The sixteenth century
Michael J. O’Dowd in The History of Medications for Women, 2020
Bernard de Gordon, professor at the famous French medical school of Montpellier, followed the fashion among medieval medical men and called his renowned book after a flower: Bernard’s manuscript, the Lilium Medicinae of 1303, was one of the most highly-regarded medical treatises of the era and was eventually published at Naples in 1480. The lily has been part of the materia medica of women since antiquity, used in the treatment of menstrual and uterovaginal disorders. Over the centuries oil of lily (and oil of almonds) was an important ingredient of the pharmacopoeia for labor, used to lubricate the mother’s vagina and the fingers of the probing midwives, and as an emollient to soothe the tissues of the birth canal. The lily-of-the-valley (Convallaria majus) contains cardiac glycosides similar to digoxin (Reynolds, 1996).
Heterocyclic Drugs from Plants
Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg in Promising Drug Molecules of Natural Origin, 2020
Cardiac glycosides inhibit the sodium-potassium ATPase pump that increases intracellular sodium (Schneider et al., 2017) which in turn accelerates the sodium-calcium exchange creating an elevation in intracellular calcium and an upgrading in cardiac contractility (Convallatoxin, 2003). The glycosides also increase cardiac vagal tone (an index of stress and stress vulnerability in mammals), which decreases cardiac sympathetic activity. Overdose of convallatoxin increases intracellular calcium which causes early after depolarization, cardiac irritability, and dysrhythmias. Although toxicity of cardiac glycoside is not common but based on other factors mild to severe toxicity may occur. In general, cardiac glycosides are administered orally and time to of action is about half an hour to two hours. The medication then peaks up between two to six hours and is excreted unchanged via kidney.
Physiological and Pathological Consequences of Streptozotocin Diabetes on the Heart
John H. McNeill in Experimental Models of Diabetes, 2018
Sarcolemmal Na+-K+-ATPase is considered to control the movement of sodium and potassium across the cell membrane. Myocardial contraction is initiated when an action potential depolarizes the sarcolemma. The action potential is triggered by an increase in sodium permeability that results in membrane depolarization. The outward movement of potassium down its concentration gradient achieves repolarization. It is evident, therefore, that a pump system is required to propel sodium out of the cell and potassium back into the cell to maintain the electrochemical gradient necessary to produce a resting membrane potential in order to establish the appropriate environment for subsequent action potentials. Depression of this sodium pump will alter the resting membrane potential and subsequently cardiac contraction. Indeed, Na+-K+-ATPase activity has been reported to be depressed in diabetic failing hearts.96 It must be pointed out that inhibition of the Na+-K+-ATPase system by agents such as cardiac glycosides is believed to be associated with an increase in intracellular calcium concentration and an increase in cardiac contractility. Thus, the role of the depressed Na+-K+-ATPase activity in explaining the diminished force of contraction under the pathophysiological situation of diabetes is unclear at present.
Foxglove poisoning: diagnostic and therapeutic differences with medicinal digitalis glycosides overdose
Published in Acta Clinica Belgica, 2022
Koen R. Maes, Pieter Depuydt, Joris Vermassen, Peter De Paepe, Walter Buylaert, Cathelijne Lyphout
Cardiac glycosides can be found in several plant leaves, flowers and seeds. These plants include but are not limited to foxglove (Digitalis purpurea), Digitalis lanata, lily of the valley (Convallaria majalis), oleander (Nerium oleander), yellow oleander (Thevetia peruviana), Strophanthus kombe, squill (Urginea maritima/sea onion/indica bulbs), dogbane (Apocynum cannabinum), and Adonis vernalisare [12]. It is important to realize that these plants contain not one but many different compounds with cardiac glycoside effects, such as digoxin, digitoxin, digitoxigenin and digoxigenin [13]. Many of these compounds have complex pharmacokinetic properties with entero-hepatic recirculation and biotransformation to active metabolites (including digoxin) and are eventually excreted by the kidneys. These characteristics result in a long plasma half-life of up to seven days [11]. The exact composition of these plants is known to be highly variable due to seasonal differences and genetic differences [13]. With regard to pharmacodynamics, the inotropic effects of different Digitalis purpurea leaf compounds have been compared by Lüllman et al. in animal studies, showing an almost equal inotropic dose-effect relationship for digoxin and digitoxin but other compounds such as digitoxigenin were shown to be even more potent. It is unknown whether these differences correlate with the risk of arrhythmias [14].
Neuroprotective effects of mitoquinone and oleandrin on Parkinson’s disease model in zebrafish
Published in International Journal of Neuroscience, 2020
İsmail Ünal, Esin Çalışkan-Ak, Ünsal V. Üstündağ, Perihan S. Ateş, Ahmet A. Alturfan, Meric A. Altinoz, Ilhan Elmaci, Ebru Emekli-Alturfan
In the MTT experiment, when mitoquinone and oleandrin were administered as neuroprotective agents against rotenone toxicity, both agents increased mitochondrial activity. Oleandrin is a cardiac glycoside that binds and inhibits Na +/K + -ATPase. Recently, new roles of cardiac glycosides in the regulation of various cellular processes have been demonstrated. Leaves and flowers have been reported to be cardiotonic, diuretic, anticancer, antibacterial, anti-fungal and expectorant [36]. In recent years, Nerium oleander has been reported to have neuroprotective activity as the herbal anticancer candidate ‘PBI-05204’ due to its oleandrin content [9]. The neuroprotective effect of oleandrin content of PBI-05204 has been suggested to be due to its neural BDNF expression enhancing effect [10].
Bibliometric profile of global scientific research on digoxin toxicity (1849–2015)
Published in Drug and Chemical Toxicology, 2020
Sa'ed H. Zyoud, William S. Waring, Samah W. Al-Jabi, Waleed M. Sweileh
Digoxin is a cardiac glycoside derived from the common foxglove digitalis purpurea and has been available for several centuries as a medicinal agent. Currently available pharmaceutical preparations include 62.5, 125, and 250 micrograms tablets, an elixir formulation containing 50 micrograms per milliliter, and intravenous ampules containing 100 or 250 micrograms per one milliliter. Its pharmacological mechanism of action is inhibition of sodium–potassium–ATPase pump, and it exerts positive inotropic effects on the myocardium and delays cardiac conduction at the atrio-ventricular node. It is used to treat chronic heart failure (CHF) and to control ventricular rate in patients with persistent or permanent atrial fibrillation. Despite extensive clinical experience over many years, there remains some controversy regarding the possibility that digoxin might have a deleterious effect on survival (Ziff and Kotecha 2016).
Related Knowledge Centers
- Arrhythmia
- Digitalis
- Methyl Group
- Organic Compound
- Secondary Metabolite
- Steroid
- Glycoside
- Heart Failure
- Sodium–Potassium Pump
- Hydroxy Group