(which contain potassium chloride), or another potassium- sparing diuretic. In addition, three groups of drugs—angiotensin- converting enzyme (ACE) inhibitors, angiotensin receptor blockers, and direct renin inhibitors—can elevate potassium levels (by suppressing aldosterone secretion), and hence should be combined with spironolactone only when clearly necessary.
Preparations, Dosage, and Administration
Spironolactone [Aldactone] is dispensed in tablets (25, 50, and 100 mg) for oral dosing. The usual adult dosage is 25 to 100 mg/day. Spironolactone is also marketed in a fixed-dose combination with hydrochlorothiazide under the brand name Aldactazide.
Safe Handling and Administration. In 2016, the National Institute for Occupational Safety and Health (NIOSH), a division of the Centers for Disease Control and Prevention, published a list of drugs considered to be potentially hazardous in healthcare settings. Spironolactone was included in this list secondary to its potential to cause fetal harm. Exposure to these drugs can pose a reproductive risk to healthcare workers who administer these drugs.
To promote safe administration, NIOSH suggests donning a protective gown and two sets of gloves when cutting or crushing tablets. For further information on this report, visit https://www.cdc.gov/niosh/topics/antineoplastic/pdf/
hazardous-drugs-list_2016-161.pdf.
Triamterene
Mechanism of Action
Like spironolactone, triamterene [Dyrenium] disrupts sodium- potassium exchange in the distal nephron. However, in contrast to spironolactone, which reduces ion transport indirectly through blockade of aldosterone, triamterene is a direct inhibitor of the exchange mechanism itself. The net effect of inhibition is antagonists—triamterene and amiloride—are currently
employed.
Spironolactone
Mechanism of Action
Spironolactone [Aldactone] blocks the actions of aldosterone in the distal nephron. Since aldosterone acts to promote sodium uptake in exchange for potassium secretion (see Fig. 41.2), inhibition of aldosterone has the opposite effect: retention of potassium and increased excretion of sodium. The diuresis caused by spironolactone is scanty because most of the filtered sodium load has already been reabsorbed by the time the filtrate reaches the distal nephron. (Recall that the degree of diuresis a drug produces is directly proportional to the amount of sodium reuptake that it blocks.)
The effects of spironolactone are delayed, taking up to 48 hours to develop (Table 41.3). Recall that aldosterone acts by stimulating cells of the distal nephron to synthesize the proteins required for sodium and potassium transport. By preventing aldosterone’s action, spironolactone blocks the synthesis of new proteins, but does not stop existing transport proteins from doing their job. Therefore, effects are not visible until the existing proteins complete their normal life cycle—a process that takes 1 or 2 days.
Therapeutic Uses
Hypertension and Edema. Spironolactone is used primar- ily for hypertension and edema. Although it can be employed alone, the drug is used most commonly in combination with a thiazide or loop diuretic. The purpose of spironolactone in these combinations is to counteract the potassium-wasting effects of the more powerful diuretics. Spironolactone also makes a small contribution to diuresis.
Heart Failure. In patients with severe heart failure, spi- ronolactone reduces mortality and hospital admissions. Benefits derive from protective effects of aldosterone blockade in the heart and blood vessels (see Chapter 48).
Other Uses. In addition to the applications already discussed, spirono- lactone can be used for primary hyperaldosteronism (see Chapter 60), pre- menstrual syndrome (see Chapter 61), polycystic ovary syndrome (see Chapter 63), and acne in young women (see Chapter 105).
Adverse Effects
Hyperkalemia. The potassium-sparing effects of spi- ronolactone can result in hyperkalemia, a condition that can produce fatal dysrhythmias. Although hyperkalemia is most likely when spironolactone is used alone, it can also develop when spironolactone is used in conjunction with potassium- wasting agents (thiazides and loop diuretics). If serum potassium rises above 5 mEq/L or if signs of hyperkalemia develop (e.g.,
Generic Name Brand Name
Time Course
Usual Adult Dosage (mg/day) Onset (hr) Duration (hr)
Spironolactone Aldactone 24–48 48–72 25–200
Triamterene Dyrenium 2–4 12–16 50–300
Amiloride Midamor 2 24 5–20
TABLE 41.3 ■ Potassium-Sparing Diuretics: Names, Dosages, and Time Course of Effects
• Undergoes minimal metabolism.
