Diuretics

Normally 99% of the filtered sodium that passes through the glomeruli is reabsorbed; 50% to 55% of sodium reabsorption occurs in the proximal tubules, 35% to 40% in the loop of Henle, 5% to 10% in the distal tubules, and <3% in the collecting tubules. Diuretics that act on the tubules closest to the glomeruli have the greatest effect in causing natriuresis (sodium loss in the urine). A classic example is the osmotic diuretic mannitol. The diuretic effect depends on the drug reaching the kidneys and its concentration in the renal tubules.

Diuretics have an antihypertensive effect because they promote sodium and water loss by blocking sodium and chloride reabsorption. This causes a decrease in fluid volume, lowering blood pressure. With fluid loss, edema (fluid retention in body tissues) should decrease, but if sodium is retained, water is also retained, and blood pressure increases.

Many diuretics cause the loss of other electrolytes, including potassium, magnesium, chloride, and bicarbonate. The diuretics that promote potassium excretion are classified as potassium-wasting diuretics, and those that promote potassium retention are called potassium-sparing diuretics.

The following five categories of diuretics are effective in removing water and sodium:

• Thiazide and thiazide-like

• Loop or high-ceiling

• Osmotic

• Carbonic anhydrase inhibitor

• Potassium-sparing

Thiazide, loop, and potassium-sparing diuretics are most frequently prescribed for hypertension and for edema associated with HF. Except for those in the potassium-sparing group, all diuretics are potassium-wasting.

Combination diuretics that contain both potassium-wasting and potassium-sparing drugs have been marketed primarily for the treatment of hypertension. Combinations have an additive effect in reducing blood pressure and are discussed in more detail in the Potassium-Sparing Diuretics section later in this chapter. Chapter 44 takes a closer look at the combinations of antihypertensive agents with hydrochlorothiazide (HCTZ).

Thiazides and Thiazide-Like Diuretics

The first thiazide, chlorothiazide (Diuril), was marketed in 1957 and followed a year later by hydrochlorothiazide. There are numerous thiazide and thiazide-like preparations. Thiazides act on the distal convoluted renal tubule, beyond the loop of Henle, to promote sodium, chloride, and water excretion. Thiazides are used to treat hypertension and peripheral edema. They are not effective for immediate diuresis and should not be used to promote fluid loss in patients with severe renal dysfunction. Table 43-1 lists thiazide and thiazide-like diuretics and their dosages, uses, and considerations. Drug dosages for hypertension and edema are similar.

TABLE 43-1

DIURETICS

GENERIC (BRAND)	ROUTE AND DOSAGE	USES AND CONSIDERATIONS
Thiazides
*Short-Acting*
chlorothiazide (Diuril)	A: PO: 250-1000 mg/d in 1-2 divided doses A: IV: 500-1000 mg/d in 1-2 divided doses C: PO: 10-20 mg/kg/d in 1-2 divided doses	For hypertension and peripheral edema. Adults may be given IV chlorothiazide, but not recommended for infants and children. Pregnancy category: C; PB: 20%-80%; : 1-2 h
hydrochlorothiazide (Esidrix, HCTZ)	See Prototype Drug Chart 43-1.
*Intermediate-Acting*
bendroflumethiazide with Nadolol (Corzide)	A: PO: 40 mg nadolol/5 mg bendroflumethiazide; max: 80/5	Treatment of hypertension and edema associated with HF and cirrhosis. Has similar effects as prototype drug HCTZ. Hypokalemia, hyperglycemia, and hyperuricemia may occur. Pregnancy category: C; PB: nadolol: 95%; bendroflumethiazide: 95%; : nadolol: 10-24 h; bendroflumethiazide: 3 h
*Long-Acting*
methyclothiazide	Hypertension/edema: A: PO: 2.5-10 mg/d; max: 5 mg/d for hypertension; 10 mg/d for edema	For hypertension and edema associated with HF and renal or liver dysfunction. Side effects and drug interactions similar to those of HCTZ. Long duration of action. Pregnancy category: B; PB: UK; : UK
Thiazide-Like Diuretics
chlorthalidone (Hygroton, Thalitone)	Hypertension: A: PO: 12.5-50 mg/d; 50 mg/d C: PO: 2 mg/kg/d Edema: A: PO: 25-100 mg/d; max: 200 mg/d	For hypertension and edema associated with HF and renal or liver dysfunction. Very long duration of action (24-72 h). Pregnancy category: B; PB: 75%; : 40-60 h
indapamide	Hypertension/edema: A: PO: 1.25-2.5 mg/d; may increase to 5 mg/d; max: 5 mg/d	For hypertension and edema. Long-acting diuretic. May be classified as loop diuretic. Pregnancy category: B; PB: 71%-79%; : 14-18 h
metolazone (Zaroxolyn)	Hypertension: A: PO: 2.5-5.0 mg/d C: PO: 0.2-0.4 mg/kg/d in divided doses Edema: A: PO: 5-20 mg/d	For hypertension and edema. Intermediate-acting diuretic. More effective than thiazides in patients with decreased renal function. Pregnancy category: B; PB: 33%; : 14 h

A, Adult; b.i.d., twice a day; C, child; d, day; h, hour; HF, heart failure; IV, intravenous; maint, maintenance; max, maximum; mo, month; PO, by mouth; PB, protein-binding; , half-life; UK, unknown; wk, week; y, year; >, greater than; <, less than.

