Inotropes and Vasopressors

Dr. Ahmad Nabries

Introduction• Inotropes : Primarily increases myocardial contractility, by increasing the velocity and the force of myocardial fibre shortening; also have effect on peripheral vasculature dan HR• Vasopressors : increases SVR

BP = CO X SVR

CO = SV X HR• Preload• Afterload• Contractility

SV

Introduction• Sympatomimetics Mimic the effects of neurotransmitter

substances of the sympathetic nervous system 

Receptors

1. Alpha : 1 & 22. Beta : 1, 2 & 33. Dopamine

Figure 2. Schematic representation of postulated mechanisms of intracellular action of α1-adrenergic agonists. α1-Receptor stimulation activates a different regulatory G protein (Gq),

which acts through the phospholipase C system and the production of 1,2-diacylglycerol (DAG) and, via phosphatidyl-inositol-4,5-biphosphate (PiP2), of inositol 1,4,5-triphosphate

(IP3).

Overgaard C B , and Džavík V Circulation. 2008;118:1047-1056Copyright © American Heart Association, Inc. All rights reserved.

Figure 1. Simplified schematic of postulated intracellular actions of β-adrenergic agonists. β-Receptor stimulation, through a stimulatory Gs-GTP unit, activates the adenyl cyclase

system, which results in increased concentrations of cAMP.

Overgaard C B , and Džavík V Circulation. 2008;118:1047-1056 Copyright © American Heart Association, Inc. All rights reserved.

• Peripheral DA1 receptors mediate renal, coronary and mesenteric arterial vasodilatation and a natriuretic response

• DA2 receptors: presynaptic receptors found on nerve endings, inhibit norepinephrine release from sympathetic nerve endings, inhibit prolactin release and may reduce vomiting

• stimulation DA1 or DA2 receptors suppresses peristalsis and may precipitate ileus

Sympatomimetics• Catecholamine• Non-catecholamine

Catecholamine• Is a monoamine, an organic compound that

has acatechol (benzene with two hydroxylside groups) and a side-chain amine

Catecholamine• Epinephrine (adrenaline), • Norepinephrine (noradrenaline) and • Dopamine All of which are produced from phenylalanine and tyrosine• Dobutamine (synthetic)• Isoproterenol (synthetic)

Non-catecholamine• Ephedrine• Pseudoephedrine• Amphetamine, • Cocaine, • Phenylephrine, • Tetrahydrozoline,• Naphazoline,• Oxymetazoline, • Ritodrine, • Metaproterenol,• Albuterol, • Terbutaline, • Salbutamol

Inotropic Agents

Phosphodiesterase Inhibitors

Phosphodiesterase 3 is an intracellular enzyme that breaks down cAMP into AMP. (PDIs) increase the level of cAMP by inhibiting its breakdown within the cell, which leads to increased myocardial contractility

These agents are potent inotropes and vasodilators and also improve diastolic relaxation (lusitropy), thus reducing preload, afterload, and SVR

Figure 4. Basic mechanism of action of PDIs. PDIs lead to increased intracellular concentration of cAMP, which increases contractility in the myocardium and leads to

vasodilation in vascular smooth muscle.

Overgaard C, Džavík V. Circulation 2008;118:1047-1056Copyright © American Heart Association, Inc. All rights reserved.

Vasopressors• Isoproterenol • Norepinephrine • Epinephrine • Ephedrine • Phenylephrine• Vasopressin • Dobutamine• Dopamine

Pharmacology

Drug Clinical Indication Dose Range Receptors Major Side Effect

α-1 α-2 β-1 β-2

Catecholamine

Dopamine Shock (cardiogenic, vasodilatory)HFSymptomatic bradycardiaunresponsive to atropine or pacing

2.0 to 20 mcg /kg/minmax 50 mcg /kg/min

+++ ++++ ++ +++++ Severe hypertension (especially inpatients taking nonselective-blockers)Ventricular arrhythmiasCardiac ischemiaTissue ischemia/gangrene (high dosesor due to tissue extravasation)

Dobutamine Low CO (decompensated HF,cardiogenic shock,sepsis-induced myocardialdysfunction)Symptomatic bradycardiaunresponsive to atropine or pacing

