(Circulation. 1999;99:1265-1270.)
© 1999 American Heart Association, Inc.
Cardiovascular Drugs |
Digitalis
From the Department of Medicine, Division of Cardiology (P.J.H.), Saint Louis University School of Medicine, St. Louis, MO; and the Cardiovascular Division (R.A.K.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
Correspondence to Ralph A. Kelly, MD, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115. E-mail rakelly{at}rics.bwh.harvard.edu
Abstract
Abstract—Cardiac
glycosides have played a prominent role in the therapy of congestive
heart failure since William Withering codified their use in his late
18th century monograph on the efficacy of the leaves of the common
foxglove plant (Digitalis purpurea). Despite their
widespread acceptance into medical practice in the ensuing 200
years, both the efficacy and the safety of this class of drugs continue
to be a topic of debate. Moreover, despite the fact that the molecular
target for the cardiac glycosides, the 
-subunit of sarcolemmal
Na+K+-ATPase (or sodium pump) found on most
eukaryotic cell membranes, has been known for several
decades, it remains controversial whether the sympatholytic or positive
inotropic effects of these agents is the mechanism most relevant to
relief of heart failure symptoms in humans with systolic
ventricular dysfunction. Herein, we review the molecular
and clinical pharmacology of this venerable class of drugs, as well as
the manifestations of digitalis toxicity and their treatment. We also
review in some detail recent clinical trials designed to examine the
efficacy of these drugs in heart failure, with a focus on the Digoxin
Investigation Group data set. Although, in our opinion, the data on
balance warrant the continued use of these drugs for the treatment of
symptoms of heart failure in patients already receiving contemporary
multidrug therapy for this disease, the use of digitalis preparations
will inevitably decline with the maturation of newer pharmacotherapies.
Key Words: drugs • digitalis • heart failure • pharmacology
This article has been cited by other articles:
 |
|
 |
|
  A. Y. Bagrov, J. I. Shapiro, and O. V. Fedorova Endogenous Cardiotonic Steroids: Physiology, Pharmacology, and Novel Therapeutic Targets Pharmacol. Rev., March 1, 2009; 61(1): 9 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Coceani Antiarrhythmic therapy for prevention of implantable cardioverter defibrillator shocks. JAMA, September 13, 2006; 296(10): 1229 - 1230. [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Kannankeril, B. M. Mitchell, S. A. Goonasekera, M. G. Chelu, W. Zhang, S. Sood, D. L. Kearney, C. I. Danila, M. De Biasi, X. H. T. Wehrens, et al. Mice with the R176Q cardiac ryanodine receptor mutation exhibit catecholamine-induced ventricular tachycardia and cardiomyopathy PNAS, August 8, 2006; 103(32): 12179 - 12184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Coceani and R. Mariotti Is amiodarone safe in heart failure? BMJ, February 11, 2006; 332(7537): 317 - 318. [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Wasserstrom and G. L. Aistrup Digitalis: new actions for an old drug Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H1781 - H1793. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Akiyama, R. Tanaka, K. Maruo, and Y. Yamane Surgical Correction of a Partial Atrioventricular Septal Defect With a Ventricular Septal Defect in a Dog J. Am. Anim. Hosp. Assoc., March 1, 2005; 41(2): 137 - 143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Y. Xu, E. Takimoto, G. J. Juang, Q. Zhang, H. Rohde, and A. C. Myers Evidence that the H1-H2 domain of {alpha}1 subunit of (Na++K+)-ATPase participates in the regulation of cardiac contraction FASEB J, January 1, 2005; 19(1): 53 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. Newman, M. W. Feinberg, and H. E. LeWine A Bitter Tale N. Engl. J. Med., August 5, 2004; 351(6): 594 - 599. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Lin, J.-L. Juang, and P. S. Wang Involvement of Cdk5/p25 in Digoxin-triggered Prostate Cancer Cell Apoptosis J. Biol. Chem., July 9, 2004; 279(28): 29302 - 29307. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Piccioni, B. R. Roman, K. H. Fischbeck, and J. P. Taylor A screen for drugs that protect against the cytotoxicity of polyglutamine-expanded androgen receptor Hum. Mol. Genet., February 15, 2004; 13(4): 437 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Syuu, H. Matsubara, S. Hosogi, and H. Suga Pressor effect of electroacupuncture on hemorrhagic hypotension Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2003; 285(6): R1446 - R1452. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J M Dernellis and M P Panaretou Effects of digoxin on left atrial function in heart failure Heart, November 1, 2003; 89(11): 1308 - 1315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Rathore, J. P. Curtis, Y. Wang, M. R. Bristow, and H. M. Krumholz Association of Serum Digoxin Concentration and Outcomes in Patients With Heart Failure JAMA, February 19, 2003; 289(7): 871 - 878. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Scoote and A. J Williams The cardiac ryanodine receptor (calcium release channel): Emerging role in heart failure and arrhythmia pathogenesis Cardiovasc Res, December 1, 2002; 56(3): 359 - 372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K Kjeldsen, A Norgaard, and M Gheorghiade Myocardial Na,K-ATPase: the molecular basis for the hemodynamic effect of digoxin therapy in congestive heart failure Cardiovasc Res, September 1, 2002; 55(4): 710 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B Swynghedauw and D Charlemagne What is wrong with positive inotropic drugs? Lessons from basic science and clinical trials Eur. Heart J. Suppl., April 1, 2002; 4(suppl_D): D43 - D49. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Ahmed, R. M. Allman, and J. F. DeLong Inappropriate Use of Digoxin in Older Hospitalized Heart Failure Patients J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2002; 57(2): M138 - 143. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. TANAKA, C.I. BERUL, M. ISHII, P.Y. JAY, H. WAKIMOTO, P. DOUGLAS, N. YAMASAKI, T. KAWAMOTO, J. GEHRMANN, C.T. MAGUIRE, et al. A Mouse Model of Congenital Heart Disease: Cardiac Arrhythmias and Atrial Septal Defect Caused by Haploinsufficiency of the Cardiac Transcription Factor Csx/Nkx2.5 Cold Spring Harb Symp Quant Biol, January 1, 2002; 67(0): 317 - 326. [Abstract] [PDF]
|
|
|
|
|
|
R. A. Incalzi, C. Pedone, M. Pahor, L. Carosella, R. Bernabei, P. Carbonin, and the GIFA Investigators Reasons Prompting Digitalis Therapy in the Acute Care Hospital J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2001; 56(6): M361 - M365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.A. Eastwood A molecular biological basis for the nutritional and pharmacological benefits of dietary plants QJM, January 1, 2001; 94(1): 45 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Rose, H. M. Qazzaz, N. Zolotarjova, B. J. Mellett, A. W. Martin, and R. Valdes Jr Sodium Pump Isoforms in Xenotransplantation: Importance of Biochemical Compatibility Clin. Chem., February 1, 2000; 46(2): 234 - 241. [Abstract] [Full Text] [PDF]
|
|