Thiazide diuretics are used primarily for patients with normal renal function. If the patient has a renal disorder and creatinine clearance is less than 30 mL/min, the effectiveness of the thiazide diuretic is greatly decreased. Thiazides cause a loss of sodium, potassium, and magnesium, but they promote calcium reabsorption. Hypercalcemia (calcium excess) may result, and the condition can be hazardous to the patient who is digitalized or has cancer that causes hypercalcemia. Thiazides affect glucose tolerance, so hyperglycemia can also occur. Thiazides should be used cautiously in patients with diabetes mellitus. Laboratory test results (e.g., electrolytes, glucose) need to be monitored.

The thiazide drug hydrochlorothiazide has been combined with selected angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, alpha-blockers, angiotensin II blockers, and centrally acting sympatholytics to control hypertension. Prototype Drug Chart 43-1 outlines the pharmacologic data for hydrochlorothiazide.

Prototype Drug Chart 43-1

Hydrochlorothiazide

Drug Class	Dosage
Thiazide diuretic Trade Names: HCT, Esidrix Pregnancy Category: B	Hypertension: A: PO: 12.5-50 mg/d; max: 50 mg/d Edema: A: PO: 25-100 mg/d in single or divided doses; max: 200 mg/d C: PO: 1-2 mg/kg/d in divided doses C: <6 mo: PO: 1-3 mg/kg/d in divided doses
Contraindications	Drug-Lab-Food Interactions
Renal failure with anuria, electrolyte depletion Caution: Hepatic dysfunction, renal dysfunction, diabetes mellitus, gout, systemic lupus erythematosus	Drug: Increase digitalis toxicity with digitalis if hypokalemia is present; increase renal toxicity with aspirin; increase potassium loss with steroids; decrease antidiabetic effect; decrease thiazide absorption and effects with NSAIDs, cholestyramine, and colestipol
	Lab: Increase serum calcium, glucose, uric acid; decrease serum potassium, sodium, magnesium
Pharmacokinetics	Pharmacodynamics
Absorption: Readily absorbed from GI tract Distribution: PB: 65% Metabolism: : 6-15 h Excretion: In urine	PO: Onset: 2 h Peak: 4 h Duration: 6-12 h
Therapeutic Effects/Uses
To increase urine output; to treat hypertension, edema from HF, hepatic cirrhosis, renal dysfunction
Mode of Action: Action is on the renal distal tubules, promoting sodium, potassium, and water excretion and decreasing preload and cardiac output; also decreases edema; acts on arterioles, causing vasodilation, thus decreasing blood pressure
Side Effects	Adverse Reactions
Dizziness, vertigo, weakness, nausea, vomiting, diarrhea, abdominal pain, hyperglycemia, constipation, rash, photosensitivity, blurred vision	Severe dehydration, hypotension, gout Life-threatening: Severe potassium depletion, marked hypotension, aplastic anemia, hemolytic anemia, thrombocytopenia, agranulocytosis, renal failure

A, Adult; C, child; d, day; GI, gastrointestinal; h, hour; HF, heart failure; maint, maintenance; mo, month; PB, protein-binding; PO, by mouth; , half-life.

Pharmacokinetics

Thiazides are well absorbed from the gastrointestinal (GI) tract. Hydrochlorothiazide has moderate protein-binding power. The half-life of the thiazide drugs is longer than that of the loop diuretics. For this reason, thiazides should be administered in the morning to avoid nocturia (nighttime urination) and sleep interruption.

Pharmacodynamics

Thiazides act directly on arterioles to cause vasodilation, which can lower blood pressure. Other action includes the promotion of sodium chloride and water excretion, resulting in a decrease in vascular fluid volume and a concomitant decrease in cardiac output and blood pressure. The onset of action of hydrochlorothiazide occurs within 2 hours. Peak concentration times are long (3 to 6 hours). Thiazides are divided into three groups, according to their duration of action: short-acting (duration less than 12 hours), intermediate-acting (duration 12 to 24 hours), and long-acting (duration more than 24 hours).

Side Effects and Adverse Reactions.

Side effects and adverse reactions of thiazides include electrolyte imbalances (hypokalemia, hypercalcemia, hypomagnesemia, and bicarbonate loss), hyperglycemia (elevated blood sugar), hyperuricemia (elevated serum uric acid level), and hyperlipidemia (elevated blood lipid level). Signs and symptoms of hypokalemia should be assessed, and serum potassium levels must be closely monitored. Potassium supplements are frequently needed. Serum calcium and uric acid levels should be checked, because thiazides block calcium and uric acid excretion. Thiazides affect the metabolism of carbohydrates, and hyperglycemia can result, especially in patients with high to high-normal blood sugar levels. Thiazides can increase serum cholesterol, low-density lipoprotein, and triglyceride levels. A drug may be ordered to lower blood lipids. Other side effects include dizziness, headache, nausea, vomiting, constipation, urticaria, or hives (rare), and blood dyscrasias (rare). Table 43-2 summarizes the serum chemistry abnormalities that can occur with thiazide use.

