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Cardiotonic agents, also known as cardiac inotropes or stimulants, have a positive impact on the myocardium (muscular layer of the heart) by enhancing its contractility. Unlike general inotropes, these agents exhibit a higher level of specificity as they selectively target the myocardium. They can be categorised into four distinct groups based on their unique mechanisms of action: cardiac glycosides, beta-adrenergic agonists, phosphodiesterase III inhibitors, and calcium sensitizers. It is important to note that certain medications, such as Milrinone and Digoxin, possess overlapping classifications due to their ability to engage multiple mechanisms of action. Their inotropic properties make cardiactonic agents critical in addressing inadequate perfusion, and acute heart failure conditions including cardiogenic shock, as well as for long-term management of heart failure. These conditions arise when the heart's ability to meet the body's needs is compromised.

Classification

1) Cardiac Glycosides

Mechanism of action

Mechanism of action of cardiac glycosides (Digitalis): inhibition of Na+/K+ ATPase

Cardiac glycosides like digoxin, primarily inhibit the sodium-potassium pump (Na+/K+ ATPase), an important protein located on the surface of cardiomyocytes (cardiac muscle cells). [1] [2] Using ATP (the cell’s energy currency), this protein facilitates the transport of extracellular potassium ions (K+) into the cell while exporting sodium ions (Na+) out, maintaining a balanced 1:1 exchange. [3] Thus, when this protein is blocked, Na+ accumulates within cardiomyocytes.

Moreover, cardiomyocytes possess another surface protein known as the sodium-calcium (Na+/Ca2+) exchanger. The accumulation of Na+ prompts its efflux from the cell, whilst concurrently allowing Ca2+ influx through this exchanger. [4]Consequently, intracellular Ca2+ levels rise.

The interaction between Ca2+ and Troponin C (TnC) is significant, as it prepares muscle fibres for the sliding filament mechanism, which explains muscle contraction. [5] With increased Ca2+ levels, interactions between Ca2+ and TnC intensify, leading to stronger contractions of the myocardiocytes. [6]Therapeutic doses of cardiac glycosides have been shown to enhance cardiac contractility, benefiting patients with impaired cardiac function, such as those with heart failure. [7]

Pharmacotherapy profile

Drug examples General indications Common side effects Cautions Special populations
Digoxin [8]

Digitalis [8]

Digitoxin [8]

Heart failure with reduced ejection fraction [9]

Atrial Fibrillation (abnormal heart rhythm) [9]

Dizziness [10] [11]

Nausea [10] [11]

Diarrhoea [10] [11]

Skin rashes [10] [11]

Vision disorders [10] [11]

Arrhythmias [10] [11]

Vomiting [10] [11]

Impaired renal function [12]

Thyroid disorders [12]

Acute coronary syndrome (blood flow to heart muscle suddenly blocked) [12]

Electrolyte disorders ( hypercalcemia, hypokalemia, hypomagnesemia) [13]

Pregnancy: can be used, may require dosage adjustment [14]

Breastfeeding: amount found in breast milk is is insignificant, harm caused to foetus not well studied [15]

Renally impaired: consider reducing initial and maintenance doses [16]

2) Beta-adrenergic agonists

Mechanism of action

General mechanism of action of beta-adrenergic agonists: activation of β1 / β2 receptors

Naturally produced hormones norepinephrine and epinephrine or synthetic drugs such as dobutamine can be collectively regarded as beta-agonists. Specifically, dobutamine selectively binds to β1 receptors located on the surface of specialised cardiac muscle cells. [17] Relative to β2 receptors, β1 is the predominant type in terms of quantity and function within the heart. [18]

Gs proteins are a subunit of a large family of receptors called G-protein-coupled receptors (GPCRs). [19] Due to the coupling nature between β1, Gs proteins, and the enzyme adenylyl cyclase, activation of Gs proteins ultimately activates adenylyl cyclase, which is responsible for converting ATP into cAMP. [20] Thus, beta-agonists will lead to elevated cAMP levels, which further activate a cAMP-dependent protein called protein-kinase A (PK-A). [21]PK-A plays a pivotal role in increasing intracellular Ca2+ levels through 2 mechanisms:

Similar to the MoA of cardiac glycosides, elevated Ca2+ eventually translates into stronger cardiac contractile force.

Pharmacotherapy profile

Drug examples General Indications Common side effects Precautions Special populations
Epinephrine [25]

Norepinephrine [25]

Dopamine [25]

Dobutamine [25]

Isoproterenol [25]

Anaphylactic shock [26] [27]

Cardiogenic shock [26] [27]

Cardiac arrest [26] [27]

Severe hypotension [26] [27]

Decompensated heart failure [26] [27]

Atrioventricular block (malfunction in heart's electrical system) [26] [27]

Arrhythmias (abnormal heart rhythm) [28] [29]

Chest pain [28] [29]

Hypertension [28] [29]

Palpitations [28] [29]

Anxiety [28] [29]

Acute myocardial infarction (heart attack) [29] [30]

Atherosclerosis (clogging of blood vessel wall) [29] [30]

Arrhythmias [29] [30]

Diabetes mellitus [29] [30]

Immediate use in cardiogenic shock or severe hypotension at risk of organ damage [31] [32]

3) Phosphodiesterase (III) inhibitors

Mechanism of action

Mechanism of action of PDE III inhibitors: inhibition of PDE3 enzyme

PDE3 inhibitors exert their effects by blocking the activity of an enzyme called PDE3. This enzyme is responsible for breaking down a molecule called cAMP, which is the key signalling molecule in our body. [33] When PDE3 is inhibited, the breakdown of cAMP is prevented, leading to increased levels of cAMP in our cells. [34]

In our heart muscle cells, when the levels of cAMP rise, it activates a protein called protein kinase A (PKA). [34] PKA acts as a switch, triggering a cascade of events that enhance the strength and efficiency of the heart's contractions. [35] This ultimately leads to improved cardiac function.

PDE3 inhibitors also have an impact on the smooth muscles found in our blood vessels. By increasing cAMP levels, these medications cause the smooth muscles to relax. [36] This relaxation has a significant benefit in our blood vessels as it leads to vasodilation, which means the blood vessels widen. [37] [38] Vasodilation helps to reduce resistance against blood flow, allowing for better circulation throughout the body. [39]

Furthermore, PDE3 inhibitors exhibit an additional effect on platelets, which are small cell fragments involved in blood clotting. [40] Increased levels of cAMP in platelets prevent their activation and reduce their ability to form blood clots. [41] By inhibiting platelet aggregation, PDE3 inhibitors contribute to maintaining healthy and smooth blood flow. [41]

Pharmacotherapy profile

Drug examples Indications Common side effects Precautions Special populations
Anagrelide [42] [43]

Cilostazol [42] [43]

Milrinone [42] [43]

Heart Failure [44]

Pulmonary Hypertension in babies [45]

Peripheral Vascular Disease [45]

Asthma [46]

Chronic Obstructive Pulmonary Disease (lung disease) [46]

Gastrointestinal discomfort [47]

Tachycardia (heart rate too fast) [47] Rapid drop in Weight [48]

Headaches [48]

Dizziness [48]

Insomnia [48]

Psychological disorder (for example anxiety) [49]

Compromised liver or kidney function with drugs that inhibit an enzyme called CYP3A4 [50]

Pre-existing ophthalmopathy (eye disorders) [51]

Avoid usage during pregnancy as it can inhibit meiosis, a specific form of cell division that takes place in oocytes, which are specialized reproductive cells in females [52]

4) Calcium sensitisers

Mechanism of action

Mechanism of action of calcium sensitizers: increase sensitivity of troponin C to Ca2+

Calcium is a vital element for regulating the contraction and relaxation of the heart muscle. [53] Calcium sensitizers are medications that increase the responsiveness of heart muscle cells to calcium, enabling more forceful contractions while conserving energy. [54] Contraction of the heart muscle relies on electrical signals that trigger the release of calcium ions. These calcium ions bind to a protein called troponin, which initiates the process of muscle contraction. [55]

Calcium sensitizers function by binding to cardiac troponin C, thereby enhancing the sensitivity of heart muscle cells to naturally occurring calcium ions. [56] This heightened sensitivity fosters a more efficient interaction between calcium and the contractile apparatus of the heart muscle. [57] Consequently, calcium can more effectively bind to actin- myosin filaments, resulting in stronger contractions without excessive calcium accumulation. [57] By reducing strain on the heart, this mechanism helps minimise the oxygen demand.

Furthermore, calcium sensitizers provide an additional benefit. They open potassium channels in the heart muscle cells, resulting in vasodilation and improved blood flow. [58] This action reduces the workload on the heart.

Pharmacotherapy profile

Drug examples Indications Common side effects Precautions Special populations
Levosimendan [59]

Milrinone [59]

Digoxin [59]

Heart failure (but no significant reduction in mortality) [60] [61]

Cardiogenic Shock [62]

Pulmonary Hypertension [63]

Post-Cardiac Surgery [64] [65]

Isolated tongue swelling [66]

Headache [66]

Nausea [66]

Palpitation [66]

Injection site irritation [67]

Renal and hepatic impairment [68] [69]

Electrolyte imbalance [70] [71]

Patients with prolong QT wave in ECG (abnormal repolarize time of heart) [72] [73]

Compelling indication in elderly patients with heart failure [74]

Positive effects in improving cardiac functions in paediatric (young) patients [75]

Clinical role in heart failure

Cardiotonic agents are typically employed as short-term and non-routine therapies for heart failure patients. [76] They are specifically reserved for those with contractile dysfunction in the left ventricles (lower chambers of the heart), low cardiac output, and low blood pressure, placing them at risk of inadequate organ perfusion. [77]While these agents assist in promoting perfusion, their potential for increased mortality and adverse side effects necessitates cautious administration at initially low doses, with careful adjustments under close monitoring. [78] [79]Given the diverse presentations of heart failure and individual patient characteristics, cardiotonic medication uses and preferences vary.

