Amiloride
side effects, nutrient depletions, herbal interactions and health notes:
Data provided by Applied Health
• According to preliminary studies involving rats amiloride has a magnesium-sparing effect in addition to its potassium-sparing effect. Consequently there is the possibility that individuals who take a magnesium supplement while also taking amiloride could build up excessively high levels of magnesium. The concurrent use of hydrochlorothiazide and amiloride would make this accumulation unlikely given the magnesium-depleting action of hydrochlorothiazide.1
• Individuals taking amiloride should refrain from taking supplemental magnesium without first consulting their prescribing physician, pharmacist, or a healthcare professional experienced in nutritional therapies.2
• Amiloride intentionally reduces urinary excretion of potassium. As a result of its role as a potassium-sparing diuretic, amiloride can produce a state of inappropriately elevated potassium levels.3
• : Individuals using potassium-sparing diuretics such as amiloride should limit their dietary intake of potassium to avoid excessive levels. Potassium supplements and potassium-containing salt substitutes, such as Lite SaltŪ, Morton's Salt Substitute and No SaltŪ, are designed for individuals suffering from potassium depletion due to other types of diuretics and should be avoided when taking potassium-sparing diuretics such as amiloride. For some individuals, foods with high potassium content may need to be limited. Several pieces of fruit per day may provide adequate potassium to elevate serum levels. Individuals taking amiloride should work with their prescribing physician to monitor potassium levels and modify their diet accordingly to avoid elevated potassium levels and associated problems.4
• The basic function of diuretics is to reduce the amount of water in the body. Therefore, by their very nature and intent diuretics, such as amiloride, increase the amount of sodium excreted in the urine.5
• Since the reduction of sodium levels in the body is purposeful, supplementation to reduce lost sodium would be counterproductive. However, if dietary changes undertaken to restrict sodium intake are successful the dosage of diuretic medications will need to be reevaluated and possibly modified. Thus, individuals with hypertension who are using a diuretic such as amiloride while also strictly limiting their salt intake should work closely with their prescribing physician to monitor and revise their prescription based on changes in their blood pressure.6
• Amiloride reduces meal-stimulated colonic absorption through inhibition of both Na+ channels and Na+/H+ exchange in colonocytes. Constipation is also a common side effect of amiloride.7
• For best therapeutic effect and safest use, amiloride should be taken consistently at least two hours apart from food, preferably at the same time each day. Individuals concerned about the timing of their meals should consult with their prescribing doctor or pharmacist.8
• Licorice can offset the pharmacological effect of amiloride. 11 beta-hydroxysteroid dehydrogenase (11 beta-DH) is the enzyme that oxidizes cortisol to inactive cortisone and prevents cortisol from acting like a mineralocorticoid at the aldosterone receptor site in the kidney. Some kinds of licorice contain glycyrrhetic acid which inhibits the action of 11 beta-DH (e.g. in the kidney) and causes cortisol to behave like aldosterone. Thus, licorice consumption can induce a mineralocorticoid excess state, most likely due to an acquired inhibition of this key enzyme, decreased transformation of cortisol into cortisone, and resultant increased cortisol levels at the mineralocorticoid receptor. In states of 11 beta-DH deficiency such as the syndrome of apparent mineralocorticoid excess (AME) and licorice ingestion, cortisol acts as a potent mineralocorticoid. Thus, by acting to enhance aldosterone effects licorice would oppose the therapeutic intent of amiloride as an aldosterone antagonist or aldosterone-inhibiting agent. Furthermore, this increased mineralocorticoid action of cortisol can cause a drop in serum potassium and an increase in serum sodium concentration, together with a metabolic alkalosis, and lead to water retention, weight gain, and increased risk of hypertension.9
• The research cited above has focussed on concentrated extracts and intravenous forms of licorice. Common "licorice" candy usually contains no actual Glycyrrhiza, other than perhaps a minute amount as flavoring. No solid conclusions can be drawn as to how much these findings relate to the use of licorice in the forms commonly used by practitioners of Western and Chinese herbal medicine. A product known as DGL (Deglycyrrhizinated Licorice) is available which retains the anti-inflammatory actions of whole licorice root without pseudo-aldosterone side effects. Individuals using amiloride should consult with their prescribing physician and/or a qualified practitioner of herbal medicine about the potential risks involved in using any form of licorice.10
References1 Devane J, Ryan MP. Br J Pharmacol. 1983 Aug;79(4):891-896; Devane J, Ryan MP. Br J Pharmacol. 1981 Feb;72(2):285-289.)