• Is pharmacologically inert (i.e., it has no direct effects on the bio- chemistry or physiology of cells).
Following IV administration, mannitol is filtered by the glomerulus. However, unlike other solutes, the drug undergoes minimal reabsorption. As a result, most of the filtered drug remains in the nephron, creating an osmotic force that inhibits passive reabsorption of water. Hence, urine flow increases.
The degree of diuresis produced is directly related to the concentration of mannitol in the filtrate: The more mannitol present, the greater the diuresis.
Mannitol has no significant effect on the excretion of potassium and other electrolytes.
Pharmacokinetics
Mannitol does not diffuse across the GI epithelium and cannot be transported by the uptake systems that absorb dietary sugars. Accordingly, to reach the circulation, the drug must be given parenterally. Following IV injection, mannitol distributes freely to extracellular water. Diuresis begins in 30 to 60 minutes and persists 6 to 8 hours. Most of the drug is excreted intact in the urine.
Therapeutic Uses
Prophylaxis of Renal Failure. Under certain conditions (e.g., dehydra- tion, severe hypotension, hypovolemic shock), blood flow to the kidney is decreased, causing a great reduction in filtrate volume. When the volume of filtrate is this low, transport mechanisms of the nephron are able to reabsorb virtually all of the sodium and chloride present, causing complete reabsorption of water as well. As a result, urine production ceases, and kidney failure ensues. The risk of renal failure can be reduced with mannitol. Here’s how.
Because filtered mannitol is not reabsorbed—even when filtrate volume is small—filtered mannitol will remain in the nephron, drawing water with it. Hence, mannitol can preserve urine flow and may thereby prevent renal failure. Thiazides and loop diuretics are not as effective for this applica- tion because, under conditions of low filtrate production, there is such an excess of reabsorptive capacity (relative to the amount of filtrate) that these drugs are unable to produce sufficient blockade of reabsorption to promote diuresis.
Reduction of Intracranial Pressure. Intracranial pressure (ICP) that has been elevated by cerebral edema can be reduced with mannitol. The drug lowers ICP because its presence in the blood vessels of the brain creates an osmotic force that draws edematous fluid from the brain into the blood. There is no risk of increasing cerebral edema because mannitol cannot exit the capillary beds of the brain.
Reduction of Intraocular Pressure. Mannitol and other osmotic agents can lower IOP by rendering the plasma hyperosmotic with respect to intraocular fluids. The hyperosmotic plasma creates an osmotic force that draws ocular fluid into the blood. Use of mannitol to lower IOP is reserved for patients who have not responded to more conventional treatment.
Adverse Effects
Edema. Mannitol can leave the vascular system at all capillary beds except those of the brain. When the drug exits capillaries, it draws water along, causing edema. Mannitol must be used with extreme caution in patients with heart disease, since it may precipitate CHF and pulmonary edema. If signs of pulmonary congestion or CHF develop, use of the drug must cease immediately. Mannitol must also be discontinued if patients with heart failure or pulmonary edema develop renal failure, because the resultant accumulation of mannitol would increase the risk of cardiac or pulmonary injury.
Other Adverse Effects. Common responses include headache, nausea, and vomiting. Fluid and electrolyte imbalance may also occur.