Cardiogenic shock leads to many harmful physiological effects

Specifically, in patients experiencing inadequate blood perfusion (with blood pressure below 80 mmHg), the American Heart Association / American College of Cardiology (ACC/AHA), recommends the use of Dobutamine and Milrinone. [80] Whereas in clinically stable patients with sufficient perfusion, cardiac inotrope use is advised against. [81] This caution is due to the heightened risk of adverse cardiovascular outcomes, including arrhythmias, detrimental heart structure remodelling, and even mortality. [82] [83]Heart failure can manifest in its life-threatening form of cardiogenic shock, with hypotension and low blood flow (hypoperfusion), placing the patient at risk of multiorgan failure. [84] In cardiogenic shock management, cardiotonic agents serve 2 functions. Norepinephrine, epinephrine, dopamine, and phenylephrine contribute mainly through their vasopressor (vasoconstrictive) functions to constrict blood vessels to correct hypotension. Whereas, dobutamine, milrinone, enoximone, and levosimendan, act to restore the heart’s pumping function. [85] To prevent further harm to the organs, cardiotonic agents are typically administered alongside oxygen, ventilatory support, and mechanical circulatory support (MCS). [86]As hypoperfusion and organ dysfunction improve, it is recommended to gradually reduce the administration of these agents. [86] However, certain patients who are unable to discontinue cardiotonic agents without experiencing recurrent heart failure symptoms, known as inotropic-dependent patients, may require prolonged usage. [87] This serves as a bridge towards more invasive management approaches, such as transplants or left ventricular assist devices (medical device to assist the heart). [88]

Heart failure patients are stratified based on their left ventricular ejection fraction, which quantifies the volume of blood expelled from the heart's lower chambers (ventricles) with each contraction. [89]According to the European Society of Cardiology (ESC), among cardiotonic agents, Digoxin is specifically recommended as a second-line option for patients with an abnormal left ventricular ejection fraction (≤40%). [90] Digoxin helps alleviate symptoms and reduce hospitalizations related to heart failure, but it does not offer any mortality-reducing benefits. [91] Digoxin may be considered in patients who remain symptomatic despite receiving treatment with a first-line combination of an ACE inhibitor (or ARNI), a beta-blocker, and a mineralocorticoid receptor antagonist (MRA). [92] It is also considered in patients with atrial fibrillation - a heart rhythm disorder characterised by irregular electrical impulses in the atria (the upper chambers of the heart). [93] This abnormal electrical activity causes the atria to contract erratically, resulting in an irregular heartbeat. [94] Treatment primarily focuses on restoring normal heart rhythm and controlling the heart rate to minimise the risk of complications, including stroke. According to the ACC/AHA guidelines, intravenous digoxin (cardiac glycoside) can be used in atrial fibrillation (Afib) to assist heartbeats. [95] In multicenter randomised controlled trials, intravenous digoxin was shown to be effective in controlling the heart rate compared to a placebo. [96] [97]

