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Diuretics. Drugs wich are used in nephrolythiasis and gout treatment.

Drugs with influence upon acid-base balance.
Diuretics (saluretics) elicit increased production of urine (diuresis). In the strict sense, the
term is applied to drugs with a direct renal action. The predominant action of such agents
is to augment urine excretion by inhibiting the reabsorption of NaCl and water.
The most important indications for diuretics are:
Mobilization of edemas: In edema there is swelling of tissues due to accumulation
of fluid, chiefly in the extracellular (interstitial) space. When a diuretic is given, increased
renal excretion of Na+ and H2O causes a reduction in plasma volume with
hemoconcentration. As a result, plasma protein concentration rises along with oncotic
pressure. As the latter operates to attract water, fluid will shift from interstitium into the
capillary bed. The fluid content of tissues thus falls and the edemas recede. The decrease
in plasma volume and interstitial volume means a diminution of the extracellular fluid
volume (EFV). Depending on the condition, use is made of: thiazides, loop diuretics,
aldosterone antagonists, and osmotic diuretics.
Antihypertensive therapy. Diuretics have long been used as drugs of first choice
for lowering elevated blood pressure. Even at low dosage, they decrease peripheral
resistance (without significantly reducing EFV) and thereby normalize blood pressure.
Therapy of congestive heart failure.
By lowering peripheral resistance, diuretics aid the heart in ejecting blood (reduction in
afterload); cardiac output and exercise tolerance are increased. Due to the increased
excretion of fluid, EFV and venous return decrease (reduction in preload,). Symptoms of
venous congestion, such as ankle edema and hepatic enlargement, subside. The drugs
principally used are thiazides (possibly combined with K+-sparing diuretics) and loop
Prophylaxis of renal failure. In circulatory failure (shock), e.g., secondary to
massive hemorrhage, renal production of urine may cease (anuria). By means of diuretics
an attempt is made to maintain urinary flow. Use of either osmotic or loop diuretics is
Each segment of the nephron:
- proximal convoluted tubule (PCT)
- thick ascending limb of the loop of Henle (TAL)
- distal convoluted tubule(DCT)
- cortical colecting tubule (CCT)
has a different mechanism for reabsorbing sodium and other ions.
1) PCT- this segment carries out isoosmotic reabsorption of amino acids, glucose, numerous
cations, sodium chloride, sodium bicarbonate.
This segment is responsible for 50% or more of the total reabsorbtion of Na.
Carbonic anhydrase ( the enzyme required for the bicarbonate reabsorption ) activates in this
2) TAL – this segment pumps Na, K, chloride out of the lumen into the interstitium of the
kidney, Ca, Mg.
TAL is responsible for the reabsorption of 30-40% of the sodium filtered at the
3) Distal convoluted tubule (DCT)


Indications: pulmonary edema (added advantage of i.g. Summary Effects: 1.. the massive sodium chloride diuresis. edema accompanied by significant metabolic alkalosis. and chloride. Excretion of Ca2+ and Mg2+ also increases. Loop diuretics Mechanism of action: This drugs inhibit the cotransport of sodium.. The final segment of the nephron is the last tubular site of sodium reabsorption and is controlled by aldosteron. With oral administration. Calcium is also rebsorption in this segment under the control of parathyroid hormone.. so that less Na+.v. Reabsorption of water occurs in the medullary collecting tubule under the control of antidiuretic hormone. 