Abstract
Introduction
Cardioactive steroids (CASs) are found in plants, animals, and insects. Their affinity for Na+−K+ ATPase is attenuated by the type of lactone at carbon 17 (C17) of the steroid backbone: those with 5-membered lactone rings, or cardenolides, are derived mostly from plants with 6-membered rings or from animals with bufadienolides. A systematic review of CAS poisoning was performed to compare the mortality rate of cardenolides and bufadienolides.
Methods
MEDLINE was searched for articles using commonly reported names of CASs, and keywords were limited to human cases only. We searched cases from 1982 to 2003, so that supportive care was similar and digoxin-specific Fab was available. Identified reports of CAS poisoning were read to exclude cases involving licensed pharmaceuticals. Inclusion criteria included hyperkalemia, gastrointestinal symptoms, electrocardiographic evidence of CAS toxicity, digoxin serum concentration, or history of exposure to a substance containing a CAS. Clinical data was collected, including information about treatment with digoxin-specific Fab and treatment outcome.
Results
Fifty-nine articles, describing 924 patients, were identified. Eight hundred ninety-seven patients (97%) ingested a CAS with a 5-membered lactone ring, and mortality was 6% (n = 54). Twenty-seven patients (2.9%) ingested a CAS with a 6-membered lactone ring, and mortality was 29.6% (n = 8). The difference in mortality rates was statistically significant (p < 0.001, [X2]). CASs with 6-member rings accounted for the highest percentage of nonsuicidal exposures.
Conclusion
Although cardenolides accounted for the majority of exposures, bufadienolides were five times more lethal than cardenolides.
Keywords: cardioactive steroids, cardenolides, bufadienolides, cardiac glycosides, digoxin
Full Text
The Full Text of this article is available as a PDF (139.0 KB).
Footnotes
There was no outside funding of any kind used for this study.
References
- 1.Ziskind B, Halioua B. Contribution of Ancient Egypt to cardiovascular medicine. Arch Mal Coeur Vaiss. 2004;97(4):370–374. [PubMed] [Google Scholar]
- 2.Wade OL. Digoxin 1785–1985. I. Two hundred years of digitalis. J Clin Hosp Pharm. 1986;11(1):3–9. doi: 10.1111/j.1365-2710.1986.tb00822.x. [DOI] [PubMed] [Google Scholar]
- 3.Eisner T, Goetz MA, Hill DE, Smedley SR, Meinwald J. Firefly “femmes fatales” acquire defensive steroids (lucibufagins) from their firefly prey. Proc Nat1 Acad Sci USA. 1997;94(18):9723–9728. doi: 10.1073/pnas.94.18.9723. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Schoner W. Endogenous cardiac glycosides, A new class of steroid hormones. Eur J Biochem. 2002;269(10):2440–2448. doi: 10.1046/j.1432-1033.2002.02911.x. [DOI] [PubMed] [Google Scholar]
- 5.Slifman NR, Obermeyer WR, Aloi BK, Musser SM, Correll WA, Cichowicz SM, Betz JM, Love LA. Contamination of botanical dietary supplements byDigitalis lanata. N Engl J Med. 1998;339(12):806–811. doi: 10.1056/NEJM199809173391204. [DOI] [PubMed] [Google Scholar]
- 6.Eddleston M, Ariaratnam CA, Sjostrom L, Jayalath S, Rajakanthan K, Rajapakse S, Colbert D, Meyer WP, Perera G, Attapattu S, Kularatne SA, Sheriff MR, Warrell DA. Acute yellow oleander (Thevetia peruviana) poisoning: cardiac arrhythmias, electrolyte disturbances, and serum cardiac glycoside concentrations on presentation to hospital. Heart. 2000;83(3):301–306. doi: 10.1136/heart.83.3.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Eddleston M, Ariaratnam CA, Meyer WP, Perera G, Kularatne AM, Attapattu S, Sheriff MH, Warrell DA. Epidemic of self-poisoning with seeds of the yellow oleander tree (Thevetia peruviana) in northern Sri Lanka. Trop Med Int Health. 1999;4(4):266–273. doi: 10.1046/j.1365-3156.1999.00397.x. [DOI] [PubMed] [Google Scholar]
- 8.Brubacher JR, Ravikumar PR, Bania T, Heller MB, Hoffman RS. Treatment of toad venom poisoning with digoxin-specific Fab fragments. Chest. 1996;110(5):1282–1288. doi: 10.1378/chest.110.5.1282. [DOI] [PubMed] [Google Scholar]
- 9.Melero CP, Medarde M, San Felician F. A short review on Cardiotonic Steroids and Their Aminoguanidine Analgues. Molecules. 2000;5:51–81. doi: 10.3390/50100051. [DOI] [Google Scholar]
- 10.Lin CS, Lin MC, Chen KS, Ho CC, Tsai SR, Ho CS, Shieh WH. A digoxin-like immunoreactive substance and atrioventricular block induced by a Chinese medicine “kyushin”. Jpn Circ J. 1989;53(9):1077–1080. doi: 10.1253/jcj.53.1077. [DOI] [PubMed] [Google Scholar]
- 11.Dasgupta A, Emerson L. Neutralization of cardiac toxins oleandrin, oleandrigenin, bufalin, and cinobufotalin by digibind: Monitoring the effect by measuring free digitoxin concentrations. Life Sci. 1998;63(9):781–788. doi: 10.1016/S0024-3205(98)00333-6. [DOI] [PubMed] [Google Scholar]
- 12.Eddleston M, Senarathna L, Mohamed F, Buckley N, Juszczak E, Sheriff MH, Ariaratnam A, Rajapakse S, Warrell D, Rajakanthan K. Deaths due to absence of an affordable antitoxin for plant poisoning. Lancet. 2003;362(9389):1041–1044. doi: 10.1016/S0140-6736(03)14415-7. [DOI] [PubMed] [Google Scholar]
- 13.Brubacher JR, Lachmanen D, Ravikumar PR, Hoffman RS. Efficacy of digoxin specific Fab fragments (Digibind) in the treatment of toad venom poisoning. Toxicon. 1999;37(6):931–942. doi: 10.1016/S0041-0101(98)00224-4. [DOI] [PubMed] [Google Scholar]
- 14.Eddleston M, Warrell DA. Management of acute yellow oleander poisoning. QJM. 1999;92(9):483–485. doi: 10.1093/qjmed/92.9.483. [DOI] [PubMed] [Google Scholar]