INOTROPES AND VASOACTIVE DRUGS

Uppers, Downers and Squeezers

Aim and Objective

Functional overview of how inotropes and vasoactive drugs work.

Explore nursing considerations.Discuss case examples.Hopefully end up feeling more confident.

It’s all about the Oxygen

For tissues to be oxygenated, 3 factors need to be considered: 1) Oxygen transfer across the alveolar-capillary

membrane

2) Oxygen attachment to haemaglobin

3) Adequate cardiac output (CO) to move the oxyhaemaglobin compound to the tissues – this is what we are talking about!

Two Limbs to Oxygenation

To increase CO we can…

1) Enhance circulating volume through fluid resuscitation (increasing preload)

2) Enhancing myocardial contractility with inotropes (their inotropic effect)

3) Manipulating heart rate with inotropes (their chronotropic effect)

Remember

Cardiac output (CO) = Heart Rate (HR) x Stroke Volume (SV)

Measuring Cardiac Output

How do we commonly evaluate?How complex is this?

Blood Pressure

BP = CO x Total Peripheral Resistance

Simple enough right???

Remember this?

Stroke Volume

Complex beast affected by preload, afterload and contractility.

Confused???

How does this stay balanced?

Parasympathetic down regulates and Sympathetic up regulates.

A&P

It’s all about the Receptors

Table 1.  Adrenergic receptor sites (SNS)ReceptorActions Locationsα ↑SVR Coronary arterioles  ↑Blood pressure Vascular smooth muscle  ↓Insulin release  

β1 ↑Heart rate Sinoatrial node↑Contractility Myocardium

β2 ↑Contractility Coronary arterioles  ↓SVR Bronchial smooth muscle    Atrioventricular node    Vascular smooth muscle

DA Vasodilation KidneyMesentery

    Heart

SVR =systemic vascular resistance. DA = Dopaminegic

Important terms – Agonist

Important terms - Antagonist

Important terms – Partial Agonist

Ok take a breather!

How do we treat this stuff?

http://www.youtube.com/watch?v=HMGIbOGu8q0

Let’s talk drugs!

In the context of the SNS, drugs:Mimic or impair (stimulate or block)Directly (agonist or antagonist)Indirectly - releasing endogenous Norad (metaraminol,

ephedrine at a1)

Let’s talk drugs!

In the context of the PNS, drugs work on:Nicotinic and

muscarinic receptors with Ach as neurotransmitter

M2 heart

Atropine - PNS

Anticholinergic drug – works as a competitive antagonist in muscarinic receptors (M2 = Heart)

Blocks slow – down signals to the heart.

Adrenaline - SNS

Non-selective b and a agonist

+inotrope and chronotrope

Vasodilates at low dose, constricts at high dose

Bronchial smooth muscle relaxant

Use in asthma?

Noradrenaline - SNS

Acts predominantly on alpha-receptors and beta-receptors in the heart.

Causes peripheral vasoconstriction (alpha-adrenergic action) and a positive inotropic effect on the heart and dilatation of coronary arteries (beta-adrenergic action).

Why is it important to assess adequate fluid loading?

Dobutamine - SNS

Direct acting inotropic whose primary activity results from stimulation of the beta-receptors of the heart while producing comparatively mild chronotropic, hypertensive, arrhythmogenic and vasodilative effects.

It does not cause the release of endogenous noradrenaline as does dopamine

Used for heart failure for the above reasons

250mg vials

Vasopressin (ADH)

increase resorption of water by the renal tubules

Cause contraction of smooth muscle of the gastrointestinal tract and of all parts of the vascular bed, especially the capillaries, small arterioles and venules, with less effect on the smooth musculature of the large veins.

20IU/ml

Metaraminol - SNS

Increases both systolic and diastolic blood pressure.

The pressor effect begins one to two minutes after intravenous injection, and lasts about 20 minutes to one hour.