2 . these reactions are slowed. Effect: the major renal effect is bicarbonate diuresis (sodium bicarbanate is excreted) Side effects: alkalinization of the urine by these drugs may cause precipitation of calcium salts and formation of renal stones. chloride. if tissue perfusion is adequate. where they inhibit Na+/K+/2Cl– cotransport. which is secreted into the tubular fluid in exchange for Na+. enhanced sensitivity to renotoxic agents. together with water. CAH catalyzes CO2 hydration/dehydration reactions: H+ + HCO3 ↔H2CO3↔H20 + CO2. The site of action of these agents is the thick portion of the ascending limb of Henle’s loop. As a result. a strong diuresis occurs within 1 h but persists for only about 4 h. transporter. When the enzyme is inhibited. The diuretic effectiveness of CAH inhibitors decreases with prolonged use. 2. and epilepsy. Membrane-permeable CO2 is taken up into the tubule cell and used to regenerate H+ and HCO3 –. intense. Loss of HCO3 – leads to acidosis. prophylaxis of acute renal hypovolemic failure. Ethacrynic acid is classed in this group although it is not a sulfonamide. HCO3 – and water are reabsorbed from the fast-flowing tubular fluid.This segment actively pumps sodium and chloride out of the lumen of the nephron (10% of sodium reabsorption). hypercalcemia. Special toxic effects include: (reversible) hearing loss. H+ captures HCO3–. these electrolytes. This segment is responsible for reabsorption 2-8% of the total filtered sodium. The effect is rapid. 4) Cortical collecting tubule (CCT). potassium. 3. edema fluid is rapidly excreted and blood volume may be significantly reduced. in renal hypovolemic failure with creatinine clearance reduction (<30 mL/min). are excreted in larger amounts. The enzyme is used in tubule cells to generate H+. refractoriness to thiazide diuretics. they inhibit sodium.There. Dorzolamide can be applied topically to the eye to lower intraocular pressure in glaucoma. and brief (high-ceiling diuresis). acute mountain sickness. potassium. leading to formation of CO2 via the unstable carbonic acid. Present indications for drugs in this class include: acute glaucoma. Carbonic anhydrase inhibitors: Mechanism of action is inhibition of carbonic anhydrase in the brush border and intracellular carbonic anhydrase in the PCT cell. Patients with hepatic disease may develop hepatic encephalopathy because of increased ammonia reabsorption. e. injection in left ventricular failure: immediate dilation of venous capacitance vessels → preload reduction). CAH is also involved in the production of ocular aqueous humor.

ethacrynic acid is a moderately effective uricosuric drug. hypokalemic alkalosis may result.  hyperazothemia. reabsorption of NaCl and water is inhibited. that of Mg2+ increases. 3. calcium excretion is significantly increased 5.hypo K. acute crisis of glaucoma Side effects: Massive use of diuretics entails a hazard of adverse effects:  the decrease in blood volume can lead to hypotension and collapse. and mobilization of edema. treatment of severe hypercalcemia. bringing an increased risk of intravascular coagulation or thrombosis.  digestive deregulations. 5. Indications are hypertension. in hypertension 4. Renal excretion of Ca2+ decreases. intoxications 6. hypertension 2. glaucoma 6. chronic therapy of edematous conditions such as heart failure. cardiac failure. The loop diuretics also have potent pulmonary vasodilating effects: the mechanism is not known Indications: -treatment of edematous states. insipid diabetes Side effects:. -they decrease the quantity of insulin 3 . Mg. hyperglycemia. 6.  blood viscosity rises due to the increase in erythro. they increase reabsorption of calcium from the urine and decrease urine calcium content 4. Mg. they enhance effects of antidiuretic hormone and have antidiuretic effect in enuresis and insufficiency of vasopresine Indications: 1. enuresis 5. Na. Na. Effects: 1. acute pulmonary edema and cerebral edema 3.  nephrotoxicity  increase the glycosides toxicity Thiazide and nonthiazide diuretics: Mechanism of action: They inhibit sodium chloride transport in the early segment of the distal convoluted tubule. in full doses. chronic renal calcium stone formation 4. thiazides produce moderate but sustained sodium and chloride diuresis 2. in the big doses they inhibit carboanhydrase 3.(heart failure and ascites) 2. increase the quantity of glucose in the blood 5. Thus.  they usually produce hypokalemic metabolic alkalosis.4.and thrombocyte concentration. Ca.  hypovolemia and cardiovascular complications  ototoxicity  hypo K.

