic anhydrase inhibitor Carbonic anhydrase inhibitor acetazolamide, dichlorphenamide methazolamide dorzolamide carbonic anhydrase inhibitor : Reil. 12 epithelial cell) proximal luminal basolateral membrane proximal + ) - 3 ) 2CO3) carbonic anhydrase brush border lipophilic CA 2CO3 2O + CO2 2CO3 2CO3 + - - ) 3 3 3) Na+- 2CO3 - symporter basolateral membrane CA 3 proxima tubule - 3 3 proximal tubule collecting duct CA titratable  13 9 carbonic anhydrase inhibitor : 11. + titratable acid collecting duct metabolic acidosis CA % HCO -3 HCO -3 Na+) - ) - Na+ % 70% Na collecting duct Na+ lumen- 14 Cl- K+ K+ channel + proton pump 8 collecting tubule 2+ ) 2+ ) -limiting) metabolic acidosis HCO -3 HCO 3- CA HCO -3 Macula densa tubuloglomerular afferent CA gastric mucosa) ciliary processes HCO -3 aqueous humour)  15 CA CA sulfonamide sulfonamides metabolic acidosis - - - hyperchloremic acidosis metabolic respiratory acidosis - - CA 16 acetazolamide -30 mg/kg methazolamide 2-10 mg/kg - glaucoma acetazolamide mg/kg methazolamide glaucoma acetazolamide CA inhibitor dorzolamide dorzolamide CA inhibitor epilepsy ) carbonic anhydrase -100° C CA queous humour)  17 mg/kg 2– 4– –3 % tubular secretion reabsorption crystallyria) hypokalemia acetazolamide paresthesia) somnolence) peripheral tissue) 18 hyponatremia, hypokalemia hyperchloremic acidosis chronic, nonconges -closure glaucoma metabolic alkalosis metabolic alkalosis - 10 mg/kg (glaucoma) - 10 – 25 mg/kg – - 10 – 30 mg/kg - 50 mg/kg 7 mg/kg - 50 mg/kg 7 mg/kg - 6 – 8 mg/kg - 6 – 8 mg/kg  19 Osmotic Diuretics) glomerulus tubule glycerin, isosorbide, mannitol urea 2 Osmotic diuretics : 11. primary site proximal tube secondary site cortical medullary 20 blood flow K+ , Ca2+, Mg2+, phosphate bicarbonate Osmotic diuretic extracellular rennin renal medullary blood flow medulla medullary tonixity descending limb Mannitol 10 osmotic diuretic : http://tmedweb.tulane.edu/pharmwiki/doku.php/all_diuretics  21 lity) t1/2) mannitol urea glycerin isolorbide - - Osmotic diuretics extracellular fluid extracellular fluid pulmonary congestion pulmonary edema mean arterial blood pressure mannitol intraocular pressure mannitol 22 Mannitol mannitol cerebral perfusion pressure Mannitol) osmotic diuretic C –168 C C –7 physically compatible amikacin sulfate, cefoxitin sodium, cimetidin tobramycin sulfate Mannitol mannitol % cisplatin  23 Mannitol mannitol Mannitol – p effect) Mannitol mannitol hemodynamic anti- 1) 2) 24 17% blood – brain barrier – 10% – mannitol anuria) mannitol lure mannitol mannitol mannitol mannitol  25 Metabolic acidosis) hypotension) ) anaphylaxis) mannitol mannitol barium rhabdomyolysis aspirin barbiturate bromide) ethylene 26 - mannitol – 25% – 0.5 gm/kg – – – 10% – furosemide dopamine - mannitol gm/kg gm/kg mannitol acute glaucoma) - 1 – 2 gm/kg – – - 1 – 3 gm/kg – 25% –  27 - 1.5 gm/kg - 1.1 – 2.2 gm/kg – - 1 – 3 gm/kg - 1 – 2 gm/kg – % - 0.25 - 2 gm/kg 20% 28 Inhibitors of Na+-K+-2CL- symport loop diuretics high- ceiling diuretics thick ascending L) % TAL ethacrynic acid, bumetanide, furosemide torsemide furosemide ethacrynic acid sulfonamide furosemide  29 loop diuretic : 11. 