课件：利尿药和降血糖药.ppt

Hydrochlorothiazide 6-Chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide The thiazide diuretics are weakly acidic with a benzothiadiaze 1,1-dioxide nucleus. Mechanism of Action The major site of action of these compounds is in the distal tubule, where these drugs compete for the chloride binding site of the Na+-C1- symporter and inhibit the reabsorption of sodium and chloride ions. They also inhibit the reabsorption of potassium and bicarbonate ions but to a lesser degree. Structure-activity Relationship The hydrogen atom at the 2-N is the most acidic. These acidic protons make possible the formation of a water-soluble sodium salt. An electron-withdrawing group is necessary at position 6 for diuretic activity. Replacement or removal of the sulfonamide at position 7 yields compounds with little or no diuretic activity. Saturation of the double bond to give a 3, 4 dihydro derivative produces a diuretic that is 10 times more than the unsaturated derivative. Substitution lipophilic group at position 3 gives a marked in the diuretic potency with a longer duration of action. Alkyl substitution on the 2-N position also decreases the polarity and increases the duration of diuretic action. Therapeutic Applications Hydrochlorothiazide is indicated in the management of hypertension either as the sole therapeutic agent, or in combination with other antihypertensives. Acetazolamide N-[5-(Aminosulfonyl)1,3,4-thiadiazol-2-yl] acetamide Acetazolamide was the first of the carbonic anhydrase inhibitors with a diuretic effect that lasts about 8-12 hours. It is used primarily for the treatment of glaucoma and absence seizures. Mechanism of Action The action of the enzyme carbonic anhydrase catalyzes the formation of carbonic acid from carbon dioxide and water. Carbonic anhydrase inhibitors induce diuresis by inhibiting the formation of carbonic acid within proximal and distal tubular cells to limit the number of hydrogen ions available to promote