2.0 to 20 mcg /kg/minmax 40 mcg /kg/min

+ +++++ +++ N/A TachycardiaIncreased ventricular response rate inpatients with atrial fibrillationVentricular arrhythmiasCardiac ischemiaHypertension (especially nonselectivebeta-blocker patients)Hypotension

Norepinephrine

Shock (vasodilatory, cardiogenic)

0.01 to 3 mcg/kg min

+++++ +++ ++ N/A ArrhythmiasBradycardiaPeripheral (digital) ischemiaHypertension (especially nonselectivebeta-blocker patients)

Drug Clinical Indication Dose Range Receptors Major Side Effect

α-1 α-2 β-1 β-2

Catecholamine

Epinephrine Shock (cardiogenic, vasodilatory)Cardiac arrestBronchospasm/anaphylaxisSymptomatic bradycardia orheart block unresponsive toatropine or pacing

Infusion: 0.01 to 0.10mcg /kg/minBolus: 1 mg IV every 3 to 5min (max 0.2 mg/kg)IM: (1:1000): 0.1 to 0.5 mg(max 1 mg)

+++++ ++++ +++ N/A Ventricular arrhythmiasSevere hypertension resulting incerebrovascular hemorrhageCardiac ischemiaSudden cardiac death

Isoproterenol Bradyarrhythmias (especiallytorsade des pointes)Brugada syndrome

2 to 10 mcg/min

0 +++++ +++++

N/A Ventricular arrhythmiasCardiac ischemiaHypertensionHypotension

Drug Clinical Indication Dose Range Receptors Major Side Effect

α-1 α-2 β-1 β-2

PDI

Milrinone Low CO (decompensated HF,after cardiotomy)

Bolus: 50 g/kg bolus over10 to 30 minInfusion: 0.375 to 0.75g kg1 min1 (doseadjustment necessary forrenal impairment)

N/A Ventricular arrhythmiasHypotensionCardiac ischemiaTorsade des pointes

Amrinone Low CO (refractory HF) Bolus: 0.75 mg/kg over 2to 3 minInfusion: 5 to 10Mcg/kg/ min

N/A Arrhythmias, enhanced AV conduction(increased ventricular response rate inatrial fibrillation)HypotensionThrombocytopeniaHepatotoxicity

Vasopressin Shock (vasodilatory, cardiogenic)Cardiac arrest

Infusion: 0.01 to 0.1 U/min(common fixed dose 0.04U/min)Bolus: 40-U IV bolus

V1 receptors (vascular smooth muscle)V2 receptors (renal collecting duct system)

ArrhythmiasHypertensionDecreased CO (at doses 0.4 U/min)Cardiac ischemiaSevere peripheral vasoconstrictioncausing ischemia (especially skin)Splanchnic vasoconstriction

Inotropes Dose Mechanism of

Action

HR Systolic Diastolic Myocard demand O2

SVR PVR

Dopamine 1-5 mcg/kg/min

Dopaminergic agonist

Increase Minimal No effect Minimal increase

Minimal increase

No effect

6-10 mcg/kg/min

Beta 1 agonist

Increase Increase No effect Increase Increase Minimal increase

11-20 Alpha agonist

Increase Increase No effect increase Significant increase

Minimal increase

Dobutamine 1-10 mcg/kg/min

Beta 1 agonist, alpha anti agonist

increase increase No effect increase Minimal effect /decrease

Minimal decrease

Inotropes Dose Mechanism of

Action

HR Systolic Diastolic Myocard demand

O2

SVR PVR

Epinephrine 0.01-1 mcg/kg/min

Beta 1 agonist>Alpha agonist

Increase Significant increase

No effect Significant increase

Increase Minimal increase

Norepinephrine

0.01-1 mcg/kg/min

Beta 1 agonist<Alpha agonist

Increase Some Increase

No effect Increase Significant increase

Minimal increase

Milrinone 0.1-1 mcg/kg/min

PDI No Change

Increase Improves Minimal increase

Decrease Decrease

Therapeutic Use

Thank youTarimo kasiah

Arigato GozaimasuDanke schon

Muchas gracias

Matursuwun

Grazie

Merci