30 thick ascending limb TAL) Cl- binding site transporter protein Na+-K+-2Cl symporter -25% Ca2+ Mg2+ Cl- lumen Ca2+ Mg2+ 8 K+ + - distal tubule carbonic anhydrase inhibitors furosemide CA 3 uric acid uric acid resistance) renal blood flow glomerular filtration rate  31 11 loop diuretic : 11. furosemide pulmonary edema 32 furosemide % -4%) glucoronide mg/kg - -60% conjugation glucolonic acid albumin extracellular fluid hyponatremia prerenal azotemia tubular necrosis Na+-K+-2Cl- symporter distal tubule renin-angiotensin-aldosterone hypochloremia alkalosis hypokalemia cardiac glycoside Mg2+ Ca2+ hypomagnesemia hypocalcemia  33 hyperuricemia uric acid glycogenolysis glycogen sulfonamide) sulfonamide sulfonamide group anuria) loop diuretic Aminoglycosides : Digitalis glycoside : Propanolol : propranolol Cisplatin : thiazide : D : diuretic response 34 acute pulmonary edema pulmonary congestion hypertension hyperkalemia potassium-sparing diuretics Br- - - loop diuretic acute pulmonary edema ascites -4 mg/kg - 2-5 mg/kg -2 mg/kg mg/kg - acute pulmonary edema - Ca2+ K2+ furosemide -1 mg/kg furosemide digoxin drug of choice acute cardiogenic pulmonary edema  35 loop diuretics 12 loop diuretics : ter Maaten et al., 2015 36 Furosemide) frusemide loop diuretic sulfonamide 203 – 205 alkaline hydroxide – 9.3 ascending distal tubule proximal tubules carbonic anhydrase aldosterone renin a) thiazide - thoracic duct guinea pig  37 oral bio - bility % 60 -75% % uremia), a) prerenal azotemia mg/kg - 2.2 – 4.4 mg/kg - 38 cardiogenic edema pulmonary edema - – 2 mg/kg - e pulmonary edema) mg/kg 1- mg/kg 1- - digoxin mg/kg mg/kg mg/kg - mg/kg - hypercalcemia - mg/kg mg/kg/hr normal saline furosemide mg/dl - hypercalcemia -16 mg/dl) normal saline furosemide mg/kg 1- normal saline glucocorticoid (acute renal failure) uremia  39 - furosemide mg/kg mg/kg mg/kg dopamine hyperkalemia - mg/kg (ascites) - -2 mg/kg - - -2 mg/kg - -3 mg/kg -2 mg/kg - 1-4 mg/kg 2- - 2-5mg/kg -4 mg/kg 4- pulmonary edema mice, rat, - 5-10 mg/kg - 500 mg mg 40 48 - 2.2 – 4.4 mg/kg - -2 mg/kg - -2 mg/kg - - acute renal failure 2-4 mg/kg - 0.3 –0.6 mg/kg - - 250 mg - 0.05 mg/300 gm - 5 mg/kg + Thia ike diuretic -Cl- symport) thiazide diuretics benzothiadiazin CA-inhibiting sulfonamides Na+-Cl- symport CA CA inhibitor CA inhibitor 3 thiazide NaCl – 2 2 thiazide-like diuretics  41 chlorothiazide hydrochlorothiazide bendroflumethiazide, chlortalidone, cyclopenthiazide indapamide Thiazide : 11. 42 uluted tubule Na+ % Na+Cl symport Na+-Cl- proximal tubule thiazide loop diuretic Na+ Cl-cotransport - 10 DCT carbonic anhydrase proximal tubule 3 Ca2+ loop diuretic DCT Ca2+ transport basolateral membrane Na+/Ca2+ exchange process thiazide Ca2+ loop diuretic thiazide diuretic K+ titratable acid uric acid uric acid proximal  43 13 Thiazide : http://tmedweb.tulane.edu/pharmwiki/doku.php/all_diuretics digitalis glycoside cardiac arrhythmia sulfonamides thiazide diuretics thiazide like diuretics 44 uric acid pro-insulin insulin - anticoagulants - digitalis glycoside, loop diuretic D - - Amphotericin B corticosteroid - chlorothiazide -40 mg/kg -4 mg/kg