Diuretics and Electrolytes

Diuretics are compounds that therapeutically affect the mammalian nephral excretion balance, increasing the net excretion of water and solutes. Thus, they modify the excretion of water and the concentration of salts in the body through the kidney so as to ensure a constant volume of body fluids. Their functions influence blood pressure and the actions of several organs. Some of the leading diuretics and electrolytes and the extent of their prescription are summarized in 

TABLE 1.12 Antidiabetic Prescriptions in the United States and Their Mode Action 

Glucophage (Diabeta, Glyburide, Glucovance, Metformin) 18.4 (1.8) 40.4 (1.4) 49.6 (2.1) A biguanide that acts by increasing the ability of insulin to bind to peripheral tissues, increasing the uptake of glucose by the muscles and other tissues. 

Humulin (Humalog, Insulin, Lantus) 18.4 (0.9) 15.3 (0.5) 11.7 (0.5) Binds to unique insulin receptors to regulate glucose levels and its metabolism. 

Glucotrol (Glipizide) 10.7 (0.5) 14.1 (0.5) 13.1 (0.6) A second generation sulfonylurea that blocks ATP-sensitive K-channels in the membrane of beta cells, stimulating the release of insulin. 

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TABLE 1.13 Diuretics and Electrolytes Prescriptions in the United States (2003-2005) ... 

Product Total Number (in millions) of Diuretics and Electrolytes Prescriptions ... 

MANAGING FLUID VOLUM E DEFICIT. The patient receiving a diuretic is observed for dehydration and electrolyte imbalances. A fluid volume deficit is most likely to occur if the patient fails to drink a sufficient amount of fluid. This is especially true in the elderly or confused patient. To prevent a fluid volume deficit, the nurse encourages patients to drink adequate oral fluids (up to 3000 mL/d, unless contraindicated). 

The osmotic diuretics urea and mannitol are administered intravenously (IV), whereas glycerin and isosorbide are administered orally Administration by the IV route may result in a rapid fluid and electrolyte imbalance, especially when these drugs are administered before surgery with the patient in a fasting state ... 

ELECTROLYTE IMBALANCE The most common adverse reaction associated with the administration of a diuretic is the loss of fluid and electrolytes (see Display 46-1), especially during initial therapy with the drug. In some patients, the diuretic effect is moderate, whereas in others a large volume of fluid is lost. Regardless of the amount of fluid lost, there is always the possibility of excessive electrolyte loss, which is potentially serious. 

DISPLAY 46-1 Signs and Symptoms of Cbmmon Fluid and Electrolyte Imbalances Associated With Diuretic Therapy... 

Whether a fluid or electrolyte imbalance occurs depends on the amount of fluid and electrolytes lost and the ability of the individual to replace them. For example, if a patient receiving a diuretic eats poorly and does not drink extra fluids, an electrolyte and water imbalance is likely to occur, especially during initial therapy with the drug. However, even when a patient drinks adequate amounts of fluid and eats a balanced diet, an electrolyte imbalance may still occur and require electrolyte replacement (see Chapter 58 and Display 58-2 for additional discussion of fluid and electrolyte imbalances). 

Older adults are particularly prone to fluid volume deficit and electrolyte imbalances (see Display 46-1) while taking a diuretic. The older adult is carefully monitored for hypokalemia (when taking the loop or thiazide diuretic and hyperkalemia (with the potassium-sparing diuretics... 

Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are members of a family of so-called natriuretic peptides, synthesized predominantly in the cardiac atrium, ventricle, and vascular endothelial cells, respectively (G13, Y2). ANP is a 28-amino-acid polypeptide hormone released into the circulation in response to atrial stretch (L3). ANP acts (Fig. 8) on the kidney to increase sodium excretion and glomerular filtration rate (GFR), to antagonize renal vasoconstriction, and to inhibit renin secretion (Ml). In the cardiovascular system, ANP antagonizes vasoconstriction and shifts fluid from the intravascular to the interstitial compartment (G14). In the adrenal cortex, ANP is a powerful inhibitor of aldosterone synthesis (E6, N3). At the hypothalamic level, ANP inhibits vasopressin secretion (S3). It has been shown that some of the effects of ANP are mediated via a newly discovered hormone, called adreno-medullin, controlling fluid and electrolyte homeostasis (S8). The diuretic and blood pressure-lowering effect of ANP may be partially due to adrenomedullin (V5). 

