Thiazide-type diuretics

Patients having high plasma renin activity (PRA) (>8 ng/(mLh)) respond best to an ACE inhibitor or a -adrenoceptor blocker those having low PRA (<1 ng/(mLh)) usually elderly and black, respond best to a calcium channel blocker or a diuretic (184). -Adrenoceptor blockers should not be used in patients who have diabetes, asthma, bradycardia, or peripheral vascular diseases. The thiazide-type diuretics (qv) should be used with caution in patients having diabetes. Likewise, -adrenoceptor blockers should not be combined with verapamil or diltiazem because these dmgs slow the atrioventricular nodal conduction in the heart. Calcium channel blockers are preferred in patients having coronary insufficiency diseases because of the cardioprotective effects of these dmgs. 

Methyldopa is effective in mild, moderate, and severe hypertension but a thiazide-type diuretic is needed to overcome the fluid retaining side effect. Methyldopa has been shown to prevent and induce regression of ventricular hypertrophy in hypertensive patients. The principal side effects are sedation, drowsiness, nasal congestion, fluid retention, and in rare occasions, hemolytic anemia. 

Agents acting in the proximal tubule are seldom used to treat hypertension. Treatment is usually initiated with a thiazide-type diuretic. Chlorthalidone and indapamide are structurally different from thiazides but are functionally related. If renal function is severely impaired (i.e., serum creatinine above 2.5 mg/dl), a loop diuretic is needed. A potassium-sparing agent may be given with the diuretic to reduce the likelihood of hypokalemia. 

Another key feature of the thiazide-type diuretics is their limited efficacy in patients whose estimated renal function is reduced, such as the elderly. For example, patients with estimates of reduced renal function, such as those with a glomerular filtration rate (GFR) below 30 mL/minute, should be considered for more potent loop type diuretics such as furosemide. Clinicians often fail to either reconsider the role of thiazide diuretics prescribed to individuals whose renal function has been declining or fail to recognize the likely prevalence of renal compromise in the elderly to begin with. 

A thiazide-type diuretic is recommended as the second agent to lower BP and provide additional CV risk reduction. 

ACE inhibitors, ARBs, /1-blockers, CCBs, and thiazide-type diuretics are all acceptable drug therapy choices. 

Clinical reports [215—222] agree that debrisoquine is an effective antihypertensive agent with a duration of action of 8-12 hours, permitting flexibility of dosage. Like other similar drugs it is potentiated by thiazide-type diuretics and other antihypertensives. In all these respects it appears to be interchangeable... 

Essential hypertension Management of essential hypertension. It can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics. 

Diuretics - Generally initiate therapy with a thiazide or other oral diuretic. Thiazide-type diuretics are drugs of choice hydrochlorothiazide or chlorthalidone are generally preferred. Reserve loop diuretics for selected patients. This therapy alone may control many cases of mild hypertension. Consider treating diuretic-induced hypokalemia (less than 3.5 mEq/L) with potassium supplementation or by adding a potassium-sparing diuretic to therapy. 

More effective than other thiazide-type diuretics in patients with impaired renal function... 

Chlorthalidone, thiazide-type diuretics, and furosemide for hypertension... 

The effects of thiazide-type diuretics on carbohydrate tolerance cannot be ignored (50). There is a definite relation between diuretic treatment, impaired glucose tolerance, and biochemical diabetes, and a possible relation with insulin resistance (64). It is well estabhshed that the effect of thiazides on blood glucose is dose-related, probably linearly, while the antihjrpertensive effect has httle relation to dose (65-67). There is relatively httle information on the time-course numerous short-term studies have shown that the blood glucose concentration increases in 4-8 weeks (68). The evidence that current low dosages impair glucose tolerance in the long term is not entirely consistent, perhaps because of differences between studies... 

Loop (high ceiling) diuretics 159 Benzothiadiazides or thiazide-type diuretics 163... 

There are no published reports on the pharmacokinetics of the thiazide-type diuretics in horses. A bolus dose of a combination of dexamethasone (5 mg) and trichlormethiazide (200 mg), a product commonly used for treatment of udder edema in periparturient cattle, is occasionally used to treat edema in horses and there are anecdotal reports that it is efficacious. Hydrochlorothiazide (0.5- 0.7mg/kg orally twice daily) has also been used to enhance urinary potassium excretion and thereby limit the increase in serum potassium concentrations during an episode of hyperkalemic periodic paralysis in horses (Beech Lindborg 1996, Spier et al 1990 see Ch. 8). However, hydrochlorothiazide was less effective than acetazolamide (see below) and phenytoin in controlling the clinical signs, but it did limit the increase in the serum potassium ion concentrations during an oral potassium chloride challenge test (Beech Lindborg 1996). 

In humans, spironolactone is absorbed readily and is metabolized in the liver to active compounds called canrenones. It is these metabolites that compete with aldosterone for its cytosolic receptor therefore, the maximal natriuretic effect is not observed until 24-48 h after treatment has been initiated. Spironolactone is indicated for the treatment of primary hyperaldosteronism but is also used in refractory edema and in secondary hyperaldosteronism consequent to use of loop or thiazide-type diuretics (Martinez-Maldonado Cordova 1990, Rose 1989, 1991, Wilcox 1991). In one study, the administration of spironolactone via nasogastric tube (1 and 2mg/kg) to ponies more than doubled the urinary excretion of sodium and reduced the urinary excretion of potassium for a period of 72 h, although there was no difference in the volume of urine produced (Alexander 1982). This suggests that spironolactone is a potassium-sparing agent in horses however, to date, no pharmacokinetic studies have been published. 

JNC7 guidelines recommend thiazide-type diuretics whenever... 

The loop diuretic-thiazide combination generally should be reserved for the inpatient setting, where the patient can be monitored closely, because it can induce a profound diuresis with severe sodium, potassium, and volume depletion. When used in the outpatient setting, very low doses or only occasional doses of the thiazide-type diuretic should be used along with close follow-up (weight, vital signs, dizziness) to avoid serious adverse events. 

Cutler JA, Davis BR. Thiazide-type diuretics and beta-adrenergic blockers as first line drug treatments for hypertension. Circulation 2008 117(20) 2691-705. 

Diuretics are used widely for the treatment of hypertension, and controlled clinical trials demonstrating reduced morbidity and mortality have been conducted with N - CL symport (thiazides and thiazide-like diuretics) but not N -K+-2C1 symport inhibitors. Nonetheless, N+-K+-2CL symport inhibitors appear to lower blood pressure as effectively as N+-C1 symport inhibitors while causing smaller perturbations in the lipid profile. However, the short ehmination half-lives of loop diuretics render them less useful for hypertension than thiazide-type diuretics. The edema of nephrotic syndrome often is refractory to other classes of... 

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