References

  1. ^ "Cases | Pharmacotherapy Principles & Practice | McGraw Hill Medical". ppp.mhmedical.com. Retrieved 2024-04-05.
  2. ^ Haviv, H.; Karlish, S. J. D. (2013-01-01), "P-Type Pumps: Na+,K+-ATPase", in Lennarz, William J.; Lane, M. Daniel (eds.), Encyclopedia of Biological Chemistry (Second Edition), Waltham: Academic Press, pp. 681–687, ISBN  978-0-12-378631-9, retrieved 2024-04-05
  3. ^ Pirahanchi, Yasaman; Jessu, Rishita; Aeddula, Narothama R. (2024), "Physiology, Sodium Potassium Pump", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  30725773, retrieved 2024-04-05
  4. ^ Ottolia, Michela; John, Scott; Hazan, Adina; Goldhaber, Joshua I. (2021-12-29). "The Cardiac Na+-Ca2+ Exchanger: From Structure to Function". Comprehensive Physiology. 12 (1): 2681–2717. doi: 10.1002/cphy.c200031. ISSN  2040-4603. PMC  8773166. PMID  34964124.
  5. ^ Ohtsuki, Iwao; Morimoto, Sachio; Kitainda, Vivian (2021-01-01), "Structural Proteins | Troponin☆", in Jez, Joseph (ed.), Encyclopedia of Biological Chemistry III (Third Edition), Oxford: Elsevier, pp. 695–700, doi: 10.1016/b978-0-12-819460-7.00204-8, ISBN  978-0-12-822040-5, retrieved 2024-04-05
  6. ^ Eisner, David A.; Caldwell, Jessica L.; Kistamás, Kornél; Trafford, Andrew W. (2017-07-07). "Calcium and Excitation-Contraction Coupling in the Heart". Circulation Research. 121 (2): 181–195. doi: 10.1161/CIRCRESAHA.117.310230. ISSN  0009-7330. PMC  5497788. PMID  28684623.
  7. ^ Bavendiek, Udo; Berliner, Dominik; Dávila, Lukas Aguirre; Schwab, Johannes; Maier, Lars; Philipp, Sebastian A.; Rieth, Andreas; Westenfeld, Ralf; Piorkowski, Christopher; Weber, Kristina; Hänselmann, Anja; Oldhafer, Maximiliane; Schallhorn, Sven; von der Leyen, Heiko; Schröder, Christoph (May 2019). "Rationale and design of the DIGIT-HF trial (DIGitoxin to Improve ouTcomes in patients with advanced chronic Heart Failure): a randomized, double-blind, placebo-controlled study". European Journal of Heart Failure. 21 (5): 676–684. doi: 10.1002/ejhf.1452. ISSN  1388-9842. PMC  6607489. PMID  30892806.
  8. ^ a b c "Cardiac Glycosides: Types and What They Treat". Cleveland Clinic. Retrieved 2024-04-05.
  9. ^ a b Gheorghiade, Mihai; Adams, Kirkwood F.; Colucci, Wilson S. (2004-06-22). "Digoxin in the Management of Cardiovascular Disorders". Circulation. 109 (24): 2959–2964. doi: 10.1161/01.CIR.0000132482.95686.87. ISSN  0009-7322. PMID  15210613.
  10. ^ a b c d e f g "Side effects of digoxin". nhs.uk. 2021-09-15. Retrieved 2024-04-05.
  11. ^ a b c d e f g Papich, Mark G. (2016-01-01), Papich, Mark G. (ed.), "Digoxin", Saunders Handbook of Veterinary Drugs (Fourth Edition), St. Louis: W.B. Saunders, pp. 241–242, ISBN  978-0-323-24485-5, retrieved 2024-04-05
  12. ^ a b c Gheorghiade, Mihai; Adams, Kirkwood F.; Colucci, Wilson S. (2004-06-22). "Digoxin in the Management of Cardiovascular Disorders". Circulation. 109 (24): 2959–2964. doi: 10.1161/01.CIR.0000132482.95686.87. ISSN  0009-7322. PMID  15210613.
  13. ^ D, Anandhi; Pandit, Vinay R.; Kadhiravan, Tamilarasu; R, Soundaravally; Prakash Raju, K. N. J. (February 2019). "Cardiac arrhythmias, electrolyte abnormalities and serum cardiac glycoside concentrations in yellow oleander (Cascabela thevetia) poisoning - a prospective study". Clinical Toxicology (Philadelphia, Pa.). 57 (2): 104–111. doi: 10.1080/15563650.2018.1499930. ISSN  1556-9519. PMID  30073854.
  14. ^ "Cardiovascular Disease Medication During Pregnancy". American College of Cardiology. Retrieved 2024-04-05.
  15. ^ "Pregnancy, breastfeeding and fertility while taking digoxin". nhs.uk. 2021-09-15. Retrieved 2024-04-05.
  16. ^ Li, Xiaozhao; Ao, Xiang; Liu, Qiong; Yang, Jinghua; Peng, Weisheng; Tang, Rong; Zhong, Yong; Meng, Ting; Gan, Lu; Zhou, Qiaoling (2014-12-01). "Intermittent low‑dose digoxin may be effective and safe in patients with chronic heart failure undergoing maintenance hemodialysis". Experimental and Therapeutic Medicine. 8 (6): 1689–1694. doi: 10.3892/etm.2014.2013. ISSN  1792-0981. PMC  4218698. PMID  25371716.
  17. ^ Farzam, Khashayar; Kidron, Ariel; Lakhkar, Anand D. (2024), "Adrenergic Drugs", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  30480963, retrieved 2024-04-05
  18. ^ Alhayek, Soubhi; Preuss, Charles V. (2024), "Beta 1 Receptors", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  30422499, retrieved 2024-04-05
  19. ^ Navarro, Gemma; Cordomí, Arnau; Brugarolas, Marc; Moreno, Estefanía; Aguinaga, David; Pérez-Benito, Laura; Ferre, Sergi; Cortés, Antoni; Casadó, Vicent; Mallol, Josefa; Canela, Enric I.; Lluís, Carme; Pardo, Leonardo; McCormick, Peter J.; Franco, Rafael (2018-02-28). "Cross-communication between Gi and Gs in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain". BMC Biology. 16 (1): 24. doi: 10.1186/s12915-018-0491-x. ISSN  1741-7007. PMC  6389107. PMID  29486745.
  20. ^ Navarro, Gemma; Cordomí, Arnau; Casadó-Anguera, Verónica; Moreno, Estefanía; Cai, Ning-Sheng; Cortés, Antoni; Canela, Enric I.; Dessauer, Carmen W.; Casadó, Vicent; Pardo, Leonardo; Lluís, Carme; Ferré, Sergi (2018-03-28). "Evidence for functional pre-coupled complexes of receptor heteromers and adenylyl cyclase". Nature Communications. 9 (1): 1242. Bibcode: 2018NatCo...9.1242N. doi: 10.1038/s41467-018-03522-3. ISSN  2041-1723. PMC  5871782. PMID  29593213.
  21. ^ Howe, Alan K. (October 2011). "Cross-talk between calcium and protein kinase A in the regulation of cell migration". Current Opinion in Cell Biology. 23 (5): 554–561. doi: 10.1016/j.ceb.2011.05.006. ISSN  0955-0674. PMC  3175278. PMID  21665456.
  22. ^ Nystoriak, Matthew A.; Nieves-Cintrón, Madeline; Patriarchi, Tommaso; Buonarati, Olivia R.; Prada, Maria Paz; Morotti, Stefano; Grandi, Eleonora; Fernandes, Julia Dos Santos; Forbush, Katherine; Hofmann, Franz; Sasse, Kent C.; Scott, John D.; Ward, Sean M.; Hell, Johannes W.; Navedo, Manuel F. (2017-01-24). "Ser1928 phosphorylation by PKA stimulates the L-type Ca2+ channel CaV1.2 and vasoconstriction during acute hyperglycemia and diabetes". Science Signaling. 10 (463): eaaf9647. doi: 10.1126/scisignal.aaf9647. ISSN  1945-0877. PMC  5297430. PMID  28119464.
  23. ^ Beard, Nicole A.; Wei, Lan; Cheung, Stephanie N.; Kimura, Takashi; Varsányi, Magdolna; Dulhunty, Angela F. (2008-10-01). "Phosphorylation of skeletal muscle calsequestrin enhances its Ca2+ binding capacity and promotes its association with junctin". Cell Calcium. 44 (4): 363–373. doi: 10.1016/j.ceca.2008.01.005. ISSN  0143-4160. PMID  19230141.
  24. ^ Rossi, Daniela; Pierantozzi, Enrico; Amadsun, David Osamwonuyi; Buonocore, Sara; Rubino, Egidio Maria; Sorrentino, Vincenzo (April 2022). "The Sarcoplasmic Reticulum of Skeletal Muscle Cells: A Labyrinth of Membrane Contact Sites". Biomolecules. 12 (4): 488. doi: 10.3390/biom12040488. ISSN  2218-273X. PMC  9026860. PMID  35454077.
  25. ^ a b c d e "Beta-agonist Medications". Cleveland Clinic. Retrieved 2024-04-05.
  26. ^ a b c d e f "Dopamine". go.drugbank.com. Retrieved 2024-04-05.
  27. ^ a b c d e f "Dopamine: Side Effects, Uses, Dosage, Interactions, Warnings". RxList. Retrieved 2024-04-05.
  28. ^ a b c d e Sears, Malcolm R. (December 2002). "Adverse effects of β-agonists". Journal of Allergy and Clinical Immunology. 110 (6): S322–S328. doi: 10.1067/mai.2002.129966. ISSN  0091-6749. PMID  12464943.
  29. ^ a b c d e f g h i Farzam, Khashayar; Kidron, Ariel; Lakhkar, Anand D. (2024), "Adrenergic Drugs", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  30480963, retrieved 2024-04-05
  30. ^ a b c d RN, Iris Dawn Tabangcora (2017-07-11). "Adrenergic Agonists (Sympathomimetics) Nursing Pharmacology Study Guide". Nurseslabs. Retrieved 2024-04-05.
  31. ^ VanValkinburgh, Danny; Kerndt, Connor C.; Hashmi, Muhammad F. (2024), "Inotropes and Vasopressors", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  29494018, retrieved 2024-04-05
  32. ^ Manolopoulos, Philip Panagiotis; Boutsikos, Ioannis; Boutsikos, Panagiotis; Iacovidou, Nicoletta; Ekmektzoglou, Konstantinos (2020-04-10). "Current use and advances in vasopressors and inotropes support in shock". Journal of Emergency and Critical Care Medicine. 4: 20. doi: 10.21037/jeccm.2019.12.03. ISSN  2521-3563.
  33. ^ "Phosphodiesterase III Inhibitor - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-04-07.
  34. ^ a b Padda, Inderbir S.; Tripp, Jayson (2024), "Phosphodiesterase Inhibitors", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  32644702, retrieved 2024-04-07
  35. ^ "Protein Kinase A - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-04-07.
  36. ^ "Phosphodiesterase Inhibitor - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-04-07.
  37. ^ "Phosphodiesterase Inhibitor - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-04-07.
  38. ^ "Increased Venous Return - Circulatory Effects - Physiological Effects Of Massage - Massage - Treatments - Physio.co.uk". www.physio.co.uk. Retrieved 2024-04-07.
  39. ^ Ramanlal, Riddhi; Gupta, Vikas (2024), "Physiology, Vasodilation", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  32491494, retrieved 2024-04-07
  40. ^ Gresele, Paolo; Momi, Stefania; Falcinelli, Emanuela (October 2011). "Anti-platelet therapy: phosphodiesterase inhibitors". British Journal of Clinical Pharmacology. 72 (4): 634–646. doi: 10.1111/j.1365-2125.2011.04034.x. ISSN  0306-5251. PMC  3195739. PMID  21649691.
  41. ^ a b Zhang, Wei; Colman, Robert W. (2007-09-01). "Thrombin regulates intracellular cyclic AMP concentration in human platelets through phosphorylation/activation of phosphodiesterase 3A". Blood. 110 (5): 1475–1482. doi: 10.1182/blood-2006-10-052522. ISSN  0006-4971. PMC  1975837. PMID  17392505.
  42. ^ a b c "PDE3 Inhibitor - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-04-05.
  43. ^ a b c Padda, Inderbir S.; Tripp, Jayson (2024), "Phosphodiesterase Inhibitors", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  32644702, retrieved 2024-04-05
  44. ^ "Phosphodiesterase 3 Inhibitors | DrugBank Online". go.drugbank.com. Retrieved 2024-04-05.
  45. ^ a b van der Lee, Robin; Peels, Barbara; Koopman-Esseboom, Corine (January 2017). "PDE3 inhibition with enoximone as first-line therapy for severe persistent pulmonary hypertension of the newborn during neonatal transport: a case report". Clinical Case Reports. 5 (1): 18–21. doi: 10.1002/ccr3.748. ISSN  2050-0904. PMC  5224780. PMID  28096983.
  46. ^ a b www.amboss.com https://www.amboss.com/us/knowledge/phosphodiesterase-inhibitors. Retrieved 2024-04-05. {{ cite web}}: Missing or empty |title= ( help)
  47. ^ a b "How Do PDE-3 Inhibitors Work? - Uses, Side Effects, Drug Names". RxList. Retrieved 2024-04-05.
  48. ^ a b c d Padda, Inderbir S.; Tripp, Jayson (2024), "Phosphodiesterase Inhibitors", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  32644702, retrieved 2024-04-05
  49. ^ "Phosphodiesterase Inhibitors: Types and Purpose". Cleveland Clinic. Retrieved 2024-04-05.
  50. ^ "PDE3 Inhibitor - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-04-05.
  51. ^ Moschos, Marilita M; Nitoda, Eirini (2016-10-19). "Pathophysiology of visual disorders induced by phosphodiesterase inhibitors in the treatment of erectile dysfunction". Drug Design, Development and Therapy. 10: 3407–3413. doi: 10.2147/DDDT.S118015. ISSN  1177-8881. PMC  5076796. PMID  27799745.
  52. ^ Li, Min; Yu, Yang; Yan, Jie; Yan, Li-Ying; Zhao, Yue; Li, Rong; Liu, Ping; Hsueh, Aaron J.; Qiao, Jie (2012). "The role of cilostazol, a phosphodiesterase 3 inhibitor, on oocyte maturation and subsequent pregnancy in mice". PLOS ONE. 7 (1): e30649. Bibcode: 2012PLoSO...730649L. doi: 10.1371/journal.pone.0030649. ISSN  1932-6203. PMC  3265514. PMID  22292006.
  53. ^ Eisner, David A.; Caldwell, Jessica L.; Kistamás, Kornél; Trafford, Andrew W. (2017-07-07). "Calcium and Excitation-Contraction Coupling in the Heart". Circulation Research. 121 (2): 181–195. doi: 10.1161/CIRCRESAHA.117.310230. ISSN  0009-7330. PMC  5497788. PMID  28684623.
  54. ^ Lehmann, Andreas; Boldt, Joachim; Kirchner, Jürgen (October 2003). "The role of Ca++-sensitizers for the treatment of heart failure". Current Opinion in Critical Care. 9 (5): 337–344. doi: 10.1097/00075198-200310000-00002. ISSN  1070-5295. PMID  14508145.
  55. ^ "Calcium Sensitizer - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-04-07.
  56. ^ Li, Monica X.; Gelozia, Shorena; Danmaliki, Gaddafi I.; Wen, Yurong; Liu, Philip B.; Lemieux, M. Joanne; West, Frederick G.; Sykes, Brian D.; Hwang, Peter M. (2018-11-01). "The calcium sensitizer drug MCI-154 binds the structural C-terminal domain of cardiac troponin C". Biochemistry and Biophysics Reports. 16: 145–151. doi: 10.1016/j.bbrep.2018.10.012. ISSN  2405-5808. PMC  6218639. PMID  30417133.
