Diuretics classes

Previously hypertensive ACE inhibitor + diuretic Class 1, Level A... 

Previously normotensive ACE inhibitor + diuretic Class Ila, Level B... 

Thiazide diuretics are useful in early cardiac failure as they are relatively mild diuretics which can mobilize the oedema. Increasing the dosage of a thiazide above the recommended dose would elicit more side effects without markedly improving therapeutic effects. Changing to a more powerful agent from a different diuretic class is preferable if the patient s condition deteriorates. 

Calcium-sparing diuretics. Diuretics that result in a relatively low rate of excretion of calcium. The sparing effect on calcium can be beneficial in hypocalcaemia. The thiazides and potassium-sparing diuretics are considered to be calcium-sparing diuretics. The thiazides cause a net decrease in calcium lost in urine the potassium-sparing diuretics cause a net increase in calcium lost in urine, but the increase is much smaller than that associated with other diuretic classes. By contrast, loop diuretics promote a significant increase in calcium excretion. This can increase risk of reduced bone density. 

The three main diuretic classes are thiazide, loop, and potassium-sparing diuretics (Table 10-1). Thiazide diuretics are considered one of the first-line agents for the treatment of HTN. Acutely, thiazide diuretics lower blood pressure by inhibiting sodium chloride cotransporters in the ascending loop of Henie and distal tubule, increasing sodium excretion and causing diuresis. The reduction in plasma volume decreases cardiac output and consequently reduces blood pressure. However, with continued therapy, the plasma volume returns to pretreatment level and there is a decrease in peripheral vascular resistance, which is responsible for the long-term anti hypertensive effects. The most common indication for thiazide diuretics is HTN. 

Diuretic class Tubular site of action Onset (hr) PO (IV) Duration of effect (hr)P0(IV) rA(hr)... 

Potassium-sparing diuretics (e.g. amiloride, spironolactone and triamterene) have a weak action on the distal tubule of the kidney, which, as the name suggests, cause retention of potassium making them suitable for combination with some of the other diuretic classes, and for some specific conditions. See ATPASE INHIBITORS. 

AFTER OPTIMIZING (ACEI, p-blockers, digoxin, diuretics) Class lll-IV... 

ACE inhibitors can be administered with diuretics (qv), cardiac glycosides, -adrenoceptor blockers, and calcium channel blockers. Clinical trials indicate they are generally free from serious side effects. The effectiveness of enalapril, another ACE inhibitor, in preventing patient mortaUty in severe (Class IV) heart failure was investigated. In combination with conventional dmgs such as vasodilators and diuretics, a 40% reduction in mortaUty was observed after six months of treatment using 2.5—40 mg/d of enalapril (141). However, patients complain of cough, and occasionally rash and taste disturbances can occur. 

Potassium-sparing by diuretic agents, particularly spironolactone, enhances the effectiveness of other diuretics because the secondary hyperaldosteronism is blocked. This class of diuretics decreases magnesium excretion, eg, amiloride can decrease renal excretion of potassium up to 80%. The most important and dangerous adverse effect of all potassium-sparing diuretics is hyperkalemia, which can be potentially fatal the incidence is about 0.5% (50). Therefore, blood potassium concentrations should be monitored carehiUy. 

Aceta2olamide, the best example of this class of diuretics (69,70), is rarely used as a diuretic since the introduction of the thia2ides. Its main use is for the treatment of glaucoma and some minor uses, eg, for the a1ka1ini2ation of the urine to accelerate the renal excretion of some weak acidic dmgs, and for the prevention of acute high altitude mountain sickness. 

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,... 

Electroneutral NaCl transport in the distal convoluted tubule is inhibited by the class of thiazide diuretics (chlorothiazide, hydrochlorothiazide, metolazone, chlorthalidone, and others). Thiazides interfere with the Cl binding site of NCC, and cause a relatively small... 

Add a second agent from a different class (diuretic if not already used). 

I have noted that NPPB is structurally related to loop diuretics of the furosemide (Fig. 2) type. These latter compounds bind to the Na 2CNK -cotransporter [16] and inhibit NaCl reabsorption in the TAL segment and NaCl secretion in epithelia such as the colonic crypt cell and rectal gland of Squalus acanthias [15]. We were able to show that only minor modification of the NPPB molecule on one side and of furosemide on the other led to compounds with altered selectivities [70,91-93]. One prototype of an intermediate blocker, i.e., a substance blocking both Na 2Cl K -cotransport and CP-channels, is torasemide (Fig. 2). Hence we have performed a systematic study in order to define the constraints defining the effectiveness of this class of substances [91]. 

P-lactam antimicrobials, erythromycin, nitrofurantoin, rifampin, sulfonamide antimicrobials, and vancomycin 0 Diuretics (all classes), NSAIDs... 

Thiadiazoles have proven of some utility as aromatic nuclei for medicinal agents. For example, the previous volume detailed the preparation of a series of "azolamide" diuretic agents based on this class of heterocycle. It is thus of note that the 1,2,5-thiadiazole ring provides the nucleus for a clinically useful agent for treatment of hypertension which operates by an entirely different mechanism, p-adrenergic blockade. In its preparation, reaction of the amide-nitrile 211 with sulfur monochloride leads directly to the substituted thiadiazole 212. ... 

Benzothiadiazines containing halogen and a sulfonamido group on the carbocyclic ring (125) form a large class of diuretic agents often referred to as... 

Diuretics are drugs that cause an increase in urine output. It is important to note that, except for the osmotic diuretics, these drugs typically enhance the excretion of solute and water. Therefore, the net effect of most diuretics is to decrease plasma volume, but cause little change in plasma osmolarity. Five classes of diuretics and their major sites of action are ... 

All drugs in this class have similar antihypertensive efficacy and fairly flat dose-response curves. The addition of low doses of a thiazide diuretic can increase efficacy significantly. 

Because these patients usually require multiple-drug therapy, diuretics and a third antihypertensive drug class (e.g., /Lblocker, CCB) are often needed. 

Strategies are available to overcome diuretic resistance (Table 75-5), a common problem in patients with ARF. Agents from different pharmacologic classes, such as diuretics that work at the distal convoluted tubule (thiazides) or the collecting duct (amiloride, triamterene, spironolactone), may be synergistic when combined with loop diuretics. Metolazone is commonly used because, unlike other thiazides, it produces effective diuresis at GFR less than 20 mL/min. 

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