Preparations, Dosage, and Administration
Mannitol [Osmitrol] is administered by IV infusion. Solutions for IV use range in concentration from 5% to 25%. Dosing is complex and varies with the objective of therapy (prevention of renal failure, lowering of ICP, lowering of IOP). The usual adult dosage for preventing renal failure is 50 to 100 gm over 24 hours. The infusion rate should be set to elicit a urine flow of at least 30 to 50 mL/hr. It should be noted that mannitol may crystallize out of solution if exposed to low temperature. Accordingly, preparations should be observed for crystals before use. Preparations that contain crystals should be warmed (to redissolve the mannitol) and then cooled to body temperature for administra- tion. A filter needle is employed to withdraw mannitol from the vial, and an in-line filter is used to prevent crystals from entering the circulation. If urine flow declines to a very low rate or ceases entirely, the infusion should be stopped.
a decrease in sodium reabsorption and a reduction in potassium secretion. Hence, sodium excretion is increased, while potassium is conserved. Because it inhibits ion transport directly, triam- terene acts much more quickly than spironolactone. Initial responses develop in hours, compared with days for spirono- lactone. As with spironolactone, diuresis with triamterene is minimal.
Therapeutic Uses
Triamterene can be used alone or in combination with other diuretics to treat hypertension and edema. When used alone, triamterene produces mild diuresis. When combined with other diuretics (e.g., furosemide, hydrochlorothiazide), triamterene augments diuresis and helps counteract the potassium-wasting effects of the more powerful diuretic. It is the latter effect for which triamterene is principally employed.
Adverse Effects
Hyperkalemia. Excessive potassium accumulation is the most significant adverse effect. Hyperkalemia is most likely when triamterene is used alone, but can also occur when the drug is combined with thiazides or loop diuretics. Caution should be employed when triamterene is used in conjunction with another potassium-sparing diuretic or with potassium supplements or salt substitutes. In addition, caution is needed if the drug is combined with an ACE inhibitor, angiotensin receptor blocker, or direct renin inhibitor.
Other Adverse Effects. Relatively common side effects include nausea, vomiting, leg cramps, and dizziness. Blood dyscrasias occur rarely.
Preparations, Dosage, and Administration
Triamterene [Dyrenium] is available in 50- and 100-mg capsules for oral use.
The usual initial dosage is 100 mg twice a day. The maximum dosage is 300 mg/day. Triamterene is also marketed in fixed-dose combinations with hydrochlorothiazide under the brand names Dyazide and Maxzide.
Amiloride
Pharmacologic Properties
Amiloride has actions similar to those of triamterene. Both drugs inhibit potassium loss by direct blockade of sodium-potassium exchange in the distal nephron. Also, both drugs produce only modest diuresis. Although it can be employed alone as a diuretic, amiloride is used primarily to counteract potassium loss caused by more powerful diuretics (thiazides, loop diuretics). The major adverse effect is hyperkalemia. Accordingly, concurrent use of other potassium- sparing diuretics or potassium supplements must be monitored closely. Caution is needed if the drug is combined with an ACE inhibitor, angiotensin receptor blocker, or direct renin inhibitor.
Preparations, Dosage, and Administration
Amiloride is supplied in 5-mg tablets for oral use. Dosing is begun at 5 mg/
day and may be increased to a maximum of 20 mg/day. Amiloride is available in a fixed-dose combination with hydrochlorothiazide.
MANNITOL: AN OSMOTIC DIURETIC
Osmotic diuretics differ from other diuretics with regard to mechanism and uses. At this time, mannitol is the only osmotic diuretic available in the United States. Three related drugs—urea, glycerin, and isosorbide—have been withdrawn.
Mechanism of Diuretic Action
Mannitol [Osmitrol] is a simple six-carbon sugar that embodies the four properties of an ideal osmotic diuretic. Specifically, the drug:
• Is freely filtered at the glomerulus.
• Undergoes minimal tubular reabsorption.
KEY POINTS
■ More than 99% of the water, electrolytes, and nutrients that are filtered at the glomerulus undergo reabsorption.
■ Most diuretics block active reabsorption of sodium and chloride, and thereby prevent passive reabsorption of water.
■ The amount of diuresis produced is directly related to the amount of sodium and chloride reabsorption blocked.
■ Drugs that act early in the nephron are in a position to block the greatest amount of solute reabsorption, and hence produce the greatest diuresis.
■ Loop diuretics block sodium and chloride reabsorption in the loop of Henle.
■ Loop diuretics produce the greatest diuresis.
■ In contrast to thiazide diuretics, loop diuretics are effective even when the glomerular filtration rate is low.
