Document Type : Original Article(s)
Authors
- Shabnam Shahsavand 1
- Mohammad Moshirfar 2
- Seyed Hassan Seyed-Sharifi 3
- Mohammad Amin Younessi-Heravi 4
- Reza Ghasemi 5
- Morteza Valaei 6
- Mohsen Yaghubi 7
1 Assistant Professor, Department of Physiology and Pharmacology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
2 Department of Orthopedic Surgery, Tehran University of Medical Sciences, Tehran, Iran
3 Department of General Surgery, Endoscopic and Minimally Invasive Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
4 Department of Medical Physics and Radiology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
5 Assistant Professor, Department of Cardiology, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran
6 Department of Internal Medicine, Razavi Hospital, Imam Reza International University, Mashhad, Iran
7 Department of Extra-Corporeal Circulation, Razavi Hospital, Imam Reza International University, Mashhad, Iran
Abstract
BACKGROUND: Digoxin is a drug for ventricular rate control in atrial fibrillation (AF). The major challenge in digoxin therapy is to adjust the appropriate concentration range for this drug due to its narrow therapeutic index. Unique physiochemical properties of drinking water affect the pharmacological actions and delivery of drugs to the body whether they are administered orally, topically, or by injection. The aim of this study was to evaluate water hardness effect on digoxin therapy in an experimental rat model.METHODS: 48 rats weighing 200-220 g were randomly assigned to three groups that received drinking water with 50, 400, and 800 mg/l hardness degrees for 28 days. Then each group was assigned into two groups. One received digoxin 0.2 mg/kg a day orally for four days. The other group received normal saline (as control group). Continuous recording of electrocardiogram (ECG) was performed by PowerLab system (AD Instruments Company) before and day 4 of digoxin treatment. Then serum samples were collected and assessed for digoxin, sodium, potassium, calcium, magnesium, blood urea nitrogen (BUN), and creatinine levels.RESULTS: Water hardness in the range of 50-800 mg/l had no effect on serum digoxin levels (P > 0.050), but consuming hard drinking water (400 and 800 mg/l) could increase serum calcium levels and then cause mortality (37.5% in both groups), following changes in ECG due to digoxin consumption.CONCLUSION: Consuming hard drinking water probably interferes with digoxin pharmacodynamics in the way of toxicity induction.
Keywords
- Yang EH, Shah S, Criley JM. Digitalis Toxicity: A fading but crucial complication to recognize. Am J Med 2012; 125(4): 337-43.
- Fuster V. Atrial fibrillation: An epidemiologic, scientific and clinical challenge. Nat Rev Cardiol 2005; 2: 225.
- Heist EK, Ruskin JN. Atrial fibrillation and congestive heart failure: Risk factors, mechanisms, and treatment. Prog Cardiovasc Dis 2006; 48(4): 256-69.
- McEvoy GK. AHFS drug information: Essentials 2006-2007. Bethesda, MD: American Society of Health-System Pharmacists; 2002. p. 1552.
- Katzung BG, Masters S, Trevor A. Basic and clinical pharmacology. New York, NY: McGraw Hill Professional, 2012.
- Bavishi C, Khan AR, Ather S. Digoxin in patients with atrial fibrillation and heart failure: A meta-analysis. Int J Cardiol 2015; 188: 99-101.
- Pastori D, Farcomeni A, Bucci T, Cangemi R, Ciacci P, Vicario T, et al. Digoxin treatment is associated with increased total and cardiovascular mortality in anticoagulated patients with atrial fibrillation. Int J Cardiol 2015; 180: 1-5.
- Eade E, Cooper R, Mitchell AR. Digoxin-time to take the gloves off? Int J Cardiol 2013; 164(3): 365-7.
- Lai SW, Lin CL, Liao KF. Digoxin use may increase the relative risk of acute pancreatitis: A population-based case-control study in Taiwan. Int J Cardiol 2015; 181: 235-8.
- Finsterer J, Stollberger C. Beneficial effect of digitoxin for heart failure from noncompaction in myotonic dystrophy 1. Int J Cardiol 2020; 160(3): e50-1.
