Digoxin
side effects, nutrient depletions, herbal interactions and health notes:
Data provided by Applied Health
• mechanism: Aluminum-containing antacids reduce the bioavailability of digoxin. nutritional concerns: Individuals taking digoxin should avoid the use of antacids, especially within two hours of taking the medication1
• Small increases in plasma calcium can increase digoxin toxicity. Digoxin also increases renal clearance. Avoid high calcium foods for two hours before and after taking digoxin. Even under a physician's care intravenous calcium can be very dangerous.2
• Digoxin decreases intracellular magnesium, thereby causing increased urinary magnesium loss. Magnesium deficiencies induced by concomitant diuretic use are very common in individuals using digoxin. Hypomagnesemia may predispose to digitalis toxicity.3
• Hypomagnesemia is known to produce a wide variety of clinical presentations, including neuromuscular irritability, cardiac arrhythmias, and increased sensitivity to digoxin. Magnesium deficiency also inhibits the therapeutic efficacy of digoxin in controlling atrial fibrillation. Refractory hypokalemia and hypocalcemia can be caused by concomitant hypomagnesemia and can be corrected with magnesium therapy.4
• Many physicians are aware of the need to monitor and prescribe for potassium depletion but do not consider the issue of magnesium deficiency unless serum levels fall below acceptable levels. Furthermore, many physicians experienced in nutritional assessment consider serum magnesium to be a very poor indicator of how much magnesium is actually in the tissues. Serum magnesium concentration is maintained within a narrow range by the kidney and small intestine since under conditions of magnesium deprivation both organs increase their fractional absorption of magnesium. If magnesium depletion continues, the bone store contributes by exchanging part of its content with extracellular fluid (ECF). The serum Mg can be normal in the presence of intracellular Mg depletion, and the occurrence of a low level usually indicates significant magnesium deficiency. Hypomagnesemia is frequently encountered in hospitalized patients and is seen most often in patients admitted to intensive care units. The detection of magnesium deficiency can be increased by measuring magnesium concentration in the urine or using the parenteral magnesium load test.5
• Individuals taking digoxin will almost always benefit from supplementation of magnesium. Studies and clinical experience indicate that 300-500 mg of magnesium per day would be an appropriate dosage level for supplementing such patients. Anyone taking digoxin should consult the prescribing physician and/or a nutritionally-oriented healthcare professional regarding the issue of magnesium supplementation.6
• Potassium deficiency induced by concomitant diuretic use are very common in individuals using digoxin, often being secondary to hypomagnesia. Hypokalemia may predispose to digitalis toxicity. Individuals taking digoxin will often benefit from increasing their intake of potassium. Many physicians who prescribe digoxin monitor for potassium depletion and prescribe potassium supplements when measurable deficiencies are found. However direct supplementation of potassium may not be appropriate since potassium pills are limited to dosages of 99 mg each and taking several at a time may cause digestive irritation. Adequate dietary potassium can easily be obtained by eating several pieces of fruit each day; for example, one banana typically provides 500 mg. Other research, including that by Schmidt et al, indicates that the impairment of extrarenal potassium homeostasis by heart failure and digoxin treatment may be counterbalanced by exercise. Anyone taking digoxin should consult the prescribing physician and/or a nutritionally-oriented healthcare professional regarding the issue of potassium supplementation.7
• Plantago psyllium (Psyllium seed husks), Cyamopsis spp. seeds (Guar gum) and potentially other sources of Dietary Fiber Hydrophilic fiber slows absorption of oral drugs and specifically reduces absorption of digoxin. Most studies thus far have indicated that the clinical implications of this reduced absorption may be negligent.8