Positive inotropic effect on the heart and has a peripheral vasoconstrictor action.

Potent sympathomimetic – alpha agonist effects, mild beta 1 effects.

Ephedrine – SNS

Stimulates both alpha and beta-adrenergic receptors indirectly and also releases endogenous noradrenaline from its storage site (particularly observed in the substantia nigra).Often used in OT due to strong direct evidence base lying in anaesthetic hypotension.

Phenylephrine - SNS

Used mostly in OTProduces vasoconstriction that lasts longer than that of adrenaline and ephedrine. Responses are more sustained than those to adrenaline, lasting 20 minutes after intravenous and as long as 50 minutes after subcutaneous injection. Its action on the heart opposite to adrenaline and ephedrine, in that it slows the heart rate and increases the stroke output, producing no disturbance in the rhythmPowerful postsynaptic alpha-receptor stimulant with little effect on the beta-receptors of the heart. A singular advantage of this drug is the fact that repeated injections produce comparable effects.

GTN – Direct Vasoactive

Glyceryl trinitrate produces a dose related dilation of both arterial and venous beds.

Decreases venous return to the heart, reducing left ventricular end diastolic pressure and pulmonary capillary wedge pressure (preload).

Arteriolar relaxation reduces systemic vascular resistance and arterial pressure (afterload).

Also dilates the coronary arteries, although this effect is short-lived.

These are also out there

Some less frequently used drugs

Dopamine - SNS

Stimulates alpha, beta and dopamine receptors. Precursor to noradrenaline chemically At infusion rates of 0.5 to 2 microgram/kg/minute, dopamine

receptors are selectively activated and blood pressure either does not change or decreases slightly.

Causes renal and mesenteric vasodilatation - Renal plasma flow, glomerular filtration rate and sodium excretion usually increase.

At infusion rates of 2 to 10 microgram/kg/minute, beta1-receptors are activated and cardiac output and systolic blood pressure increase.

The total peripheral resistance is relatively unchanged because of peripheral vasoconstriction (alpha effect) and muscle vasodilatation (beta effect).

At infusion rates above 10 microgram/kg/minute, alpha-receptors are activated, causing vasoconstriction, and both systolic and diastolic pressures increase

200mg Ampoules

Isoprenaline

Acts on the heart, smooth muscle of bronchi, skeletal muscle vasculature and gastrointestinal tract.Increases cardiac output due to its positive inotropic and chronotropic actions and by increasing venous return. Also lowers peripheral vascular resistance. The rate of discharge of cardiac pacemakers is increased.Great option in complete heart block.

Milrinone

Selective phosphodiesterase inhibitor which has positive inotropic and vasodilatory activity. Milrinone improves hemodynamics and biventricular function in patients with ventricular dysfunction by increasing stroke volume index, increasing left ventricular contractility, producing pulmonary vasodilation. Used in heart failure due to minimal chronotropic effect

Sodium Nitroprusside (SNP) – Direct Vasoactive

Potent relaxation of vascular smooth muscle and consequent dilatation of peripheral arteries and veins.Non-selective compared to GTN .

Levosimendan

Developed for the treatment of decompensated heart failure and is used intravenously when patients with heart failure require immediate initiation of drug therapy. It increases the sensitivity of the heart to calcium, thus increasing cardiac contractility without a rise in intracellular calcium.Exerts its effect by increasing calcium sensitivity of myocytes by binding to cardiac troponin C in a calcium-dependent manner. It also has a vasodilatory effect, by opening adenosine triphosphate (ATP)-sensitive potassium channels in vascular smooth muscle to cause smooth muscle relaxation.

Ok…….

Inotropic drugs are potentially dangerous so be very thorough checking.

Vascular access needs to be spot on.On central line always endeavour to use

distal, brown lumen (in furthest)Wear gloves when preparing.Know what the drug does and why we use it.Don’t EVER make a mistake with

inotropes!!!