sympathomimetic - a drug which mimics the effects of the sympathetic system. Modern drugs used for heart disease are all β1 agonists.
These drugs may be used for short term inotropic support of a failing myocardium. They have a very short half life and therefore are only really useful as either an iv bolus or as constant rate infusions; ie in intensive care. They are therefore normally used only in acute heart failure. Traditionally, dobutamine has been used in dogs and horses, and dopamine in people, but there is no good reason for this. Adrenaline is cheap, and is the best drug to treat anaphylaxis in the field. This means that it should always be available and you must memorise the dose rate. Sympathomimetics are primarily used as inotropes, usually for their β1 agonist effects, but β1 receptor activation also increases automaticity of myocardial cells so ventricular ectopic beats are a common sign of overdose. These may progress to ventricular tachycardia or even ventricular fibrillation, so ECG monitoring is necessary. Since the object of therapy is to increase arterial blood pressure, this is usually monitored directly.
Tolerance to β1 receptor activation can occur after as little as 8 hours so long term use is usually limited to 3 days maximum.
α1 receptor agonists produce vasocontriction, which can sometimes be useful, and sometimes dangerous. The vasoconstrictor effects of adrenaline are useful in anaphylaxis, but not usually in acute heart failure. Relatively selective α1 agonists such as methoxamine or ephedrine are not used much these days (except in the bladder): fluids are usually used instead.
| effect on | rate | force | SVR | ABP |
| adrenaline | ++ | +++ | +++ | +++ |
| noradrenaline | - | 0/+ | +++ | +++ |
| dopamine | 0 | +++ | 0/- | ++ |
| isoprenaline | +++ | +++ | - | +/- |
| dobutamine | + | +++ | + | +++ |
| dopexamine | 0/+ | +++ | 0 | +++ |
nb: different effects occur at different doses (SVR = systemic vascular resistance; ie, vasoconstriction: ABP = arterial blood pressure)
Adrenaline (epinephrine USAN) is an agonist at β1 and α1 receptors in the heart (positive inotrope and chronotrope) and all adrenergic receptors peripherally (predominantly arteriolar constriction and a subsequent increase in afterload).
Adrenaline usually comes as a 1:1000 solution in brown ampoules (it is light and oxygen sensitive), but it should be diluted to at least 1:10,000 before use. It can be mixed with most iv fluids for infusion.
Indications
Side effects
tachyarrhythmias leading to ventricular ectopic beats and ultimately ventricular fibrillation in overdose - monitor ECG and feel pulse for irregularities. nb tachyarrhythmias are more likely in the presence of halothane.
Dose of adrenaline
Dilute to 1:10,000 (100µg/mL)
• 20 µg/kg im or
• 5 - 20 µg/kg iv or
• 20µg/kg intratracheal, or as a last resort only
• 2 µg/kg intracardiac (avoid if possible)
This may have to be given in an emergency - memorise the dose!
Noradrenaline (norepinephrine USAN) is mainly an α agonist (vasoconstriction) but has some useful β1 effects at higher doses. It is indicated for haemostasis of mucosae and has been used for systemic vasoconstriction. It is contraindicated in heart failure (increases afterload).
Isoprenaline (isoproterenol USAN) is a synthetic β1 and β2 receptor agonist which increases heart rate more than other catecholamines. It decreases peripheral vascular resistance by its β2 effects. This may cause a decrease in blood pressure. It has no real place in the treatment of heart failure as it has a positive chronotropic effect ie. increase heart rate, and a potential to cause malignant ventricular dysrhythmias. It is occasionally used to increase heart rate in third degree heart block (but a pacemaker is better).
Dopamine is an endogenous precursor of noradrenaline but also
has direct effects. At a low dose (2µg/kg/min) it is a dopamine receptor
agonist and causes renal, mesenteric, (coronary, cerebral) arteriolar vasodilatation.
At a medium dose (2 - 5µg/kg/min) it acts at β1 receptors
to produce positive inotropy. At a slightly higher dose (5 - 10µg/kg/min)
it acts at β1 receptors to cause positive chronotropy and increased
automaticity as well. At high doses (>10µg/kg/min) it affects α1 receptors, either directly or by causing the release of noradrenaline, and causes
vasoconstriction.
Since it must be given by infusion, dopamine is usually only used in intensive
care, as a positive inotrope in acute heart failure or in shock when renal and
mesenteric flow is decreased from vasoconstriction.
Side effects are dose dependent and include tachycardia, supraventricular
and / or ventricular arrhythmias, vomiting, hypotension, and vasoconstriction.
Since it is used by infusion and it has a very short half life treatment of
toxicity is by slowing or stopping it
Contraindications - ventricular fibrillation & uncorrected arrhythmias
It is always given by infusion, starting at a low dose (1 µg/kg/min).
Effects are monitored (ECG, ABP) and rate increased until the desired effect
has been reached or toxicity (tachycardia, ventricular ectopic beats) occurs.
Accurate control of infusion rate requires an infusion pump.
Dobutamine is a synthetic catecholamine with predominant β1 agonist effects which increase contractility and is relatively non-arrhythmic.
It favours cardiac output redistribution to coronary and skeletal muscle beds.
Renal and mesenteric flows also increase due to a total increase in cardiac
output. It enhances AV conduction resulting in mild positive chronotropic effect
It is used to increase contractility in patients in acute heart failure (horses
under anaesthesia), and for short term stabilisation of chronic heart failure
until longer acting drugs can take effect.
Side effects are similar to dopamine.
Dopexamine is similar to dopamine but longer acting. Not available in NZ at present.
Since most inotropes act to increase intracellular calcium, it seems logical to use calcium salts (gluconate / chloride) as inotropes. They can be effective and used to be used for this purpose, especially after cardiac arrest, but they are much better at causing contraction of smooth muscle than cardiac muscle. This means that they produce intense vasoconstriction - in the coronary and cerebral vessels this will potentiate or even cause ischaemia. Calcium has been shown to reduce survival in acute heart failure and should not be used as an inotrope. Indeed, modern practice is to use calcium channel blockers to cause coronary and cerebral vasodilatation in cardiac intensive care, despite the small reducution in cardiac output they cause.
Sypathomimetic inotropes lecture
