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Sunday, February 3, 2013

Diuretics

Diurectic is a drug that promotes renal excretion of electrolytes and water, useful in treating generalized edema. Diuretic lowers blood pressure primarily by depleting body sodium stores. Initially, diuretics reduce blood pressure by reducing blood volume and cardiac output; peripheral vascular resistance may increase.

Carbonic Anhydrase Inhibitors (CAI)
Mechanism of Action: Mainly to inhibit carbonic anhydrase enzymes in the proximal convoluted tubule, eyes and central nervous system in noncompetitivly inhibition. Prevent the enzyme from providing the tubular hydrogen ions needed for exchange with sodium, reducing sodium absorption in the proximal tubule and enhancing sodium's subsequent exchange with the potassium in the distal tubule. The urine output has alkaline pH, because these drugs increase water, sodium, potassium and bicarbonate excretion.
Uses: Treatment for glaucoma, acute mountain sickness (high altitude, meniere's disease), reduce edema as adjunct diuretic, reduce intraocular pressure (retard aqueous humor formation), to alkalinize urine, and use as anticonvulsant drug in the therapy of petit mal epilepsy.
Drugs: Acetazolamide, Dorzolamide, Brinzolamide
Side Effects: Metabolic acidosis, hypokalemia, drowsiness, paresthesia, hypersensitivity (in sulfonamides)

Loop Diuretics (High-ceiling drug)
Mechanism of Action: It inhibits the sodium, potassium and chloride transported at the Loop of Henle. Loop diuretics do not cause change in pH of the urine.
Uses: Acute pulmonary edema, ascites, hypercalcemia, edema from CHF and renal disease.
Drugs: Furosemide (Sulfonamide derivative), Ethacrynic acid (phenoxyactetic acid), Bumetanide
Side Effects: Hypokalemia, hypovolemia, ototoxicity, hypersensitivity to sulfonamide, hypocalcemia, leg cramps, orthostatic hypotension, thrombocytopenia.

Thiazide Diuretics
Mechanism of Action: Inhibit the sodium - chloride symporter at the distal convoluted tubule. These drugs are increasing water, sodium, chloride, potassium, and bicarbonate excretion and decreased calcium excretion and uric acid secretion making urine output alkaline in nature.
Uses: Hypertension, hypocalcemia, nephrolithiasis due to calcium, chronic edema and CHF.
Drugs: Hydrochlorothiazide (sulfonamide derivative)
Side Effects: Hyponatremia, hypokalemia, hyperglycemia, hyperuricemia, hyperlipidemia, allergy to sulfonamide

Potassium-Sparing Diuretics
Mechanism of Action: Spironolactone - aldosterone antagonist in the collecting tubule; and Amiloride blocks inhibit sodium-potassium ATPase enzymes that inhibits active transport of sodium and potassium at the distal tubule, decreasing potassium secretion; Triameterene - acts directly on the distal tubule.
Uses: CHF taking digoxin, Potassium wasting with diuretics, aldosteronism (Conn's syndrome)
Drugs: Spironolactone, eplerenone (steroids derivatives), amiloride and triamterene
Side Effects: Hyponatremia, hyperkalemia (with K supplements and ACE inhibitors), gynecomastia (Spironolactone)

Osmotic Diuretics
Mechanism of Action: Osmotic effect in the Glomerulus, Loop of Henle and proximal convoluted tubules. They are inert chemicals that are freely filtered, but poorly absorbed in those sites. They increase the osmolarity of the filtrate in the glomerular, they limit tubular reabsorption of water, and, subsequently, promote diuresis.
Uses: Increased intracranial pressure for lithium toxicity and reduce  intracranial pressure in neurologic conditions. They also prevent and treat oliguria and anuria and helps to reduce intraocular pressure.
Drugs: Mannitol, Glycerin, isosorbide, urea (rarely used)
Side Effects: hypovolemia (increased blood volume), hypernatremia, pulmonary edema, headache and blurred vision.
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