TABLE 43-2

SERUM CHEMISTRY ABNORMALITIES ASSOCIATED WITH THIAZIDES

SERUM CHEMISTRY PARAMETER	ABNORMAL RESULTS
Electrolytes, Normal Levels
Potassium, 3.5-5.3 mEq/L	Hypokalemia (low serum potassium). Potassium is excreted from the distal renal tubule.
Magnesium, 1.8-3.0 mg/dL	Hypomagnesemia (low serum magnesium). Potassium and sodium loss prompt magnesium loss.
Calcium, 4.5-5.5 mEq/L	Hypercalcemia (elevated serum calcium). Thiazides may block calcium excretion.
Chloride, 95-105 mEq/L	Hypochloremia (low serum chloride). Sodium and potassium losses produce chloride loss.
Bicarbonate, 24-28 mEq/L	Minimal bicarbonate loss from proximal tubule.
Uric acid, 2.8-8.0 mg/dL	Hyperuricemia (elevated uric acid). Thiazides can block uric acid excretion.
Blood sugar, 70-110 mg/dL	Hyperglycemia (increased blood sugar). Thiazides increase fasting blood sugar levels and those of prediabetic state.
Blood Lipids
Cholesterol: <200 mg/dL LDL: <100 mg/dL Triglyceride: 10-190 mg/dL	Can elevate cholesterol, LDLs, and triglycerides.

LDL, Low-density lipoprotein.

Contraindications.

Thiazides are contraindicated for use in renal failure. Symptoms of severe kidney impairment or shutdown include oliguria (marked decrease in urine output), elevated blood urea nitrogen (BUN), and elevated serum creatinine.

Drug Interactions.

Of the numerous thiazide drug interactions, the most serious occurs with digoxin. Thiazides can cause hypokalemia, which enhances the action of digoxin, and digitalis toxicity can occur. Potassium supplements are frequently prescribed, and serum potassium levels are monitored. Thiazides also induce hypercalcemia, which enhances the action of digoxin, resulting in possible digitalis toxicity. Signs and symptoms of digitalis toxicity (bradycardia, nausea, vomiting, visual changes) should be reported. Thiazides enhance the action of lithium, and lithium toxicity can occur. Thiazides potentiate the action of other antihypertensive drugs, which may be used to advantage in combination drug therapy for hypertension.

Loop (High Ceiling) Diuretics

The loop, or high-ceiling, diuretics act on the thick ascending loop of Henle to inhibit chloride transport of sodium into the circulation (inhibit passive reabsorption of sodium). Sodium and water are lost, together with potassium, calcium, and magnesium. Loop diuretics can affect blood sugar and increase uric acid levels. Drugs in this group are extremely potent and cause marked depletion of water and electrolytes. This high diuretic potential is the reason they are often called high-ceiling diuretics or potassium-wasting diuretics. The effects of loop diuretics are dose-related (i.e., increasing the dose increases the effect and response of the drug). More potent than thiazides for promoting diuresis (inhibiting reabsorption of sodium two to three times more effectively), loop diuretics are less effective as antihypertensive agents.

Loop diuretics should not be prescribed if a thiazide could alleviate body fluid excess. If furosemide (Lasix) alone is not effective in removing body fluid, a thiazide may be added, but furosemide should never be combined with another loop diuretic. Furosemide is usually administered as an oral dose in the morning or intravenously when the patient's condition warrants immediate removal of body fluid, for example, in cases of acute heart failure or pulmonary edema.

Nursing Process

Patient-Centered Collaborative Care

Diuretics: Thiazides

Assessment

Assess vital signs, weight, urine output, and serum chemistry values (electrolytes, glucose, uric acid) for baseline levels.

Check peripheral extremities for presence of edema. Note pitting edema.

Obtain a history of drugs and herbal supplements taken daily. Review for drugs and herbals that may cause drug interaction (digoxin, corticosteroids, antidiabetics, ginkgo, licorice).

Nursing Diagnoses

Risk for deficient fluid volume related to use or overuse of thiazides

Impaired urinary elimination related to kidney dysfunction

Excess fluid volume related to body fluid retention

Planning

Patient's blood pressure will be decreased and/or return to normal value.

Patient's edema will be decreased.

Patient's serum chemistry levels will remain within normal ranges.

Nursing Interventions

Monitor vital signs and serum electrolytes, especially potassium, glucose, uric acid, and cholesterol levels. Report changes. If patient is taking digoxin and hypokalemia occurs, digitalis toxicity frequently results.

Observe for signs and symptoms of hypokalemia (e.g., muscle weakness, leg cramps, cardiac dysrhythmias).

Monitor patient's weight daily. Weight gain of 2.2 lb is equivalent to 1 L of body fluids.

Note urine output to determine fluid loss or retention.

Patient Teaching

General

Emphasize the need for adherence. Patient may not “feel better” for some time or may not “feel worse” if treatment is missed or discontinued.

Suggest that patient take hydrochlorothiazide in early morning to avoid sleep disturbance resulting from nocturia.

Instruct patient to keep drugs out of reach of small children. Request childproof bottle.

Inform patient that certain herbal products may interact with thiazide diuretics (Herbal Alert 43-1).

