CLINICAL PHARMACOLOGY 2003 (PART 28)

The kidneys comprise only 0.5% of body weight, yet they receive 25% of the cardiac output. Drugs that affect renal function have important roles in cardiac failure and hypertension. Disease of the kidney must be taken into account when prescribing drugs that are eliminated by it. Diuretic drugs: their sites and modes of action, classification, adverse effects and uses in cardiac, hepatic, renal and other conditions. Carbonic anhydrase inhibitors. Cation-exchange resins and their uses. Alteration of urine pH Drugs and the kidney. Adverse effects. Drug-induced renal disease: by direct and indirect biochemical effects and by immunological effects. Prescribing...
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CLINICAL PHARMACOLOGY 2003 (PART 28) 26Kidney and genitourinary tractSYNOPSIS Diuretic drugsThe kidneys comprise only 0.5% of bodyweight, yet they receive 25% of the cardiac (See also Ch. 23)output. Drugs that affect renal function haveimportant roles in cardiac failure and Definition. A diuretic is any substance which in-hypertension. Disease of the kidney must be creases urine and solute excretion. This wide defi-taken into account when prescribing drugs that nition, however, includes substances not commonlyare eliminated by it. thought of as diuretics, e.g. water. To be therapeuti-• Diuretic drugs: their sites and modes of cally useful a diuretic should increase the output action, classification, adverse effects and uses of sodium as well as of water, since diuretics are in cardiac, hepatic, renal and other normally required to remove oedema fluid, com- conditions posed of water and solutes, of which sodium is the• Carbonic anhydrase inhibitors most important. Diuretics are among the most• Cation-exchange resins and their uses commonly-used drugs, perhaps because the evolu-• Alteration of urine pH tionary advantages of sodium retention have left an aging population without salt-losing mechanismsDrugs and the kidney of matching efficiency.• Adverse effects Each day the body produces 1801 of glomerular• Drug-induced renal disease: by direct and filtrate which is modified in its passage down the indirect biochemical effects and by renal tubules to appear as 1.51 of urine. Thus a 1% immunological effects reduction in reabsorption of tubular fluid will more• Prescribing for renal disease: adjusting the than double urine output. Clearly, drugs that act on dose according to the characteristics of the tubule have considerable scope to alter body the drug and to the degree of renal fluid and electrolyte balance. Most clinically useful impairment diuretics are organic anions, which are transported• Nephrolithiasis and its management directly from the blood into tubular fluid. The• Pharmacological aspects of micturition following brief account of tubular function with• Benign prostatic hyperplasia particular reference to sodium transport will help to• Erectile dysfunction explain where and how diuretic drugs act; it should be read with reference to Figure 26.1. 529 26 K I D N E Y A N D G E N I TO U R I N A R Y T R A C TSITES AND MODES OF ACTION ions a small change in osmolality laterally across the tubular epithelium is converted into a steepProximal convoluted tubule vertical osmotic gradient. The high osmotic pressure in the medullary interstitium is sustained by theSome 65% of the filtered sodium is actively trans- descending and ascending vasa recta, long bloodported from the lumen of the proximal tubule by vessels of capillary thickness which lie close to thethe sodium pump (Na+, K+-ATPase). Chloride is loops of Henle and act as countercurrent exchangers,absorbed passively, accompanying the sodium; for the incoming blood receives sodium from thebicarbonate is also absorbed, through the action of outgoing blood.2 Frusemide (furosemide), bumetanide,carbonic anhydrase. These solute shifts give rise to piretanide, torasemide and ethacn/nic acid act principallythe iso-osmotic reabsorption of water, with the result at site 2 by inhibiting the three-ion transporterthat > 70% of the glomerular filtrate is returned to system, thus preventing sodium ion reabsorptionthe blood from this section of the nephron. The ...