(2) an inhibition of aldosteronestimulated protein synthesis would become noticeable only if existing proteins had become nonfunctional and needed to be replaced by de novo synthesis. They may cause hyperkalemic metabolic acidosis. Spironolactone may cause endocrine abnormalities. K. Its hormonal effect on protein synthesis leads to augmentation of the reabsorptive capacity of tubule cells.g.g. edema with hypopotassemia. because the opposing effects on K+ excretion cancel each other. vertigo . duration of action. and antiandrogenic effects. hypertension 3. Clinical uses include conditions of increased aldosterone secretion. Effects: All three drugs cause an increase in sodium clearance and a decrease in potassium and hydrogen ion excretion and therefore quality as “potassium sparing” diuretics. The mineralocorticoid aldosterone promotes the reabsorption of Na+ (Cl– and H2O follow) in exchange for K+. Body cells lack transport mechanisms for polyhydric alcohols such as mannitol and 4 .. Two possible explanations are: (1) the conversion of spironolactone into and accumulation of the more slowly eliminated metabolite canrenone. By combining with and blockng the intracellular aldosterone receptor.hyperuricemia . A particular adverse effect results from interference with gonadal hormones. The diuretic effect of spironolactone develops fully only with continuous administration for several days. they reduce the expression of genes controlling synthesis of sodium ion channels and Na. ATP-ase. liver cirrhosis with ascites. Mechanism of action: They are antagonist (competitive or noncompetitive) of aldosterone in the collecting tubules. are antagonists at the aldosterone receptor and attenuate the effect of the hormone. increase minute-volume of blood and increase also the renal circulation and filtration.nausea.and hypoNa These drugs should never be given with potassium drugs. Indications: 1. These drugs are suitable for oral administration. Since NaCl and H2O are reabsorbed together in the proximal tubules. Also dyspepsia can occurs Osmotic diuretics Mode of action: They increase osmotic pressure of plasma. Both inhibit the entry of Na+. e. Their diuretic effectiveness is relatively minor.. as well as its metabolite canrenone. hence its exchange for K+ and H+.. vomiting. Spironolactone has 24-72 h. They blocking the sodium channels in the same portion of the nephron. e. hydrochlorothiazide. while the effects on secretion of NaCl complement each other. They are mostly used in combination with thiazide diuretics. Amiloride and triamterene have duration of action of 12-24 hours. Na+ concentration in the tubular fluid does not change despite the extensive reabsorption of Na+ and H2O. in association with other diuretics for hypopotassemia prevention Side effects: hyperpotassemia. Spironolactone. or hyperaldosteronism 2. including ginecomastia.dermatitis Potassium-sparing diuretics These agents act in the distal portion of the distal tubule and the proximal part of the collecting ducts where Na+ is reabsorbed in exchange for K+ or H+. as evidenced by the development of gynecomastia (enlargement of male breast).

in part because the reduced concentration gradient towards the interior of tubule cells means a reduced driving force for Na+ influx. When Na ions are taken up into the tubule cell. headache. 6) All nephron: Osmotic diuretics: mannitol. They also cannot be reabsorbed from the tubular fluid after glomerular filtration. mobilization of brain edema.ethacrine acid . in the intoxications.furosemide . The result of osmotic diuresis is a large volume of dilute urine. These agents bind water osmotically and retain it in the tubular lumen. which are thus prevented from penetrating cell membranes. they need to be given by intravenous infusion.cyclopentazide . Classification: according to the place of action: 1) Glomerulus .hydrochorthiazide . acute renal failure. Rebound effect.carboanhydrase inhibitors .polythiazide b) non thiazide diuretics . acute crisis of glaucoma. The fall in urine Na+ concentration reduces Na+ reabsorption.glycosides . triamterene.sorbitol.clopamide 5) Terminal portion of the cortical collecting tubule and collecting tubule: antagonists of aldosterone: a) competitive: spironolactone b) noncompetitive: amiloride. 5 .methylxantines . pulmonary edema. nausea.bumetamide 4) distal convoluted tubule(DCT) (initial portion) a) thiazide diuretics . and acute glaucomacerebral edema. dehydrations. vomiting. phlebitis.chlortalidon . Therefore.vasodiltors 2) proximal convoluted tubule (PCT) .acetazilamide (diacarb) 3) thick ascending limb of the loop of Henle (TAL) . water cannot follow in the usual amount. larynges edema. shock cases. acute renal failure. thrombosis. urea. Indications: prophylaxis of renal hypovolemic failure. Side effects: hypoNa. exacerbation of heart failure and pulmonary edema.