Herbal Alert 43-1

Diuretics

• Aloe can decrease the serum potassium level, thereby causing hypokalemia, when taken with a potassium-wasting diuretic such as a thiazide.

• Gingko may increase blood pressure when taken with thiazide diuretics.

• Licorice can increase potassium loss, leading to hypokalemia.

• Hawthorne may potentiate hypotension.

Self-Administration

Instruct patient or family member on how to take blood pressure and record daily results.

Side Effects

Instruct patient to slowly change positions from lying to standing, because dizziness may occur as a result of orthostatic (postural) hypotension.

Advise patient who may be prediabetic to have blood sugar checked periodically, because large doses of hydrochlorothiazide increase blood glucose levels.

Suggest that patient use sunblock when in direct sunlight for photosensitivity

Diet

Teach patient to eat foods rich in potassium (fruits, fruit juices, and vegetables). Potassium supplements may be ordered.

Instruct patient to take drugs with food to avoid gastrointestinal upset.

Cultural Considerations

Respect cultural practices and values. If patient from a different background tells the health care provider that she or he does not eat fruits and vegetables, the nurse may have two options: to encourage patient to eat fruits and vegetables, or to contact health care provider so that an adequate potassium supplement can be prescribed to overcome potassium loss. An interpreter may be necessary.

Emphasize importance of patient taking potassium supplement with potassium-wasting diuretic. In addition, advise patient of consequences and dangers of not taking potassium supplements or lacking appropriate nutrition while taking potassium-wasting diuretics. Monitor serum potassium levels.

Evaluation

Evaluate the effectiveness of drug therapy. Patient's blood pressure and edema will be reduced, and blood chemistry will remain within normal range.

Determine absence of side effects and adverse reactions to therapy.

Loop diuretics can increase renal blood flow up to 40%. Furosemide is a frequently prescribed diuretic for patients whose creatinine clearance is less than 30/min and for those with end-stage renal disease. This group of diuretics causes excretion of calcium, unlike thiazides, which inhibit calcium loss.

The first loop diuretic marketed was ethacrynic acid (Edecrin), followed by furosemide (Lasix) and then bumetanide (Bumex), which is more potent than furosemide on a milligram-for-milligram basis. Furosemide and bumetanide are derivatives of sulfonamides. Ethacrynic acid, a phenoxyacetic acid derivative, is a seldom-chosen loop diuretic. It is usually reserved for patients who are allergic to sulfa drugs. Prototype Drug Chart 43-2 lists the drug data for the loop diuretic furosemide.

Prototype Drug Chart 43-2

Furosemide

Drug Class	Dosage
Loop diureticTrade Names: LasixPregnancy Category: C	A: PO: 20-80 mg single dose/d; may increase in 6-8 h, 20-40 mg; maint: 40-120 mg/d; max: 600 mg/d
	A: IM/IV: 20-40 mg over 1-2 min IV; repeat 20 mg in 2 h; max: 4 mg/min inf
	C: PO: 1-2 mg/kg single dose; repeat in 6-8 h max: 6 mg/kg/d
	C: IM/IV: 1-2 mg/kg single dose; repeat 1 mg/kg in 6-12 h; max: 6 mg/kg/d
Contraindications	Drug-Lab-Food Interactions
Presence of severe electrolyte imbalances, hypovolemia, anuria, hepatic coma, hypersensitivity to sulfonamides Caution: Heart failure, diabetes mellitus, hypotension, systemic lupus erythematosus, gout, patients with hearing impairment	Drug: Increase orthostatic hypotension with alcohol; increase ototoxicity with aminoglycosides; increase bleeding with anticoagulants; increase potassium loss with steroids, Amphotericin B, amiodarone; increase digitalis toxicity and cardiac dysrhythmias with digoxin and hypokalemia; increase lithium toxicity; increase amphotericin B ototoxicity and nephrotoxicity Food: licorice may increase potassium loss
	Lab: Increase BUN, blood/urine glucose, serum uric acid, ammonia; decrease potassium, sodium, calcium, magnesium, chloride serum levels Herbs: Hawthorn may potentiate hypotension, Ginseng may decrease action of loop diuretics
Pharmacokinetics	Pharmacodynamics
Absorption: PO: Readily absorbed from GI tract Distribution: PB: 95% Metabolism: : 30-60 min Excretion: In urine, some in feces; crosses placenta	PO: Onset: less than 60 min Peak: 1-4 h Duration: UK IV: Onset: 5 min Peak: 20-30 min Duration: 2 h
Therapeutic Effects/Uses
To treat fluid retention/fluid overload caused by HF, renal dysfunction, cirrhosis; hypertension; acute pulmonary edema
Mode of Action: Inhibition of sodium and water reabsorption from loop of Henle and distal renal tubules; potassium, magnesium, and calcium also may be excreted
Side Effects	Adverse Reactions
Nausea, diarrhea, electrolyte imbalances, vertigo, abdominal cramping, constipation, rash, headache, weakness, ECG changes, blurred vision, photosensitivity, muscle cramping	Severe dehydration; marked hypotension, hyperglycemia, gout, hearing loss Life-threatening: Renal failure, thrombocytopenia, agranulocytosis

A, Adult; BUN, blood urea nitrogen; C, child; d, day; ECG, electrocardiogram; GI, gastrointestinal; h, hour; HF, heart failure; IM, intramuscular; inf, infusion; IV, intravenous; max, maximum; min, minute; PB, protein-binding; PO, by mouth; , half-life.

