INOTROPES

                                                                                                                                       INOTROPES

MEDICATION

n  Chronotrophic effect - HR effect

n  Positive Inotrophic effect - stimulate myocardial contractility

n  sympathomimetic -  mimic sympathetic nervous system

ACTION OF RECEPTORS

n  Alpha1 (µ1)

¨  Ý glycogenolysis, smooth muscle contraction  (blood vessels, genitourinary tract)

n  Alpha2 (µ2)

¨  smooth muscle relaxation (GIT), smooth muscle contraction (some vascular beds), inhibition of lipolysis, renin release, platelet aggregation & insulin secretion

n  Beta1   (b1)

¨  stimulation of lipolysis, myocardial contraction (Ý rate, Ý force of contraction)

n  Beta2   (b2)

¨  Ý hepatic gluconeogenesis; Ý hepatic glycogenolysis; Ý muscle glycogenolysis; Ý release of insulin, glucagon & renin; smooth muscle relaxation (bronchi, blood vessels, genitourinary tract, GIT)

ADRENALINE:

n Mixed µ & b properties

n naturally produced by adrenal gland as part of body’s response to stress

n low dose stimulates b receptors to Ý HR, cardiac conduction, contractility & vasodilation & therefore \Ý CO

n as dose Ý receptors stimulated ÞÝ vascular resistance & BP

n impact on CO depends on hearts ability to pump against Ý after load

n Ý HR, may precipitate ventricular arrhythmias in ischaemic heart

NOR ADRENALINE

n Largely µ stimulation

n low dose b1 recepors activated, produces mild Ý contractility Þ Ý CO

n higher doses, inotrophic effect limited by marked vaso constriction mediated by µ receptors

n its major effect is on peripheral resistance with little direct cardiac action

n Ý tone affects renal arteries & leads to ß renal blood flow

n Ý BP at expense of impaired perfusion of peripheral organs & Ý cardiac work

n Ý myocardial O2 consumption

DOPAMINE

n naturally occurring precursor of noradrenaline

n both µ & b effects & dopaminergic receptors in renal & mesenteric blood vessels

n < 5mcg/kg/min - dilates renal arteries Þ improved renal blood flow Þ Ý urine output

n > 5mcg/kg/min - Ý CO with Ý myocardial contractility & ß PVR through  b1 stimulation

n >20mcg/kg/min - Ý PVR & HR, predominantly µ stimulating effect Þ vasoconstriction acts much as noradrenaline at high doses

DOBUTAMINE

n synthetic catacholamine, a derivation of dopamine

n largely b1 stimulant effect \ acts primarily on myocardial contractility

n some b2 stimulation mild vasodilation

n stimulates myocardial contractility Þ Ý CO & BP

n has little effect on HR & PVR

n acts by predominantly stimulating b receptors (mostly b1) with minimal µ receptor effect

n high dose Þ Ý HR & ß PVR

n less chronotropic effect than dopamine, but Ý contractility effect

n useful in treatment of heart failure

MILRINONE

nCombined positive inotropic (potent) & vasodilating effects

nreductions in preload, afterload & pulmonary vascular resistance

nphosphodiesterase inhibitor

nhypotension may occur from vasodilation

nused in combination with adrenaline or nor adrenaline, often for weaning

nmust be adequately filled to reduce hypotension & slowly introduced

ARAMINE

n Both µ & b effect

n potent pressor effect by stimulating heart & peripheral vasoconstriction

n Ý BP

n often used post anaesthetic

ISOPRENALINE

nalmost pure b effect with action on both the heart muscle & peripheral blood vessels

nhas powerful chronotropic effect

nproduces dramatic Ý HR, conduction & contractility via b1 & vasodilation via b2 stimulation

nalso produces vasodilation of pulmonary arteries & bronchodilation

ncan Þ PVC’s & VT

nÝ myocardial O₂ consumption

EPHEDRINE SULPHATE

nSympathomimetic ÞÝ contractility, conduction velocity,  automaticity & chronotrophic effect Þ ÝBP

nreduces bronchial spasm

nrapid onset 

             

DIGOXIN

na cardiac glycoside

nslow onset of action, high risk of toxicity

nslow sinus rate & ß AV conduction used in control of supraventricular arrhythmias

nenhances myocardial contractility

                       

MAGNESIUM

nnecessary co-factor for the membrane enzyme Na⁺-K⁺ Atpase

nlack of Mg⁺⁺ may lead to intracellular K⁺ depletion, unable to be repleted until  adequate Mg⁺⁺ administered

nintrinsic antiarrhythmic action

AMIODARONE

nNot an inotrope but a potent antiarrhythmic, frequently seen in critical care units

nprolongs action potential duration & increases refractoriness of all cardiac tissue

nNa⁺ channel blockage, antiadrenergic, Ca⁺⁺ channel blockage & antifibrillatory effects

nmajor action is on AV node, causing a delay in intranodal conduction

nused in suppressing SVT & VT

ncauses some cardiac depression, but CI often unchanged due to vasodilator properties

PROSTAGLANDIN

n      PGE₂ or prostin

n      vasodilator,  antagonizes thromboxane A₂ & inhibits platelet aggregation

n      improves peripheral O₂ utilization in critically ill patients