  57. ^ a b Kuo, Ivana Y.; Ehrlich, Barbara E. (February 2015). "Signaling in Muscle Contraction". Cold Spring Harbor Perspectives in Biology. 7 (2): a006023. doi: 10.1101/cshperspect.a006023. ISSN  1943-0264. PMC  4315934. PMID  25646377.
  58. ^ Priest, Birgit T; McDermott, Jeff S (2015-08-20). "Cardiac ion channels". Channels. 9 (6): 352–359. doi: 10.1080/19336950.2015.1076597. ISSN  1933-6950. PMC  4850049. PMID  26556552.
  59. ^ a b c "Cardiotonic Agents | DrugBank Online". go.drugbank.com. Retrieved 2024-04-05.
  60. ^ Sakata, Yasushi (April 2013). "[Clinical significance of calcium sensitizer]". Clinical Calcium. 23 (4): 575–582. ISSN  0917-5857. PMID  23545748.
  61. ^ Louhelainen, Marjut; Merasto, Saara; Finckenberg, Piet; Vahtola, Erik; Kaheinen, Petri; Levijoki, Jouko; Mervaala, Eero (May 2010). "Effects of the calcium sensitizer OR-1896, a metabolite of levosimendan, on post-infarct heart failure and cardiac remodelling in diabetic Goto–Kakizaki rats". British Journal of Pharmacology. 160 (1): 142–152. doi: 10.1111/j.1476-5381.2010.00680.x. ISSN  0007-1188. PMC  2860214. PMID  20412071.
  62. ^ "Early Utilization of Mechanical Circulatory Support in Acute Myocardial Infarction Complicated by Cardiogenic Shock | HeartRecovery.com". www.heartrecovery.com. Retrieved 2024-04-05.
  63. ^ Tsapenko, Mykola V; Tsapenko, Arseniy V; Comfere, Thomas BO; Mour, Girish K; Mankad, Sunil V; Gajic, Ognjen (October 2008). "Arterial pulmonary hypertension in noncardiac intensive care unit". Vascular Health and Risk Management. 4 (5): 1043–1060. doi: 10.2147/vhrm.s3998. ISSN  1176-6344. PMC  2605326. PMID  19183752.
  64. ^ Leivaditis, Vasileios; Grapatsas, Konstantinos; Papaporfyriou, Anastasia; Galanis, Michail; Koletsis, Efstratios; Charokopos, Nikolaos; Haussmann, Erich; Kaplunov, Vladislav; Papatriantafyllou, Athanasios; Dahm, Manfred (August 2023). "The Perioperative Use of Levosimendan as a Means of Optimizing the Surgical Outcome in Patients with Severe Heart Insufficiency Undergoing Cardiac Surgery". Journal of Cardiovascular Development and Disease. 10 (8): 332. doi: 10.3390/jcdd10080332. ISSN  2308-3425. PMC  10455812. PMID  37623345.
  65. ^ Beiras-Fernandez, Andres; Kornberger, Angela; Oberhoffer, Martin; Kur, Felix; Weis, Marion; Vahl, Christian-Friedrich; Weis, Florian (August 2019). "Levosimendan as rescue therapy in low output syndrome after cardiac surgery: effects and predictors of outcome". The Journal of International Medical Research. 47 (8): 3502–3512. doi: 10.1177/0300060519835087. ISSN  0300-0605. PMC  6726822. PMID  30909776.
  66. ^ a b c d Dal, Aleyna; Taslidere, Bahadir (2023-04-30). "Unusual Excessive Swelling of the Tongue after Calcium Acetate Ingestion: A Case Report". Eurasian Journal of Toxicology. 5 (1): 17–19. doi: 10.51262/ejtox.1236194. ISSN  2667-8675.
  67. ^ Lehtonen, Lasse (2004-09-01). "Levosimendan: A calcium-sensitizing agent for the treatment of patients with decompensated heart failure". Current Heart Failure Reports. 1 (3): 136–144. doi: 10.1007/s11897-004-0023-6. ISSN  1546-9549. PMID  16036037.
  68. ^ Masarone, Daniele; Kittleson, Michelle M.; Pollesello, Piero; Marini, Marco; Iacoviello, Massimo; Oliva, Fabrizio; Caiazzo, Angelo; Petraio, Andrea; Pacileo, Giuseppe (2022-10-29). "Use of Levosimendan in Patients with Advanced Heart Failure: An Update". Journal of Clinical Medicine. 11 (21): 6408. doi: 10.3390/jcm11216408. ISSN  2077-0383. PMC  9659135. PMID  36362634.
  69. ^ academic.oup.com https://academic.oup.com/ced/article-abstract/28/1/34/6627092?login=false. Retrieved 2024-04-05. {{ cite web}}: Missing or empty |title= ( help)
  70. ^ Verzicco, Ignazio; Regolisti, Giuseppe; Quaini, Federico; Bocchi, Pietro; Brusasco, Irene; Ferrari, Massimiliano; Passeri, Giovanni; Cannone, Valentina; Coghi, Pietro; Fiaccadori, Enrico; Vignali, Alessandro; Volpi, Riccardo; Cabassi, Aderville (2020-05-19). "Electrolyte Disorders Induced by Antineoplastic Drugs". Frontiers in Oncology. 10: 779. doi: 10.3389/fonc.2020.00779. ISSN  2234-943X. PMC  7248368. PMID  32509580.
  71. ^ Kass, David A.; Solaro, R. John (2006-01-17). "Mechanisms and Use of Calcium-Sensitizing Agents in the Failing Heart". Circulation. 113 (2): 305–315. doi: 10.1161/CIRCULATIONAHA.105.542407. ISSN  0009-7322. PMID  16418450.
  72. ^ Liu, Peng; Wang, Lu; Han, Dan; Sun, Chaofeng; Xue, Xiaolin; Li, Guoliang (2020). "Acquired long QT syndrome in chronic kidney disease patients". Renal Failure. 42 (1): 54–65. doi: 10.1080/0886022X.2019.1707098. ISSN  0886-022X. PMC  6968512. PMID  31878817.
  73. ^ "Drug-induced QT prolongation and Torsades de Pointes - the facts". www.medsafe.govt.nz. Retrieved 2024-04-05.
  74. ^ Zhang, Dengqing; Yao, Yuanqing; Qian, Jun; Huang, Jing (2015-08-20). "Levosimendan Improves Clinical Outcomes of Refractory Heart Failure in Elderly Chinese Patients". Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 21: 2439–2445. doi: 10.12659/MSM.893580. ISSN  1234-1010. PMC  4548701. PMID  26289557.
  75. ^ Silvetti, Simona; Silvani, Paolo; Azzolini, Maria Luisa; Dossi, Roberto; Landoni, Giovanni; Zangrillo, Alberto (2015). "A systematic review on levosimendan in paediatric patients". Current Vascular Pharmacology. 13 (1): 128–133. doi: 10.2174/1570161112666141127163536. ISSN  1875-6212. PMID  25440597.
  76. ^ Hansen, Benjamin Lautrup; Kristensen, Søren Lund; Gustafsson, Finn (2024-01-18). "Use of Inotropic Agents in Advanced Heart Failure: Pros and Cons". Cardiology: 1–15. doi: 10.1159/000536373. ISSN  0008-6312. PMID  38237564.
  77. ^ Authors/Task Force Members; McDonagh, Theresa A.; Metra, Marco; Adamo, Marianna; Gardner, Roy S.; Baumbach, Andreas; Böhm, Michael; Burri, Haran; Butler, Javed; Čelutkienė, Jelena; Chioncel, Ovidiu; Cleland, John G.F.; Coats, Andrew J.S.; Crespo-Leiro, Maria G.; Farmakis, Dimitrios (January 2022). "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC". European Journal of Heart Failure. 24 (1): 4–131. doi: 10.1002/ejhf.2333. hdl: 2434/966600. ISSN  1388-9842. PMID  35083827.
  78. ^ Ahmad, Tariq; Miller, P. Elliott; McCullough, Megan; Desai, Nihar R.; Riello, Ralph; Psotka, Mitchell; Böhm, Michael; Allen, Larry A.; Teerlink, John R.; Rosano, Giuseppe M. C.; Lindenfeld, Joann (September 2019). "Why has positive inotropy failed in chronic heart failure? Lessons from prior inotrope trials". European Journal of Heart Failure. 21 (9): 1064–1078. doi: 10.1002/ejhf.1557. ISSN  1879-0844. PMC  6774302. PMID  31407860.
  79. ^ Bistola, V.; Chioncel, O. (September 2017). "Inotropes in acute heart failure". Continuing Cardiology Education. 3 (3): 107–116. doi: 10.1002/cce2.59. ISSN  2059-1594.
  80. ^ Goldhaber, Joshua I.; Hamilton, Michele A. (2010-04-13). "Role of Inotropic Agents in the Treatment of Heart Failure". Circulation. 121 (14): 1655–1660. doi: 10.1161/CIRCULATIONAHA.109.899294. ISSN  0009-7322. PMC  2861129. PMID  20385962.
  81. ^ Nagao, Kazuya; Kato, Takao; Yaku, Hidenori; Morimoto, Takeshi; Inuzuka, Yasutaka; Tamaki, Yodo; Yamamoto, Erika; Yoshikawa, Yusuke; Kitai, Takeshi; Taniguchi, Ryoji; Iguchi, Moritake; Kato, Masashi; Takahashi, Mamoru; Jinnai, Toshikazu; Ikeda, Tomoyuki (2022-01-01). "Current use of inotropes according to initial blood pressure and peripheral perfusion in the treatment of congestive heart failure: findings from a multicentre observational study". BMJ Open. 12 (1): e053254. doi: 10.1136/bmjopen-2021-053254. ISSN  2044-6055. PMC  8783828. PMID  35058261.
  82. ^ academic.oup.com https://academic.oup.com/eurheartj/article/40/44/3626/5123545. Retrieved 2024-04-05. {{ cite web}}: Missing or empty |title= ( help)
  83. ^ Bistola, Vasiliki; Arfaras-Melainis, Angelos; Polyzogopoulou, Eftihia; Ikonomidis, Ignatios; Parissis, John (2019-09-11). "Inotropes in Acute Heart Failure: From Guidelines to Practical Use: Therapeutic Options and Clinical Practice". {{ cite journal}}: Cite journal requires |journal= ( help)
  84. ^ Kosaraju, Ateet; Pendela, Venkata Satish; Hai, Ofek (2024), "Cardiogenic Shock", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  29489148, retrieved 2024-04-05
  85. ^ Shankar, Aditi; Gurumurthy, Gayathri; Sridharan, Lakshmi; Gupta, Divya; Nicholson, William J; Jaber, Wissam A; Vallabhajosyula, Saraschandra (2022-02-07). "A Clinical Update on Vasoactive Medication in the Management of Cardiogenic Shock". Clinical Medicine Insights. Cardiology. 16: 11795468221075064. doi: 10.1177/11795468221075064. ISSN  1179-5468. PMC  8829716. PMID  35153521.
  86. ^ a b Laghlam, Driss; Benghanem, Sarah; Ortuno, Sofia; Bouabdallaoui, Nadia; Manzo-Silberman, Stephane; Hamzaoui, Olfa; Aissaoui, Nadia (2024-03-30). "Management of cardiogenic shock: a narrative review". Annals of Intensive Care. 14 (1): 45. doi: 10.1186/s13613-024-01260-y. ISSN  2110-5820. PMC  10980676. PMID  38553663.
  87. ^ Guglin, Maya; Kaufman, Marc (2014-05-20). "Inotropes do not increase mortality in advanced heart failure". International Journal of General Medicine. 7: 237–251. doi: 10.2147/IJGM.S62549. ISSN  1178-7074. PMC  4038527. PMID  24899821.
  88. ^ Gustafsson, Finn; Damman, Kevin; Nalbantgil, Sanem; Van Laake, Linda W.; Tops, Laurens F.; Thum, Thomas; Adamopoulos, Stamatis; Bonios, Michael; Coats, Andrew JS; Crespo-Leiro, Maria G.; Mehra, Mandeep R.; Filippatos, Gerasimos; Hill, Loreena; Metra, Marco; Jankowska, Ewa (April 2023). "Inotropic therapy in patients with advanced heart failure. A clinical consensus statement from the Heart Failure Association of the European Society of Cardiology". European Journal of Heart Failure. 25 (4): 457–468. doi: 10.1002/ejhf.2814. ISSN  1388-9842. PMID  36847113.
  89. ^ "Ejection Fraction Heart Failure Measurement". www.heart.org. Retrieved 2024-04-05.
  90. ^ Authors/Task Force Members; McDonagh, Theresa A.; Metra, Marco; Adamo, Marianna; Gardner, Roy S.; Baumbach, Andreas; Böhm, Michael; Burri, Haran; Butler, Javed; Čelutkienė, Jelena; Chioncel, Ovidiu; Cleland, John G.F.; Coats, Andrew J.S.; Crespo-Leiro, Maria G.; Farmakis, Dimitrios (January 2022). "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC". European Journal of Heart Failure. 24 (1): 4–131. doi: 10.1002/ejhf.2333. hdl: 2434/966600. ISSN  1388-9842. PMID  35083827.
  91. ^ Digitalis Investigation Group (1997-02-20). "The Effect of Digoxin on Mortality and Morbidity in Patients with Heart Failure". New England Journal of Medicine. 336 (8): 525–533. doi: 10.1056/NEJM199702203360801. ISSN  0028-4793. PMID  9036306.
  92. ^ Authors/Task Force Members; McDonagh, Theresa A.; Metra, Marco; Adamo, Marianna; Gardner, Roy S.; Baumbach, Andreas; Böhm, Michael; Burri, Haran; Butler, Javed; Čelutkienė, Jelena; Chioncel, Ovidiu; Cleland, John G.F.; Coats, Andrew J.S.; Crespo-Leiro, Maria G.; Farmakis, Dimitrios (January 2022). "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC". European Journal of Heart Failure. 24 (1): 4–131. doi: 10.1002/ejhf.2333. hdl: 2434/966600. ISSN  1388-9842. PMID  35083827.
  93. ^ "Atrial fibrillation". nhs.uk. 2017-10-20. Retrieved 2024-04-05.
  94. ^ "Atrial fibrillation - Symptoms and causes". Mayo Clinic. Retrieved 2024-04-05.
  95. ^ Joglar, José A.; Chung, Mina K.; Armbruster, Anastasia L.; Benjamin, Emelia J.; Chyou, Janice Y.; Cronin, Edmond M.; Deswal, Anita; Eckhardt, Lee L.; Goldberger, Zachary D.; Gopinathannair, Rakesh; Gorenek, Bulent; Hess, Paul L.; Hlatky, Mark; Hogan, Gail; Ibeh, Chinwe (2024-01-02). "2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines". Circulation. 149 (1): e1–e156. doi: 10.1161/CIR.0000000000001193. ISSN  0009-7322. PMC  11095842. PMID  38033089.
  96. ^ Dieleman, Joseph L.; Cao, Jackie; Chapin, Abby; Chen, Carina; Li, Zhiyin; Liu, Angela; Horst, Cody; Kaldjian, Alexander; Matyasz, Taylor; Scott, Kirstin Woody; Bui, Anthony L.; Campbell, Madeline; Duber, Herbert C.; Dunn, Abe C.; Flaxman, Abraham D. (2020-03-03). "US Health Care Spending by Payer and Health Condition, 1996-2016". JAMA. 323 (9): 863–884. doi: 10.1001/jama.2020.0734. ISSN  0098-7484. PMC  7054840. PMID  32125402.
  97. ^ Dai, Haijiang; Zhang, Quanyu; Much, Arsalan Abu; Maor, Elad; Segev, Amit; Beinart, Roy; Adawi, Salim; Lu, Yao; Bragazzi, Nicola Luigi; Wu, Jianhong (2021-10-28). "Global, regional, and national prevalence, incidence, mortality, and risk factors for atrial fibrillation, 1990-2017: results from the Global Burden of Disease Study 2017". European Heart Journal. Quality of Care & Clinical Outcomes. 7 (6): 574–582. doi: 10.1093/ehjqcco/qcaa061. ISSN  2058-1742. PMC  8557444. PMID  32735316.
Retrieved from " https://en.wikipedia.org/?title=Cardiotonic_agent&oldid=1234177749"
From Wikipedia, the free encyclopedia

