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• W2049666572 abstract "An 84-year-old woman was referred to the hypertension clinic for management of refractory hypertension marked by medication intolerance. Onset of hypertension was at approximately age 78. Four years before this referral she was hospitalized for syncope with a heart rate in the 40s and a serum sodium of 127 while taking hydrochlorothiazide and atenolol. A reduced dose of atenolol was poorly tolerated due to dizziness and unsteadiness. Lisinopril caused dry mouth and cough, and clonidine was also discontinued because of a dry mouth. Both nifedipine and felodipine, each tried as monotherapy, caused intolerable leg swelling. She was started on losartan which was well tolerated up to 100 mg daily, but her systolic blood pressure (BP) remained greater than 180 mm Hg at the office and at home. The patient had a body mass index of 22; her weight was 121 lb. Sitting BP in both arms was 182/74 mm Hg; standing BP in the right arm was 178/82 mm Hg. Cardiac examination revealed a grade 2/6 early peaking systolic murmur in the aortic area. There were no carotid or femoral bruits, and pedal pulses were intact. Edema was absent. The patient lived independently. Past medical history was remarkable only for controlled hyperthyroidism on methimazole and osteoporosis taking alendronate. She had no complaints. Baseline laboratory studies revealed serum sodium 136 mEq/dL (normal 135–145 mEq/dL), potassium 4.5 mEq/dL (normal 3.5–4.5 mEq/dL), blood urea nitrogen (BUN) 26 mg/dL (normal <19 mg/dL), creatinine 1.1 mg/dL (normal 0.6–1.1 mg/dL), estimated glomerular filtration rate (eGFR) 47 cc/min (normal >89 cc/min), fasting glucose 97 mg/dL (normal 70–99 mg/d), total cholesterol 142 mg/dL (normal <200 mg/dL), uric acid 4.5 mg/dL (normal 2.7–6.6 mg/dL), and thyroid stimulating hormone (TSH) 1.63 µIU/mL (normal 0.4–4.0 µIU/mL). An echocardiogram revealed mild aortic stenosis, mild concentric left ventricular hypertrophy, and a left ventricular ejection fraction of 70%. She was prescribed furosemide 10 mg daily but became fatigued and stopped it within 2 weeks. Spironolactone 25 mg daily was added to losartan, which was reduced to 50 mg daily, and the patient felt well with home and office systolic BPs decreasing to the 120s; a follow-up serum sodium of 132 mEq/dL was noted. She was asked to stop the spironolactone; sodium was 135 mEq/dL. A week later a home BP was 218/128 mm Hg and she restarted spironolactone 25 mg BID on her own, reducing her dosage to 25 mg daily a few days later when her home BPs responded. Her home BP machine was found to be accurate. Despite the BP reducing efficacy of spironolactone, hyponatremia returned within a week and then stabilized over 4 months with sodiums of 133, 128, 130, and 131 mEq/dL. Serum potassiums were 4.4, 4.6, 4.7, and 4.6 mEq/dL with consistent creatinines of 1.1 and eGFRs of 47 cc/min. The patient felt well on losartan 50 mg and spironolactone 25 mg daily. She was asked to stop the spironolactone and start long acting diltiazem 120 mg daily. Her serum sodium was 135 mEq/dL, but systolic pressures rose above 180 mm Hg. Diltiazem was discontinued because of fatigue, and spironolactone was resumed by the patient with return of controlled BP but a decrease in serum sodium. She was asked to stop spironolactone again and try to control BP with amlodipine 2.5 mg and losartan; edema recurred and she restarted spironolactone. The course of her BP and serum sodium and potassium response on and off spironolactone is summarized in Table I. The patient repeatedly denied increased thirst or water drinking. Additional laboratory summarized in Table II was obtained to characterize the recurrent hyponatremia and showed adaptation to early-onset volume depletion. The patient has continued to feel well with controlled BP maintained on losartan 50 mg and spironolactone 25 mg daily. This elderly woman had medication intolerances to hydrochlorothiazide, furosemide, atenolol, lisinopril, clonidine, nifedipine, amlodipine, felodipine, nifedipine, and diltiazem, but tolerated an angiotensin receptor blocker (ARB), losartan, as well as spironolactone. Excellent BP reduction has been reported with low dose add-on spironolactone