Thiazide diuretics tubule affected

Thiazide diuretics (benzothiadia-zines) include hydrochlorothiazide, benzthiazide, trichlormethiazide, and cyclothiazide. A long-acting analogue is chlorthalidone. These drugs affect the intermediate segment of the distal tubules, where they inhibit a Na+/Ch cotransport, Thus, reabsorption of NaQ and water is inhibited. Renal excretion of Ca decreases, that of Mg + increases. Indications are hypertension, cardiac failure, and mobilization of edema. 

Mechanism of action The thiazide derivatives act mainly in the distal tubule to decrease the reabsorption of Na+ by inhibition of a Na+/CI cotransporter on the luminal membrane (see Figure 23.2). They have a lesser effect in the proximal tubule. As a result, these drugs increase the concentration of Na+ and Cl- in the tubular fluid. The acid-base balance is not usually affected. [Note Because the site of action of the thiazide derivatives is on the luminal membrane, these drugs must be excreted into the tubular lumen to be effective. Therefore, with decreased renal function, thiazide diuretics lose efficacy.]... 

It has been amply observed that the thiazide diuretics enhance urinaiy excretion of both Na and H2O by specifically inhibiting Na reabsorption located in the cortical (thick) portion of the ascending limb of Henle s loop and also in the early distal tubules. Besides, they also progressively cause an increase in the excretion of Cl, and HCO3 (to a lesser extent) ions. However, the latter efiect is predominantly by virtue of their mild carbonic anhydrase-inhibitory action. Importantly, due to their site of action, they invariably interfere with the dilution whereas, the concentration of urine is not affected appreciably. 

The thiazides are the most widely used of the diuretic drugs. They are sulfonamide derivatives and are related in structure to the carbonic anhydrase inhibitors. The thiazides have significantly greater diuretic activity than acetazolamide, and they act on the kidney by different mechanisms. All thiazides affect the distal tubule, and all have equal maximum diuretic effect, differing only in potency, expressed on a per -milligram basis. 

Interactions. Several types of drug interfere with lithium excretion by the renal tubules, causing the plasma concentration to rise. These include diuretics (thiazides more than loop type), ACE inhibitors and angiotensin-11 antagonists, and nonsteroidal anti-inflammatory analgesics. Theophylline and sodium-containing antacids reduce plasma lithium concentration. The effects can be important because lithium has such a low therapeutic ratio. Diltiazem, verapamil, carbamazepine and pheny-toin may cause neurotoxicity without affecting the plasma lithium. Concomitant use of thioridazine should be avoided as ventricular arrhythmias may result. 

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