hydrochlorothiazide - hydrochlorothiazide  45 ) thiazide cortical diluting segment rennin aldosterone thiazide thiazide neurogenic nephrogenic 46 % – – – 14.8 hypochloremic alkalosis magnesemia) hyperparathyroid-like effect)  47 sulfonamide thiazide furosemide thiazide a) thiazide calcium oxalate chlorothiazide thiazide (nephrogenic diabetes insipidus) - 0.5 - 1.0 mg/kg - 2.5 – 5 mg/kg - 1 mg/kg – spironolactone 1 – 2mg/kg 48 calcium oxalate - 2 mg/kg - 2.2 mg/kg urinalysis – - furosemide furosemide – 4 mg/kg - 2 – 4 mg/kg - 1 mg/kg – spiroholactone mg/kg - furosemide - Potassium-Sparing Diuretics o agonists) o renal epithelial Na+ channels  49 aldosterone aldosterone Alsosterone mineralocorticoid Na+ Cl- K+ + aldosterone typical steroid hormone aldosterone MRs late distal tubule collecting duct MR- aldosterone complex specific sequences DNA multiple gene products aldosterone- Na+ NaCl K+ + 4 aldosterone : http://www.uky.edu/~mtp/Diuretic_Drugs.htm 50 aldosterone antagonists of mineralocorticoid receptors aldosterone antagonists aldosterone mineralocorticoid MR-aldosterone complex aldosterone antagonists : 11.  51 specific competiti antagonist aldosterone receptor aldosterone cytoplasm distal tubule collecting duct MR-spironolactone complex aldosterone Na+ K+ Na+ K+ Ca2+ aldosterone Na+-K+ transport aldosterone antagonist Na+ K+ 10-20 3 2-3 aldosterone aldosterone mineralocorticoid late distal tubules collecting duct aldosterone- K+ + late distal tubules collecting duct aldosterone MRs aldosterone- ) aldosterone spironolactone calcium channel blocker 52 5 aldosterone antagonist late distal tubule collecting duct : 11. aldosterone antagonists hypekalemia dehydration hyponatremia spironolactone -  53 Spironolactone aldosterone 198 -207 C aldosterone distal titratable acid CA hyperaldosteronism proximal thiazide loop diuretic hypokalemia % - spironolactone canrenone % canrenone canrenone - canrenone 54 % canrenone - hyperkalemia, hyponatremia BUN acidosis hyperkalemia spironolactone testosterone tumorigenic) canrenone spironolactone amiloride, triamterene hyperkalemia  55 hyperkalemia spironolactone indomethacin - inhibitors) captopril, enalapril lactone digoxin digitoxin aspirin spironolactone furosemide CHF - 1-2 mg/kg furosemide - hypokalemia -4 mg/kg (ascites) - 1-2 mg/kg - - -8 mg/kg CHF 56 - 1-2 mg/kg furosemide inhibitor - 1 mg/kg renal epithelial Na+ channels triamterene ® ® ) ) organic base organic base secretory mechanism proximal tubules inhibitors of renal epithelial Na+channels : 11.  57 triamterene amiloride sodium channel luminal membrane late distal tubule collecting duct Na+ % 16 renal epithelial Na+channel : 11. 58 amiloride triamterene 10 Na+ epithelium channel NaCl lumen- K+ + , Ca2+ Mg2+ renal blood flow glomerular filtration rate Amiloride 15-25%) triamterene - hydroxytriamterene sulfate triamterene triamterene folic acid antagonist triamterene megaloblastosis folic acid amiloride triamterene thiazide loop diuretic  59 r- PO) erythropoietin erythropoietin ) reticulocyte) - -alpha) urenic 7 erythropoietin 60 % - autoantibody mucocutaneous ulcer rat mg/kg -18 - units/kg hematocrit, 37-45%  61 