DIURETICS CARBONIC ANHYDRASE INHIBITORS THIAZIDE THIAZIDE-LIKE OSMOTIC DIURETICS LOOP DIURETICS POTASSIUM SPARING DIURETICS
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1 DIURETICS A diuretic is any substance that promotes diuresis, that is, the increased production of urine. This includes forced diuresis. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way. CARBONIC ANHYDRASE INHIBITORS THIAZIDE THIAZIDE-LIKE OSMOTIC DIURETICS LOOP DIURETICS POTASSIUM SPARING DIURETICS
2 OSMOTIC DIURETICS Substances that increase osmolality but have limited tubular epithelial cell permeability. They work primarily by expanding extracellular fluid and plasma volume, therefore increasing blood flow to the kidney, particularly the peritubular capillaries. This reduces medullary osmolality and thus impairs the concentration of urine in the loop of Henle. Furthermore, the limited tubular epithelial cell permeability increases osmolality and thus water retention in the filtrate DRUG ADMIN ASBORBANCE PP BINDING PLASMATIC HALF-LIFE METAB. ELIMIN. MANNITOLO (Isotol ), Soluz 5%/fl I.V. VERY LOW Oral availability: 20% --- 1,5 h Liver 10% RENAL MEDICAL USE Mannitol is used for diuresis in treatment and prevention of reduced urine production in acute kidney failure, for reducing intracranial pressure and brain mass in people with swelling in the brain (cerebral edema), for reducing intraocular pressure, and irrigation of the urinary bladder to promote urinary excretion of toxic materials. ADVERSE EFFECTS Pulmonary congestion, fluid and electrolyte imbalance, dry mouth, thirst, headache, blurred vision, dizziness, nausea, and chest pain.
3 CARBONIC ANHYDRASE INHIBITORS Carbonic anhydrase inhibitors cause increased excretion of bicarbonate with accompanying sodium, potassium and water, resulting in an increased flow of alkaline urine. They inhibit transport of bicarbonate into the interstitium from the proximal convoluted tubule. Therefore less sodium is reabsorbed, causing greater sodium, bicarbonate and water loss in the urine. The carbonic anhydrases are a family of enzymes that catalyze the rapid interconversion of carbon dioxide and water (CO 2 + H 2 O) to bicarbonate and protons (HCO 3- e H + ) or vice versa, a reversible reaction that occurs relatively slowly in the absence of a catalyst. Carbonic anhydrases participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone reabsorption, formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid.
4 CARBONIC ANHYDRASE INHIBITORS ACETAZOLAMIDE METHAZOLAMIDE SYSTEMIC USE: ORAL OR IV ADMINISTRATION DORZOLAMIDE BRINZOLAMIDE LOCAL USE: EYE INSTILLATION
5 THIAZIDES and THIAZIDE-LIKE DIURETICS Thiazide-type diuretics act on the distal convoluted tubule and inhibit the sodiumchloride symporter leading to a retention of water in the urine, as water normally follows penetrating solutes. Frequent urination is due to the increased loss of water that has not been retained from the body as a result of a concomitant relationship with sodium loss from the convoluted tubule. The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure. On the other hand, the long-term effect is due to an unknown vasodilator effect that decreases blood pressure by decreasing resistance.
6 THIAZIDES and THIAZIDE-LIKE HYDROCHOROTHIAZIDE CHLORTHALIDONE INDAPAMIDE
7 LOOP DIURETICS These drugs inhibit the Na-K-2Cl symporter in the medullary thick ascending limb. High ceiling diuretics may cause a substantial diuresis up to 20% of the filtered load of NaCl and water. This is large in comparison to normal renal sodium reabsorption which leaves only about 0.4% of filtered sodium in the urine. Loop diuretics inhibit the body's ability to reabsorb sodium at the ascending loop in the nephron, which leads to an excretion of water in the urine, whereas water normally follows sodium back into the extracellular fluid.
8 LOOP DIURETICS FUROSEMIDE FUROSEMIDE 25 mg/cpr; 50, 250, 500 mg/f DRUG ADMIN ABSOR PP BINDING ETHACRINIC Acid 50 mg/cpr;50 mg/f OS: mg IM, IV: mg OS: 25-50mgx2 EV: mg 60-70% Bio orale: 100% PLASMA HALF-LIFE 91-99% m METAB Liver 10% glicuron ELIMIN Kidney 60-90% Bile duct % 90% 1-4 h Liver Kidney 70%
9 LOOP DIURETICS DIURETIC RESISTANCE
10 POTASSIUM SPARING DIURETICS The term "potassium-sparing" refers to an effect rather than a mechanism or location; nonetheless, the term almost always refers to two specific classes that have their effect at similar locations: 1. EPITHELIAL SODIUM CHANNEL BLOCKERS: 2. ALDOSTERONE ANTAGONISTS
11 POTASSIUM SPARING DIURETICS FARMACO SOMM ASSORBIM LEGAME PROTEICO EMIVITA PLASM METAB ELIMIN IDROCLOROTIAZIDE + AMILORIDE (Moduretic ) 50mg + 5 mg/cps; OS: 5 mg/die Biodispon 50% scarso 6-9 h Renale 50% Fecale: 40-50% FUROSEMIDE + TRIAMTERENE (Fluss40 ) OS: mgx2 Biodispon 30-70% 55-65% 1,5-2,5 h Epatico Renale 50% FARMACO SOMM ASSORBIM LEGAME PROTEICO EMIVITA PLASM METAB ELIMIN SPIRONOLATTONE (Aldactone ) 25 mg/cps; 100 mg/conf OS: mgx2 Biodispon 73% 90% 1,4 h 16,5 h Epatico Metabolita attivo canrenone Renale 57% Fecale: 41%
12 DIURETICS - SUMMARY
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