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
SV

Preload
Afterload
Contractility

Introduction
Sympatomimetics
Mimic the effects of neurotransmitter
substances of the sympathetic nervous
system

Receptors
1. Alpha : 1 & 2
2. Beta : 1, 2 & 3
3. Dopamine

Figure 2. Schematic representation of postulated mechanisms of intracellular action of 1adrenergic agonists. 1-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 Davk V Circulation. 2008;118:1047-1056

Copyright American Heart Association, Inc. All rights reserved.

Figure 1. Simplified schematic of postulated intracellular actions of -adrenergic agonists. Receptor stimulation, through a stimulatory Gs-GTP unit, activates the adenyl cyclase
system, which results in increased concentrations of cAMP.

Overgaard C B , and Davk V Circulation. 2008;118:10471056 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 sidechain 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, Davk V. Circulation 2008;118:1047-1056

Copyright 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

-1

-2

-1

-2

+++

++++

++

+++++

Severe hypertension
(especially in
patients taking nonselective
-blockers)
Ventricular arrhythmias
Cardiac ischemia
Tissue ischemia/gangrene
(high doses
or due to tissue
extravasation)

Catecholamine
Dopamine

Shock (cardiogenic,
vasodilatory)
HF
Symptomatic
bradycardia
unresponsive to atropine
or pacing

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

Dobutamine

Low CO
(decompensated HF,
cardiogenic shock,
sepsis-induced
myocardial
dysfunction)
Symptomatic
bradycardia
unresponsive to atropine
or pacing

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

+++++

+++

N/A

Tachycardia
Increased ventricular
response rate in
patients with atrial fibrillation
Ventricular arrhythmias
Cardiac ischemia
Hypertension (especially
nonselective
beta-blocker patients)
Hypotension

Norepinephrine

Shock (vasodilatory,
cardiogenic)

0.01 to 3
mcg/kg min

+++++

+++

++

N/A

Arrhythmias
Bradycardia
Peripheral (digital) ischemia
Hypertension (especially
nonselective
beta-blocker patients)

Drug

Clinical Indication

Dose Range

Receptors

Major Side Effect

-1

-2

-1

-2

+++++

++++

+++

N/A

Ventricular arrhythmias
Severe hypertension
resulting in
cerebrovascular hemorrhage
Cardiac ischemia
Sudden cardiac death

+++++

++++
+

N/A

Ventricular arrhythmias
Cardiac ischemia
Hypertension
Hypotension

Catecholamine
Epinephrine

Shock (cardiogenic,
vasodilatory)
Cardiac arrest
Bronchospasm/anaphyl
axis
Symptomatic
bradycardia or
heart block
unresponsive to
atropine or pacing

Isoproterenol

Bradyarrhythmias
(especially
torsade des pointes)
Brugada syndrome

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

2 to 10 mcg/min

Drug

Clinical Indication

Dose Range

Receptors
-1

-2

Major Side Effect

-1

-2

PDI
Milrinone
Low CO
(decompensated HF,
after cardiotomy)

Bolus: 50 g/kg bolus

over
10 to 30 min
Infusion: 0.375 to
0.75
g kg1 min1 (dose
adjustment
necessary for
renal impairment)

N/A

N/A

Amrinone

Low CO (refractory HF)

Bolus: 0.75 mg/kg

over 2
to 3 min
Infusion: 5 to 10
Mcg/kg/ min

Vasopressin

Shock (vasodilatory,
cardiogenic)
Cardiac arrest

Infusion: 0.01 to 0.1

U/min
(common fixed dose
0.04
U/min)
Bolus: 40-U IV bolus

Ventricular arrhythmias
Hypotension
Cardiac ischemia
Torsade des pointes

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

Arrhythmias, enhanced AV
conduction
(increased ventricular response
rate in
atrial fibrillation)
Hypotension
Thrombocytopenia
Hepatotoxicity
Arrhythmias
Hypertension
Decreased CO (at doses 0.4
U/min)
Cardiac ischemia
Severe peripheral
vasoconstriction
causing ischemia (especially
skin)
Splanchnic vasoconstriction

Inotropes

Dopamine

Dobutamine

Dose

Mechanis
m of
Action

1-5
mcg/kg/
min

Dopamine
rgic
agonist

6-10
mcg/kg/
min

HR

Systolic

Diastolic

Myocard
demand O2

SVR

PVR

Increase

Minimal

No effect

Minimal
increase

Minimal
increase

No effect

Beta 1
agonist

Increase

Increase

No effect

Increase

Increase

Minimal
increase

11-20

Alpha
agonist

Increase

Increase

No effect

increase

Significan
t increase

Minimal
increase

1-10
mcg/kg/
min

Beta 1
agonist,
alpha anti
agonist

increase

increase

No effect

increase

Minimal
effect
/decrease

Minimal
decrease

Inotropes

Dose

Mechanis
m of
Action

HR

Systolic

Diastolic

Myocard
demand
O2

SVR

PVR

Epinephrine

0.01-1
mcg/kg/
min

Beta 1
agonist>A
lpha
agonist

Increase

Significant
increase

No effect

Significant
increase

Increase

Minimal
increase

Norepineph
rine

0.01-1
mcg/kg/
min

Beta 1
agonist<A
lpha
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

Grazie
Muchas gracias
Thank you

Tarimo kasiah

Arigato Gozaimasu
Danke schon

Matursuwun

Merci