Pharmacokinetics

Loop diuretics are rapidly absorbed by the GI tract. These drugs are highly protein bound with half-lives that vary from 30 minutes to 1.5 hours. Loop diuretics compete for protein-binding sites with other highly protein-bound drugs.

Pharmacodynamics

Loop diuretics have a great saluretic (sodium-chloride–losing) or natriuretic (sodium-losing) effect and can cause rapid diuresis, decreasing vascular fluid volume and causing a decrease in cardiac output and blood pressure. Because furosemide is a more potent diuretic than thiazide diuretics, it causes a vasodilatory effect; thus renal blood flow increases before diuresis. Furosemide is used when other conservative measures, such as sodium restriction and use of less potent diuretics, fail. The oral dose of furosemide is usually twice that of an intravenous (IV) dose.

The onset of action of loop diuretics occurs within 30 to 60 minutes. The onset of action for IV furosemide is 5 minutes. Duration of action is shorter than that of the thiazides.

Side Effects and Adverse Reactions.

The most common side effects of loop diuretics are fluid and electrolyte imbalances such as hypokalemia, hyponatremia, hypocalcemia, hypomagnesemia, and hypochloremia. Hypochloremic metabolic alkalosis may result, which can worsen hypokalemia. Orthostatic hypotension can occur. Thrombocytopenia, skin disturbances, and transient deafness are rarely seen. Table 43-3 lists the physiologic and laboratory changes associated with loop diuretics.

TABLE 43-3

PHYSIOLOGIC AND LABORATORY CHANGES ASSOCIATED WITH LOOP DIURETICS

PHYSIOLOGIC/LABORATORY CHANGES	POSSIBLE EFFECTS OF LOOP (HIGH-CEILING) DIURETICS
Physiologic Changes
Hypotension	Postural (orthostatic) hypotension can result because of ECFV deficit.
Ototoxicity	Hearing impairment, although rare, may occur. It is more common with use of ethacrynic acid. Diuretics in other categories are not considered ototoxic. Caution: Avoid taking a loop diuretic with a drug that can be ototoxic, such as an aminoglycoside.
Skin disturbances	Pruritus, urticaria, exfoliative dermatitis, and purpura may occur in some persons allergic to the drug or when taking the loop diuretic in high doses over a long period.
Photosensitivity	When exposed to sun or sunlamp for a prolonged time, severe sunburn could result. Patient should use sunblock and avoid long sun exposure.
Hypovolemia	Excess extracellular fluid is lost through increased urine excretion.
Laboratory Changes
Hypokalemia, hypomagnesemia, hyponatremia, hypocalcemia, hypochloremia	Potassium, magnesium, sodium, calcium, and chloride are lost from the body from increased urine excretion. Chloride, an anion, is attached to the cations potassium and sodium; thus, chloride is lost along with potassium and sodium.
Hyperglycemia	Increased glycogenolysis may contribute to elevated blood sugar level. Patients with diabetes should closely monitor blood glucose levels when taking a loop diuretic.
Hyperuricemia	Elevated uric acid levels are common in patients susceptible to gout.
Elevated BUN and creatinine	These elevations may result from ECFV loss. Hemoconcentration can cause elevated BUN and creatinine levels, which are reversible when fluid volume returns to normal levels.
Thrombocytopenia, leukopenia	Decreases in platelet and white blood cell counts are rare, but they should be closely monitored.
Elevated lipids	Loop diuretics can decrease high-density lipoproteins (HDL) and increase low-density lipoproteins (LDL). Patients with elevated cholesterol levels should have their HDL and LDL levels checked. Regardless of the lipid effects, loop diuretics are useful for patients with serious fluid retention caused by a cardiac condition such as HF.

BUN, Blood urea nitrogen; ECFV, extracellular fluid volume; HF, heart failure.

Drug Interactions.

The major drug interaction is with digitalis preparations. If the patient takes digoxin with a loop diuretic, digitalis toxicity can result. Hypokalemia enhances the action of digoxin and increases the risk for digitalis toxicity. The patient needs potassium replacement with food or supplements. Serum potassium levels should be closely monitored, especially when the patient is taking high dosages of loop diuretics. Table 43-4 lists the data for the four loop diuretics.