in the absence of hyperaldosteronism in small studies of 23 and 42 patients.1,2 The systolic BP reduction in these studies has been in excess of 20 mm Hg (Figure 1).2 A retrospective analysis has shown BP reduction of 23.2/12.5 mm Hg with spironolactone as add-on therapy. This is significantly greater than other agents tested which reduced BP by 7.6/5.8 mm Hg.3 In the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), a subset of 1411 patients was prescribed spironolactone as a fourth line agent with a mean BP reduction of 22/10 mm Hg4 (Figure 2). Success with spironolactone may occasionally be related to the presence of relatively increased aldosterone levels in association with sleep apnea5 or obesity; adipose tissue produces angiotensinogen and fatty acids stimulate aldosterone.6 However, this woman had a normal weight with a BMI of 22. A mean BP decrease more than 50/10 mm Hg was noted on four occasions when spironolactone was added to existing therapy. Spironolactone-induced reduction in systolic blood pressure (BP) and diastolic BP at 6 weeks, 3 months, and 6 months follow-up in subjects with resistant hypertension. Significant systolic BP reduction exceeding 20 mm Hg is demonstrated. Reprinted with permission from Nishizaka et al.2 Mean blood pressure (BP) before and during spironolactone treatment in 1411 Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) patients when spironolactone was used as the fourth drug. Significant systolic BP (SBP) reduction in excess of 20 mm Hg is demonstrated. CL indicates confidence limit; DBP, diastolic blood pressure. Reprinted with permission from Chapman et al.4 This patient exhibited hyponatremia following hydrochlorothiazide with serum sodium decreasing to 127 mEq/dL approximately 10 days following the use of this medication. Her hospitalization for syncope was explained by bradycardia secondary to atenolol given the fact that a serum sodium of 128 mEq/dL was later well tolerated with spironolactone. In the Systolic Hypertension in the Elderly Program (SHEP), 4.1% of patients age 60 and over had at least one serum sodium ≤130 mEq/dL on chlorthalidone.7 Female gender is generally recognized as a risk factor for thiazide-related hyponatremia,8–11 especially, as in the present case, in women with low body weight who are more likely to suffer volume retraction.11 Patients older than 70 are 3.87 times more likely to become hyponatremic on thiazides than those under age 70.12 In the majority of cases, thiazide-induced hyponatremia occurs within 2 weeks of beginning therapy.12–14 Polydipsia with a reduction in serum osmolality and impaired water excretion has been observed as a first-dose effect in susceptible individuals.15 Certainly this case, with female gender, age >75, and a relatively low body weight, had all the recognized risk factors for the thiazide-related syndrome of inappropriate antidiuretic hormone (SIADH). Other common drug-related causes of hyponatremia including nonsteroidal agents (NSAIDs) and selective serotonin reuptake inhibitors (SSRIs)16 were not present. Spironolactone-related hyponatremia has been described in at least 2 scenarios: treatment of heart failure, as well as resistant hypertension unrelated to hyperaldosteronism. Spironolactone is commonly used in heart failure and cirrhosis, fluid overload conditions where dilutional hyponatremia is representative of decompensated underlying disease. In heart failure, spironolactone is almost always used in conjunction with loop diuretics, and hyponatremia in this situation has been attributed to an excessive natriuretic response to spironolactone.17 Reports have been variable. Seven of 1037 (6%) patients in one heart failure clinic, 90% of whom were taking a loop diuretic, experienced hyponatremia with spironolactone18; 32 of 110 (31%) patients, 90% of whom were taking a loop diuretic, had hyponatremia with spironolactone in another heart failure study.19 The ASCOT experience with spironolactone in patients with resistant hypertension showed a significant decrease in serum sodium, though the difference was small: 138 mEq/L compared with 140 mEq/L.4Table III lists the metabolic effects of spironolactone in ASCOT. Spironolactone-induced impairment of aldosterone-mediated