Cardiac glycoside
Cardiac glycoside | |
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Na+ /K+ -ATPase | |
External links | |
MeSH | D002301 |
Legal status | |
In Wikidata |
Cardiac glycosides are a class of
Classification
General structure
The general structure of a cardiac glycoside consists of a steroid molecule attached to a sugar (glycoside) and an R group.[4] The steroid nucleus consists of four fused rings to which other functional groups such as methyl, hydroxyl, and aldehyde groups can be attached to influence the overall molecule's biological activity.[4] Cardiac glycosides also vary in the groups attached at either end of the steroid. Specifically, different sugar groups attached at the sugar end of the steroid can alter the molecule's solubility and kinetics; however, the lactone moiety at the R group end only serves a structural function.[5]
In particular, the structure of the ring attached at the R end of the molecule allows it to be classified as either a cardenolide or bufadienolide. Cardenolides differ from bufadienolides due to the presence of an "enolide," a five-membered ring with a single double bond, at the lactone end. Bufadienolides, on the other hand, contain a "dienolide," a six-membered ring with two double bonds, at the lactone end.[5] While compounds of both groups can be used to influence the cardiac output of the heart, cardenolides are more commonly used medicinally, primarily due to the widespread availability of the plants from which they are derived.
Classification
Cardiac glycosides can be more specifically categorized based on the plant they are derived from, as in the following list. For example, cardenolides have been primarily derived from the foxglove plants Plant cardenolides
Other cardenolides
Bufadienolides
Mechanism of action
Cardiac glycosides affect the
/Ca2+
. Thus, calcium ions are also not extruded and will begin to build up inside the cell as well.[12][13]
The disrupted calcium homeostasis and increased cytoplasmic calcium concentrations cause increased calcium uptake into the sarcoplasmic reticulum (SR) via the SERCA2 transporter. Raised calcium stores in the SR allow for greater calcium release on stimulation, so the myocyte can achieve faster and more powerful contraction by cross-bridge cycling.[1] The refractory period of the AV node is increased, so cardiac glycosides also function to decrease heart rate. For example, the ingestion of digoxin leads to increased cardiac output and decreased heart rate without significant changes in blood pressure; this quality allows it to be widely used medicinally in the treatment of cardiac arrhythmias.[1]
Non-cardiac uses
Cardiac glycosides were identified as
Clinical significance
Cardiac glycosides have long served as the main medical treatment to
Nevertheless, due to questions of toxicity and dosage, cardiac glycosides have been replaced with synthetic drugs such as ACE inhibitors and beta blockers and are no longer used as the primary medical treatment for such conditions. Depending on the severity of the condition, though, they may still be used in conjunction with other treatments.[11]
Toxicity
From ancient times, humans have used cardiac-glycoside-containing plants and their crude extracts as arrow coatings, homicidal or suicidal aids, rat poisons, heart tonics, diuretics and emetics, primarily due to the toxic nature of these compounds.[6] Thus, though cardiac glycosides have been used for their medicinal function, their toxicity must also be recognized. For example, in 2008 US poison centers reported 2,632 cases of digoxin toxicity, and 17 cases of digoxin-related deaths.[18] Because cardiac glycosides affect the cardiovascular, neurologic, and gastrointestinal systems, these three systems can be used to determine the effects of toxicity. The effect of these compounds on the cardiovascular system presents a reason for concern, as they can directly affect the function of the heart through their inotropic and chronotropic effects. In terms of inotropic activity, excessive cardiac glycoside dosage results in cardiac contractions with greater force, as further calcium is released from the SR of cardiac muscle cells. Toxicity also results in changes to heart chronotropic activity, resulting in multiple kinds of dysrhythmia and potentially fatal ventricular tachycardia. These dysrhythmias are an effect of an influx of sodium and decrease of resting membrane potential threshold in cardiac muscle cells. When taken beyond a narrow dosage range specific to each particular cardiac glycoside, these compounds can rapidly become dangerous. In sum, they interfere with fundamental processes that regulate membrane potential. They are toxic to the heart, the brain, and the gut at doses that are not difficult to reach. In the heart, the most common negative effect is premature ventricular contraction.[6][19]
References
- ^ PMID 27780131.
- PMID 24613328.
- PMID 21182478.
- ^ a b "Cardiac Glycosides". www.people.vcu.edu. Retrieved 2017-05-25.
- ^ ISBN 9780849369919.
- ^ a b c "Cardiac Glycoside Plant Poisoning: Practice Essentials, Pathophysiology, Etiology". Medscape. WebMD. 2017-05-05.
- ^ a b "Pharmacognosy 2|Digital Textbook Library". www.tankonyvtar.hu. Retrieved 2017-06-08.
- PMID 32252891.
- ISBN 978-0-85404-691-1.
- PMID 12608856.
- ^ ISBN 9781442564411.
- S2CID 1537056.
- ^ "CV Pharmacology | Cardiac Glycosides (Digitalis Compounds)". cvpharmacology.com. Retrieved 2017-06-08.
- PMID 34355491.
- PMID 31799499.
- PMID 31636264.
- ^ "How Is Heart Failure Treated? - NHLBI, NIH". www.nhlbi.nih.gov. Retrieved 2017-06-08.
- PMID 20028214.
- PMID 22998989.
External links
- Media related to Cardiac glycosides at Wikimedia Commons