Thiazide diuretics consist of two distinct groups: those containing a benzothiadiazine ring, such as hydro-chlorothiazide and chlorothiazide, referred to as thiazide diuretics, and those that lack this heterocyclic structure but contain an unsubstituted sulfonamide group. The latter are called thiazidelike diuretics; they include metola-zone, xipamide, and indapamide. The major thiazide and thiazidelike drugs available in the United States are bendroflumethiazide, benzthiazide, chlorothiazide, hy-drochlorothiazide, hydroflumethiazide, methyclothiazide, polythiazide, and trichlormethiazide; and chlorthalidone, indapamide, metolazone, and quinethazone, respectively.
Despite the structural distinctions, the drugs share the functional attribute of increasing sodium and chloride excretion by inhibiting Na+-Cl" cotransport in distal convoluted tubules.
Although chlorothiazide and its subsequently developed congeners (Table 21.2) retain the sulfamyl group SO2NH2, which is necessary for carbonic anhydrase inhibition, their primary effect does not rely on carbonic anhydrase inhibition.
The thiazidelike compounds, including chlorthali-done (Hygroton), quinethazone (Hydromox), and metolazone (Zaroxolyn) have similar mechanisms of action, but they differ substantially from one another in their duration of action, the degree of carbonic anhy-drase inhibition, and the dose required for maximum natriuretic activity.
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