THIAZIDE& THIAZIDE LIKE DIURETICS
This group of agents includes thiazides, containing a benzothiadiazine molecular structure, and also thiazide-like drugs with similar actions but without the benzothiadiazine structure, including chlortha-lidone (Thalitone), quinethazone (Hydromox), metolazone (Zaroxolyn), and indapamide (Lozol). These diuretics act at the distal tubule, including the connecting segment, and inhibition of sodium reabsorption at this site impairs diluting but not concentrating ability. They compete for the Cl − site on the luminal Na+–Cl − carrier protein. When given alone, thiazide and thiazide-like diuretics increase Na+ excretion to only 3–5% of the filtered load because of enhanced compensatory Na+ reab-sorption in the collecting tubules. They also possess carbonic anhydrase–inhibiting activity in the prox-imal tubule, which is usually masked by sodium reabsorption in the loop of Henle and which is probably responsible for the marked diuresis often seen when they are combined with loop diuret-ics. In contrast to their effects on sodium excre-tion, thiazide and thiazide-like diuretics augment Ca2+ reabsorption in the distal tubule. Indapamide has some vasodilating properties and is the only thiazide or thiazide-like diuretic with significant hepatic excretion.
Th iazide and thiazide-like diuretics are often selected as first-line agents in the treatment of hyperten-sion , and they have been shown to improve long-term outcomes in this disorder.
Th ese drugs are used to treat mild to moderate edema and congestive heart failure related to mild to moderate sodium overload.
Th iazide and thiazide-like diuretics are often used to decrease calcium excretion in patients with hyper-calciuria who form renal stones.
The efficacy of these agents in this disorder reflects their ability to impair diluting capacity and increase urine osmolality .
Th ese agents are only given orally.
Although thiazide and thiazide-like diuretics deliver less sodium to the collecting tubules than loop diuretics, the increase in sodium excretion is enough to enhance K + secretion and frequently results in hypokalemia. Enhanced H+ secretion can also occur, resulting in metabolic alkalosis. Impairment of renal diluting capacity may produce hyponatremia. Hyperuricemia, hyperglycemia, hypercalcemia, and hyperlipidemia may also be seen.