Cardiotonic agents, also known as cardiac inotropes or stimulants, have a positive impact on the myocardium (muscular layer of the heart) by enhancing its contractility. Unlike general inotropes, these agents exhibit a higher level of specificity as they selectively target the myocardium. They can be categorised into four distinct groups based on their unique mechanisms of action: cardiac glycosides, beta-adrenergic agonists, phosphodiesterase III inhibitors, and calcium sensitizers. It is important to note that certain medications, such as Milrinone and Digoxin, possess overlapping classifications due to their ability to engage multiple mechanisms of action. Their inotropic properties make cardiactonic agents critical in addressing inadequate perfusion, and acute heart failure conditions including cardiogenic shock, as well as for long-term management of heart failure. These conditions arise when the heart's ability to meet the body's needs is compromised.

Classification

1) Cardiac Glycosides

Mechanism of action

Mechanism of action of cardiac glycosides (Digitalis): inhibition of Na+/K+ ATPase

Cardiac glycosides like digoxin, primarily inhibit the sodium-potassium pump (Na+/K+ ATPase), an important protein located on the surface of cardiomyocytes (cardiac muscle cells). [1] [2] Using ATP (the cell’s energy currency), this protein facilitates the transport of extracellular potassium ions (K+) into the cell while exporting sodium ions (Na+) out, maintaining a balanced 1:1 exchange. [3] Thus, when this protein is blocked, Na+ accumulates within cardiomyocytes.

Moreover, cardiomyocytes possess another surface protein known as the sodium-calcium (Na+/Ca2+) exchanger. The accumulation of Na+ prompts its efflux from the cell, whilst concurrently allowing Ca2+ influx through this exchanger. [4]Consequently, intracellular Ca2+ levels rise.

The interaction between Ca2+ and Troponin C (TnC) is significant, as it prepares muscle fibres for the sliding filament mechanism, which explains muscle contraction. [5] With increased Ca2+ levels, interactions between Ca2+ and TnC intensify, leading to stronger contractions of the myocardiocytes. [6]Therapeutic doses of cardiac glycosides have been shown to enhance cardiac contractility, benefiting patients with impaired cardiac function, such as those with heart failure. [7]

Pharmacotherapy profile

Drug examples General indications Common side effects Cautions Special populations
Digoxin [8]

Digitalis [8]

Digitoxin [8]

Heart failure with reduced ejection fraction [9]

Atrial Fibrillation (abnormal heart rhythm) [9]

Dizziness [10] [11]

Nausea [10] [11]

Diarrhoea [10] [11]

Skin rashes [10] [11]

Vision disorders [10] [11]

Arrhythmias [10] [11]

Vomiting [10] [11]

Impaired renal function [12]

Thyroid disorders [12]

Acute coronary syndrome (blood flow to heart muscle suddenly blocked) [12]

Electrolyte disorders ( hypercalcemia, hypokalemia, hypomagnesemia) [13]

Pregnancy: can be used, may require dosage adjustment [14]

Breastfeeding: amount found in breast milk is is insignificant, harm caused to foetus not well studied [15]

Renally impaired: consider reducing initial and maintenance doses [16]

2) Beta-adrenergic agonists

Mechanism of action

General mechanism of action of beta-adrenergic agonists: activation of β1 / β2 receptors

Naturally produced hormones norepinephrine and epinephrine or synthetic drugs such as dobutamine can be collectively regarded as beta-agonists. Specifically, dobutamine selectively binds to β1 receptors located on the surface of specialised cardiac muscle cells. [17] Relative to β2 receptors, β1 is the predominant type in terms of quantity and function within the heart. [18]

Gs proteins are a subunit of a large family of receptors called G-protein-coupled receptors (GPCRs). [19] Due to the coupling nature between β1, Gs proteins, and the enzyme adenylyl cyclase, activation of Gs proteins ultimately activates adenylyl cyclase, which is responsible for converting ATP into cAMP. [20] Thus, beta-agonists will lead to elevated cAMP levels, which further activate a cAMP-dependent protein called protein-kinase A (PK-A). [21]PK-A plays a pivotal role in increasing intracellular Ca2+ levels through 2 mechanisms:

Similar to the MoA of cardiac glycosides, elevated Ca2+ eventually translates into stronger cardiac contractile force.

Pharmacotherapy profile

Drug examples General Indications Common side effects Precautions Special populations
Epinephrine [25]

Norepinephrine [25]

Dopamine [25]

Dobutamine [25]

Isoproterenol [25]

Anaphylactic shock [26] [27]

Cardiogenic shock [26] [27]

Cardiac arrest [26] [27]

Severe hypotension [26] [27]

Decompensated heart failure [26] [27]

Atrioventricular block (malfunction in heart's electrical system) [26] [27]

Arrhythmias (abnormal heart rhythm) [28] [29]

Chest pain [28] [29]

Hypertension [28] [29]

Palpitations [28] [29]

Anxiety [28] [29]

Acute myocardial infarction (heart attack) [29] [30]

Atherosclerosis (clogging of blood vessel wall) [29] [30]

Arrhythmias [29] [30]

Diabetes mellitus [29] [30]

Immediate use in cardiogenic shock or severe hypotension at risk of organ damage [31] [32]

3) Phosphodiesterase (III) inhibitors

Mechanism of action

Mechanism of action of PDE III inhibitors: inhibition of PDE3 enzyme

PDE3 inhibitors exert their effects by blocking the activity of an enzyme called PDE3. This enzyme is responsible for breaking down a molecule called cAMP, which is the key signalling molecule in our body. [33] When PDE3 is inhibited, the breakdown of cAMP is prevented, leading to increased levels of cAMP in our cells. [34]

In our heart muscle cells, when the levels of cAMP rise, it activates a protein called protein kinase A (PKA). [34] PKA acts as a switch, triggering a cascade of events that enhance the strength and efficiency of the heart's contractions. [35] This ultimately leads to improved cardiac function.

PDE3 inhibitors also have an impact on the smooth muscles found in our blood vessels. By increasing cAMP levels, these medications cause the smooth muscles to relax. [36] This relaxation has a significant benefit in our blood vessels as it leads to vasodilation, which means the blood vessels widen. [37] [38] Vasodilation helps to reduce resistance against blood flow, allowing for better circulation throughout the body. [39]

Furthermore, PDE3 inhibitors exhibit an additional effect on platelets, which are small cell fragments involved in blood clotting. [40] Increased levels of cAMP in platelets prevent their activation and reduce their ability to form blood clots. [41] By inhibiting platelet aggregation, PDE3 inhibitors contribute to maintaining healthy and smooth blood flow. [41]

Pharmacotherapy profile

Drug examples Indications Common side effects Precautions Special populations
Anagrelide [42] [43]

Cilostazol [42] [43]

Milrinone [42] [43]

Heart Failure [44]

Pulmonary Hypertension in babies [45]

Peripheral Vascular Disease [45]

Asthma [46]

Chronic Obstructive Pulmonary Disease (lung disease) [46]

Gastrointestinal discomfort [47]

Tachycardia (heart rate too fast) [47] Rapid drop in Weight [48]

Headaches [48]

Dizziness [48]

Insomnia [48]

Psychological disorder (for example anxiety) [49]

Compromised liver or kidney function with drugs that inhibit an enzyme called CYP3A4 [50]

Pre-existing ophthalmopathy (eye disorders) [51]

Avoid usage during pregnancy as it can inhibit meiosis, a specific form of cell division that takes place in oocytes, which are specialized reproductive cells in females [52]

4) Calcium sensitisers

Mechanism of action

Mechanism of action of calcium sensitizers: increase sensitivity of troponin C to Ca2+

Calcium is a vital element for regulating the contraction and relaxation of the heart muscle. [53] Calcium sensitizers are medications that increase the responsiveness of heart muscle cells to calcium, enabling more forceful contractions while conserving energy. [54] Contraction of the heart muscle relies on electrical signals that trigger the release of calcium ions. These calcium ions bind to a protein called troponin, which initiates the process of muscle contraction. [55]

Calcium sensitizers function by binding to cardiac troponin C, thereby enhancing the sensitivity of heart muscle cells to naturally occurring calcium ions. [56] This heightened sensitivity fosters a more efficient interaction between calcium and the contractile apparatus of the heart muscle. [57] Consequently, calcium can more effectively bind to actin- myosin filaments, resulting in stronger contractions without excessive calcium accumulation. [57] By reducing strain on the heart, this mechanism helps minimise the oxygen demand.

Furthermore, calcium sensitizers provide an additional benefit. They open potassium channels in the heart muscle cells, resulting in vasodilation and improved blood flow. [58] This action reduces the workload on the heart.

Pharmacotherapy profile

Drug examples Indications Common side effects Precautions Special populations
Levosimendan [59]

Milrinone [59]

Digoxin [59]

Heart failure (but no significant reduction in mortality) [60] [61]

Cardiogenic Shock [62]

Pulmonary Hypertension [63]

Post-Cardiac Surgery [64] [65]

Isolated tongue swelling [66]

Headache [66]

Nausea [66]

Palpitation [66]

Injection site irritation [67]

Renal and hepatic impairment [68] [69]

Electrolyte imbalance [70] [71]

Patients with prolong QT wave in ECG (abnormal repolarize time of heart) [72] [73]

Compelling indication in elderly patients with heart failure [74]

Positive effects in improving cardiac functions in paediatric (young) patients [75]

Clinical role in heart failure

Cardiotonic agents are typically employed as short-term and non-routine therapies for heart failure patients. [76] They are specifically reserved for those with contractile dysfunction in the left ventricles (lower chambers of the heart), low cardiac output, and low blood pressure, placing them at risk of inadequate organ perfusion. [77]While these agents assist in promoting perfusion, their potential for increased mortality and adverse side effects necessitates cautious administration at initially low doses, with careful adjustments under close monitoring. [78] [79]Given the diverse presentations of heart failure and individual patient characteristics, cardiotonic medication uses and preferences vary.

