Page 268 - Basic _ Clinical Pharmacology ( PDFDrive )

15 Diuretic Agents
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Ramin Sam, MD, Harlan E. Ives, MD, PhD,
& David Pearce, MD

C ASE STUD Y

A 65-year-old man has a history of diabetes and chronic weeks later, the patient presents to the emergency depart-
kidney disease with baseline creatinine of 2.2 mg/dL. Despite ment with symptoms of weakness, anorexia, and generalized
five different antihypertensive drugs, his clinic blood pres- malaise. His blood pressure is now 91/58 mm Hg, and he
sure is 176/92 mm Hg; he has mild dyspnea on exertion and has lost 15 kg in 2 weeks. His laboratory tests are signifi-
2–3+ edema on exam. He has been taking furosemide 80 mg cant for a serum creatinine of 10.8 mg/dL. What has led to
twice a day for 1 year now. At the clinic visit, hydrochlorothi- the acute kidney injury? What is the reason for the weight
azide 25 mg daily is added for better blood pressure control loss? What precautions could have been taken to avoid this
and also to treat symptoms and signs of fluid overload. Two hospitalization?

Abnormalities in fluid volume and electrolyte composition are Table 15–1). Several autacoids, which exert multiple, complex effects
common and important clinical disorders. Drugs that block spe- on renal physiology (adenosine, prostaglandins, and urodilatin, a
cific transport functions of the renal tubules are valuable clinical renal autacoid closely related to atrial natriuretic peptide), are also
tools in the treatment of these disorders. Although various agents discussed. The second section describes the pharmacology of diuretic
that increase urine volume (diuretics) have been described since agents. Many diuretics exert their effects on specific membrane trans-
antiquity, it was not until 1937 that carbonic anhydrase inhibitors port proteins in renal tubular epithelial cells. Other diuretics exert
were first described and not until 1957 that a much more useful osmotic effects that prevent water reabsorption (mannitol), inhibit
and powerful diuretic agent (chlorothiazide) became available. enzymes (acetazolamide), or interfere with hormone receptors in renal
Technically, a “diuretic” is an agent that increases urine volume, epithelial cells (vaptans, or vasopressin antagonists). The physiology
whereas a “natriuretic” causes an increase in renal sodium excretion of each nephron segment is closely linked to the basic pharmacology
and an “aquaretic” increases excretion of solute-free water. Because of the drugs acting there, which is discussed in the second section.
natriuretics almost always also increase water excretion, they are The third section of the chapter describes the clinical applications of
usually called diuretics. Osmotic diuretics and antidiuretic hormone diuretics.
antagonists (see Agents That Alter Water Excretion) are aquaretics
and are not directly natriuretic. Most recently, an entirely new class
of agents has been developed that block urea transport. These agents ■ RENAL TUBULE TRANSPORT
result in increased urine output and increased urea excretion but not MECHANISMS
increased excretion of electrolytes. Even though they are technically
aquaretics, they have also been referred to as urearetics. These agents PROXIMAL TUBULE
are not yet available for therapy but are in early investigational stages.
This chapter is divided into three sections. The first section covers Sodium bicarbonate (NaHCO ), sodium chloride (NaCl),
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major renal tubule transport mechanisms. The nephron is divided glucose, amino acids, and other organic solutes are reabsorbed
structurally and functionally into several segments (Figure 15–1, via specific transport systems in the early proximal tubule

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