- Rathore SS, Wang Y, Krumholz HM. Sex-based differences in the effect of digoxin for the treatment of heart failure. N Engl J Med 2002; 347(18): 1403-11.
- Vella A, Gerber TC, Hayes DL, Reeder GS. Digoxin, hypercalcaemia, and cardiac conduction. Postgrad Med J 1999; 75(887): 554-6.
- Levine M, Nikkanen H, Pallin DJ. The effects of intravenous calcium in patients with digoxin toxicity. J Emerg Med 2011; 40(1): 41-6.
- Gupta A, Su M, Greller H, Majlesi N, Hoffman RS. Digoxin and calcium: The verdict is still out. J Emerg Med 2010; 39(1): 102-3.
- Cotruvo JA, Bartram J. Calcium and magnesium in drinking-water: Public health significance. Geneva, Switzerland: World Health Organization; 2009.
- Ogata F, Nagai N, Ito Y, Kawasaki N. Fundamental study on effect of high-mineral drinking water for osteogenesis in calciprivia ovariectomized rats. Yakugaku Zasshi 2014; 134(5): 679-85.
- Sumano LH, Gutierrez OL, Aguilera R, Rosiles MR, Bernard BM, Gracia MJ. Influence of hard water on the bioavailability of enrofloxacin in broilers. Poult Sci 2004; 83(5): 726-31.
- Mestre AS, Nabico A, Figueiredo PL, Pinto MsL, Santos MSC, Fonseca IM. Enhanced clofibric acid removal by activated carbons: Water hardness as a key parameter. Chem Eng J 2016; 286: 538-48.
- Couto Jr OM, Matos I, da Fonseca IM, Arroyo PA, da Silva EA, de Barros MAlSeD. Effect of solution pH and influence of water hardness on caffeine adsorption onto activated carbons. Can J Chem Eng 2015; 93(1): 68-77.
- Evans AO, Marsh JM, Wickett RR. The uptake of water hardness metals by human hair. J Cosmet Sci 2011; 62(4): 383-91.
- Hayes JM, Eichman J, Katz T, Gilewicz R. Stability of florfenicol in drinking water. J AOAC Int 2003; 86(1): 22-9.
- Wasana HM, Aluthpatabendi D, Kularatne WM, Wijekoon P, Weerasooriya R, Bandara J. Drinking water quality and chronic kidney disease of unknown etiology (CKDu): Synergic effects of fluoride, cadmium and hardness of water. Environ Geochem Health 2016; 38(1): 157-68.
- Razzaque S, Aidrus F, Kumar A, Kumar A, Ghauri I, Ullah S. Hypertension in people consuming hard water in Haji Samoa Goth Keti-Bundar Sindh. Annals of Abbasi Shaheed Hospital & Karachi Medical & Dental College 2015; 20(1): 17.
- American Public Health Association. Standard methods for the examination of water and wastewater. Denver, CO: American Water Works Association; 1999.
- Yoshida A, Fujita M, Owada E, Ito K. Effects of diltiazem on plasma and tissue digoxin levels in mice. J Pharmacobiodyn 1984; 7(8): 511-6.
- Malmasi AA, Selk Ghafari M, Sorouri S. Electrocardiographic manifestation of digoxin toxicity in a Pomeranian dog. Iranian Journal of Veterinary Medicine 2009; 3(1): 55-8. [In Persian].
- Hammad SAE-H, Amin SA, El-Seidy AM, Habib NM. Clinical study of poisoned cases by some drugs admitted to the Menoufia poisoning control center over 1 year (2011), with a focus on ECG changes. Menoufia Medical Journal 2014; 27(2): 260.
- Sonnenblick M, Abraham AS, Meshulam Z, Eylath U. Correlation between manifestations of digoxin toxicity and serum digoxin, calcium, potassium, and magnesium concentrations and arterial pH. Br Med J (Clin Res Ed) 1983; 286(6371): 1089-91.