Cardiogenic shock leads to many harmful physiological effects

Specifically, in patients experiencing inadequate blood perfusion (with blood pressure below 80 mmHg), the American Heart Association / American College of Cardiology (ACC/AHA), recommends the use of Dobutamine and Milrinone. [80] Whereas in clinically stable patients with sufficient perfusion, cardiac inotrope use is advised against. [81] This caution is due to the heightened risk of adverse cardiovascular outcomes, including arrhythmias, detrimental heart structure remodelling, and even mortality. [82] [83]Heart failure can manifest in its life-threatening form of cardiogenic shock, with hypotension and low blood flow (hypoperfusion), placing the patient at risk of multiorgan failure. [84] In cardiogenic shock management, cardiotonic agents serve 2 functions. Norepinephrine, epinephrine, dopamine, and phenylephrine contribute mainly through their vasopressor (vasoconstrictive) functions to constrict blood vessels to correct hypotension. Whereas, dobutamine, milrinone, enoximone, and levosimendan, act to restore the heart’s pumping function. [85] To prevent further harm to the organs, cardiotonic agents are typically administered alongside oxygen, ventilatory support, and mechanical circulatory support (MCS). [86]As hypoperfusion and organ dysfunction improve, it is recommended to gradually reduce the administration of these agents. [86] However, certain patients who are unable to discontinue cardiotonic agents without experiencing recurrent heart failure symptoms, known as inotropic-dependent patients, may require prolonged usage. [87] This serves as a bridge towards more invasive management approaches, such as transplants or left ventricular assist devices (medical device to assist the heart). [88]

Heart failure patients are stratified based on their left ventricular ejection fraction, which quantifies the volume of blood expelled from the heart's lower chambers (ventricles) with each contraction. [89]According to the European Society of Cardiology (ESC), among cardiotonic agents, Digoxin is specifically recommended as a second-line option for patients with an abnormal left ventricular ejection fraction (≤40%). [90] Digoxin helps alleviate symptoms and reduce hospitalizations related to heart failure, but it does not offer any mortality-reducing benefits. [91] Digoxin may be considered in patients who remain symptomatic despite receiving treatment with a first-line combination of an ACE inhibitor (or ARNI), a beta-blocker, and a mineralocorticoid receptor antagonist (MRA). [92] It is also considered in patients with atrial fibrillation - a heart rhythm disorder characterised by irregular electrical impulses in the atria (the upper chambers of the heart). [93] This abnormal electrical activity causes the atria to contract erratically, resulting in an irregular heartbeat. [94] Treatment primarily focuses on restoring normal heart rhythm and controlling the heart rate to minimise the risk of complications, including stroke. According to the ACC/AHA guidelines, intravenous digoxin (cardiac glycoside) can be used in atrial fibrillation (Afib) to assist heartbeats. [95] In multicenter randomised controlled trials, intravenous digoxin was shown to be effective in controlling the heart rate compared to a placebo. [96] [97]

