Vasoactive and Inotropic Drugs

VASOACTIVE AND INOTROPIC DRUGS

Terminology

Inotrope – an agent that affects contraction. Can be positive or negative.
Chronotrope – an agent that affects heart rate. Can be positive or negative.
Vasopressor – an agent that tends to increase blood pressure by increasing total peripheral resistance.
Vasoconstrict – the narrowing of blood vessels resulting from the contraction of the muscular wall.
​Vasodilate – the widening of the blood vessels.

Introduction

This document summarises very briefly the effects that may be seen with central flow and/or pressure when some common haemodynamic drugs are given. Note: patients may respond differently and this is only a guide.
The autonomic nervous system is responsible for maintaining normal functions such as blood pressure and blood flow. It has two divisions; the parasympathetic and the sympathetic systems. The parasympathetic is generally concerned with conservation of energy and maintenance of organ function during periods of minimal activity, while the sympathetic acts when the ‘fight or flight’ response is required. There is a natural balance between the two systems.
The parasympathetic nervous system contributes to regulation of heart function through the vagus nerve where it slows the rate, but has little or no control over the blood vessels.
The sympathetic nervous system has an excitatory influence on heart rate and contractility and controls the smooth muscle tone of the blood vessels. It maintains them in a state of tonic activity (continuous activity). The increases in sympathetic activity will increase the constriction or visa versa. The main types of adrenergic receptors mentioned here are alpha (α), beta (β) and dopamine (DA), with some of their subtypes that interact with the sympathetic neuromediators. Only those associated with haemodynamics are discussed here. Generally, α receptors cause constriction, while β cause dilation and increased contractility. Some blood vessels are supplied with both these constrictor and dilator receptors.
An adrenergic agonist is a drug that stimulates a response from the adrenergic receptors. Inotropes are agents that increase myocardial contractility (inotropy) e.g. adrenaline, dobutamine. Vasopressors are agents that cause vasoconstriction leading to increased systemic and/or pulmonary vascular resistance (SVR, PVR) e.g. noradrenaline, metaraminol. Inodilators are agents with inotropic effects that also cause vasodilation leading to decreased SVR and/or PVR e.g. dobutamine. Other agents included e.g. dopamine.
The following mnemonics may help to understand where the adrenoreceptors are located and their general actions.

  • ‘1 heart and 2 lungs’ refers to α1 and β1 being found in the heart, while α2 and β2 will be found in the lungs (remember also that α1 and β2 will be found in blood vessels).
  • Alpha has the symbol α – imagine this is a fish and is drawn as a piece of string. If the ends of the string are pulled apart, the circle of the symbol (representing the vessel) will constrict. Beta-receptors are ‘B’igger and ‘B’etter and dilate vessels and increase heart rate.

A breakdown of the main adrenoreceptors only related to haemodynamics and their actions is listed in the following table:

Type Tissue Actions
Alpha 11) Most vascular smooth muscle Constriction
Heart Increased force of constriction (inotropy)
Alpha 22) Vascular adreneric nerve terminals Inhibition of sympathetic activity. Has central and peripheral effects – BP ↑ or ↓
Beta 11) Heart Increased rate (chronotropy) and force of contraction
Beta 22) Bronchi, uterine and vascular smooth muscle Relaxation – causes dilation
Beta 33) Heart Increased force of contraction in healthy heart Cardioprotective in heart failure – has negative inotropic effect
Dopamine (DA1) Vascular bed of brain, splanchnic organs<, kidneys and coronary arteries Increases peripheral resistance (vasoconstriction) but can vasodilate renal and gut circulation. Can also increase vascular resistance systemically

Table 1. General details of alpha, beta and dopamine receptors.

The following drugs have these types of effects:

Receptor Alpha 1 Beta 1 Beta 2 DA1
Metaraminol +++ + 0 0
Adrenaline (epinephrine) +/++ ++ + 0
  Noradrenaline (norepinephrine) +++ +++ + 0
Phenylephrine ++ 0 0 0
Dobutamine + ++ +/++ 0
Dopamine ++ + 0 +++
Dopexamine 0 + +++ ++
Ephedrine ++ ++ 0 0

Table 2. Common haemodynamic drug actions on adrenorecptors.

Then consider how these drugs will affect central flow as seen by the ODM+ and blood pressure.

Drug FTc PV HR SV CO BP
Metaraminol
Adrenaline (Epinephrine) low dose (no definition for low or high dose – is patient specific) ↑↓or ↔
Adrenaline (Epinephrine) high dose (no definition for low or high dose – is patient specific)
Noradrenaline (norepinephrine) ↓or occasionally ↑
Phenylephrine
Dobutamine ↑↓or ↔
Dopamine (low dose – 1-5 mcg/kg/min)
Dopamine (medium dose – 5-10 mcg/kg/min) ↔or↓ ↑↓or ↔
Dopamine (high dose – 10-15 mcg/kg/min) ↑or↓ ↑or↓ ↑↓or ↔
Dopexamine ↓or ↔

Table 3. Potential effects of common haemodynamic drugs on central flow and BP.

Take hom messages

Take Home Messages

  • This is a complex subject and haemodynamic drugs may have more than one effect.
  • Metaraminol (and noradrenaline to some extent) has effects that can be seen easily – if used to treat a falling BP, the flow will decrease as BP increases. This is not necessarily treating the underlying cause and in some instances, may make things worse for the patient (see ‘Under Pressure?’ document). Ideally CO should be optimised before commencing vasoactive drugs.
  • Using ODM+ will allow central flow to be assessed precisely when these drugs are used.

Bibliography

  • Benham-Hermetz J., Lambert M. and Stephens C.M.Core Training. Cardiovascular failure, inotropes and vasopressors. BJ Hospital Medicine 2012; 73(5). ucl.ac.uk/anaesthesia/StudentsandTrainees
  • Critical Care Compendium. Inotropes, vasopressors and other vasoactive agents. Life in the Fast Lane. lifeinthefastlane.com
  • Murphy P. Handbook of Critical Care. Science Press.
  • Overgard C.B. & Džavík V. Inotropes and Vasoporessors. 2008;118:1047-1056.
  • Porth C.M. Pathophysiology: Concepts of Altered Health States, 2002 6th Lippincott, Williams and Wilkins.
  • Pratt O. and Gwinnutt C. Tutorial of the Week. The Autonomic Nervous System. Anesthesia UK. anaesthesiauk.com