An inotrope is an agent that alters the force or energy of
muscular contractions. Negatively inotropic agents weaken the force of
muscular contractions. Positively inotropic agents increase the strength of muscular contraction.
The term ''inotropic state'' is most commonly used in reference to various
drugs that affect the strength of
contraction of heart muscle. However, it can also refer to
pathological conditions. For example,
enlarged heart muscle can increase inotropic state, whereas
dead heart muscle can decrease it.
Medical uses
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
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar ...
in the
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
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.
Positive inotropic agents
By increasing the concentration of intracellular
calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar ...
or increasing the sensitivity of receptor proteins to calcium, positive inotropic agents can increase
myocardial contractility. Concentrations of intracellular calcium can be increased by increasing influx into the cell or stimulating release from the sarcoplasmic reticulum.
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
An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells ...
, while T-type channels are important in initiating them.
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
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...
,
cardiogenic shock
Cardiogenic shock (CS) is a medical emergency resulting from inadequate blood flow due to the dysfunction of the ventricles of the heart.Textbooks of Internal MedicinHarrison's Principles of Internal Medicine 16th Edition, The McGraw-Hill Compan ...
,
septic shock,
myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which ma ...
,
cardiomyopathy
Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. ...
, etc.
Examples of positive inotropic agents include:
*
Digoxin
Digoxin (better known as Digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. Digoxin is o ...
*
Berberine
Berberine is a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids found in such plants as ''Berberis vulgaris'' (barberry), ''Berberis aristata'' (tree turmeric), ''Mahonia aquifolium'' (Oregon grape), ''Hydras ...
*
Calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar ...
*Calcium sensitisers
**
Levosimendan
Levosimendan (INN) is a calcium sensitizer used in the management of acutely decompensated congestive heart failure. It is marketed under the trade name Simdax ( Orion Corporation). Overall the drug has a two fold mechanism of action. It leads t ...
*
Catecholamines
**
Dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...
**
Dobutamine
**
Dopexamine
Dopexamine is a synthetic analogue of dopamine that is administered intravenously in hospitals to reduce exacerbations of heart failure and to treat heart failure following cardiac surgery. It is not used often, as more established drugs like e ...
**
Adrenaline (epinephrine)
**
Isoproterenol (isoprenaline)
**
Noradrenaline (norepinephrine)
*
Angiotensin II
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adr ...
*
Eicosanoids
**
Prostaglandins
*
Phosphodiesterase inhibitors
**
Enoximone
**
Milrinone
**
Amrinone
Amrinone, also known as inamrinone, and sold as Inocor, is a pyridine phosphodiesterase 3 inhibitor. It is a drug that may improve the prognosis in patients with congestive heart failure. Amrinone has been shown to increase the contractions initia ...
**
Theophylline
*
Glucagon
*
Insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism ...
Negative inotropic agents
Negative inotropic agents decrease myocardial
contractility and are used to decrease cardiac workload in conditions such as
angina
Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease.
Angina is typically the result of obstr ...
. While negative inotropism may precipitate or exacerbate heart failure, certain beta blockers (e.g.
carvedilol,
bisoprolol and
metoprolol) have been believed to reduce
morbidity and
mortality in
congestive heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...
.
Examples of negative inotropic agents include:
*
Beta blockers
*Non-dihydropyridine
Calcium channel blocker
Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...
s
**
Diltiazem
Diltiazem, sold under the brand name Cardizem among others, is a calcium channel blocker medication used to treat high blood pressure, angina, and certain heart arrhythmias. It may also be used in hyperthyroidism if beta blockers cannot be ...
**
Verapamil
Class IA
antiarrhythmics
Antiarrhythmic agents, also known as cardiac dysrhythmia medications, are a group of pharmaceuticals that are used to suppress abnormally fast rhythms ( tachycardias), such as atrial fibrillation, supraventricular tachycardia and ventricular tac ...
such as
*
Quinidine
*
Procainamide
*
Disopyramide
Class IC antiarrhythmics such as
*
Flecainide
*
Isovoacangine
*
Voacristine
See also
*
Bathmotropic Bathmotropic often refers to modifying the degree of excitability specifically of the heart; in general, it refers to modification of the degree of excitability (threshold of excitation) of musculature in general, including the heart. It especiall ...
*
Dromotropic
*
Pressors
Notes
References
{{Cardiovascular physiology
Cardiovascular physiology