Inotrope#Positive inotropic agents

Both positive and negative inotropes are used in the management of various cardiovascular conditions. The choice of agent depends largely on specific pharmacological effects of individual agents with respect to the condition. One of the most important factors affecting inotropic state is the level of calcium in the cytoplasm of the muscle cell. Positive inotropes usually increase this level, while negative inotropes decrease it. However, not all positive and negative drugs affect calcium release, and, among those that do, the mechanism for manipulating the calcium level can differ from drug to drug.

While it is often recommended that vasopressors are given through a central line due to the risk of local tissue injury if the medication enters the local tissues, they are likely safe when given for less than two hours through good peripheral intravenous catheterization.{{cite journal | vauthors = Loubani OM, Green RS | title = A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral intravenous catheters and central venous catheters | journal = Journal of Critical Care | volume = 30 | issue = 3 | pages = 653.e9–653.17 | date = June 2015 | pmid = 25669592 | doi = 10.1016/j.jcrc.2015.01.014 }}

{{main|Cardiotonic agent}}

By increasing the concentration of intracellular calcium or increasing the sensitivity of receptor proteins to calcium, positive inotropic agents can increase myocardial contractility.{{cite encyclopedia | vauthors = Gordon S, Saunders A |encyclopedia=The Merck Veterinary Manual |title=Positive Inotropes |url=http://www.merckvetmanual.com/mvm/pharmacology/systemic_pharmacotherapeutics_of_the_cardiovascular_system/positive_inotropes.html |date=November 2015 |access-date=2016-11-28 }} Concentrations of intracellular calcium can be increased by increasing influx into the cell or stimulating release from the sarcoplasmic reticulum.{{cite journal |title=Use of inotropes in critical care |journal=Clinical Pharmacist | date = January 2010 | vauthors = Berry W, McKenzie C |volume=2 |page=395 |url=http://www.pharmaceutical-journal.com/learning/learning-article/use-of-inotropes-in-critical-care/11049283.article |access-date=2016-11-28 }}

Once in the cell, calcium can pass through one of two channels: the L-type calcium channel (long-lasting) and the T-type calcium channel (transient). These channels respond to voltage changes across the membrane differently: L-type channels respond to higher membrane potentials, open more slowly, and remain open longer than T-type channels.

Because of these properties, L-type channels are important in sustaining an action potential, while T-type channels are important in initiating them.{{cite book | vauthors = Sherwood L |title=Human Physiology, From Cells to Systems |edition=7th |year=2008 |publisher=Cengage Learning |isbn=9780495391845 }}

By increasing intracellular calcium, via the action of the L-type channels, the action potential can be sustained for longer and therefore, contractility increases.

Positive inotropes are used to support cardiac function in conditions such as decompensated congestive heart failure, cardiogenic shock, septic shock, myocardial infarction, cardiomyopathy, etc.{{cite journal | vauthors = Oba Y, Lone NA | title = Mortality benefit of vasopressor and inotropic agents in septic shock: a Bayesian network meta-analysis of randomized controlled trials | journal = Journal of Critical Care | volume = 29 | issue = 5 | pages = 706–710 | date = October 2014 | pmid = 24857641 | doi = 10.1016/j.jcrc.2014.04.011 }}

Examples of positive inotropic agents include:{{cn|date=January 2019}}

• Digoxin
• Berberine
• Calcium
• Calcium sensitisers
• Levosimendan{{cite journal | vauthors = Hu Y, Wei Z, Zhang C, Lu C, Zeng Z | title = The effect of levosimendan on right ventricular function in patients with heart dysfunction: a systematic review and meta-analysis | journal = Scientific Reports | volume = 11 | issue = 1 | pages = 24097 | date = December 2021 | pmid = 34916560 | pmc = 8677770 | doi = 10.1038/s41598-021-03317-5 | bibcode = 2021NatSR..1124097H }}
• Catecholamines
• Dopamine
• Dobutamine
• Dopexamine
• Adrenaline (epinephrine)
• Isoproterenol (isoprenaline)
• Noradrenaline (norepinephrine)
• Angiotensin II
• Eicosanoids
• Prostaglandins{{cite journal | vauthors = Schrör K, Hohlfeld T | title = Inotropic actions of eicosanoids | journal = Basic Research in Cardiology | volume = 87 | issue = 1 | pages = 2–11 | year = 1992 | pmid = 1314558 | doi = 10.1007/BF00795384 | s2cid = 29440212 }}
• Phosphodiesterase inhibitors
• Enoximone
• Milrinone
• Amrinone
• Theophylline
• Glucagon
• Insulin

Negative inotropic agents decrease myocardial contractility and are used to decrease cardiac workload in conditions such as angina. While negative inotropism may precipitate or exacerbate heart failure in the short term, certain beta blockers (e.g. carvedilol, bisoprolol and metoprolol) have been believed to reduce long-term morbidity and mortality in congestive heart failure.{{cite journal | vauthors = Xu T, Huang Y, Zhou H, Bai Y, Huang X, Hu Y, Xu D, Zhang Y, Zhang J | display-authors = 6 | title = β-blockers and risk of all-cause mortality in patients with chronic heart failure and atrial fibrillation-a meta-analysis | journal = BMC Cardiovascular Disorders | volume = 19 | issue = 1 | pages = 135 | date = June 2019 | pmid = 31159740 | pmc = 6547467 | doi = 10.1186/s12872-019-1079-2 | doi-access = free }}

Examples of negative inotropic agents include:

• Beta blockers{{cite journal | vauthors = Chatterjee S, Biondi-Zoccai G, Abbate A, D'Ascenzo F, Castagno D, Van Tassell B, Mukherjee D, Lichstein E | display-authors = 6 | title = Benefits of β blockers in patients with heart failure and reduced ejection fraction: network meta-analysis | journal = BMJ | volume = 346 | issue = jan16 1 | pages = f55 | date = January 2013 | pmid = 23325883 | pmc = 3546627 | doi = 10.1136/bmj.f55 }}
• Non-dihydropyridine Calcium channel blockers
• Diltiazem
• Verapamil

Class IA antiarrhythmics such as

• Quinidine
• Procainamide
• Disopyramide

Class IC antiarrhythmics such as

• Flecainide
• Isovoacangine
• Voacristine

• Bathmotropic
• Dromotropic
• Vasoconstrictors

{{Reflist|group=help}}

{{reflist}}

{{Cardiovascular physiology}}

Category:Cardiovascular physiology