Chapt15 Diuretic Agents

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    07-Dec-2015

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diuretic drugs pharmacology

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  • 15 Diuretics*

  • Diuretics : Natriuretic : excretion Natriuretics water excretion diuretics osmotic diuretics are diuretics that are not directly natriuretic.Caffeinedose

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  • Carbonic Anhydrase Inhibitors (Acetazolamide, Diamox) 1. Carbonic Anhyduase (nephron) : (1) H2O+CO2 H2CO3 HCO3-+H+ (2) Carbonic Anhydrase Inhibtor : HCO3- NaHCO3 diuresis

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  • 2.Clinical Indications:A. Glaucoma :Carbonic Anhydrase Inhibitor

  • B. urinary Alkalinization : uric acid , cystine , carbonic anhydrase inhibitor pH cystine (in cystinuria) *

  • C. Metabolic Alkalosis Metabolic alkalosis total body K+ , volume , mineralocorticoid level metabolic alkalosis , acetazolamide . acetazloamide respiratory acidosis metabolic alkalosis *

  • D. Acute mountain sickness (High altitude sickness) : 3000. weakness , dizziness , insomnia , headache , nausea . pulmonary or cerebral edema. Dichlorphenamide cerebrospinal fluid cerebrospinal fluid and brain pH E. Other uses carbonic anhydrase inhibitor epilepsy , hypokalemic periodic paralysis urinary phosphate severe hyperphosphatemia *

  • 3. Toxicity : (1) Hyperchloremic metabolic acidosis body HCO3-acidosis (2) Renal Stones bicarbonaturic response phosphaturia and hypercalciuria carbonic anhydrase inhibitor factor ( citrate ) pH , (3) Renal potassium wasting HCO3- (lumen-negative electrical potential ) Na+, k+*

  • 4. Contraindications : carbonic anhydrase inhibitor (Acetazolamide) NH4+ NH3 ammonia hyperammonemia hepatic encephalopathy()*

  • Loop Diuretics : (Furosemide , Lasix ) 1. Loop Diuretics NaCl Loop of Henle (thick ascending limb TAL) acidosis ( high ceiling diuretics) organic mercurial diuretics TAL NaCl , Furosemide(hypercalcemia) (Lasix blood volumesaline infusion) *

  • Loop Diuretics : (Furosemide , Lasix ) (Bumetanide, Bumex) 2. clinical Indications Bumetanide acute pulmonary edema. (1) Hyperkalemia : loop diuretics k+ (2) Acute Renal Failure : loop diuretics k+ . acute renal failure (3) Anion overdose bromide,fluoride,iodide TAL loop diuretic saline solution Na+,Cl-, depletion*venous capacitance

  • 3. Toxicity : (1)Hypokalemic metabolic alkalosis loop diuretics salt TAL salt k+ and H+ hypokalemic metabolic alkalosis (2) Ototoxicity ototoxicity ototoxic agent (aminoglycoside ) (3) Hyperuricemia uric acid loop diuretics *

  • 3. Toxicity : (4) Hypomagnesemia loop diuretics magnesium depletion (5) Allergic and other Reactions,

    4. Contraindications : hepatic cirrhosis , renal failure *

  • . Thiazides (Trichlormethiazide , Diurese ) 1. Thiazides ( distal convoluted tubule )(DCT) NaCl (Na+/Cl- cotransporter NCC) Thiazides natriuresis ? Thiazides Ca++(,)

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  • 2.Clinical Indications : (1)Hypertension (2)Heart failure (3)Nephrolithiasis due to idiopathic hypercalciuria () (4)Nephrogenic diabetes insipidus ()

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  • . Thiazides (Trichlormethiazide , Diurese ) 3. Toxicity (1) Hypokalemic Metabolic Alkalosis and Hyperuricemia toxicityloop diuretics (2) Impaired carbohydrate tolerance hyperglycemia (DM ) insulinDM (Type I) ptchlorothiazide furosemide, spironolactone, acetazolamide. (3) Hyperlipidemia total serum cholesterol LDL 5-15% (4) Hyponatremia . thiazides