25-50 Units/kg 75-100 mg/kg - - -145 units/kg units/kg units/kg 14% units/kg) units/kg - -40% - 50-150 U/kg - 50-150 U/kg - 62 - - Escherichia coli, Coliform, Proteus, Pseudomonas aeruginosa sulfadiazine trimethoprim trimethoprim fluoroquinolone penicillin, tetracyline nitrofurantoin Urine fers) Acidifiers acidifiers Methionine Ascorbic acid Ammonium chloride mg/kg -500 mg/kg Ammonium sulphate  63 Methionine) 1 methionine Methionine l-form lipotrope choline methionine 2 cysteine methionine sulfhydryl methyl methionine sulfuric acid methionine -body -body hemolytic anemia) methionine methimoglobinemia -body aminogly coside erythromycin 64 methionine methionine mercaptan-like compound acidosis urate methionine disulfide - - - – 1,500 mg - 0.2 –  65 - 20 – - mg/kg 11 mg/kg mg/kg - Ascorbic acid C : 100 – 500 mg : 100 mg : 2 g/kg acidosis sulphonamides 66 metabolic acidosis - 20 mg/kg - 8 - : 200 mg/kg 1-2 4 - : 200 – 500 mg/kg 3-4 - 1-2 12  67 Urine alkalinisers) Alkalinisers urate alkalinisers potassium citrate, sodium bicarbonate sodium citrate Potassium citrate calcium oxilate urate : 75 mg/kg Sodium Bicarbonate baking soda, sodium hydrogen carbonate, sodium acid carbonate 3 bicarbonate : carbonic acid buffer buffer 68 metabolic alkalosis, okalemia), hypernatremia metabolic respiratory alkalosis hypochloremic alkalosis hypocalcemia hypocalcemia metabolic acidosis hypercalcemia hyperkalemia  69 - 650 - – – – 7.5 70 ) xanthine oxidase inhibitor allopurinol oxpurinol metabolite xanthine oxidase oxypurines hypoxanthine, xanthine uric acid hepatic microsomal enzyme allopurinol uric acid allopurinol xanthine oxidase superoxide anion radicals hemorrhagic shock 18 allopurinol  71 % Allopurinol % allopurinol oxypruinol Xanthine oxidase allopurinol oxypurinol allopurinol - oxypurinol - uric acid calcium oxalate gout allopurinol 72 allopurinol mg/kg xanthine allopurinol cyclophosphamide urocosuric agents probenecid sulfinpyrazone oxypurinol xanthine oxidase inhibition methionine, ammonium chloride uric acid amoxicillin ampicillin uric acid urate - 7-10 mg/kg 3 urate : creatinine % - mg/kg / - -20 mg/kg  73 - - purine 10 mg/kg mg/kg urate - 9 mg/kg/ - : mg 74 system) 7 19 lower urinary tract) 2007.  75 7 - - - - sympathetic) storage phase) - parasympathetic) system) sympathetic -adrenergic receptor 76 detrusor -adrenergic receptor external urethral sphincter spinal afferent pathway 20 storage phase cerebral cortex midbrain spinal pathway cholinergic receptors detrusor muscle  77 21 urinary incontenence) 2 3 1) bethanechol chloride 2) 3) oxybutynin 78 Bethanechol chloride) cholinergic ester amine parasympathomimetic drug cholinergic receptor muscarinic nicotinic hydrolysis cholinesterase acetylcholine peristalsis peristalsis tone detrusor muscle bladder bladder metoclopramide neostigmine -  79 - - - - - - - cholinergic reactions atropine muscarinic effect Drug interaction cholinergic Carbacol anticholinesterase neostigmine 80 - 2.5 – 10 mg – 25 mg - 1.25 – 5 mg - 1.25 – 7.5 mg detrusor muscle - 0.025 – 0.075 mg/kg -175 C mucosa uterine tone epiphyseal anabolic  81 gonadotropin perianal gland adenoma prostatic hyperplasia