Clinical Use of Digitalis: A State of the Art Review

Abstract

The history of digitalis is rich and interesting, with the first use usually attributed to William Withering and his study on the foxglove published in 1785. However, some knowledge of plants with digitalis-like effects used for congestive heart failure (CHF) was in evidence as early as Roman times. The active components of the foxglove (Digitalis purpurea and Digitalis lanata) are classified as cardiac glycosides or cardiotonic steroids and include the well-known digitalis leaf, digitoxin, and digoxin; ouabain is a rapid-acting glycoside usually obtained from Strophanthus gratus. These drugs are potent inhibitors of cellular membrane sodium-potassium adenosine triphosphatase (Na/K-ATPase). For most of the twentieth century, digitalis and its derivatives, especially digoxin, were the available standard of care for CHF. However, as the century closed, many doubts, especially regarding safety, were raised about their use as other treatments for CHF, such as decreasing the preload of the left ventricle, were developed. Careful attention is needed to maintain the serum digoxin level at ≤ 1.0 ng/ml because of the very narrow therapeutic window of the medication. Evidence for benefit exists for CHF with reduced ejection fraction (EF), also referred to as heart failure with reduced EF (HFrEF), especially when considering the combination of mortality, morbidity, and decreased hospitalizations. However, the major support for using digoxin is in atrial fibrillation (AF) with a rapid ventricular response when a rate control approach is planned. The strongest support of all for digoxin is for its use in rate control in AF in the presence of a marginal blood pressure, since all other rate control medications contribute to additional hypotension. In summary, these days, digoxin appears to be of most use in HFrEF and in AF with rapid ventricular response for rate control, especially when associated with hypotension. The valuable history of the foxglove continues; it has been modified but not relegated to the garden or the medical history book, as some would advocate.

Bright and Early: Inhibiting Human Cytomegalovirus by Targeting Major Immediate-Early Gene Expression or Protein Function

“…Inhibition of HCMV by cardiac glycosides is effective against clinical and GCV-resistant strains and exhibits additive activity when administered to cells in combination with GCV [362,363,365,366]. Members of this compound family have been used clinically for the treatment of heart conditions such as congestive heart failure, although toxicity and dosage issues mean that they are increasingly replaced with synthetic drugs such as ACE inhibitors and beta-blockers [368]. Clinical development as antiviral drugs has not yet been undertaken, but medicinal chemistry approaches have demonstrated the ability to improve antiviral activity and selectivity [369].…”

The use of animal models to study cell transplantation in neuropathic hearing loss

“…Ouabain is derived from Stropanthus gratus, a member of the liana family, whose leaves and seeds have been used for both traditional medicine and arrow poison in many African countries. Latterly, it has been adopted in Western medicine as an agent for the treatment of hypotension and cardiac issues (Whayne, 2018). It acts by inhibiting the α subunit of the Na + , K + -ATPase pump (NKA); NKA is a ubiquitous heterotrimeric enzyme consisting of catalytic α and β subunits and a regulatory γ subunit which work together to move sodium and potassium ions across cell membranes against their concentration gradient using ATP as an energy source.…”

Opportunities and Challenges in Development of Phytopharmaceutical Drug in India- A SWOT Analysis

“…17,18 Table 1 showed the list of few phytopharmaceuticals and their therapeutic benefits. [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] India has a well-established long history of safe and continuous use of many herbal drugs and phytopharmaceuticals through officially recognized alternative systems of health viz. Ayurveda, Yoga, Unani, Siddha, Homeopathy and Naturopathy.…”