Long-term use of diuretics results in a fall in systemic vascular resistance by unknown mechanisms that helps to sustain the reduction in arterial pressure.
Antihypertensive therapy with diuretics is particularly effective when coupled with reduced dietary sodium intake. The efficacy of these drugs is derived from their ability to reduce blood volume, cardiac output, and with long-term therapy, systemic vascular resistance.
Thiazide diuretics, particularly chlorthalidone, are considered "first-line therapy" for stage 1 hypertension. Potassium-sparing, aldosterone-blocking diuretics e. Heart failure leads to activation of the renin-angiotensin-aldosterone system, which causes increased sodium and water retention by the kidneys. This in turn increases blood volume and contributes to the elevated venous pressures associated with heart failure, which can lead to pulmonary and systemic edema.
Long-term treatment with diuretics may also reduce the afterload on the heart by promoting systemic vasodilation, which can lead to improved ventricular ejection.
When treating heart failure with diuretics, care must be taken to not unload too much volume because this can depress cardiac output. For example, if pulmonary capillary wedge pressure is 25 mmHg point A in figure and pulmonary congestion is present, a diuretic can safely reduce that elevated pressure to a level e.
The reason for this is that heart failure caused by systolic dysfunction is associated with a depressed, flattened Frank-Starling curve. However, if the volume is reduced too much, stroke volume will fall because the heart will now be operating on the ascending limb of the Frank-Starling relationship. If the heart failure is caused by diastolic dysfunction , diuretics must be used very carefully so as to not impair ventricular filling.
In diastolic dysfunction, ventricular filling requires elevated filling pressures because of the reduced ventricular compliance. Most patients in heart failure are prescribed a loop diuretic because they are more effective in unloading sodium and water than thiazide diuretics. In mild heart failure, a thiazide diuretic may be used. Capillary hydrostatic pressure and therefore capillary fluid filtration is strongly influenced by venous pressure click here for more details.
Therefore, diuretics, by reducing blood volume and venous pressure, lower capillary hydrostatic pressure, which reduces net capillary fluid filtration and tissue edema. Because left ventricular failure can cause life-threatening pulmonary edema, most heart failure patients are treated with a loop diuretic to prevent or reduce pulmonary edema. Diuretics may also be used to treat leg edema caused by right-sided heart failure or venous insufficiency in the limb.
Specific drugs comprising the five class of diuretics are listed in the following table. The peak effect occurs within the first or second hour. The duration of diuretic effect is 6 to 8 hours. When possible, loop diuretics should be administered in the morning, and evening doses should be avoided unless urgent so that sleep is not disturbed.
Nurses should continually monitor for dehydration and electrolyte imbalances that can occur with excessive diuresis, such as dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, arrhythmia, or gastrointestinal disturbances such as nausea and vomiting. Use cautiously in the geriatric population who have decreased renal function. Kidney function should be monitored closely for all patients because this is a potent medication that works within the kidney tubules.
Monitor the patient closely for hypokalemia if furosemide is used concomitantly with digoxin. Hypokalemia may increase the risk of digoxin toxicity. Adverse effects include dehydration, hypotension, and electrolyte imbalances such as hypokalemia. If using IV route, the administration must be given slowly to reduce the risk of the patient developing ototoxicity. Advise patients to change position slowly as they may experience orthostatic changes. Patients should also report weight gain of more than three pounds in a day to their healthcare provider.
Patients should also be encouraged to enjoy potassium-rich foods during loop diuretic drug therapy. Subclass Prototype-. Monitor weight Based on indication; decreased blood pressure or edema Dehydration. Smith is a year-old widow who has lived alone for the past 5 years. Three years ago she was hospitalized for an MI, which resulted in heart failure.
She is compliant with her medications, which include digoxin Lanoxin 0. Recently Mrs. She has not taken her potassium for a week.
Publication types English Abstract Review. Substances Antihypertensive Agents Diuretics Vasopressins. Her baseline creatinine was normal.