glucoronide ia) normochromic normocytic anemia thrombocytopenia neutropenia – mg/kg cystic endometrial hyperplasia - - 82 - - mg/ mg/  83 - 0.1 – 0.5 mg - -2 mg es ) perianal gland adenoma prostatic hyperplasia - 0.1-1 mg - - benign prostatic hypertrophy -1 mg - -1 mg - mg 0.1- 0.3 mg/kg - 0.1-1 mg - mg mg Oxybutynin urinary antispasmodic agent 84 oxybutynin -like) -like) spasmolytic detrusor oxybutynin. Oxybutynin Oxybutynin o o o o o mitral stenosis, tachycardia, chronic heart failure o o  85 o o o - 0.2 mg/kg 3-4 1.25-3.75 - 1.25-5 mg/ 2-3 - 2-5 mg/ 2-3 - 0.5-1.0 mg/ 4 - 0.5-1.25 mg/ 3-4 86 ) Antidiuretic supraoptic neclei pituitary gland) collecting duct coronary catecholamine chromaffin cell aldosterone Amino acid peptide hormone 8- 8-lysin ar plasma osmolality osmolality threshold mOsm/kg plasma osmolality  87 22 plasma osmolality : Knepper et al., 2015. 2. hypovolemia hypotension osmolality - 10%) % - 30% 88 prostaglandin 1 receptor 2 receptor cAMP collecting duct 2 receptor factors 23 : 20Pressure/BP016  89 – extracellular fluid – supraoptic par pituitary stalk hyperadenocorticism hyperthyroidism hypercalcemic disorders renal failure pyelonephritis osmolality osmolality Desmopressin acetate 90 -desamino-8-L- acting) 2 receptor 1 receptor water intoxication chronic nephritis Uterine stimulants) relaxin corpus luteum placenta oxytocin ergot alkaloids  91 Oxytocin cyclic 8-amino acid peptide hypothalamus posterior pituitary oxytocin receptors myometrial cells oxytocin oxytocin drug of choice oxytocin oxytocin uterine rupture anaphylactoid oxytocin oxytocin antidiuretic hormone-like effects oxytocin Oxytocin sensory stimuli oxytocin oxytocin : oxytocin oxytocin estrogen estrogen oxytocin 92 : oxytocin milk letdown - oxytocin - oxytocinase - uterine inertia ) - - agalactia ) - oxytocin dystocia ) oxytocin  93 oxytocin tetany : 1- calcium gluconate 10% 3-5 ml oxytocin : primary uterine inertia 5-20 : primary uterine inertia - 30- : 40- 94 5-alpha reductase inhibitor 5-alpha reductase inhibitor benign prostatic hypertrophy finasteride 5-alpha-reductase testosterone finasteride : et al., 2008.  95 % blood brain barrier seminal fluid Benign prostatic hypertrophy - 96 1. Boothe, D.M., 2012. Pharmacology & Therapeutics. Boothe, D.M., editor. 2nd Missouri. p. 624-639. 2. , 2008. Benign. 62, 1076-1086. 3. manual of editors. 2nd -40. 4. comparison between rasburicase and allopurinol in children withlymphoma or -3003. 5. Knepper, M.A., Kwon, T., and Nielsen Molecular Physiology of Water Balance.N... Med. 372, 1349-1358. rd 6. edition, Mosby th 7. ition. Willey-Blackwell, 8. domestic animals. 4th - -358.  97 9. 2011. Regulation of renal fu - l th 10. 11. uses. published 2/01/12/bja ceaccp.mkr063.full.pdf+html 12. benign -545. 13. Clinical Pharmacology & Therapeutics. Boothe, D.M., editor. 2nd Missouri. p. 640-671. 9, 2147-2163. 15. T 2015. Diuretic response in acute heart failure — therapy. Nat. -192. 16. https://global.britannica.com/science/Bowmans-capsule 17. https://www.pinterest.com/hokiern69/ems-renal/ 18. http://www.uky.edu/~mtp/Diuretic_Drugs.htm 19. http://doctorlib.info/pharmacology/manual/26.html