Thiazide diuretics, listing

Each era of medicinal chemistry has been marked by intensive concentration on some structural type in a large number of laboratories. One need only look back in this book to the tables of sulfonamides, barbiturates, and thiazide diuretics, noting the small time span covered by the references to each list. The benzodiazepines have provided such a focus for the past decade. 

Additional adverse reactions of these drugs are listed in tiie Summary Drug Table Diuretics. When a potassium-sparing diuretic and a thiazide diuretic are given together, tiie adverse reactions associated with both drugp may be seen. 

There are a number of extremely important thiazide diuretics not listed above. These widely used drugs include hydroflumethiazid, trichlormethiazide, methylcyclothiazide, cyclothiazide, benzothiazide, diazoxide, and others, whose methods of synthesis and pharmacological action are practically identical to those listed above. 

Some pharmacokinetic characteristics and the initial and usual maintenance dosages of hydrochlorothiazide are listed in Table 11-2. Although thiazide diuretics are more natriuretic at higher doses (up to 100-200 mg of hydrochlorothiazide), when used as a single agent, lower doses (25-50 mg) exert as much antihypertensive effect as do higher doses. In contrast to thiazides, the blood pressure response to loop diuretics continues to increase at doses many times greater than the usual therapeutic dose. 

Thiazide Diuretics. Thiazide drugs share a common chemical nucleus as well as a common mode of action. These drugs act primarily on the early portion of the distal tubule of the nephron, where they inhibit sodium reabsorption. By inhibiting sodium reabsorption, more sodium is retained within the nephron, creating an osmotic force that also retains more water in the nephron. Since more sodium and water are passed through the nephron, where they will ultimately be excreted from the body, a diuretic effect is produced. Thiazides are the most frequently used type of diuretic for hypertension. Specific types of thiazide drugs are listed in Table 21-3. 

Although they are widely used in the management of heart failure, loop and thiazide diuretics have not been shown to prolong survival. However, spironolactone and eplerenone must be added to the list of medications that offer improved survival for patients with heart failure. 

Although one thiazide diuretic may be 100 times more potent than another weight for weight, all these drugs have essentially the same properties. Their mechanism of action (inhibition of sodium and chloride reabsorption in the distal convoluted tubule of the kidney) is identical and they can therefore be dealt with as a group. Thiazidelike diuretics, structurally different from the thiazides, have similar actions. Thiazide and thiazide-like diuretics are listed in Table 1. 

Diuretics related to the thiazides. Several compounds, although strictly not thiazides, share structural similarities with them and probably act at the same site on the nephron they therefore exhibit moderate therapeutic efficacy. Overall, these substances have a longer duration of action, are used for oedema and hypertension and their profile of adverse effects is similar to that of the thiazides. They are listed below. 

The era of benzothiadiazines began with the synthesis (1957) and discovery of the valuable diuretic properties of chlorthiazide (CTZ). Today, the thiazides and several related isosteres and analogs (Fig. 10-16) constitute a major drug group in the treatments of CHF and hypertension. Many such cyclic sulfamoyl compounds have been synthesized and tested since then about a dozen are currently in use and are listed in Table 10-11. 

List the major applications and the toxicities of thiazides, loop diuretics, and potassium-sparing diuretics. 

The potassium-depleting diuretics (i.e. loop diuretics or thiazide and related diuretics) are listed in Table 26.1 , (p.944). Acetazolamide, a weak diuretic, has also been predicted to cause hypokalaemia in the presence of corticosteroids. However, hypokalaemia seen with acetazolamide is rarely clinically significant, and therefore the risks are lower... 

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