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• W2894889128 abstract "SESSION TITLE: Medical Student/Resident Pharmacotherapeutics SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Metolazone is an agent with pharmacologic characteristics similar to those of thiazide diuretics. However, it has a longer elimination half life [1]. Metolazone is slightly more efficacious than other thiazide diuretics because it has an additional diuretic effect in the proximal nephron [2], yet its differences from the rest of the thiazides are commonly neglected. CASE PRESENTATION: We present the case of a 52yo man who came into the ED because of one week of increasing generalized body weakness and muscle cramps. This patient had a history of Diastolic Dysfunction. On admission, Sodium Level was 114. He had recently been started on Metolazone 5mg. On admission patient had adequate mental status. He showed some signs of overload, thus we started him on NS at 100ml/hr thinking of hypoosmolar hyponatremia.Next day, he had worsening mental status. Na was found to be 110. Our hyponatremia workup showed serum osmolality of 241 and a urine osmolality of 563. Urine electrolytes were as follows: Na 139; Cl of 181; K of 31. At this point 3% NaCl was started and he was transferred to the ICU. Over 24 hours, he received about 800ml of NaCl 3% which only increased his Na to 114. At this point, we stopped hypertonic saline. Upon repeat checks, our Na went further down to 111. Which made us resume 3% NaCl. As we went into the 48h window, with over 1700ml of NaCl 3% we were able to achieve Na levels of 117. We stopped 3% NaCl at this point. During the next 5 days he started correcting slowly. By the end of 8 days his Na level was 131. A highly unusual presentation. DISCUSSION: The plasma concentration-time curve following IV administration of Metolazone to normal adults corresponds to a two compartment system. One third of the drug is distributed into the tissue pool, of this, only one third is in the plasma compartment. The rest of the pool appears to be reflected in the accumulation of Metolazone in erythrocytes [3]. This medication has also shown to have longer half life on patients with heart failure and chronic kidney disease. [4]We think that in patients with Polycythemia, if regular dosing of Metholazone is used, a progressive accumulation of this drug can occur which could lead to severe metabolic derangements as demonstrated on this patient. He had severe salt diuresis. His Urinary Sodium was 139, his Cl in Urine was 181, despite the severe hyponatremia with Na of 114 and Hypochloremia of 70. He also presented with hypokalemia, admission K of 2.7, hyperglycemia, as well as hypomagnesemia, all of which are known side effects of thiazide drugs. [5] CONCLUSIONS: There are not many studies available which take into consideration Metolazone's unique pharmacologic properties within the Thiazide group. We think there should be further studies exploring the pharmacokinetics of this medication in especially susceptible populations such as patients with Polycythemia, CKD and Heart Failure. Reference #1: 1. Elwaleed A. Elhassan, Robert W Schrier, in Comprehensive Clinical Nephrology (Fourth Edition), 2010. Reference #2: 3. Belair EJ, Cohen AI, Yelnosky J, in Renal Excretion of Metolazone, a new Diuretic. Br. J. Pharmac. (1972), 45, 476-479. Reference #3: 4. Tilstone WJ, Dargie H, in Pharmacokinetics of metolazone in normal subjects and in patients with cardiac or renal failure. Clin Pharmacol Ther. 1974 Aug; 16(2): 322-9. DISCLOSURES: No relevant relationships by Christian Abreu-Ramirez, source=Web Response No relevant relationships by Joseph-Leslie Pean, source=Web Response" @default.
• W2894889128 created "2018-10-12" @default.
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• W2894889128 date "2018-10-01" @default.
• W2894889128 modified "2023-09-25" @default.
• W2894889128 title "SEVERE HYPONATREMIA REFRACTORY TO TREATMENT: A CASE OF METOLAZONE INTOXICATION" @default.
• W2894889128 doi "https://doi.org/10.1016/j.chest.2018.08.754" @default.
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