■ Loop diuretics can cause dehydration through excessive fluid loss.
■ Loop diuretics can cause hypotension by decreasing blood volume and relaxing venous smooth muscle.
■ Loop diuretics can cause hearing loss which, fortunately, is usually reversible.
■ Hypokalemia caused by loop diuretics is a special problem for patients taking digoxin.
■ Thiazide diuretics block sodium and water reabsorption in the early distal convoluted tubule.
■ Thiazide diuretics produce less diuresis than loop diuretics.
■ Thiazide diuretics are ineffective when glomerular filtration rate is low.
■ Like the loop diuretics, thiazide diuretics can cause dehydra- tion and hypokalemia. However, thiazides do not cause hearing loss.
■ Thiazide-induced hypokalemia is a special problem for patients taking digoxin.
■ Potassium-sparing diuretics act by directly or indirectly blocking sodium-potassium “exchange” in the distal convoluted tubule.
■ Potassium-sparing diuretics cause only modest diuresis.
■ Potassium-sparing diuretics are used primarily to counteract potassium loss in patients taking loop diuretics or thiazides.
■ The principal adverse effect of potassium-sparing diuretics is hyperkalemia.
■ Because of the risk of hyperkalemia, use caution when combining potassium-sparing diuretics with one another or with potassium supplements, and in patients taking ACE inhibitors, angiotensin receptor blockers, or direct renin inhibitors.
■ Loop diuretics and thiazides are used to treat hypertension and edema associated with heart failure, cirrhosis, and kidney disease.
Please visit http://evolve.elsevier.com/Lehne for chapter- specific NCLEX® examination review questions.
Summary of Major Nursing Implications
aLOOP DIURETICS Bumetanide
Ethacrynic acid Furosemide Torsemide
Preadministration Assessment Therapeutic Goal
Loop diuretics are indicated for patients with (1) pulmonary edema associated with congestive heart failure; (2) edema of hepatic, cardiac, or renal origin that has been unresponsive to less effective diuretics; (3) hypertension that cannot be controlled with thiazide and potassium-sparing diuretics; and (4) all patients who need diuretic therapy but have low renal blood flow.
Baseline Data
For all patients, obtain baseline values for weight, blood pressure (sitting and supine), pulse, respiration, and electrolytes (sodium, potassium, chloride). For patients with edema, record sites and extent of edema. For patients with ascites, measure abdominal girth. For acutely ill patients (e.g., severe CHF), assess lung sounds.
Identifying High-Risk Patients
Use with caution in patients with cardiovascular disease, renal impairment, diabetes mellitus, or a history of gout, and in patients who are pregnant or taking digoxin, lithium, ototoxic drugs, NSAIDs, or antihypertensive drugs.
Implementation: Administration Routes
Furosemide and Bumetanide. Oral, IV, IM.
Ethacrynic Acid and Torsemide. Oral, IV.
Administration
Oral. Dosing may be done once daily, twice daily, or on alternate days. Instruct patients who are using once-a-day or alternate-day dosing to take their medication in the morning. Instruct patients using twice-a-day dosing to take their medication at 8:00 AM and 2:00 PM (to minimize nocturia).
Advise patients to administer furosemide with food if GI upset occurs.
Parenteral. Administer IV injections slowly (over 1 to 2 minutes). For high-dose therapy, administer by continuous infusion. Discard discolored solutions.
Promoting Adherence
Increased frequency of urination is inconvenient and can discourage adherence. To promote adherence, inform patients that treatment will increase urine volume and frequency of voiding, and that these effects will subside 6 to 8 hours after dosing. Inform patients that nighttime diuresis can be mini- mized by avoiding dosing late in the day.
Ongoing Evaluation and Interventions Evaluating Therapeutic Effects
Monitor blood pressure and pulse rate, weigh the patient daily, and evaluate for decreased edema.
Monitor intake and output. Notify the prescriber if oliguria (urine output less than 25 mL/hr) or anuria (no urine output) develops.
Instruct outpatients to weigh themselves daily (using the same scale), preferably in the morning before eating. Also, instruct them to maintain a weight record and to report excessive weight gain or loss.