Ten days later, the patient presented to the emergency department ED with 3 days of worsening somnolence and confusion. She had a seizure in the ED, which was treated with lorazepam, and she was admitted to the intensive care unit. The critical care provider consulted a nephrologist, and both agreed the severe symptomatic hyponatremia and hypokalemia had been caused by the chlorthalidone.
She had gradual improvement in her serum sodium and mental status over the next few days, and she was discharged home on hospital day 5. This case illustrates how a commonly used medicine can lead to severe adverse events when not used judiciously and cautiously, especially in vulnerable patients.
Specifically, the case highlights some of the risks associated with diuretics. Chlorthalidone is a member of the class of thiazide diuretics, which are among the most widely used, effective, and least costly medications available.
Thiazides are first-line antihypertensives 1 , with all-cause mortality benefits equivalent to angiotensin-converting enzyme inhibitors or calcium channel antagonists. Other adverse effects include hypokalemia, hypomagnesemia, and hypercalcemia. Thiazide diuretics are one of the most common causes of hyponatremia. Thiazide diuretics act by reducing reabsorption of sodium and chloride in the distal renal tubules, which causes excretion of sodium in excess of water hypertonic urine. Loop diuretics therefore do not cause hyponatremia, and in fact may cause hypernatremia when water losses are not sufficiently replaced.
The hyponatremia that is occasionally observed under treatment with loop diuretics is usually due to the conditions they are commonly used to treat, namely heart failure and ascites.
Thiazides can help reduce water retention in patients with mild congestive heart failure loop diuretics are indicated in case of more severe symptoms , and worsening heart failure was a possible cause of the pitting edema of the bilateral lower extremities observed in this year-old woman. Her edema also worsened over the course of weeks, whereas symptoms generally appear more suddenly when edema is caused by heart failure exacerbation or deep vein thrombosis.
Therefore, it appears likely that her increasing pitting edema was due to a more benign cause such as worsening venous insufficiency. The effectiveness of thiazide diuretics, or any diuretics for that matter, in treating edema of causes other than heart failure, liver disease, or renal disease is poor, and their adverse effects usually outweigh any benefits.
However, the patient should be monitored closely, and diuretic treatment should be stopped if weight loss or a clear reduction in the swelling does not occur over the course of several days. Nevertheless, thiazide diuretics remain a valuable therapeutic option in treating hypertension, and most patients do not develop hyponatremia. In fact, patients treated with thiazides generally don't experience meaningfully altered serum sodium concentrations.
However, certain individuals may be particularly susceptible 2 , and a growing body of research has identified risk factors. In addition, a genetic predisposition is likely, given a high degree of reproducibility of hyponatremia on single-dose thiazide rechallenge.
Given that this patient had several nonmodifiable risk factors female gender, heart failure, diabetes, and prior history of hyponatremia , starting treatment with a dose of 50 mg chlorthalidone was not a wise choice. For the treatment of hypertension, Either of these doses would also have been more appropriate if the chlorthalidone had been prescribed for her edema.
In susceptible individuals, hyponatremia can develop rapidly after the initiation, and measuring sodium levels on the day of initiation and soon thereafter may have prevented the severe course of hyponatremia experienced by this woman. Evidence-based guidelines to prevent thiazide-induced hyponatremia are lacking, so it is natural to be influenced by hindsight bias after hearing about a case like this one. However, several reasonable preventive steps have been recommended although based on limited evidence 5 : i avoid thiazides in patients with a history of thiazide-induced hyponatremia; ii start with a low dose; iii counsel patients on the risk of excessive fluid intake; iv consider monitoring urea and electrolytes within 1—2 weeks after initiation in high-risk patients; and iv monitor electrolytes periodically thereafter.
In addition, electronic health records EHRs could be harnessed to improve safe prescribing. The EHR could highlight risk factors for hyponatremia at the point of thiazide prescription, remind providers that thiazides cause hyponatremia, and notify providers when routine monitoring has been missed.
Faculty Disclosure: Dr. Dreischulte has declared that neither he, nor any immediate member of his family, has a financial arrangement or other relationship with the manufacturers of any commercial products discussed in this continuing medical education activity. In addition, the commentary does not include information regarding investigational or off-label use of pharmaceutical products or medical devices.
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