References

  1. ^ "Cases | Pharmacotherapy Principles & Practice | McGraw Hill Medical". ppp.mhmedical.com. Retrieved 2024-04-05.
  2. ^ Haviv, H.; Karlish, S. J. D. (2013-01-01), "P-Type Pumps: Na+,K+-ATPase", in Lennarz, William J.; Lane, M. Daniel (eds.), Encyclopedia of Biological Chemistry (Second Edition), Waltham: Academic Press, pp. 681–687, ISBN  978-0-12-378631-9, retrieved 2024-04-05
  3. ^ Pirahanchi, Yasaman; Jessu, Rishita; Aeddula, Narothama R. (2024), "Physiology, Sodium Potassium Pump", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  30725773, retrieved 2024-04-05
  4. ^ Ottolia, Michela; John, Scott; Hazan, Adina; Goldhaber, Joshua I. (2021-12-29). "The Cardiac Na+-Ca2+ Exchanger: From Structure to Function". Comprehensive Physiology. 12 (1): 2681–2717. doi: 10.1002/cphy.c200031. ISSN  2040-4603. PMC  8773166. PMID  34964124.
  5. ^ Ohtsuki, Iwao; Morimoto, Sachio; Kitainda, Vivian (2021-01-01), "Structural Proteins | Troponin☆", in Jez, Joseph (ed.), Encyclopedia of Biological Chemistry III (Third Edition), Oxford: Elsevier, pp. 695–700, doi: 10.1016/b978-0-12-819460-7.00204-8, ISBN  978-0-12-822040-5, retrieved 2024-04-05
  6. ^ Eisner, David A.; Caldwell, Jessica L.; Kistamás, Kornél; Trafford, Andrew W. (2017-07-07). "Calcium and Excitation-Contraction Coupling in the Heart". Circulation Research. 121 (2): 181–195. doi: 10.1161/CIRCRESAHA.117.310230. ISSN  0009-7330. PMC  5497788. PMID  28684623.
  7. ^ Bavendiek, Udo; Berliner, Dominik; Dávila, Lukas Aguirre; Schwab, Johannes; Maier, Lars; Philipp, Sebastian A.; Rieth, Andreas; Westenfeld, Ralf; Piorkowski, Christopher; Weber, Kristina; Hänselmann, Anja; Oldhafer, Maximiliane; Schallhorn, Sven; von der Leyen, Heiko; Schröder, Christoph (May 2019). "Rationale and design of the DIGIT-HF trial (DIGitoxin to Improve ouTcomes in patients with advanced chronic Heart Failure): a randomized, double-blind, placebo-controlled study". European Journal of Heart Failure. 21 (5): 676–684. doi: 10.1002/ejhf.1452. ISSN  1388-9842. PMC  6607489. PMID  30892806.
  8. ^ a b c "Cardiac Glycosides: Types and What They Treat". Cleveland Clinic. Retrieved 2024-04-05.
  9. ^ a b Gheorghiade, Mihai; Adams, Kirkwood F.; Colucci, Wilson S. (2004-06-22). "Digoxin in the Management of Cardiovascular Disorders". Circulation. 109 (24): 2959–2964. doi: 10.1161/01.CIR.0000132482.95686.87. ISSN  0009-7322. PMID  15210613.
  10. ^ a b c d e f g "Side effects of digoxin". nhs.uk. 2021-09-15. Retrieved 2024-04-05.
  11. ^ a b c d e f g Papich, Mark G. (2016-01-01), Papich, Mark G. (ed.), "Digoxin", Saunders Handbook of Veterinary Drugs (Fourth Edition), St. Louis: W.B. Saunders, pp. 241–242, ISBN  978-0-323-24485-5, retrieved 2024-04-05
  12. ^ a b c Gheorghiade, Mihai; Adams, Kirkwood F.; Colucci, Wilson S. (2004-06-22). "Digoxin in the Management of Cardiovascular Disorders". Circulation. 109 (24): 2959–2964. doi: 10.1161/01.CIR.0000132482.95686.87. ISSN  0009-7322. PMID  15210613.
  13. ^ D, Anandhi; Pandit, Vinay R.; Kadhiravan, Tamilarasu; R, Soundaravally; Prakash Raju, K. N. J. (February 2019). "Cardiac arrhythmias, electrolyte abnormalities and serum cardiac glycoside concentrations in yellow oleander (Cascabela thevetia) poisoning - a prospective study". Clinical Toxicology (Philadelphia, Pa.). 57 (2): 104–111. doi: 10.1080/15563650.2018.1499930. ISSN  1556-9519. PMID  30073854.
  14. ^ "Cardiovascular Disease Medication During Pregnancy". American College of Cardiology. Retrieved 2024-04-05.
  15. ^ "Pregnancy, breastfeeding and fertility while taking digoxin". nhs.uk. 2021-09-15. Retrieved 2024-04-05.
  16. ^ Li, Xiaozhao; Ao, Xiang; Liu, Qiong; Yang, Jinghua; Peng, Weisheng; Tang, Rong; Zhong, Yong; Meng, Ting; Gan, Lu; Zhou, Qiaoling (2014-12-01). "Intermittent low‑dose digoxin may be effective and safe in patients with chronic heart failure undergoing maintenance hemodialysis". Experimental and Therapeutic Medicine. 8 (6): 1689–1694. doi: 10.3892/etm.2014.2013. ISSN  1792-0981. PMC  4218698. PMID  25371716.
  17. ^ Farzam, Khashayar; Kidron, Ariel; Lakhkar, Anand D. (2024), "Adrenergic Drugs", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  30480963, retrieved 2024-04-05
  18. ^ Alhayek, Soubhi; Preuss, Charles V. (2024), "Beta 1 Receptors", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  30422499, retrieved 2024-04-05
  19. ^ Navarro, Gemma; Cordomí, Arnau; Brugarolas, Marc; Moreno, Estefanía; Aguinaga, David; Pérez-Benito, Laura; Ferre, Sergi; Cortés, Antoni; Casadó, Vicent; Mallol, Josefa; Canela, Enric I.; Lluís, Carme; Pardo, Leonardo; McCormick, Peter J.; Franco, Rafael (2018-02-28). "Cross-communication between Gi and Gs in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain". BMC Biology. 16 (1): 24. doi: 10.1186/s12915-018-0491-x. ISSN  1741-7007. PMC  6389107. PMID  29486745.
  20. ^ Navarro, Gemma; Cordomí, Arnau; Casadó-Anguera, Verónica; Moreno, Estefanía; Cai, Ning-Sheng; Cortés, Antoni; Canela, Enric I.; Dessauer, Carmen W.; Casadó, Vicent; Pardo, Leonardo; Lluís, Carme; Ferré, Sergi (2018-03-28). "Evidence for functional pre-coupled complexes of receptor heteromers and adenylyl cyclase". Nature Communications. 9 (1): 1242. Bibcode: 2018NatCo...9.1242N. doi: 10.1038/s41467-018-03522-3. ISSN  2041-1723. PMC  5871782. PMID  29593213.
  21. ^ Howe, Alan K. (October 2011). "Cross-talk between calcium and protein kinase A in the regulation of cell migration". Current Opinion in Cell Biology. 23 (5): 554–561. doi: 10.1016/j.ceb.2011.05.006. ISSN  0955-0674. PMC  3175278. PMID  21665456.
  22. ^ Nystoriak, Matthew A.; Nieves-Cintrón, Madeline; Patriarchi, Tommaso; Buonarati, Olivia R.; Prada, Maria Paz; Morotti, Stefano; Grandi, Eleonora; Fernandes, Julia Dos Santos; Forbush, Katherine; Hofmann, Franz; Sasse, Kent C.; Scott, John D.; Ward, Sean M.; Hell, Johannes W.; Navedo, Manuel F. (2017-01-24). "Ser1928 phosphorylation by PKA stimulates the L-type Ca2+ channel CaV1.2 and vasoconstriction during acute hyperglycemia and diabetes". Science Signaling. 10 (463): eaaf9647. doi: 10.1126/scisignal.aaf9647. ISSN  1945-0877. PMC  5297430. PMID  28119464.
  23. ^ Beard, Nicole A.; Wei, Lan; Cheung, Stephanie N.; Kimura, Takashi; Varsányi, Magdolna; Dulhunty, Angela F. (2008-10-01). "Phosphorylation of skeletal muscle calsequestrin enhances its Ca2+ binding capacity and promotes its association with junctin". Cell Calcium. 44 (4): 363–373. doi: 10.1016/j.ceca.2008.01.005. ISSN  0143-4160. PMID  19230141.
  24. ^ Rossi, Daniela; Pierantozzi, Enrico; Amadsun, David Osamwonuyi; Buonocore, Sara; Rubino, Egidio Maria; Sorrentino, Vincenzo (April 2022). "The Sarcoplasmic Reticulum of Skeletal Muscle Cells: A Labyrinth of Membrane Contact Sites". Biomolecules. 12 (4): 488. doi: 10.3390/biom12040488. ISSN  2218-273X. PMC  9026860. PMID  35454077.
  25. ^ a b c d e "Beta-agonist Medications". Cleveland Clinic. Retrieved 2024-04-05.
  26. ^ a b c d e f "Dopamine". go.drugbank.com. Retrieved 2024-04-05.
  27. ^ a b c d e f "Dopamine: Side Effects, Uses, Dosage, Interactions, Warnings". RxList. Retrieved 2024-04-05.
  28. ^ a b c d e Sears, Malcolm R. (December 2002). "Adverse effects of β-agonists". Journal of Allergy and Clinical Immunology. 110 (6): S322–S328. doi: 10.1067/mai.2002.129966. ISSN  0091-6749. PMID  12464943.
  29. ^ a b c d e f g h i Farzam, Khashayar; Kidron, Ariel; Lakhkar, Anand D. (2024), "Adrenergic Drugs", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  30480963, retrieved 2024-04-05
  30. ^ a b c d RN, Iris Dawn Tabangcora (2017-07-11). "Adrenergic Agonists (Sympathomimetics) Nursing Pharmacology Study Guide". Nurseslabs. Retrieved 2024-04-05.
  31. ^ VanValkinburgh, Danny; Kerndt, Connor C.; Hashmi, Muhammad F. (2024), "Inotropes and Vasopressors", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  29494018, retrieved 2024-04-05
  32. ^ Manolopoulos, Philip Panagiotis; Boutsikos, Ioannis; Boutsikos, Panagiotis; Iacovidou, Nicoletta; Ekmektzoglou, Konstantinos (2020-04-10). "Current use and advances in vasopressors and inotropes support in shock". Journal of Emergency and Critical Care Medicine. 4: 20. doi: 10.21037/jeccm.2019.12.03. ISSN  2521-3563.
  33. ^ "Phosphodiesterase III Inhibitor - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-04-07.
  34. ^ a b Padda, Inderbir S.; Tripp, Jayson (2024), "Phosphodiesterase Inhibitors", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  32644702, retrieved 2024-04-07
  35. ^ "Protein Kinase A - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-04-07.
  36. ^ "Phosphodiesterase Inhibitor - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-04-07.
  37. ^ "Phosphodiesterase Inhibitor - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-04-07.
  38. ^ "Increased Venous Return - Circulatory Effects - Physiological Effects Of Massage - Massage - Treatments - Physio.co.uk". www.physio.co.uk. Retrieved 2024-04-07.
  39. ^ Ramanlal, Riddhi; Gupta, Vikas (2024), "Physiology, Vasodilation", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  32491494, retrieved 2024-04-07
  40. ^ Gresele, Paolo; Momi, Stefania; Falcinelli, Emanuela (October 2011). "Anti-platelet therapy: phosphodiesterase inhibitors". British Journal of Clinical Pharmacology. 72 (4): 634–646. doi: 10.1111/j.1365-2125.2011.04034.x. ISSN  0306-5251. PMC  3195739. PMID  21649691.
  41. ^ a b Zhang, Wei; Colman, Robert W. (2007-09-01). "Thrombin regulates intracellular cyclic AMP concentration in human platelets through phosphorylation/activation of phosphodiesterase 3A". Blood. 110 (5): 1475–1482. doi: 10.1182/blood-2006-10-052522. ISSN  0006-4971. PMC  1975837. PMID  17392505.
  42. ^ a b c "PDE3 Inhibitor - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-04-05.
  43. ^ a b c Padda, Inderbir S.; Tripp, Jayson (2024), "Phosphodiesterase Inhibitors", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  32644702, retrieved 2024-04-05
  44. ^ "Phosphodiesterase 3 Inhibitors | DrugBank Online". go.drugbank.com. Retrieved 2024-04-05.
  45. ^ a b van der Lee, Robin; Peels, Barbara; Koopman-Esseboom, Corine (January 2017). "PDE3 inhibition with enoximone as first-line therapy for severe persistent pulmonary hypertension of the newborn during neonatal transport: a case report". Clinical Case Reports. 5 (1): 18–21. doi: 10.1002/ccr3.748. ISSN  2050-0904. PMC  5224780. PMID  28096983.
  46. ^ a b www.amboss.com https://www.amboss.com/us/knowledge/phosphodiesterase-inhibitors. Retrieved 2024-04-05. {{ cite web}}: Missing or empty |title= ( help)
  47. ^ a b "How Do PDE-3 Inhibitors Work? - Uses, Side Effects, Drug Names". RxList. Retrieved 2024-04-05.
  48. ^ a b c d Padda, Inderbir S.; Tripp, Jayson (2024), "Phosphodiesterase Inhibitors", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  32644702, retrieved 2024-04-05
  49. ^ "Phosphodiesterase Inhibitors: Types and Purpose". Cleveland Clinic. Retrieved 2024-04-05.
  50. ^ "PDE3 Inhibitor - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-04-05.
  51. ^ Moschos, Marilita M; Nitoda, Eirini (2016-10-19). "Pathophysiology of visual disorders induced by phosphodiesterase inhibitors in the treatment of erectile dysfunction". Drug Design, Development and Therapy. 10: 3407–3413. doi: 10.2147/DDDT.S118015. ISSN  1177-8881. PMC  5076796. PMID  27799745.
  52. ^ Li, Min; Yu, Yang; Yan, Jie; Yan, Li-Ying; Zhao, Yue; Li, Rong; Liu, Ping; Hsueh, Aaron J.; Qiao, Jie (2012). "The role of cilostazol, a phosphodiesterase 3 inhibitor, on oocyte maturation and subsequent pregnancy in mice". PLOS ONE. 7 (1): e30649. Bibcode: 2012PLoSO...730649L. doi: 10.1371/journal.pone.0030649. ISSN  1932-6203. PMC  3265514. PMID  22292006.
  53. ^ Eisner, David A.; Caldwell, Jessica L.; Kistamás, Kornél; Trafford, Andrew W. (2017-07-07). "Calcium and Excitation-Contraction Coupling in the Heart". Circulation Research. 121 (2): 181–195. doi: 10.1161/CIRCRESAHA.117.310230. ISSN  0009-7330. PMC  5497788. PMID  28684623.
  54. ^ Lehmann, Andreas; Boldt, Joachim; Kirchner, Jürgen (October 2003). "The role of Ca++-sensitizers for the treatment of heart failure". Current Opinion in Critical Care. 9 (5): 337–344. doi: 10.1097/00075198-200310000-00002. ISSN  1070-5295. PMID  14508145.
  55. ^ "Calcium Sensitizer - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2024-04-07.
  56. ^ Li, Monica X.; Gelozia, Shorena; Danmaliki, Gaddafi I.; Wen, Yurong; Liu, Philip B.; Lemieux, M. Joanne; West, Frederick G.; Sykes, Brian D.; Hwang, Peter M. (2018-11-01). "The calcium sensitizer drug MCI-154 binds the structural C-terminal domain of cardiac troponin C". Biochemistry and Biophysics Reports. 16: 145–151. doi: 10.1016/j.bbrep.2018.10.012. ISSN  2405-5808. PMC  6218639. PMID  30417133.