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  • (5) Allergic Reactions hemolytic anemia () thrombocytopenia () acute necrotizing pancreatitis() (6) Other Toxicities weakness , fatigability , impotence 4. Contraindications : hepatic cirrhosis , renal failure , heart failure *

  • . Potassium-Sparing Diuretics (Spironolactone , Aldactone ) (Amiloride) 1. amiloridealdosterone Na+ channel K+ mineralocorticoid receptor (spironolactone ) cortical collecting tubule (CCT)Na+(Amiloride , Triamterene , Dyrenium) (aldosterone CCT Na+ , K+) *

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  • 2.Clinical Indications mineralocorticoid excess hyperaldosteronism (aldosteronism) ,CHF, amiloride Li+ Spironolactone *

  • 3. Toxicity (1) Hyperkalemia (2) Hyperchloremic Metabolic Acidosis (3) Gynecomastia : ( ) Gynecomastia , impotence , benign prostatic hyperplasia (4) Acute Renal Failure (5) Kidney stone 4. Contraindications hyperkalemia renin-angiotensin system (b-blocker or ACE inhibitorshyperkalemia) spironolactone*

  • Agents that alter water excretion : () Osmotic Diuretics (Mannitol) 1. : Henles loop mannitol () (water diuresis) mannitol , mannitol G-I () 30-60min mannitol natriuresis () water diuresis() hypernatremia*

  • 2. Clinical Indication : (1) (increase of urine volume) (2) (Reduction of intracranial and intraocular pressure) mannitol 1-2g/kg mannitol I.V. 60-90 (3)brain injury and cerebral edemapt, edematous brain*

  • 3. Toxicity (1) (Extracellular Volume expansion) : mannitol heart failure , , , , (2) , : mannitol , (hypernatremia) k+(hyperkalemia)*

  • () Antidiuretic hormone 1. ADH agonist Vasopressin desmopressin (antidiuretic hormone , ADH) ADH ADHnonapeptide 6amino-acid ring 3 amino-acid side chain vasopressin desmopressin (central diabetes insipidus) vasopressin G-proein receptor : V1a receptor : vasopressin vasoconstriction V1b receptor : corticotropes ACTH V2 receptor :vasopressin *

  • () Antidiuretic hormone V1a phospholipase C inositol + triphosphate Ca++ V2adenylyl cyclase V1 vasoconstriction agonist :Terlipressin () V2 antidiuretic analog : Ddavp (1-deamino D-Arg8 arginine vasopressin) central diabetes insipidus *

  • 2. Antidiuretic hormone (ADH) antagonist V1a receptor antagonist : relcovaptan , heart failure () V1a and V2 antagonist conivaptan (YM087) Tolvaptan-V2 antagonist V2 affinityV1 receptor30FDA*

  • . Diuretic Combinations 1. Loop agents and thiazides :hypokalemia Thiazides mild natriuresis ? Loop diuretics 2-6 hr. NaCl TAL (thick ascending limb ) DCT (distal convoluted tubule) :k+k+(pot-sparing diuretics) *

  • . Diuretic Combinations 2. Potassium-sparing diuretics and loop agents or thiazides Loop agent thiazides hypokalemia NaCl KCl potassium- sparing diuretics (Spironolactone) renal insufficiency ACE inhibitor potassium sparing diuretics hyperkalemia

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  • . Diuretic Combinations 3. Limanic-depressive disordernephrogenic diabetes insipidusthiazide(Li+)Li+(Li+) amiloride (Pot-sparing)Li-induced polyuria () (amilorideLi+Na+) (Amiloride ,)*

  • . Clinical pharmacology of diuretics urinary eletrolyte excretion p.253 tab15-1 *

  • : (). Edematous states ( ) *

  • 1.Congestive Heart failure loop diuretics thiazides 2.Kidney disease and renal failure Acetazolamide (Diamox , metabolic acidosis) loop diuretic (hyperkalemia) 3. Hepatic cirrhosis (portal hydrostatic pressure ) ,(plasma oncotic pressure ) (edema) (ascites) *

  • depletion of intravascular volume hypokalemia m