TABLE 43-4

DIURETICS: LOOP, OSMOTICS, AND CARBONIC ANHYDRASE INHIBITORS

GENERIC (BRAND)	ROUTE AND DOSAGE	USES AND CONSIDERATIONS
Loop
bumetanide	A: PO: 0.5-2.0 mg/d; max: 10 mg/d IV: 0.5-1 mg/dose slowly over 1 min; repeat in 2-4 h	Treatment of renal disease and hypertension and edema associated with HF. Similar effects as furosemide. Pregnancy category: C; PB: 96%; : 1-1.5 h
ethacrynic acid (Edecrin)	A: PO: 50-100 mg/d or b.i.d.; max: 400 mg/d C: PO: 1 mg/kg/d; max: 3 mg/kg/d A: IV: 0.5-1 mg/kg/dose or 50-100 mg/d C: IV: 1 mg/kg once daily	For severe edema (pulmonary and peripheral). Potent diuretic with rapid action. Also used for hypercalcemia. Moderate to high doses may cause ototoxicity. Pregnancy category: B; PB: 95%; : 1-1.5 h
furosemide (Lasix)	See Prototype Drug Chart 43-2.
torsemide (Demadex)	Hypertension: A: PO: Initially: 5 mg/d; maint: PO: 5-10 mg/d; HF: A: PO/IV: 10-20 mg/d; max: 200 mg/d	Similar to furosemide. Pregnancy category: B; PB: 97%-99%; : 2-4 h
Osmotics
mannitol	ICP/IOP: A: IV: Initially 1-2 g/kg followed by 0.25-1 g/kg; 15%-25% sol infused over 30-90 min Edema, ascites, or oliguria: A: IV: 50-100 g; 10%-20% sol infused over 90 min–6 h	For oliguria and decreasing ICP. To prevent acute renal failure. Used in narrow-angle glaucoma for reducing IOP. Patient should have effective renal function. Potent diuretic. Pregnancy category: C; PB: UK; : 15 min–1.5 h
Carbonic Anhydrase Inhibitors
acetazolamide (Diamox)	Glaucoma: A: PO/IV: 250 mg once daily/q.i.d.; max: 1 g/d A: IV: 500 mg, may repeat in 2-4 h; max: 1 g/d A: SR: 500 mg q12h; max: 1000 mg/d Edema: A: PO: IV: 250-375 mg in morning	For edema, treating absence (petit mal) seizures, and open-angle glaucoma. May cause hyperglycemia, hyperuricemia, and hypercalcemia. Metabolic acidosis can result. Pregnancy category: C; PB: 90%; : 10-15 h
methazolamide (Neptazane)	A: PO: 50-100 mg b.i.d./t.i.d.; max: 300 mg/d	Similar to dichlorphenamide. Pregnancy category: C; PB: 50%-60%; : 14 h

A, Adult; b.i.d., twice a day; C, child; d, day; h, hour; HF, heart failure; ICP, intracranial pressure; inf, infusion; IOP, intraocular pressure; IV, intravenous; maint, maintenance dose; max, maximum; min, minute; PB, protein-binding; PO, by mouth; sol, solution; SR, sustained-release; , half-life; t.i.d., three times a day; UK, unknown; y, year; >, greater than.

Osmotic Diuretics

Osmotic diuretics increase the osmolality (concentration) and sodium reabsorption in the proximal tubule and loop of Henle. Sodium, chloride, potassium (to a lesser degree), and water are excreted. This group of drugs is used to prevent kidney failure, to decrease intracranial pressure (ICP) (e.g., in cerebral edema), and to decrease intraocular pressure (IOP) (e.g., in glaucoma). Mannitol is a potent osmotic potassium-wasting diuretic frequently used in emergency situations such as ICP and IOP. In addition, mannitol can be used with cisplatin and carboplatin in cancer chemotherapy to induce a frank diuresis and decreased side effects of treatment.

Mannitol is the most frequently prescribed osmotic diuretic, followed by urea. Diuresis occurs within 1 to 3 hours after IV administration. Table 43-4 describes Mannitol.

Side Effects and Adverse Reactions.

The side effects and adverse reactions of mannitol include fluid and electrolyte imbalance, pulmonary edema from rapid shift of fluids, nausea, vomiting, tachycardia from rapid fluid loss, and acidosis. Crystallization of mannitol in the vial may occur when the drug is exposed to a low temperature. The vial should be warmed to dissolve the crystals. The mannitol solution should not be used for IV infusion if crystals are present and have not been dissolved.

Contraindications.

Mannitol must be given with extreme caution to patients who have heart disease and HF. It should be immediately discontinued if the patient develops HF or renal failure.

Nursing Process

Patient-Centered Collaborative Care

Diuretics: Loop

Assessment

Obtain a history of drugs that are taken daily. Note if patient is taking a drug that may interact with loop diuretic (e.g., alcohol, aminoglycosides, anticoagulants, corticosteroids, lithium, amphotericin B, digitalis). Recognize that furosemide is highly protein-bound and can displace other protein-bound drugs such as warfarin (Coumadin).

Assess vital signs, serum electrolytes, weight, and urine output for baseline levels.

Compare patient's drug dose with recommended dose, and report discrepancy.

Note whether patient is hypersensitive to sulfonamides.

Nursing Diagnoses

Risk for deficient fluid volume related to fluid loss with excessive use of loop diuretics

Risk for electrolyte imbalance (potassium deficit related to excessive use of loop diuretics)

Planning

Patient's edema and/or hypertension will be decreased.

Patient's serum chemistry levels will remain within normal ranges.

Nursing Interventions

Monitor urinary output to determine body fluid gain or loss. Urinary output should be at least 30 mL/h or 600 mL/24 h.

Notify health care provider if urine output does not increase. Severe renal disorder may be present.

Weigh patient to determine fluid loss or gain. A loss of 2.2 lb is equivalent to a fluid loss of 1 L.

Monitor vital signs. Be alert for marked decrease in blood pressure.

Administer IV furosemide slowly; hearing loss may occur if rapidly injected.