  57. ^ a b Kuo, Ivana Y.; Ehrlich, Barbara E. (February 2015). "Signaling in Muscle Contraction". Cold Spring Harbor Perspectives in Biology. 7 (2): a006023. doi: 10.1101/cshperspect.a006023. ISSN  1943-0264. PMC  4315934. PMID  25646377.
  58. ^ Priest, Birgit T; McDermott, Jeff S (2015-08-20). "Cardiac ion channels". Channels. 9 (6): 352–359. doi: 10.1080/19336950.2015.1076597. ISSN  1933-6950. PMC  4850049. PMID  26556552.
  59. ^ a b c "Cardiotonic Agents | DrugBank Online". go.drugbank.com. Retrieved 2024-04-05.
  60. ^ Sakata, Yasushi (April 2013). "[Clinical significance of calcium sensitizer]". Clinical Calcium. 23 (4): 575–582. ISSN  0917-5857. PMID  23545748.
  61. ^ Louhelainen, Marjut; Merasto, Saara; Finckenberg, Piet; Vahtola, Erik; Kaheinen, Petri; Levijoki, Jouko; Mervaala, Eero (May 2010). "Effects of the calcium sensitizer OR-1896, a metabolite of levosimendan, on post-infarct heart failure and cardiac remodelling in diabetic Goto–Kakizaki rats". British Journal of Pharmacology. 160 (1): 142–152. doi: 10.1111/j.1476-5381.2010.00680.x. ISSN  0007-1188. PMC  2860214. PMID  20412071.
  62. ^ "Early Utilization of Mechanical Circulatory Support in Acute Myocardial Infarction Complicated by Cardiogenic Shock | HeartRecovery.com". www.heartrecovery.com. Retrieved 2024-04-05.
  63. ^ Tsapenko, Mykola V; Tsapenko, Arseniy V; Comfere, Thomas BO; Mour, Girish K; Mankad, Sunil V; Gajic, Ognjen (October 2008). "Arterial pulmonary hypertension in noncardiac intensive care unit". Vascular Health and Risk Management. 4 (5): 1043–1060. doi: 10.2147/vhrm.s3998. ISSN  1176-6344. PMC  2605326. PMID  19183752.
  64. ^ Leivaditis, Vasileios; Grapatsas, Konstantinos; Papaporfyriou, Anastasia; Galanis, Michail; Koletsis, Efstratios; Charokopos, Nikolaos; Haussmann, Erich; Kaplunov, Vladislav; Papatriantafyllou, Athanasios; Dahm, Manfred (August 2023). "The Perioperative Use of Levosimendan as a Means of Optimizing the Surgical Outcome in Patients with Severe Heart Insufficiency Undergoing Cardiac Surgery". Journal of Cardiovascular Development and Disease. 10 (8): 332. doi: 10.3390/jcdd10080332. ISSN  2308-3425. PMC  10455812. PMID  37623345.
  65. ^ Beiras-Fernandez, Andres; Kornberger, Angela; Oberhoffer, Martin; Kur, Felix; Weis, Marion; Vahl, Christian-Friedrich; Weis, Florian (August 2019). "Levosimendan as rescue therapy in low output syndrome after cardiac surgery: effects and predictors of outcome". The Journal of International Medical Research. 47 (8): 3502–3512. doi: 10.1177/0300060519835087. ISSN  0300-0605. PMC  6726822. PMID  30909776.
  66. ^ a b c d Dal, Aleyna; Taslidere, Bahadir (2023-04-30). "Unusual Excessive Swelling of the Tongue after Calcium Acetate Ingestion: A Case Report". Eurasian Journal of Toxicology. 5 (1): 17–19. doi: 10.51262/ejtox.1236194. ISSN  2667-8675.
  67. ^ Lehtonen, Lasse (2004-09-01). "Levosimendan: A calcium-sensitizing agent for the treatment of patients with decompensated heart failure". Current Heart Failure Reports. 1 (3): 136–144. doi: 10.1007/s11897-004-0023-6. ISSN  1546-9549. PMID  16036037.
  68. ^ Masarone, Daniele; Kittleson, Michelle M.; Pollesello, Piero; Marini, Marco; Iacoviello, Massimo; Oliva, Fabrizio; Caiazzo, Angelo; Petraio, Andrea; Pacileo, Giuseppe (2022-10-29). "Use of Levosimendan in Patients with Advanced Heart Failure: An Update". Journal of Clinical Medicine. 11 (21): 6408. doi: 10.3390/jcm11216408. ISSN  2077-0383. PMC  9659135. PMID  36362634.
  69. ^ academic.oup.com https://academic.oup.com/ced/article-abstract/28/1/34/6627092?login=false. Retrieved 2024-04-05. {{ cite web}}: Missing or empty |title= ( help)
  70. ^ Verzicco, Ignazio; Regolisti, Giuseppe; Quaini, Federico; Bocchi, Pietro; Brusasco, Irene; Ferrari, Massimiliano; Passeri, Giovanni; Cannone, Valentina; Coghi, Pietro; Fiaccadori, Enrico; Vignali, Alessandro; Volpi, Riccardo; Cabassi, Aderville (2020-05-19). "Electrolyte Disorders Induced by Antineoplastic Drugs". Frontiers in Oncology. 10: 779. doi: 10.3389/fonc.2020.00779. ISSN  2234-943X. PMC  7248368. PMID  32509580.
  71. ^ Kass, David A.; Solaro, R. John (2006-01-17). "Mechanisms and Use of Calcium-Sensitizing Agents in the Failing Heart". Circulation. 113 (2): 305–315. doi: 10.1161/CIRCULATIONAHA.105.542407. ISSN  0009-7322. PMID  16418450.
  72. ^ Liu, Peng; Wang, Lu; Han, Dan; Sun, Chaofeng; Xue, Xiaolin; Li, Guoliang (2020). "Acquired long QT syndrome in chronic kidney disease patients". Renal Failure. 42 (1): 54–65. doi: 10.1080/0886022X.2019.1707098. ISSN  0886-022X. PMC  6968512. PMID  31878817.
  73. ^ "Drug-induced QT prolongation and Torsades de Pointes - the facts". www.medsafe.govt.nz. Retrieved 2024-04-05.
  74. ^ Zhang, Dengqing; Yao, Yuanqing; Qian, Jun; Huang, Jing (2015-08-20). "Levosimendan Improves Clinical Outcomes of Refractory Heart Failure in Elderly Chinese Patients". Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 21: 2439–2445. doi: 10.12659/MSM.893580. ISSN  1234-1010. PMC  4548701. PMID  26289557.
  75. ^ Silvetti, Simona; Silvani, Paolo; Azzolini, Maria Luisa; Dossi, Roberto; Landoni, Giovanni; Zangrillo, Alberto (2015). "A systematic review on levosimendan in paediatric patients". Current Vascular Pharmacology. 13 (1): 128–133. doi: 10.2174/1570161112666141127163536. ISSN  1875-6212. PMID  25440597.
  76. ^ Hansen, Benjamin Lautrup; Kristensen, Søren Lund; Gustafsson, Finn (2024-01-18). "Use of Inotropic Agents in Advanced Heart Failure: Pros and Cons". Cardiology: 1–15. doi: 10.1159/000536373. ISSN  0008-6312. PMID  38237564.
  77. ^ Authors/Task Force Members; McDonagh, Theresa A.; Metra, Marco; Adamo, Marianna; Gardner, Roy S.; Baumbach, Andreas; Böhm, Michael; Burri, Haran; Butler, Javed; Čelutkienė, Jelena; Chioncel, Ovidiu; Cleland, John G.F.; Coats, Andrew J.S.; Crespo-Leiro, Maria G.; Farmakis, Dimitrios (January 2022). "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC". European Journal of Heart Failure. 24 (1): 4–131. doi: 10.1002/ejhf.2333. hdl: 2434/966600. ISSN  1388-9842. PMID  35083827.
  78. ^ Ahmad, Tariq; Miller, P. Elliott; McCullough, Megan; Desai, Nihar R.; Riello, Ralph; Psotka, Mitchell; Böhm, Michael; Allen, Larry A.; Teerlink, John R.; Rosano, Giuseppe M. C.; Lindenfeld, Joann (September 2019). "Why has positive inotropy failed in chronic heart failure? Lessons from prior inotrope trials". European Journal of Heart Failure. 21 (9): 1064–1078. doi: 10.1002/ejhf.1557. ISSN  1879-0844. PMC  6774302. PMID  31407860.
  79. ^ Bistola, V.; Chioncel, O. (September 2017). "Inotropes in acute heart failure". Continuing Cardiology Education. 3 (3): 107–116. doi: 10.1002/cce2.59. ISSN  2059-1594.
  80. ^ Goldhaber, Joshua I.; Hamilton, Michele A. (2010-04-13). "Role of Inotropic Agents in the Treatment of Heart Failure". Circulation. 121 (14): 1655–1660. doi: 10.1161/CIRCULATIONAHA.109.899294. ISSN  0009-7322. PMC  2861129. PMID  20385962.
  81. ^ Nagao, Kazuya; Kato, Takao; Yaku, Hidenori; Morimoto, Takeshi; Inuzuka, Yasutaka; Tamaki, Yodo; Yamamoto, Erika; Yoshikawa, Yusuke; Kitai, Takeshi; Taniguchi, Ryoji; Iguchi, Moritake; Kato, Masashi; Takahashi, Mamoru; Jinnai, Toshikazu; Ikeda, Tomoyuki (2022-01-01). "Current use of inotropes according to initial blood pressure and peripheral perfusion in the treatment of congestive heart failure: findings from a multicentre observational study". BMJ Open. 12 (1): e053254. doi: 10.1136/bmjopen-2021-053254. ISSN  2044-6055. PMC  8783828. PMID  35058261.
  82. ^ academic.oup.com https://academic.oup.com/eurheartj/article/40/44/3626/5123545. Retrieved 2024-04-05. {{ cite web}}: Missing or empty |title= ( help)
  83. ^ Bistola, Vasiliki; Arfaras-Melainis, Angelos; Polyzogopoulou, Eftihia; Ikonomidis, Ignatios; Parissis, John (2019-09-11). "Inotropes in Acute Heart Failure: From Guidelines to Practical Use: Therapeutic Options and Clinical Practice". {{ cite journal}}: Cite journal requires |journal= ( help)
  84. ^ Kosaraju, Ateet; Pendela, Venkata Satish; Hai, Ofek (2024), "Cardiogenic Shock", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID  29489148, retrieved 2024-04-05
  85. ^ Shankar, Aditi; Gurumurthy, Gayathri; Sridharan, Lakshmi; Gupta, Divya; Nicholson, William J; Jaber, Wissam A; Vallabhajosyula, Saraschandra (2022-02-07). "A Clinical Update on Vasoactive Medication in the Management of Cardiogenic Shock". Clinical Medicine Insights. Cardiology. 16: 11795468221075064. doi: 10.1177/11795468221075064. ISSN  1179-5468. PMC  8829716. PMID  35153521.
  86. ^ a b Laghlam, Driss; Benghanem, Sarah; Ortuno, Sofia; Bouabdallaoui, Nadia; Manzo-Silberman, Stephane; Hamzaoui, Olfa; Aissaoui, Nadia (2024-03-30). "Management of cardiogenic shock: a narrative review". Annals of Intensive Care. 14 (1): 45. doi: 10.1186/s13613-024-01260-y. ISSN  2110-5820. PMC  10980676. PMID  38553663.
  87. ^ Guglin, Maya; Kaufman, Marc (2014-05-20). "Inotropes do not increase mortality in advanced heart failure". International Journal of General Medicine. 7: 237–251. doi: 10.2147/IJGM.S62549. ISSN  1178-7074. PMC  4038527. PMID  24899821.
  88. ^ Gustafsson, Finn; Damman, Kevin; Nalbantgil, Sanem; Van Laake, Linda W.; Tops, Laurens F.; Thum, Thomas; Adamopoulos, Stamatis; Bonios, Michael; Coats, Andrew JS; Crespo-Leiro, Maria G.; Mehra, Mandeep R.; Filippatos, Gerasimos; Hill, Loreena; Metra, Marco; Jankowska, Ewa (April 2023). "Inotropic therapy in patients with advanced heart failure. A clinical consensus statement from the Heart Failure Association of the European Society of Cardiology". European Journal of Heart Failure. 25 (4): 457–468. doi: 10.1002/ejhf.2814. ISSN  1388-9842. PMID  36847113.
  89. ^ "Ejection Fraction Heart Failure Measurement". www.heart.org. Retrieved 2024-04-05.
  90. ^ Authors/Task Force Members; McDonagh, Theresa A.; Metra, Marco; Adamo, Marianna; Gardner, Roy S.; Baumbach, Andreas; Böhm, Michael; Burri, Haran; Butler, Javed; Čelutkienė, Jelena; Chioncel, Ovidiu; Cleland, John G.F.; Coats, Andrew J.S.; Crespo-Leiro, Maria G.; Farmakis, Dimitrios (January 2022). "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC". European Journal of Heart Failure. 24 (1): 4–131. doi: 10.1002/ejhf.2333. hdl: 2434/966600. ISSN  1388-9842. PMID  35083827.
  91. ^ Digitalis Investigation Group (1997-02-20). "The Effect of Digoxin on Mortality and Morbidity in Patients with Heart Failure". New England Journal of Medicine. 336 (8): 525–533. doi: 10.1056/NEJM199702203360801. ISSN  0028-4793. PMID  9036306.
  92. ^ Authors/Task Force Members; McDonagh, Theresa A.; Metra, Marco; Adamo, Marianna; Gardner, Roy S.; Baumbach, Andreas; Böhm, Michael; Burri, Haran; Butler, Javed; Čelutkienė, Jelena; Chioncel, Ovidiu; Cleland, John G.F.; Coats, Andrew J.S.; Crespo-Leiro, Maria G.; Farmakis, Dimitrios (January 2022). "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC". European Journal of Heart Failure. 24 (1): 4–131. doi: 10.1002/ejhf.2333. hdl: 2434/966600. ISSN  1388-9842. PMID  35083827.
  93. ^ "Atrial fibrillation". nhs.uk. 2017-10-20. Retrieved 2024-04-05.
  94. ^ "Atrial fibrillation - Symptoms and causes". Mayo Clinic. Retrieved 2024-04-05.
  95. ^ Joglar, José A.; Chung, Mina K.; Armbruster, Anastasia L.; Benjamin, Emelia J.; Chyou, Janice Y.; Cronin, Edmond M.; Deswal, Anita; Eckhardt, Lee L.; Goldberger, Zachary D.; Gopinathannair, Rakesh; Gorenek, Bulent; Hess, Paul L.; Hlatky, Mark; Hogan, Gail; Ibeh, Chinwe (2024-01-02). "2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines". Circulation. 149 (1): e1–e156. doi: 10.1161/CIR.0000000000001193. ISSN  0009-7322. PMC  11095842. PMID  38033089.
  96. ^ Dieleman, Joseph L.; Cao, Jackie; Chapin, Abby; Chen, Carina; Li, Zhiyin; Liu, Angela; Horst, Cody; Kaldjian, Alexander; Matyasz, Taylor; Scott, Kirstin Woody; Bui, Anthony L.; Campbell, Madeline; Duber, Herbert C.; Dunn, Abe C.; Flaxman, Abraham D. (2020-03-03). "US Health Care Spending by Payer and Health Condition, 1996-2016". JAMA. 323 (9): 863–884. doi: 10.1001/jama.2020.0734. ISSN  0098-7484. PMC  7054840. PMID  32125402.
  97. ^ Dai, Haijiang; Zhang, Quanyu; Much, Arsalan Abu; Maor, Elad; Segev, Amit; Beinart, Roy; Adawi, Salim; Lu, Yao; Bragazzi, Nicola Luigi; Wu, Jianhong (2021-10-28). "Global, regional, and national prevalence, incidence, mortality, and risk factors for atrial fibrillation, 1990-2017: results from the Global Burden of Disease Study 2017". European Heart Journal. Quality of Care & Clinical Outcomes. 7 (6): 574–582. doi: 10.1093/ehjqcco/qcaa061. ISSN  2058-1742. PMC  8557444. PMID  32735316.
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