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DIURETICS

Type of diuretics	Drug	Primary Site of action	Other sites	effect on renal hemodynamics	Excreted ions	pH	uses	Adverse effects
Carbonic anhydrase inhibition [abolish NaHCO3 reabsorption in proximal tubule]	Acetazolamide (DIAMOX), Dichlorphenamide (DARAMIDE), Methazolamide (GLAUCTABS).	Proximal tubular epithelial cells	Collecting ducts	Increase delivery of solutes to the macula densa , increase afferent arteriolar resistance and reduces renal blood flow and GFR	Increasing HCO3 –  & phosphate excretion	Increase in urinary Ph –> metabolic acidosis	Edema, treat epilepsy, relief in patients with high-altitude illness or mountain sickness , useful in pts with familial periodic paralysis, treatment of dural ectasia in individulas with marfansyndrome, of sleep apnea, and of idiopathic intracranial hypertension , correct metabolic alkalosis.	Large doses exhibit drowsiness and paresthesias, worsen hepatic encephalopathy , calculus formation and ureteral colic owing to precipitation of calcium phospahte salts in alkaline urine , worsen metabolic or resp.acidosis, reduce weak organic bases excretion
Osmotic diuretics [net Na+ reabsorption ceases]	Glycerin (osmoglyn),  isosorbide (ismotic), mannitol (osmitrol), urea (uraphil). Gly and Iso – orally., Mannitol and urea – IV.	Loop of Henle	Proximal tubule	Increase RBF, dilate afferent arteriole, dilute plasma, increase GFR.	Increase excreation of Na+ , K+, Ca+2, Mg+2, Cl-, HCO3- and phosphate.	----	Mannitol –> dialysis of disequilibrium syndrome, Mannitol and urea reduce cerebral edema and brain mass before and after neurosurgery.  Used to control intraocular pressure in acute glaucoma	Pts with heart failure or pulmonary congestion cause Frank pulmonary edema. Containdicated in anuric’s. urea cause thrombosis/pain not administered If Impaired liver function. Mannitol and urea contraindicated in active cranial bleeding. Glycerin metabolized –> Hyperglycemia.
Inhibitors of Na+_K+_ 2Cl- symport (Loop diuretics, high ceiling diuretics) Type of diuretics	Furosemide (Lasix), Bumetamide (bumex), ethacrynic acid(edecrin), torsemide(demadex), axosemide, piretanide, tripamide. Drug	Thick ascending limb Primary Site of action	Other sites	Increase total RBF, powerful stimulators of renin release, block TGF by inhibiting salt effect on renal hemodynamics	Increase Na+, K+, Cl- , Mg2+, Ca2+, HCO3- ,and phosphate(carbo nic Excreted ions	pH	For acute pulmonary edema, chronic congestive heart failure, hypertension, ascites of liver cirrhosis, uses	Dehydration and electrolyte depletion, asymptomatic hyperuricemia, hypergycemia, increase plasma LDL, decrease in plasma HDL, blocks the kidney ability to concentrate Adverse effects
	Acutely loop diuretics – Increase uric acid excretion Chronic – reduced uric acid excretion	Mutations in genes coding for symporter causes BARTTER syndrome(inherited hypokalemic alkalosiswith salt wasting and hypotension)		transport into the macula densa so that m.densa no longer can detect NaCl concentrations in tubular fluid.	anhydrase inhibiting drugs)		hypercalcemi a treatment, combination with hypertonic saline treat for Hyponatrmia.	urine during hydropenia, impair kidney ability to excrete dilute urine during water diuresis, hypochloremic alkalosis, hyponatremia, hypomagnesemia, hypocalcemia, Ototoxicity(ethacrynic acid more often),
Inhibitors of Na+_Cl- symport ( Thiazide and Thiazide like diuretics)	Bendroflumethaizide(naturetin), chlorothiazine(diuril), hydrochlorothiazide(hydrodiuril), hydroflumethiazide(saluron), methyclothiazide(enduron), polythiazide(renese), tricholoromethiazide(naqua), chlorthalodone(hygroton), indapamide, metolazone, quinethazone.	DCT {mutations in NaCl symporter cause a form of inherited hypokalemic alkalosis called GITELMAN syndrome}	Proximal tubule	Don’t effect RBF, reduce GFR owing to increase in intratubular pressure, little or no influence on TGF.	Increase Na+&Cl- , HCO3- , phosphate ,k+and titrable acid ,uric acid excretion. Chronic-decrease Ca2+excretion		Treat edema associated with CHF, liver cirrhosis, nephrotic syndrome, chronic renal failure, acute glomerulo nephritis. Best therapy for uncomplicated hypertension, treat Ca2+nephrolithiasis, treat osteoporosis, nephrogenic diabetes insipidus, Br- intoxication management.	*Erectile dysfunction, hypokalemia, hyponatremia, hypotension, metabolic alkalosis, hypomagnesemia, hyper calcemia, hyper urecemia, prolonged QT interval by quinidine – TORSADES DE POINTES ( polymorphic ventricular tachycardia)
Type of diuretics	Drug	Primary Site of action	Other sites	effect on renal hemodynamics	Excreted ions	pH	Uses	Adverse effects
Inhibitors of renal epithelial Na+ channels (K+ - sparing diuretics)	Amiloride (midamor), Triamtrene (Dyrenium)-weak folic acid antagonist	Late distal tubule and collecting duct		Little or no effect, Don’t alter TGF.	Mildly increases Na+ and Cl- excretion, decreases K+, H+,Ca2+& Mg2+ excretion rates		Pentamidine and high dose trimethoprim to treat Pneumocystis jiroveci in AIDS patients. Treat edema or hypertension, LIDDLE SYNDROME,amiloride reduce BP in pts carry T594M polymorphism. Amiloride improves mucociliary clearance and useful for lithium induced nephrogenic diabetes insipidus.	*Hyperkalemia, cirrhotic patients are prone to Megaloblastosis because of folic acid deficiency , triamtrene reduce glucose tolerance , induce photo sensitization associated with interstitial nephritis and renal stones. TRIAMTRENE:- nausea, vomiting, leg cramps & dizziness. AMILORIDE:- nausea, vomiting, diarrhea and headache.
Antagonists of mineralocorticoid receptors {MR} (aldosterone antagonists, K+ sparing diuretics)	Spironolactone(aldactone), Eplerenone(Inspra), Canrenone, potassium canrenoate	Late distal tubule and collecting duct		Little or no effect, do not alter TGF. {spironolactone 1st passage through LIVER}	Similar to Na+channel inhibitors.		Edema and hypertension, SPIRONOLACTONE:- *diuretic of choice in hepatic cirrhosis, treat resistant hypertension due to primary hyper aldosterinoism and of refractory edema associated with secondary aldosteronism.	*Hyperkalemia, metabolic acidosis in cirrhotic patients , salicylates reduce tubular secretion of canrenone and decrease diuretic efficacy of spironolactone , spironolactone – gynecomastia, impotence, menstrual irregularities.
Inhibitors of the nonspecific cation channel: atrial natriuretic peptides	nesiritide	Inner meduallary collecting duct (IMCD)	Proximal and distal nephron	GFR increases in normal pts, may inc, decr, or no change in CHF patients	Na+ excretion increases		Nesiritide reduce symptoms and hemodynamic parameters in those w/ dyspnea not hypertensive, limited in those with acute CHF w/ shortness of breath at rest	Increase in serum creatinine conc due to decreasein ECF, decrease in BP and activation of renin angiotensin-aldosterone system