Observe for signs and symptoms of hypokalemia (less than 3.5 mEq/L), such as muscle weakness, abdominal distention, leg cramps, and/or cardiac dysrhythmias.

Monitor serum potassium levels, especially when patient is taking digoxin. Hypokalemia enhances action of digitalis, causing digitalis toxicity.

Patient Teaching

General

Advise patient to take furosemide in morning and not in evening to prevent sleep disturbance and nocturia.

Side Effects

Teach patient to rise slowly from lying or sitting to standing to prevent dizziness resulting from fluid loss.

Diet

Suggest taking furosemide with food to avoid nausea.

Cultural Considerations

Respect cultural practices and values. If patient from a different background tells health care provider that she or he does not eat fruits and vegetables, the nurse may have two options: to encourage patient to eat fruits and vegetables or to contact health care provider so that an adequate potassium supplement can be prescribed to overcome potassium loss. An interpreter may be necessary.

Emphasize the importance of patient taking potassium supplement with potassium-wasting diuretic. In addition, advise patient of consequences and dangers of not taking potassium supplements or lacking appropriate nutrition while taking potassium-wasting diuretics.

Evaluation

Evaluate effectiveness of drug action, such as decreased fluid retention or fluid overload, decreased respiratory distress, and increased cardiac output.

Check for side effects and increased urine output.

Carbonic Anhydrase Inhibitors

The carbonic anhydrase inhibitors acetazolamide, dichlorphenamide, ethoxzolamide, and methazolamide block the action of the enzyme carbonic anhydrase, which is needed to maintain the body's acid-base balance (hydrogen and bicarbonate ion balance). Inhibition of this enzyme causes increased sodium, potassium, and bicarbonate excretion. With prolonged use, metabolic acidosis can occur.

This group of drugs is used primarily to decrease IOP in patients with open-angle (chronic) glaucoma. These drugs are not used in narrow-angle or acute glaucoma. Other uses include diuresis, management of epilepsy, and treatment of high-altitude or acute mountain sickness. Table 43-4 presents the drug data for carbonic anhydrase inhibitor diuretics. The drug may also be used for a patient in metabolic alkalosis who needs a diuretic. Carbonic anhydrase inhibitors may be alternated with a loop diuretic.

Side Effects and Adverse Reactions.

Acetazolamide can cause fluid and electrolyte imbalance, metabolic acidosis, nausea, vomiting, anorexia, confusion, orthostatic hypotension, and crystalluria. Hemolytic anemia and renal calculi can also occur. These drugs are contraindicated during the first trimester of pregnancy.

Potassium-Sparing Diuretics

Potassium-sparing diuretics, which are weaker than thiazides and loop diuretics, are used as mild diuretics or in combination with another diuretic (e.g., hydrochlorothiazide, antihypertensive drugs). Continuous use of potassium-wasting diuretics requires a daily oral potassium supplement, because the kidneys excrete potassium, sodium, and body water. However, potassium supplements are not used when the patient takes a potassium-sparing diuretic; in fact, serum potassium excess, called hyperkalemia, results when a potassium supplement is taken with a potassium-sparing diuretic. The serum potassium should be periodically monitored when the patient continuously takes a potassium-sparing diuretic. If the serum potassium level is greater than 5.3 mEq/L, the patient should discontinue the potassium-sparing diuretic and restrict foods high in potassium.

Potassium-sparing diuretics act primarily in the collecting duct renal tubules and late distal tubule to promote sodium and water excretion and potassium retention. The drugs interfere with the sodium-potassium pump controlled by the mineralocorticoid hormone aldosterone (sodium retained and potassium excreted).

Spironolactone (Aldactone), an aldosterone antagonist discovered in 1958, was the first potassium-sparing diuretic. Aldosterone is a mineralocorticoid hormone that promotes sodium retention and potassium excretion. Spironolactone blocks the action of aldosterone and inhibits the sodium-potassium pump (i.e., potassium is retained and sodium is excreted). Spironolactone (Aldactone) has been prescribed by cardiologists for patients with cardiac disorders because of its potassium-retaining effect. As a result of the action of spironolactone, the heart rate is more regular, and the possibility of myocardial fibrosis is decreased. The effects of spironolactone may take 48 hours.

Amiloride (Midamor), triamterene (Dyrenium), and eplerenone (Inspra) are additional commonly prescribed potassium-sparing diuretics. Amiloride and eplerenone are effective as antihypertensive agents. Triamterene is useful in the treatment of edema caused by HF or cirrhosis of the liver. Low doses of spironolactone (Aldactone) and eplerenone are effective for chronic HF. Spironolactone, amiloride, triamterene, and eplerenone should not be taken with ACE inhibitors and angiotensin II receptor blockers (ARBs) because they can also increase serum potassium levels. Prototype Drug Chart 43-3 provides the pharmacologic data for spironolactone.

