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 (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.
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.
Positive inotropic agents
By increasing the concentration of intracellular calcium 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, 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.
Examples of positive inotropic agents include:
- Calcium sensitisers
- Cardiac myosin activators
- Angiotensin II
- Phosphodiesterase inhibitors
Negative inotropic agents
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. Quite recently, however, the effectiveness of beta blockers has come under renewed critical scientific scrutiny.
Examples of negative inotropic agents include:
Class IA antiarrhythmics such as
Class IC antiarrhythmics such as
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