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MODERATOR PRESENTER
DR. PRABHAVATHY DR.RAVITEJA.V
Inotropes
Drugs that affect the strength of contraction of heart
muscle (myocardial contractility).
Positively inotropic agents ↑strength of muscular
contraction.
Negatively inotropic agents weaken the force of
muscular contractions.
Term “inotrope” generally used to describe positive
effect
Contd…
Both positive and negative inotropes are used in the
management of various cardiovascular conditions.
The choice of agent depends largely on specific
pharmacological effects of individual agents with
respect to the condition.
One of the most important factor affecting inotropic
state is the level of calcium in the cytoplasm of the
muscle cell.
Positive inotropes usually increase this level, while
negative inotropes decrease it.
Positive inotropic agents:
↑Myocardial contractility
Used to support cardiac function in conditions such as:
a) Decompensated CHF,
b) Cardiogenic shock,
c) Septic shock,
d) Myocardial infarction,
e) Cardiomyopathy, etc.
Contd…
Positive inotropic agents include:
1) Calcium
2) Calcium sensitizers: Levosimendan
3) Cardiac myosin activators: Omecamtiv
4) Catecholamines:
• Dopamine
• Dobutamine
• Dopexamine
• Epinephrine (adrenaline)
• Isoprenaline (isoproterenol)
• Norepinephrine (noradrenaline)
Contd…
5) Cardiac glycosides: Digoxin
6) Phosphodiesterase (PDEIII) inhibitors:
• Enoximone, Piroximone
• Milrinone
• Amrinone
7) Prostaglandins: PGE₂
8) Glucagon
Negative inotropic agents
↓Myocardial contractility, and are used to ↓cardiac
workload in conditions such as angina.
While negative inotropism may precipitate or
exacerbate heart failure,
Certain beta blockers (e.g. carvedilol, bisoprolol and
metoprolol) have been believed to reduce morbidity
and mortality in congestive heart failure.
Contd…
1) Beta blockers
2) Calcium channel blockers:
Diltiazem
Verapamil
Clevidipine
3) Class IA antiarrhythmics such as:
Quinidine
Procainamide
Disopyramide
4) Class IC antiarrhythmics such as:
Flecainide
Adrenergic Agents
Alpha1-adrenergic effects:
• Vascular smooth muscle contraction
Alpha2-adrenergic effects:
• Vascular smooth muscle relaxation
Beta-Adrenergic Agents
Beta1-adrenergic effects:
o Direct cardiac effects
• Inotropy (improved cardiac contractility)
• Chronotropy (increased heart rate)
Beta2-adrenergic effects:
• Vasodilation
• Bronchodilation
Dopaminergic Agents
Dopaminergic Agents classified as D1 & D2
• D1-receptors mediates vasodilation in kidney,
intestine, & heart
• D2-antiemetic action of droperidol
Recepter selectivity of adrenergic agonists.1
Ephedrine 3 ++ ? ++ + 0 0
Norepinephrine2 ++ ++ ++ 0 0 0
Dopamine2 ++ ++ ++ + ++ +++
Ephedrine ↑↑ ↑↑ ↑↑ ↑ ↑↑ ↓↓
Dobutamine ↑ ↑ ↑↑↑ ↓ 0 ↑
Epinephrine
Low Dose
(<0.05-0.1 mcg/kg/min)
High Dose
β1 predominantly
(> 0.1 μg/kg/min)
↑HR
↓ Duration of Systole
↑ Myocardial contract α1 predominantly
Periph. arteriolar dil. Vasoconstriction
↑/ ↓ Renal BF ↓ Renal BF
↑ Renin secretion ↓ Splanchnic BF
↑/ ↓ Splanchnic BF ↑ Glucose
↑ Glucose
Hypokalemia
Contd…
Uses:
T/t for anaphylaxis & ventricular fibrillation
Complications:
Cerebral hemorrhage
Coronary ischaemia
Ventricular dysrhythmias
Volatile anesthetics, particularly halothane,
potentiate the dysrhthmic effects of
epinephrine(10µg/kg)
Contd…
Dosing & Packing:
Emergency situation (eg, cardiac arrest & shock), iv
bolus 0.05-1 mg, depending on the severity of
cardiovascular compromise
Major anaphylactic reactions 100-500µg (repeated, if
necessary) followed by infusion
To improve myocardial contractility or HR, a
continuous infusion is prepared (1 mg in 250 ml
[4µg/ml]) & run @ 2-20µg/min
Contd…
Reduce bleeding from operative sites
Local anesthetics solutions containing 1:200,000
(5µg/ml) or 1:400,000 (2.5µg/ml)- less systemic
absorption & longer duration of action
Epinephrine is available in vials & prefilled syringes
containing:
a) 1:1000 (1mg/ml)
b) 1:10,000 (0.1mg/ml [100µg/ml])
c) 1:100,000 (10µg/ml)- for pediatric use
Contd…
Common contraindication:
Hypertension.