Prototype Drug Chart 43-3

Spironolactone

Drug Class	Dosage
Potassium-sparing diuretic Trade Name: Aldactone	Edema: A: PO: 25-200 mg/d in divided doses; max: 400 mg/d
Pregnancy Category: C	C: PO: 1.5-3.3 mg/kg/d in divided doses; max: 3.3 mg/kg/d Hypertension: A: PO: 50-100 mg/d; max: 400 mg/d
Contraindications	Drug-Lab-Food Interactions
Severe kidney or hepatic disease, anuria, severe hyperkalemia Caution: Renal or hepatic dysfunction, diabetes mellitus	Drug: Increase serum potassium level with potassium supplements; increase effects of antihypertensives and lithium; life threatening: hyperkalemia if given with ACE inhibitor
	Lab: Increase serum potassium level; may increase BUN, AST, alkaline phosphatase levels; decrease serum sodium, chloride
Pharmacokinetics	Pharmacodynamics
Absorption: PO: Rapidly absorbed from GI tract Distribution: PB: 90% Metabolism: : 1.5-2 h Excretion: In urine, mostly as metabolites and bile	PO: Onset: UK Peak: 2-3 d Duration: 2-3 days or longer
Therapeutic Effects/Uses
To increase urine output; to treat fluid retention/overload associated with HF, hepatic cirrhosis, or nephrotic syndrome
Mode of Action: Acts on distal renal tubules to promote sodium and water excretion and potassium retention
Side Effects	Adverse Reactions
Nausea, vomiting, diarrhea, rash, dizziness, headache, weakness, dry mouth, photosensitivity	Life-threatening: Severe hyperkalemia, thrombocytopenia, megaloblastic anemia

A, Adult; ACE, angiotensin-converting enzyme; AST, aspartate aminotransferase; BUN, blood urea nitrogen; C, child; d, day; GI, gastrointestinal; h, hour; HF, heart failure; PB, protein-binding; p.c., after meals; PO, by mouth; , half-life.

When potassium-sparing diuretics are used alone, they are less effective than when used in combination to reduce body fluid and sodium. These drugs are usually combined with a potassium-wasting diuretic, primarily hydrochlorothiazide or a loop diuretic. The combination of potassium-sparing and potassium-wasting diuretics intensifies the diuretic effect and prevents potassium loss. The common combination diuretics contain spironolactone and hydrochlorothiazide (Aldactazide), amiloride and hydrochlorothiazide (HCTZ), and triamterene and hydrochlorothiazide (Dyazide, Maxzide). Table 43-5 lists the potassium-sparing diuretics and the combination potassium-wasting and potassium-sparing diuretics.

TABLE 43-5

DIURETICS: POTASSIUM-SPARING

GENERIC (BRAND)	ROUTE AND DOSAGE	USES AND CONSIDERATIONS
Single Agents
amiloride HCl (Midamor)	A: PO: 5-10 mg/d; max: 20 mg/d	For diuretic-induced hypokalemia; used for hypertension, HF, and cirrhosis of the liver. Monitor serum potassium level to detect hyperkalemia. Pregnancy category: B; PB: 40%; : 6-9 h
eplerenone (Inspra)	A: PO: 25-50 mg/d; max: 100 mg/d for hypertension; 50 mg/d for HF	For hypertension or chronic HF post MI. Approved in 2002. Also classified as a selective aldosterone receptor blocker. Serum potassium should be monitored to detect hyperkalemia. Pregnancy category: B ; PB: 50%; : 4-6 h
spironolactone (Aldactone)	See Prototype Drug Chart 43-3.
triamterene (Dyrenium)	A: PO: Initially 50-100 mg b.i.d.; max: 300 mg/d	For edema and hypokalemia. May increase excretion of magnesium. May cause severe hyperkalemia with resultant life-threatening cardiac dysrhythmias. Pregnancy category: C; PB: 67%; : 1-2 h
Combinations
amiloride HCl and hydrochlorothiazide (Moduretic)	A: PO: 1-2 tab (amiloride 5 mg/hydrochlorothiazide 50 mg)	Combinations contain potassium-wasting and potassium-sparing diuretics. Drugs are to control hypertension and edema. They are used to prevent the occurrence of hypokalemia.
spironolactone and hydrochlorothiazide (Aldactazide)	A: PO: 1 tab (25 mg spironolactone/25 mg HCTZ); max: 200 mg/d of each	Same as Moduretic
triamterene and hydrochlorothiazide (Dyazide, Maxzide)	A: PO: 1-2 cap p.c. (triamterene 37.5 mg/hydrochlorothiazide 25 mg)	Same as Moduretic

A, Adult; b.i.d., twice a day; C, child; cap, capsule; d, day; h, hour; HF, heart failure; MI, myocardial infarction; PB, protein-binding; p.c., after meals; PO, by mouth; , half-life; tab, tablet; UK, unknown.

Side Effects and Adverse Reactions.

The main side effect of these drugs is hyperkalemia. Caution must be used when giving potassium-sparing diuretics to a patient with poor renal function, because the kidneys excrete 80% to 90% of potassium. Urine output should be at least 600 mL/day. Patients should not use potassium supplements while taking potassium-sparing diuretics, unless the serum potassium level is low. If a potassium-sparing diuretic is given with antihypertensive ACE inhibitors, hyperkalemia could become severe or life threatening, because both drugs retain potassium. Monitoring serum potassium levels is essential to safe drug therapy. GI disturbances (anorexia, nausea, vomiting, diarrhea, and numbness and tingling of the hands and feet) can occur.

Nursing Process

Patient-Centered Collaborative Care