• Crataegus species leaves/flowers/fruit (Hawthorn) mechanism: Hawthorn is a mild cardiotonic herb. It has moderate positive inotropic effects and can thus potentiate cardiac glycosides including digoxin. Hawthorn is used in herbal therapeutics as an adjunctive in reducing the dose and amounts of cardioactive pharmaceuticals used by patients with heart conditions. Hawthorn should not be used concurrently with any cardiovascular medication without consulting a physician or qualified herbalist. Patients on existing digoxin therapy should be monitored while taking Hawthorn and the digoxin dose adjusted as necessary.9
• Cytisus scoparius (Scotch Broom, flowering tops) Scotch broom contains cardioactive alkylamines including sparteine. The herb has anti-arryhthmic and cardiodepressant activity and is diuretic and cathartic. It is hypertensive due to peripheral vasoconstrictive effects. Cytisus is used therapeutically by healthcare professionals trained in herbal medicine in combination with Convallaria for treatment of cardiac edema in congestive heart failure. Cytisus may interact with digoxin and related drugs unpredictably due to multiple cardiac and circulatory effects. It should not be used concurrently with digoxin therapy.10
• Digitalis (Foxglove) and other plants containing cardiac glycosides. Naturally occurring cardiac glycosides have a limited distribution confined to a few dozen species scattered across several genera, principally the Asclepiadaceae and Apocyanaceae. Concentrations of glycosides are generally well below 1%. Three genera contain sufficient concentrations of glycosides for commercial extraction: Digitalis spp.- Foxgloves - (Scrophulariaceae), Urginia spp. - Squills - (Liliaceae) and Strophanthus (Apocynaceae). These plants are described as cardioactive by herbalists, as opposed to the milder cardiotonic herbs such as Hawthorn. Due to their toxicity, these herbs are not available to the public. Neither Digitalis or Strophanthus are commonly used in herbal therapeutics and in many countries their use is legally restricted. Convallaria majalis and Urginia maritima are listed in the British Herbal Pharmacopoeia. Their cardenolides have low cumulative toxicity compared to Digitalis, and these plants are used by professional herbalists. See Weiss (1988) for an excellent discussion of use of cardiac glycoside herbs. Contamination of commercial crude herb with Digitalis has been reported. Recently, the FDA recalling several products after herb teas containing Plantain caused side effects attributable to Digitalis contamination. One study analyzed several herbal teas and found digitalis like factors present in small concentrations in several samples, particularly those containing Asclepias tuberosa (Pleurisy Root).11
• Common herbs containing cardiac glycosides: Asclepias tuberosa (Pleurisy Root )* Convallaria majalis (Lily of the Valley) Scrophularia nodosa (Figwort) * Urginea maritima (Squill bulb) Note: * These herbs contain therapeutically insignificant quantities of glycosides. Restricted or unusual herbs containing cardiac glycosides: Adonis vernalis (Pheasants Eye) Apocynum cannabinum (Canadian Hemp Root) toxic Digitalis species (Foxglove) toxic Helleborus niger (Black Hellebore) toxic Helleborus viride (Christmas Rose) toxic Nerium oleander (Rose Laurel) toxic Strophanthus spp. (Ouabain, Kombe) toxic Thevetia neriifolia (Yellow Oleander) toxic Common herbs containing cardiac glycosides: Asclepias tuberosa (Pleurisy Root )* Convallaria majalis (Lily of the Valley) Scrophularia nodosa (Figwort) * Urginea maritima (Squill bulb) Note: * These herbs contain therapeutically insignificant quantities of glycosides. Restricted or unusual herbs containing cardiac glycosides: Adonis vernalis (Pheasants Eye) Apocynum cannabinum (Canadian Hemp Root) toxic Digitalis species (Foxglove) toxic Helleborus niger (Black Hellebore) toxic Helleborus viride (Christmas Rose) toxic Nerium oleander (Rose Laurel) toxic Strophanthus spp. (Ouabain, Kombe) toxic Thevetia neriifolia (Yellow Oleander) toxicherb possibly affecting drug pharmacokinetics: Eleutherococcus senticosus (Siberian Ginseng) report: A case of elevated serum digoxin level in a patient taking Siberian ginseng and digoxin was reported by McRae. The mechanism of interaction remains unclear and since the ECG was unchanged, it is possible that the herb interfered with the digoxin assay.: Individuals taking digoxin should advise their prescribing physician before commencing Siberian ginseng consumption to ensure adequate monitoring of both plasma drug levels and cardiac signs12