renal sodium resorption has been described in an elderly woman.20 Spironolactone is generally a weak natriuretic agent with diuretic activity related to the level of aldosterone. A rise in serum osmolality from 296 to 329 mOsm/kg was noted in this patient when the serum sodium decreased from 136 to 131 mEq/L, and the serum aldosterone went from 11 ng/dL at baseline to 13 ng/dL 7 days following spironolactone initiation. The recurrent hyponatremia is best explained therefore by an individual sensitivity to the diuretic effect of this agent, rather than a hypoaldosterone effect or drug related SIADH. Possibly, the hyponatremia would have been worse without losartan, since ARBs may mitigate hyponatremia in conditions where a highly activated renin-angiotensin-aldosterone-system may cause hyponatremia.17,21 ARBs have also been used to reduce dipsogenic drive in heart failure patients and reduce hyponatremia.17,21 What level of hyponatremia should be considered tolerable? Otherwise asymptomatic hyponatremia with serum sodiums of 126±5 mEq/L has been associated with an increased risk of a fall.22 These patients were found to perform significantly worse with attention and gait testing. Pre-existing asymptomatic hyponatremia is also a recognized risk factor for symptomatic hyponatremia. In a series of 47 patients, the mean asymptomatic serum sodium was 128.7 mmol/L, compared with a mean symptomatic sodium of 118.7 mmol/L.23 Most symptomatic hyponatremic subjects suffered mental status change. Therefore, particularly in an individual already at an elevated risk of falling and mental changes due to age, serum sodiums of at least 130 mEq/L should be used as a guide. Even a temporary superimposed condition may be enough to tip such a patient into hyponatremia significant enough to require hospitalization. An enteritis, a period of suboptimal oral intake, a urinary infection, or a short term NSAID could precipitate this occurrence. Such patients should be counseled to take measures to recognize and avoid these problems. This 85-year-old woman with successfully controlled hypertension on losartan and spironolactone has red flags attached to this medication combination. Foremost is the risk of hyperkalemia, which can be life threatening.24–29 Risk factors for this interaction include chronic kidney disease, age, and a dose of spironolactone greater than 25 mg daily.25 In elderly patients, especially thin ones, a normal or minimally elevated serum creatinine can be a misleading indicator of GFR and may mask the increased chance of potentially life threatening hyperkalemia resulting from an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker interaction with spironolactone.26 Low aldosterone levels in elderly patients made lower by spironolactone may predispose to hypoaldosterone-related hyperkalemia.29 Additionally, this patient with serum sodiums which were usually about 130–133 mEq/L required counseling to continue moderate but not excessive fluid intake and to alert her physician in case of poor intake or loss of fluid via gastrointestinal or urinary routes. Despite multiple attempts to use alternative antihypertensive agents, she demonstrated recurrent intolerance along with a well tolerated response to spironolactone. With informed discussion, she felt her quality of life was excellent, which permitted her to continue to live independently with controlled BPs. The patient has felt comfortable monitoring her home BP, coming to the laboratory for testing of renal function and electrolytes at 2–3 month intervals, and seeing her primary physician regularly." @default.
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• W2049666572 title "Well Tolerated Spironolactone-Related Hyponatremia" @default.
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• W2049666572 cites W2039340766 @default.
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• W2049666572 cites W2080767749 @default.
• W2049666572 cites W2084285962 @default.
• W2049666572 cites W2090293679 @default.
• W2049666572 cites W2093923107 @default.
• W2049666572 cites W2111111770 @default.
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• W2049666572 cites W2769696378 @default.
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