1 Whang EE, et al. J Surg Res. 1996 Feb 1;60(2):303-306
1 Devane J, Ryan MP. Urinary magnesium excretion during amiloride administration in saline-loaded rats. Br J Pharmacol. 1979 Nov;67(3):493P.
1 Gomez-Sanchez EP, Gomez-Sanchez CE. Effect of central amiloride infusion on mineralocorticoid hypertension. Am J Physiol 1994 Nov;267(5 Pt 1):E754-758.
1 Kleyman TR and Cragoe EJ Jr, The Mechanism of Action of Amiloride. Semin Nephrol, 1988, 8(3):242-248.
1 Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998 Nov 9;158(20):2200-2211. (Review)
1 Pratesi C, Scali M, Zampollo V, Zennaro MC, De Lazzari P, Lewicka S, Vecsei P, Armanini D. Effects of licorice on urinary metabolites of cortisol and cortisone. J Hypertens Suppl 1991 Dec;9(6):S274-275.
1 Roe DA. Diet and Drug Interactions. New York, Van Nostrand Reinhold, 1989: 146.
1 Threlkeld DS, ed. Diuretics and Cardiovasculars, Potassium-Sparing Diuretics, Spironolactone. In: Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Jul 1993.
2 N/A
3 N/A
4 Stepan VM, et al. Eur J Gastroenterol Hepatol 1997 Oct;9(10):1001-1004
5 N/A
6 Roe DA. 1989:146
7 N/A
8 Threlkeld DS, ed. Jul 1993
9 Miller LG. Arch Intern Med 1998 Nov 9;158(20):2200-2211; Lee YS, et al. Clin Pharmacol Ther 1996 Jan;59(1):62-71; Pratesi C, et al. J Hypertens Suppl 1991 Dec;9(6):S274-275; Nanahoshi M. Nippon Naibunpi Gakkai Zasshi 1967 Mar 20;42(12):1312-1319.)
10 Devane J, Ryan MP. Evidence for a magnesium-sparing action by amiloride during renal clearance studies in rats. Br J Pharmacol. 1983 Aug;79(4):891-896. Abstract: The potassium-sparing diuretic, amiloride, reduced the fractional excretion of magnesium in anaesthetized rats. Alterations in glomerular filtration rate (GFR), the filtered load of magnesium, arterial blood pressure, the status of the extracellular fluid volume, plasma aldosterone concentration and acid-base balance were not involved. It was concluded that amiloride exerted a magnesium-sparing effect by a direct renal action. Devane J, Ryan MP. The effects of amiloride and triamterene on urinary magnesium excretion in conscious saline-loaded rats. Br J Pharmacol. 1981 Feb;72(2):285-289. Abstract: 1 The potassium-sparing diuretics, triamterene and amiloride, reduced urinary magnesium excretion in conscious saline-loaded rats. 2 Urinary magnesium-conservation was also detected when amiloride was used in combination with the potent 'loop-blocking' diuretic, frusemide.
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Disclaimers
The information in Drug Watch is provided as a courtesy to NewsTarget readers by Applied Health Solutions in cooperation with Healthway Solutions. Although the information is presented with scientific references, we do not wish to imply that this represents a comprehensive list of considerations about any specific drug, herb or nutrient. Nor should this information be considered a substitute for the advice of your doctor, pharmacist, or other healthcare practitioner. Please read the disclaimer about the intentions and limitations of the information provided on these pages. It is important to tell your doctor and pharmacist about all other drugs and nutritional supplements that you are taking if they are recommending a new medication. Copyright © 2007 by Applied Health Solutions, Inc. All rights reserved.
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