• Johne, et al, conducted a preclinical trial which showed that coadministration of standardized Hypericum extracts (900 mg daily) with digoxin (0.25 mg daily) in healthy subjects resulted in the previously stabilized plasma digoxin levels significantly decreasing compared to placebo after a single dose and after ten days.13
• Since digoxin is renally excreted Johne A, et al, suggest the mechanism of increased clearance may involve induction of P-glycoprotein drug transporters. Patients stabilized on digoxin should advise their prescribing physician before consuming extracts of Hypericum. Physicians should always enquire about herb usage when prescribing digoxin, along with standard questions about concurrent medications. Ernst has suggested that interactions due to induction of cytochrome P450 enzymes by Hypericum extracts may require a re-evaluation of the safety of Hypericum extracts.14
• Many herbal cathartics act via anthraquinone constituents causing irritation of the large intestines. Other purgatives contain cucurbitacins which are drastic purgatives not used in herbal medicine. Mild herbal laxatives act hepatically to increase bile flow and are unlikely to cause diarrhea. Theoretically, herbal cathartics are subject to laxative abuse as are commercial pharmaceutical laxatives. Excessive doses or chronic inappropriate use of such herbs could cause diarrhea leading to electrolyte depletion and hence potassium loss in the stool.Herbal diuretics act in different ways, generally resulting in increased volume of diluted urine. Some herbs described as "diuretic" are in fact anti-inflammatory (demulcents) or antiseptic agents rather than aquaretics. In herbal therapeutics cardiac edema is specifically treated with Taraxacum fol (Dandelion Leaf), which has a diuretic strength equivalent to furosemide but contains high enough concentrations of potassium to make supplementation unnecessary. Herbal diuretics if used chronically in excessive amounts may cause potassium depletion via loss in the urine.15
References1 Rodin SM, Johnson BF. Clin Pharmacokinet. 1988 Oct;15(4):227-244; Roe DA. 84, 1989; Gugler R, Allgayer H. Clin Pharmacokinet. 1990 Mar;18(3):210-219
2 Kupfer S, Kosovsky JD. J Clin Invest 1965 44:1132-1143
3 Toffaletti J. Analyt Chem 1991 63(12):192R-194R; al-Ghamdi SM, et al. Am J Kidney Dis 1994 Nov;24(5):737-752
4 Toffaletti J. Analyt Chem 1991 63(12):192R-194R; Young IS, et al. Br J Clin Pharmacol. 1991 Dec;32(6):717-721; Lewis R, et al. Br J Clin Pharmacol. 1991 Feb;31(2):200-203
5 al-Ghamdi SM, et al. Am J Kidney Dis 1994 Nov;24(5):737-752; Marz R. 1997
6 Kinlay S, Buckley NA. J Toxicol Clin Toxicol 1995;33(1):55-59; Sueta CA, et al. Magnes Res 1995 Dec;8(4):389-401
7 Schmidt TA, et al. Cardiovasc Res 1995 Apr;29(4):506-511
8 Huupponen R, et al. Eur J Clin Pharmacol 1984;26(2):279-281; Johnson BF, et al. J Clin Pharmacol 1987 Jul;27(7):487-490
9 Not Available.
10 British Herbal Pharmacopeia, 1983
11 Longerich L, et al. Clin Invest Med 1993 Jun;16(3):210-218
12 McRae S. CMAJ 1996 Aug 1;155(3):293-295, Comment in: CMAJ 1996 Nov 1;155(9):1237
13 Johne A, et al. Clin Pharmacol Ther 1999 Oct;66(4):338-345
14 Ernst E. Lancet, Dec 11, 1999; 354, 9195
15 al-Ghamdi SM, Cameron EC, Sutton RA. Magnesium deficiency: pathophysiologic and clinical overview. Am J Kidney Dis 1994 Nov;24(5):737-752. (Review) American Herbal Products Association. Botanical Safety Handbook. Boca Raton, FL: CRC Press, 1997.
15 Brinker F. Botanical Medicine Research Summaries. In: Eclectic Dispensatory of Botanical Therapeutics, Vol. II. Sandy, OR: Eclectic Medical Publications, 1995. Brinker F. Herb Contraindications and Drug Interactions. Sandy, OR: Eclectic Institute, 1997. Brinker F. To Health With Herbs from Eclectic Dispensatory of Botanical Therapeutics. Vol. I, Alstat, E (comp.). Portland, OR: Eclectic Medical Publications, 1989. Brinker F. The Toxicology of Botanical Medicines. Rev. 2nd ed., Sandy, OR: Eclectic Medical Publications, 1996. BHP. The British Herbal Pharmacopeia, BHMA, Bournemouth, UK, 1983. Cohen L, Kitzes R. JAMA 1984;251:730. (Letter) Cohen L, Kitzes R. Magnesium sulfate and digitalis-toxic arrhythmias. JAMA 1983 May 27;249(20):2808-2810.
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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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