Page 284 - Basic _ Clinical Pharmacology ( PDFDrive )

270 SECTION III Cardiovascular-Renal Drugs

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This reduction is sensed as insufficient effective arterial blood collecting tubule. Patients who do not adhere to a low Na diet
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volume and leads to salt and water retention, which expands blood must take oral KCl supplements or a K -sparing diuretic.
volume and eventually causes edema formation. Judicious use of Recently, there has been interest in the use of vaptans in heart
diuretics can mobilize this interstitial edema without significant failure, not only to treat hyponatremia but also to treat volume
reductions in plasma volume. However, excessively rapid diuretic overload. Electrolyte dysfunction is less likely with a combination
therapy may compromise the effective arterial blood volume and of diuretics and vaptans as opposed to higher doses of the diuret-
reduce the perfusion of vital organs. Therefore, the use of diuret- ics alone.
ics to mobilize edema requires careful monitoring of the patient’s
hemodynamic status and an understanding of the pathophysiology
of the underlying illness. KIDNEY DISEASE AND RENAL FAILURE
A variety of diseases interfere with the kidney’s critical role in
HEART FAILURE volume homeostasis. Although some renal disorders cause salt
wasting, most cause retention of salt and water. When renal failure
When cardiac output is reduced by heart failure, the resultant is severe (GFR < 5 mL/min), diuretic agents are of little benefit,
changes in blood pressure and blood flow to the kidney are sensed because glomerular filtration is insufficient to generate or sustain a
as hypovolemia and lead to renal retention of salt and water. This natriuretic response. However, a large number of patients, and even
physiologic response initially increases intravascular volume and dialysis patients, with milder degrees of renal insufficiency (GFR of
venous return to the heart and may partially restore the cardiac 5–15 mL/min), can be treated with diuretics with some success.
output toward normal (see Chapter 13). There is still interest in the question as to whether diuretic
If the underlying disease causes cardiac output to deteriorate therapy can alter the severity or the outcome of acute renal failure.
despite expansion of plasma volume, the kidney continues to retain This is because “nonoliguric” forms of acute renal insufficiency
salt and water, which then leaks from the vasculature and becomes have better outcomes than “oliguric” (<400–500 mL/24 h urine
interstitial or pulmonary edema. At this point, diuretic use becomes output) acute renal failure. Almost all studies done to address this
necessary to reduce the accumulation of edema, particularly in the question have shown that diuretic therapy helps in the short-term
lungs. Reduction of pulmonary vascular congestion with diuretics fluid management of some of these patients with acute renal
may actually improve oxygenation and thereby improve myocardial failure, but that it has no impact on the long-term outcome.
function. Reduction of preload can reduce the size of the heart, Many glomerular diseases, such as those associated with diabetes
allowing it to work at a more efficient fiber length. Edema associ- mellitus or systemic lupus erythematosus, exhibit renal retention of
ated with heart failure is generally managed with loop diuretics. In salt and water. The cause of this sodium retention is not precisely
some instances, salt and water retention may become so severe that known, but it probably involves disordered regulation of the renal
a combination of thiazides and loop diuretics is necessary. microcirculation and tubular function through release of vasocon-
In treating the heart failure patient with diuretics, it must strictors, prostaglandins, cytokines, and other mediators. When
always be remembered that cardiac output in these patients is being edema or hypertension develops in these patients, diuretic therapy
maintained in part by high filling pressures. Therefore, excessive can be very effective.
use of diuretics may diminish venous return and further impair Certain forms of renal disease, particularly diabetic nephropa-
cardiac output. This is especially critical in right ventricular heart thy, are frequently associated with development of hyperkalemia
failure. Systemic, rather than pulmonary, vascular congestion is the at a relatively early stage of renal failure. This is often due to type
hallmark of this disorder. Diuretic-induced volume contraction pre- IV renal tubular acidosis. In these cases, a thiazide or loop diuretic
dictably reduces venous return and can severely compromise cardiac will enhance K excretion by increasing delivery of salt to the K -
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output if left ventricular filling pressure is reduced below 15 mm Hg secreting collecting tubule.
(see Chapter 13). Reduction in cardiac output, resulting from either Patients with renal diseases leading to the nephrotic syndrome
left or right ventricular dysfunction, also eventually leads to renal often present complex problems in volume management. These
dysfunction resulting from reduced perfusion pressures. patients may exhibit fluid retention in the form of ascites or
Diuretic-induced metabolic alkalosis, exacerbated by hypokale- edema but have reduced plasma volume due to reduced plasma
mia, is another adverse effect that may further compromise cardiac oncotic pressures. This is very often the case in patients with
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function. This complication can be treated with replacement of K “minimal change” nephropathy. In these patients, diuretic use
and restoration of intravascular volume with saline; however, severe may cause further reductions in plasma volume that can impair
heart failure may preclude the use of saline even in patients who GFR and may lead to orthostatic hypotension. Most other causes
have received excessive diuretic therapy. In these cases, adjunctive of nephrotic syndrome are associated with primary retention of
use of acetazolamide helps to correct the alkalosis. salt and water by the kidney, leading to expanded plasma volume
Another serious toxicity of diuretic use in the cardiac patient and hypertension despite the low plasma oncotic pressure. In
is hypokalemia. Hypokalemia can exacerbate underlying cardiac these cases, diuretic therapy may be beneficial in controlling the
arrhythmias and contribute to digitalis toxicity. This can usu- volume-dependent component of hypertension.
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ally be avoided by having the patient reduce Na intake while In choosing a diuretic for the patient with kidney disease,
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taking diuretics, thus decreasing Na delivery to the K -secreting there are a number of important limitations. Acetazolamide must