Nonsteroidal anti-inflammatory drugs.allopurinol . organ meats. Inflammatory mediators. The drug of choice is colchicine.Milk. During the early stage of inflammation. and eggs are low in purines and are recommended. the inflammation intensifies—the gout attack flares up. glucocorticoids may be indicated. resulting in its destruction by selfdigestion and damage to the adjacent tissue. whereby ameboid mobility and phagocytotic activity are prevented. Effective prophylaxis of gout attacks requires urate blood levels to be lowered to less than 6 mg/100 mL. 10 mg). The typical gout attack consists of a highly painful inflammation of the first metatarsophalangeal joint (“podagra”). methylprednesolone .5 mg hourly until pain subsides or gastrointestinal disturbances occur.diclofenac triamcinolone Salycilates are contraindicated in gout because they increase the quantity of uric acid in the blood Gout is an inherited metabolic disease that results from hyperuricemia.probenecid . such as indomethacin and phenylbutazone.g. urate crystals are phagocytosed by polymorphonuclear leukocytes (1) that engulf the crystals by their ameboid cytoplasmic movements (2). Uricostatics decrease urate production. Uricozuric remedies 2. are released (4). probably due to inhibition of mitoses in the rapidly dividing gastrointestinal epithelial cells.indomethacin.. maximal daily dose.ethebenecid . Lysosomal enzymes are liberated into the granulocyte. Diet.phenylbutasone. dexamethasone . vomiting. the end-product of purine degradation. inhibit xanthine oxidase. Active remedies in gout crisis . are also effective.Drugs with are used in gout treatment. and diarrhea. The most common adverseeffects of colchicine are abdominal pain. Gout attacks are triggered by precipitation of sodium urate crystals in the synovial fluid of joints.. It is known as a “spindle poison” because it arrests mitosis at metaphase by inhibiting contractile spindle proteins. Colchicine is usually given orally (e.colchicine non steroid anti-inflammatory drugs : glucocorticoids .ibuprofen. which catalyzes urate 6 . an elevation in the blood of uric acid. as well as its accumulating metabolite alloxanthine (oxypurinol). More granulocytes are attracted and suffer similar destruction. unable to degrade the sodium urate.urodan 2. Uricoinhibitor remedies . In severe cases. The phagocytic vacuole fuses with a lysosome (3).g. Classification 1. Further ameboid movement dislodges the crystals and causes rupture of the phagolysosome. an alkaloid from the autumn crocus (Colchicum autumnale). dairy products. however. Allopurinol. Its antigout activity is due to inhibition of contractile proteins in the neutrophils. Coffee and tea are permitted since the methylxanthine caffeine does not enter purine metabolism.sulphinpyrazone . Treatment of the gout attack aims to interrupt the inflammatory response. prednisolone . The lysosomal enzymes are. such as prostaglandins and chemotactic factors. 0. Purine (cell nuclei)-rich foods should be avoided. e.

