Diuretics antihypertensive agents

Diuretics. The diuretic and antihypertensive agent bendrodumethia2ide [73 8-3] is a ben2otriduoride-based pharmaceutical. 

Diuretics are needed to return to normal the expanded extracellular volume that other antihypertensive agents produce, such as fluid retention and blood volume expansion, via compensatory mechanisms of the body. The loss of efficacy of antihypertensive agents can be restored if a diuretic is used concomitandy. In the treatment of hypertension, high ceiling or loop diuretics, such as furosemide, ethacrynic acid, and bumetanide, are no more efficacious than the thiazide-type of diuretics. In fact, these agents cause more side effects, such as dehydration, metaboHc alkalosis, etc, and therefore, should not be used except in situations where rapid elimination of duid volume is cleady indicated. 

Ketanserin (25) is an antihypertensive agent acting as an antagonist at both the serotonin-S2 and Qj-adrencrgic receptors [22]. Bendroflumethiazide (26) is the most notable in a class of diuretic-antihypertensive agents [5]... 

Thiazide diuretics have a venerable history as antihypertensive agents until the advent of the angiotensin-converting enzyme (ACE) inhibitors this class of drugs completely dominated first line therapy for hypertension. The size of thi.s market led until surprisingly recently to the syntheses of new sulfonamides related to the thiazides. Preparation of one of the last of these compounds starts by exhaustive reduction of the Diels-Alder adduct from cyclopentadiene and malei-mide (207). Nitrosation of the product (208), followed by reduction of the nitroso group of 209,... 

Patients with asymptomatic left ventricular systolic dysfunction and hypertension should be treated with P-blockers and ACE inhibitors. Those with heart failure secondary to left ventricular dysfunction and hypertension should be treated with drugs proven to also reduce the morbidity and mortality of heart failure, including P-blockers, ACE inhibitors, ARBs, aldosterone antagonists, and diuretics for symptom control as well as antihypertensive effect. In African-Americans with heart failure and left ventricular systolic dysfunction, combination therapy with nitrates and hydralazine not only affords a morbidity and mortality benefit, but may also be useful as antihypertensive therapy if needed.66 The dihydropyridine calcium channel blockers amlodipine or felodipine may also be used in patients with heart failure and left ventricular systolic dysfunction for uncontrolled blood pressure, although they have no effect on heart failure morbidity and mortality in these patients.49 For patients with heart failure and preserved ejection fraction, antihypertensive therapies that should be considered include P-blockers, ACE inhibitors, ARBs, calcium channel blockers (including nondihydropyridine agents), diuretics, and others as needed to control blood pressure.2,49... 

Most racemization reactions are catalyzed by acid and/or by base. A notable exception is the spontaneous racemization of the diuretic and antihypertensive agent, chlorthalidone, which undergoes... 

Diuretics, ACE inhibitors, ARBs, and CCBs are primary agents acceptable as first-line options based on outcome data demonstrating CV risk reduction benefits (Table 10-2). /TBIockers may be used either to treat a specific compelling indication or as combination therapy with a primary antihypertensive agent for patients without a compelling indication. 

When diuretics are combined with other antihypertensive agents, an additive hypotensive effect is usually observed because of independent mechanisms of action. Furthermore, many nondiuretic antihypertensive agents induce salt and water retention, which is counteracted by concurrent diuretic use. 

Triamterene is also a diuretic with distal tubule action and potassium retaining properties. It is not generally used alone as an antihypertensive agent. 

Thus, diuretics, alone or in combination with other antihypertensive agents, represent the cornerstone of our antihypertensive armamentarium. 

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... 

Another important diuretic contains both triamterene and hydrochlorothiazide. Triamterene is a diuretic and is known to increase sodium and chloride ion excretion but not potassium ion. It is used in conjunction with a hydrothiazide, which is an excellent diuretic but also gives significant loss of potassium and bicarbonate ions. If the triamterene were not included potassium chloride would have to be added to the diet. Hydrochlorothiazide is an antihypertensive agent as well but, unlike other antihypertensives, it lowers blood pressure only when it is too high, and not in normotensive individuals. These two drugs are made by a number of different manufacturers and do not appear in our top 35 list, but they would rank high if all brands were combined. 

The molecular mechanism of diuretics acting as antihypertensive agents is not completely clear however, use of diuretics causes a significant increase in the amount of water and electrolytes excreted in urine, which leads to a reduction in the volume of extracellular fluid and plasma. This in turn leads to a reduction of cardiac output, which is the main parameter responsible for a drop in arterial blood pressure and venous blood return. Cardiac output is gradually restored, but the hypotensive effect remains, possibly because of the reduced peripheral resistance of vessels. It is also possible that diuretics somehow lower vascular activity of noradrenaline and other factors of pressure in the organism. Methods of synthesizing thiazide diuretics used for hypertension are described in the preceding chapter. Chapter 21. 

Reduction in blood pressure caused by treprostinil may be exacerbated by drugs that by themselves alter blood pressure, such as diuretics, antihypertensive agents, or vasodilators. Because treprostinil inhibits platelet aggregation, there is also a potential for increased risk of bleeding, particularly among patients maintained on anticoagulants. 

Concomitant therapy - When adding a diuretic or other antihypertensive agent, reduce dosage to 1 or 2 mg 3 times a day and then retitrate. 

Minoxidil may produce serious adverse effects. It can cause pericardial effusion, occasionally progressing to tamponade it can exacerbate angina pectoris. Reserve for hypertensive patients who do not respond adequately to maximum therapeutic doses of a diuretic and 2 other antihypertensive agents. 

Losartan may be administered with other antihypertensive agents. If blood pressure is not controlled by losartan alone, a low dose of a diuretic may be added. Hydrochlorothiazide has an additive effect. 

Adults - Initially, 50 to 100 mg/day in single or divided doses. May also be combined with diuretics, which act more proximally, and with other antihypertensive agents. Continue treatment for 2 weeks or more because the maximal response may not occur sooner. Individualize dosage. 

Thiazide diuretics are effective antihypertensive agents in black hypertensive patients and studies suggest that they cause a greater decrease in blood pressure in black patients than in whites. The better hypotensive response in black hypertensive patients is probably due to the fact that, in comparison with whites, more black patients have an expanded intracellular volume and low plasma renin activity. In developing countries, in which the majority of black people live, the cost of therapy is important. Thiazide diuretics are because of their low cost important baseline drugs in the treatment of hypertension. 

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