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. 

Fluid and electrolyte balance Monitor fluid and electrolyte balance and body weight. Give with a diuretic to prevent fluid retention and possible CHF a loop diuretic is usually required. If used without a diuretic, retention of several hundred mEq salt and corresponding volumes of water can occur in a few days, leading to increased plasma and interstitial fluid volume and local or generalized edema. 

These agents are potent diuretics excess amounts can lead to a profound diuresis with water and electrolyte depletion. 

Glycerin Suppository [Laxative] Uses Constipation Action Hyperosmolar laxative Dose Adults. 1 adult supp PR PRN Feds. 1 infant supp PR daily-bid PRN Caution [C, ] Disp Supp SE D Interactions T Effects W/ diuretics EMS Monitor ECG and BP for signs of hypovolemia and electrolyte disturbances d/t D OD Unlikely but may cause severe D and dehydration symptomatic and supportive... 

Older patients with CHF may be faced with multiple therapies of diuretics, ACE inhibitors/angioten-sion II blockers and beta-blockers. This puts them at risk of hypotension, orthostatic hypotension, azo-taemia and electrolyte imbalance. Drugs should be added carefully, starting at low dose and patients should be monitored for volume depletion and changes in serum creatinine and electrolyte concentrations. 

Clayton JA, Rodgers S, Blakey J, Avery A, Hall IP. Thiazide diuretic prescription and electrolyte abnormalities in primary care. Br J Clin Pharmacol 2006 61(l) 87-95. 

The ability of certain drugs to increase both fluid and electrolyte loss has led to their use in the clinical management of fluid and electrolyte disorders, for example, edema. Regardless of the cause of the syndrome associated with edema, the common factor is almost invariably an increased retention of Na. The aim of diuretic therapy is to enhance Na+ excretion, thereby promoting negative Na" balance. This net Na" (and fluid) loss leads to contraction of the overexpanded extracellular fluid compartment. 

C. Although still highly controversial, the initial use of a thiazide diuretic for monotherapy has been recommended by the Joint National Committee on Detection, Evaluation and treatment of High Blood Pressure. Triamterene and Aldactone are rarely used alone and exhibit no antihypertensive activity. A recent study found that the loop diuretics bumetanide and furosemide effectively reduced blood pressure. Serum lipid levels were less affected than with thiazide diuretics or chlorthalidone. However, thiazide diuretics are a more conservative and approved approach for the initial treatment of hypertension that avoid the more dramatic fluid and electrolyte shifts that occur with loop diuretics. 

The degree of blockade can be influenced by body pH and electrolyte balance. Hypokalemia due to diarrhea, renal disease, or use of potassium-depleting diuretics potentiates the effect of nondepolarizing blockers. By contrast, hyperkalemia may oppose the actions of d-tubocurarine but enhance the end plate response to succinylcholine. The effectiveness of d-tubocurarine is reduced by alkalosis. 

Mechanism of Action A sulfonamide derivative that acts as a thiazide diuretic and antihypertensive. As a diuretic, blocks reabsorption of water and the electrolytes sodium and potassium at cortical diluting segment of distal tubule. As an antihypertensive, reduces plasma and extracellular fluid volume, decreases peripheral vascular resistance (PVR) by direct effect on blood vessels. Therapeutic Effect Promotes diuresis, reduces BP. 

Mechanism of Action An osmotic diuretic, antiglaucoma, and antihemolytic agent that elevates osmotic pressure of theglomerular filtrate, inhibiting tubular reabsorption of water and electrolytes, resulting in increased flow of water into interstitial fluid and plasma. Therapeutic Effect Produces diuresis reduces lOP reduces iCP and cerebral edema. 

Fluid and electrolyte imbalance and CHF may occur, especially if a diuretic is not given concurrently with minoxidil. 

These are the most efficacious agents available for inducing marked water and electrolyte excretion. The peak diuresis is far greater than that observed maximally with other diuretics. The drugs in this group include furosemide, bumetanide and ethacrynic acid and the main site of action is the thick ascending limb of loop of Henle, thus they are often called loop diuretics. ... 

These agents tend to increase renal blood flow without increasing filtration rate, which reduces fluid and electrolyte reabsorption in the proximal tubule and may augment the initial diuretic response. 

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