Pheochromocytoma.
Caution with heart failure angina and
hyperthyroidism.
Isoprenaline
(Isoproterenol)
Synthetic catecholamine
Non-specific pure β- agonist with minimal alpha-
adrenergic effects.
β₁- effects ↑HR, contractility , CO
SBP may ↑ or remain unchanged, but β₂- stimulation
↓PVR & DBP
↑Myocardial O₂ demand while ↓O₂ supply, making
isoproterenol or any pure β- agonist a poor inotropic
choice in most situations
Contd…
Causes inotropy, chronotropy, and systemic and
pulmonary vasodilatation.
Indications: bradycardia, decreased CO,
bronchospasm (bronchodilator).
Contd…
Dosing & Packing:
Occasionally used to maintain HR following heart
transplantation.
Dose starts at 0.01 mcg/kg/min and is increased to
2.0 mcg/kg/min for desired effect.
Avoid in patients with subaortic stenosis, and
hypertrophic cardiomyopathy or TOF lesions because
increases the outflow gradient
Supplied in 1-ml (2 mg/ml) ampules containing 2 mg
Norepinephrine
(Noradrenaline)
Direct α₁- stimulation with little β₂- activity induces
intense vasoconstriction of arterial & venous vessels
↑Myocardial contractility from β₁- effects, along with
peripheral vasoconstriction contributes to ↑arterial
BP
↑SBP & DBP both, but ↑afterload & reflex
bradycardia prevent any ↑CO
↓Renal & splanchnic blood flow & ↑myocardial O₂
requirements limit the outcome benefits of
norepinephrine in management of refractory shock.
Contd…
Norepinephrine has been used with an α- blocker (eg,
phentolamine) in an attempt to take advantage of its
β- activity without the profound vasoconstriction
caused by α- stimulation
Extravasation of norepinephrine at the site of IV
administration can cause tissue necrosis
Dosing & Packing:
Bolus 0.1µg/kg or
Continuous infusion @ 2-20µg/kg/min (due to its
short half life)
Ampules contain 2 mg of norepinephrine in 4 ml
prostaglandins
The effects of prostaglandins on cardiac function are
complex & depend on direct inotropic effects, the
activity of the SNS relative to PNS, & the metabolic
status of heart
PGE₂ produces an ↑in HR & myocardial contractility
by direct inotropic effects as well as by ↑reflex SNS
activity
PGE₂(Dinoprostone) produces ↑ in HR &CO
CADIAC GLYCOSIDES
Minimal ↑ HR
↑ CO
Diastolic
Relaxation
Minimal ↑ in
O2 demand ↓ SVR
↓ PVR
Enoximone & piroximone
Imidazole derivatives that act as highly selective PDE III
inhibition to ↑myocardial contractility
Half-life 4.3 hrs
Metabolized mainly by liver
Dose: 0.5 mg/kg IV f/b 5-20 µg/kg/min continuous
infusion
COMPARISON BETWEEN LEVOSIMENDAN,
MILRINONE AND DOBUTAMINE
Feature Levosimendan Milrinone Dobutamine
Selectivity
for β₁- Hepatic
ISA α-Blockade T1/2
Receptors Metabolism
Atenolol + 0 0 0 6-7
Esmolol + 0 0 0 -1/4
Labetalol 0 + + 4
Metoprolol + 0 0 + 3-4
Propranolol 0 0 + 4-6
Pulmonary inotropes :
vasodilators • dobutamine, Vasoconstrictors
•isoproterenol,
• epinephrine,
•PDE inhibitors
Clinical Application
1st Line Agent 2nd Line Agent
Septic Shock Norepinephrine Vasopressin
Epinephrine
Phenylephrine (Adrenalin)
Heart Failure Dopamine Milrinone
Dobutamine
Cardiogenic Shock Norepinephrine
Dobutamine
Anaphylactic Shock Epinephrine (Adrenalin) Vasopressin
Neurogenic Shock Phenylephrine
Anesthesia
Hypotension -induced Phenylephrine
Following
CABG Epinephrine
Thank You!