In acute conditions requiring rapid diuresis and careful monitoring, a Foley catheter may be used. The catheter should be emptied before drug injection, and output should be monitored hourly and recorded.
Minimizing Adverse Effects
Hyponatremia, Hypochloremia, and Dehydration.
Loss of sodium, chloride, and water can cause hyponatremia, hypochloremia, and severe dehydration. Signs of dehydration include dry mouth, unusual thirst, and oliguria. Withhold the drug if these appear.
Dehydration can promote thromboembolism. Monitor the patient for symptoms (headache; pain in the chest, calves, or pelvis), and notify the prescriber if these develop.
The risk of dehydration and its sequelae can be minimized by (1) initiating therapy with low doses, (2) adjusting the dosage carefully, (3) monitoring weight loss daily, and (4) using an intermittent dosing schedule.
Hypotension. Monitor blood pressure. If it falls precipi- tously, withhold medication and notify the prescriber.
Teach patients to monitor their blood pressure, and instruct them to notify the prescriber if it drops substantially.
Inform patients about signs of postural hypotension (diz- ziness, light-headedness), and advise them to sit or lie down if these occur. Inform patients that postural hypotension can be minimized by rising slowly and by dangling legs off the bed before standing.
Hypokalemia. If serum potassium falls below 3.5 mEq/L, fatal dysrhythmias may result. Hypokalemia can be minimized by consuming potassium-rich foods (e.g., nuts, dried fruits, spinach, citrus fruits, potatoes, bananas), taking potassium supplements, or using a potassium-sparing diuretic. Teach
patients the signs and symptoms of hypokalemia (e.g., irregular heartbeat, muscle weakness, cramping, flaccid paralysis, leg discomfort, extreme thirst, confusion), and stress the importance of showing up for regular blood tests.
Ototoxicity. Inform patients about possible hearing loss and instruct them to notify the prescriber if a hearing
deficit develops. Exercise caution when loop diuretics are used concurrently with other ototoxic drugs, especially aminoglycosides.
Hyperglycemia. Loop diuretics may elevate blood glucose levels in diabetic patients. Advise these patients to be especially diligent about monitoring blood glucose.
Hyperuricemia. Loop diuretics frequently cause asymp- tomatic hyperuricemia, although gout-prone patients may experience a gouty attack. Inform patients about signs of gout (tenderness or swelling in joints), and instruct them to notify the prescriber if these occur.
Minimizing Adverse Interactions
Digoxin. By lowering potassium levels, loop diuretics increase the risk of fatal dysrhythmias from digoxin. Serum potassium levels must be monitored and maintained above 3.5 mEq/L.
Lithium. Loop diuretics can suppress lithium excretion, thereby causing the drug to accumulate, possibly to toxic levels. Plasma lithium should be monitored routinely. If drug levels become elevated, lithium dosage should be reduced.
Ototoxic Drugs. The risk of hearing loss from loop diuretics is increased in the presence of other ototoxic drugs, especially aminoglycosides. Exercise caution when such combinations are employed.
THIAZIDES AND RELATED DIURETICS Chlorothiazide
Chlorthalidone Hydrochlorothiazide Indapamide
Methyclothiazide Metolazone
Thiazide diuretics have actions much like those of the loop diuretics. Hence, nursing implications for the thiazides are nearly identical to those of the loop diuretics.
Preadministration Assessment Therapeutic Goal
Thiazide diuretics are indicated for hypertension and edema.
Baseline Data
For all patients, obtain baseline values for weight, blood pressure (sitting and supine), pulse, respiration, and electrolytes (sodium, chloride, potassium). For patients with edema, record sites and extent of edema.
Identifying High-Risk Patients
Use with caution in patients with cardiovascular disease, renal impairment, diabetes mellitus, or a history of gout and in patients taking digoxin, lithium, or antihypertensive drugs.
Implementation: Administration Routes
Oral. All thiazide-type diuretics.
Intravenous. Chlorothiazide.
Summary of Major Nursing Implications
a—cont’d
Continued