Compared with whole blood or plasma.5–1. volume substitution is only transiently needed and therefore complete elimination of these colloids from the body is clearly desirable. (1) do not readily leave the circulation and are poorly filtrable in the renal glomerulus.45% with glucose c) hypertonic sol NaCl 5%. i. benzbromarone (100 mg/d). acesol. promote renal excretion of uric acid. or sulfinpyrazone. 20% or 40% B) Plasma Volume Expanders a) in shock Dextran40. electrolytes. and are free of pathogens such as hepatitis B or C or AIDS viruses. such as probenecid. A) In dehydration states 1) saline solution a) isotonic solution: sol. replenishment of the circulation is essential. polypeptides.5 mg/d). Blood plasma consists basically of water.e. At the start of therapy.e. and plasma proteins. To eliminate the threat of shock. as from the reduction in volume of circulating blood. uricosurics are contraindicated. polymers. administration of a plasma volume expander may be sufficient. They saturate the organic acid transport system in the proximal renal tubules. but they can be prevented by concurrent administration of colchicine (0. gelatin. have a longer shelf life.formation from hypoxanthine via xanthine. b) hypotonic sol. NaCl 0. a plasma substitute need not contain plasma proteins.. Allopurinol is given orally (300–800 mg/d). In patients with urate stones in the urinary tract. and (2) bind water along with its solutes due to their colloid osmotic properties. Ringer. Uricosurics..70.. With moderate loss of blood. like plasma proteins. The immediate threat results not so much from the loss of erythrocytes. dextran and hydroxyethyl starch. as well as the polypeptide.9%. gout attacks may occur. In this manner. These precursors are readily eliminated via the urine. oxygen carriers. making it unavailable for urate reabsorption. Drugs with influence upon acid-base balance. b) Systemic intoxications : haemodes c) Digestive intoxications: enterodez C)For correction of electrolyte deregulations -in hypocalemia rehydron Plasma Volume Expanders Major blood loss entails the danger of life-threatening circulatory failure. On the other hand. hypovolemic shock. : NaCl 0. which has a smaller transport capacity. it is well tolerated and is the drug of choice for gout prophylaxis. i. However. 7 . Except for infrequent allergic reactions. gelatinol. plasma substitutes offer several advantages: they can be produced more easily and at lower cost. 10%. Three colloids are currently employed as plasma volume expanders— the two polysaccharides. These can be suitably replaced with macromolecules (“colloids”) that. Urate elimination is then inhibited and a gout attack is possible. When underdosed. they will maintain circulatory filling pressure for many hours. they inhibit only the acid secretory system.

unlike dextran 70. As for microcirculatory improvement. it is metabolized more slowly and retained significantly longer in blood than would be the case with infused starch. larger molecules will accumulate due to the more rapid renal excretion of the smaller ones. may directly reduce the aggregability of erythrocytes by altering their surface properties. but not for hemodilution. By virtue of its hydroxyethyl groups. Commercial solutions contain dextran of a mean molecular weight of 70 kDa (dextran 70) or 40 kDa (lower-molecularweight dextran. The most important adverse effect results from the antigenicity of dextrans. The chain length of single molecules. varies widely. dextran solutions are used for hemodilution in the management of blood flow disorders. Hydroxyethyl starch resembles dextrans in terms of its pharmacological properties and therapeutic applications. in circulatory disturbances. Apart from restoring blood volume. which may lead to an anaphylactic reaction. however. 8 . With prolonged use. Consequently. Smaller dextran molecules can be filtered at the glomerulus and slowly excreted in urine. Gelatin colloids consist of crosslinked peptide chains obtained from collagen.Dextran is a glucose polymer formed by bacteria and linked by a 1!6 instead of the typical 1!4 bond. it is occasionally emphasized that low-molecular-weight dextran. They are employed for blood replacement. the larger ones are eventually taken up and de degraded by cells of the reticuloendothelial system. Hydroxyethyl starch (hetastarch) is produced from starch. dextran 40). the molecular weight of dextran circulating in blood will tend towards a higher mean molecular weight with the passage of time.