Inotrope

An inotrope[help 1] 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 (myocardial contractility). However, it can also refer
to pathological conditions. For example, enlarged heart muscle (ventricular hypertrophy) can
increase inotropic state, whereas dead heart muscle (myocardial infarction) can decrease it.

Medical uses[edit]
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 tissue, they are likely safe when given for less
than two hours in a good peripheral iv.[6]

Positive inotropic agents[edit]

By increasing the concentration of intracellular calcium or increasing the sensitivity of receptor
proteins to calcium, positive inotropic agents can increase myocardial contractility.[7] Concentrations
of intracellular calcium can be increased by increasing influx into the cell or stimulating release from
the sarcoplasmic reticulum.[8]
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.[9]
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.
Examples of positive inotropic agents include:[citation needed]

 Digoxin
 Berberine
 Calcium
 Calcium sensitisers
o Levosimendan
 Catecholamines
o Dopamine
o Dobutamine
o Dopexamine
o Adrenaline (epinephrine)
o Isoproterenol (isoprenaline)
o Noradrenaline (norepinephrine)
 Angiotensin II
 Eicosanoids
o Prostaglandins[10]
 Phosphodiesterase inhibitors
o Enoximone
o Milrinone
o Amrinone
o Theophylline
 Glucagon
 Insulin

Negative inotropic agents[edit]

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, certain beta blockers (e.g. carvedilol, bisoprolol and metoprolol) have been believed to
reduce morbidity and mortality in congestive heart failure.
Examples of negative inotropic agents include:

 Beta blockers
 Non-dihydropyridine Calcium channel blockers
o Diltiazem
o Verapamil
Class IA antiarrhythmics such as

 Quinidine
 Procainamide
 Disopyramide
Class IC antiarrhythmics such as

 Flecainide
Isovoacangine Voacristine
Chronotropic
Chronotropic effects (from chrono-, meaning time, and tropos, "a turn") are those that change
the heart rate.
Chronotropic drugs may change the heart rate and rhythm by affecting the electrical conduction
system of the heart and the nerves that influence it, such as by changing the rhythm produced
by the sinoatrial node. Positive chronotropes increase heart rate; negative chronotropes decrease
heart rate.
A dromotrope affects atrioventricular node (AV node) conduction. A positive dromotrope increases
AV nodal conduction, and a negative dromotrope decreases AV nodal conduction. A lusitrope is an
agent that affects diastolic relaxation.
Many positive inotropes affect preload and afterload.

Negative chronotropes[edit]
Chronotropic variables in systolic myocardial left and right. Left sided systolic chronotropy can be
appreciated as Aortic Valve open to close time. Right sided variables are represented by pulmonary
valve open to close time. Inverted as diastolic chronotropy, the variables are aortic valve close to
open and pulmonic close to open time. Pharmaceutical manipulation of chronotropic properties was
perhaps first appreciated by the introduction of digitalis, though it turns out that digitalis has
an inotropic effect rather than a chronotropic effect.

 Beta blockers such as metoprolol

 Acetylcholine
 Digoxin
 The non-dihydropyridine calcium channel blockers diltiazem and verapamil

Positive chronotropes[edit]

 Most Adrenergic agonists
 Atropine
 Dopamine
 Epinephrine
 Isoproterenol
 Milrinone
 Theophylline[1]