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