Renal/urinary Pharmacology

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Osmotic Diuretics

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Examples - mannitol, urea, glycerin, isosrbide.
Properties - freely filtered with no reabsorption. increases urine volume. Mannitol is IV, urea is IV or PO but tastes narst, glcerin and isosrbide PO.
Met/Excr - mannitol and urea are inert, glycerin is converted to glucose.
Indications - mannitol prevents and is early tx for acute renal failure caused by trauma/surgery. can also temporarily decrease cerebrospinal pressure. Mannitol, glycerin, and isosorbide transiently decrease intraocular pressure in acute narrow angle glaucoma. urea is used less often than mannitol. glycerin and isosrbide are just for opthalmologic procedures.
SE, Tox - headache, n/v common. can decomponsate pts with CHF. mannitol and cause pseudohyponatremia. urea can cuase thrombosis. glycerin can cause hyperglycemia/glycosuria.

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Acetazolamide and Dorzolamide

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Class - Carbonic Anyhdrase Inhibitors
Properties - blocks CA --> inhibits exchange of H+ for Na+ in the PROXIMAL CONVOLUTED TUBULE, interfering with reabsoprtion of Na+ and bicarb. Weak diuretic action and leads to increased Na+, K+, and bicarb in urine.
Indications - acetazolamide is used primarily for glaucoma because it decreases ocular pressure by reducing aqueous humor formation. used to alkalinize urine for diuresis of weak acids (eg aspirin OD), can be an adjuvent in epilepsy but tolerance develops.
SE, Tox - drowsiness, paresthesias, myopia (nearsightedness). Met. acidosis due to decrease bicarb reabsoprtion. hypokalemia, rare hypersensitivity (rash, fever bone marrow suppression), renal calculus formation.

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Thiazide Diuretics

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Examples - chlorothiazide, hydrochlorothiazide, benzthiaside, indapmide, metolazone.
Properties - sulfonamide derivatives that promote diuresis by inhibiting reabs of NaCl in EARLY DISTAL TUBULE by blocking the Na/Cl constransporter. The increased sodium load promotes increased K secretion into urine. Increased excretion of Na, Cl, K, Mg. promote Ca reabsorption. actively secreted unchanged in the proximal tubules.
Indications - mild hypertension. alone or in combo for edema, esp in CHF. reduce hypercalciuria in pts with renal calculi. can also be used in tx of diabetes inspidus.
SE, Tox - hypokalemia (watch out with digitalis!) hyperuricemia, hypercalcemia, hyperglycemia (in diabetics), rashes, phtosensitivity, fever, hyperlipidemia (except indapamide), sexual dysfunction (wah-wah).

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Why am I so frightened right now?

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Cuz the man who lives in our fridge is making really angry noises and there's a moth that keeps flying into my head.

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Loop Diuretics

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Examples - ethacrynic acid, furosemide, bumetanide, torsemide.
Properties - inhibit reabsorption of electrolytes in THICK ASCENDING LIMB by blocking the Na/K/Cl cotransporter. MOST EFFECTIVE DIURETICS. increased excretion of Na, K, Ca, Mg. PO or IV. rapid onset.
Indications - CHF with pulmonary edema, liver failure, renal failure. IV for acute pulmonary edema. too potent for mild hypertension. hypercalcemia.
sE, Tox - hypotension, hypokalemia, met alkalosis, hyperuricemia, OTOTOXICITY (transient or permanent), allergic interstitial nephritis, hyperglycemia (less than with thiazides) GI disturbances).
Interactions - decrease the effect of oral hypoglycemics. decreases renal lithium clearance. additive effect on ototoxicity and nephrotoxicity with aminoglycosides.
ethacrynic acid is the only one that's not a sulfonamide therefore you can use it in pts with sulfa allergies.

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Potassium Sparing Diuretics

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Examples - spironolactone, triamterene, amiloride.
Properties - act at collecting tubule to inhibit reabsorption of Na and secretion of K. spironolactone is a structural analog of aldo thereby blocking aldo's activity. triamterene and amiloride directly inhibit reabsorption of Na which indirectly inhibits the secretion of K. spironolactone is PO and met in liver - it needs endogenous aldo! the others don't.
Indications - in combo with thiazides to prevent hypokalemia. edamatous states with high aldo (hepatic cirrhosis, nephrotic syndrome, cardiac failure), dx and treat primary hyperaldo with spironolactone. treat PCOD and female hirsutism (spironolactone).
SE, Tox - sprionolactone = hyperkalemia, gynecomastia, nausea, dyspepsia. triamterene = hyperkalemia, n/v, leg crampes, megaloblastic anemia in pts with alcoholic cirrhosis (inhibits DHF reductase in pts with reduced stores/intake of folate). amiloride = hyperkalemia, n/v, diarrhea, headache.

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Democlocycline

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Properties - antagonizes ADH
Indications - SIADH.

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Drugs that cause SIADH

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carbamazepine (seizures, manic) TCAs, thiazides, phenothiazines (neuroleptics?), chlorpropamide (sulfonylura for DM), cisplatin (anti-neoplastic)