Long-acting diuretics

ACE inhibitors - AT antagonists - Alpha blockers - Beta blockers Isolated syslolic hypertension (older patienls) - Diuretics preferred (generally Thiazides) - Long-acting dihydropyridine calcium channel blocker... 

Blockers (without ISA) are first-line therapy in chronic stable angina and have the ability to reduce BP, improve myocardial consumption, and decrease demand. Long-acting CCBs are either alternatives (the nondihy-dropyridines verapamil and diltiazem) or add-on therapy (dihydropy-ridines) to /1-blockers in chronic stable angina. Once ischemic symptoms are controlled with /1-blocker and/or CCB therapy, other antihypertensive drugs (e.g., ACE inhibitor, ARB) can be added to provide additional CV risk reduction. Thiazide diuretics may be added thereafter to provide additional BP lowering and further reduce CV risk. 

It is now becoming apparent that a single daily dose (rather than 2-3 doses per day) significantly enhances patient compliance and, therefore, effectiveness of treatment. For this reason, the long-acting diuretics which can be administered once a day offer an important advantage chlorthalidone, metolazone, trichlor-methiazide can be administered once a day with a 24 hour natriuretic effect. 

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. 

Low-dose diuretics and /3-blockers, which have demonstrated positive effects on mortality, are indicated as first choice treatment. This is still maintained in the new recommendations for patients with uncomplicated hypertension (Table 5). However, other treatments are recommended for hypertensive patients with associated diseases (Table 6). Hypertension with diabetes or renal dysfunction must be treated with an ACE inhibitor in the first instance. Patients with myocardial infarction should be treated with /S-blockers and in specific cases with an ACE inhibitors. For patients with heart failure, the treatment of choice is an ACE inhibitor and diuretics. For older patients with isolated SBP, low-dose diuretics are recommended as the first step treatment and some of the CCB with long acting profile can be considered an alternative treatment. 

ACE-I OR ARB - usually in combination with a diuretic Low-dose thiazide or thiazide-like diuretic OR long-acting CCB... 

Thiazide diuretics are not effective with advanced renal insufficiency (serum creatinine level of 221 omol/l) and loop diuretics are needed, often at relatively large doses. Combining a loop diuretic with a long-acting thiazide diuretic, such as meto-lazone, is effective in patients resistant to a loop-diuretic alone. Potassium-sparing diuretics should be avoided in patients with renal insufficiency. 

Heart failure severe hypotension may result in patients taking diuretics, or who are hypovolaemic, hyponatraemic, elderly, have renal impairment or with systolic blood pressure < 100 mmFlg. A test dose of captopril 6.25 mg by mouth may be given because its effect lasts only 4-6 h. If tolerated, the preferred long-acting ACE inhibitor may then be initiated in low dose. 

Brown MJ, Palmer CR, Castaigne A, de Leeuw PW, Mancia G, Rosenthal T, Ruilope LM. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet 2000 356(9227) 366-72. 

Torasemide is a long-acting loop diuretic promoted for use in hypertension. Like piretanide, it is claimed to be potassium neutral, but the assertion is premature. There is no evidence that torasemide has metabolic advantages over thiazides (SEDA-16, 226) (SEDA-17, 264) (SEDA-18, 237). 

For the practicing physician, this interaction is not of major clinical importance since either increasing the diuretic dose or, if possible, discontinuation of the NSAID will permit reinstitution of the desired diuretic response. In patients who are well controlled on a stable regimen of chronic loop diuretics use, the intercurrent need for long term use of an NSAID will typically lead to increasing the dosage of the loop agent, or the addition of a diuretic that acts in the distal nephron. 

Case Conclusion Diuretics and beta-blockers are first-line agents for treating HTN. Because this patient has asthma, beta-blockers should be avoided. Calcium channel blockers are favorable therapeutic options in patients with both angina and HTN. Because her heart rate is low, diltiazem and verapamil are not optimal choices because they can slow down AV nodal conduction. A long-acting dihydrof ridine, amlodipine, was started. 

Long-acting CCBs traditionally have been viewed as alternatives to /3-blockers in chronic stable angina. The INVEST study has compared /3-blocker with diuretic therapy with nondihydropyridine CCB with ACE inhibitor therapy in this population and has shown no difference in cardiovascular risk reduction. Nonetheless, the preponderance of data are with /3-blockers, and they remain therapy of choice. ... 

The SHEP was a landmark double-blind, placebo-controlled trial that evaluated active treatment (chlorthalidone-based, with atenolol or reserpine as add-on therapy) for isolated systolic hypertension. A 36% reduction in total stroke, a 27% reduction in coronary artery disease, and 55% reduction in heart failure were demonstrated versus placebo. The Systolic Hypertension-Europe (Syst-Eur) was another placebo-controlled trial that evaluated treatment with a long-acting dihydropyridine CCB. Treatment resulted in a 42% reduction in stroke, 26% reduction in coronary artery disease, and 29% reduction in heart failure. Similar findings were observed in a Chinese population with isolated systolic hypertension. These data clearly demonstrate reductions in cardiovascular morbidity and mortality in older patients with isolated systolic hypertension, especially with thiazide diuretics and long-acting dihydropyridine CCBs. 

Trichlormethiazide belongs to the class of long-acting diuretic and antihypertensive thiazide. Dose Usual, 2 to 4 mg twice daily maintenance 2 to 4 mg once per day. 

Poly thiazide is a potent long-acting diuretic and anti-hypertensive agent. 

The drug is an orally effective as well as long-acting thiazide diuretic and antihypertensive. It resembles CTZ with respect to its pharmacologic actions, therapeutic uses and untoward effects. 

Masuyama T, Tsujino T, Origasa H, Yamamoto K, Akasaka T, Hirano Y, et al. Superiority of long-acting to short-acting loop diuretics in the treatment of congestive heart failure. Circulation J Official Journal of the Japanese Circulation Society 2012 76(4) 833-42. 

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