Inotropes & Vasopressors

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Inotropes Vasopressors
Applied Sciences Lecture Course

• Dr Cathy Armstrong
• SpR In Anaesthesia Clinical Fellow in
  Undergraduate Medical Education
• Manchester Royal Infirmary
• March 2011

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Objectives

• Define the terms Inotrope vasopressor
• Discuss basic physiological principles
• Discuss drug classification
• Sympathomimetics
• Other
• Describe some clinical uses

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Inotropes Vs. Vasopressors
V
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Inotropes

• Drugs that affect the force of contraction of
  myocardial muscle
• Positive or negative
• Term inotrope generally used to describe
  positive effect

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Vasopressor

• Drugs that stimulates smooth muscle contraction
  of the capillaries arteries
• Cause vasoconstriction a consequent rise in
  blood pressure

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Which of these drugs does NOT cause a positive
inotropic effect?

• Adrenaline
• Calcium
• Digoxin
• Enoximone
• Nifedipine
• Glucagon

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Main Goal
Tissue perfusion oxygenation
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Physiological Principles
MAP CO x SVR CO HR x SV
Preload Contractility Afterload
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Basic principles - Vasopressors
MAP CO x SVR CO HR x SV
Preload Contractility Afterload
1
r4
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Basic principles - Inotropes
MAP CO x SVR CO HR x SV
Preload Contractility Afterload
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Mixed action drugs
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Use of inotropes vasopressors
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Drug Classification

• Sympathomimetics
• Naturally occurring
• Synthetic
• Other inotropes
• cAMP dependent
• cAMP independent
• Other vasopressors

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Sympathomimetics

• Sympathetic nervous system

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Sympathomimetics

• Drugs that stimulate adrenergic receptors
• G-protein coupled receptors

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Which adrenoceptor mediates cardiac muscle
contraction?

• ?1
• ?2
• ?1
• ?2

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Which adrenoceptor mediates vascular smooth
muscle contraction?

• ?1
• ?2
• ?1
• ?2

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Main classes of Adrenoceptor

• ? receptors
• ?1
• Located in vascular smooth muscle
• Mediate vasoconstriction
• ?2
• Located throughout the CNS, platelets
• Mediate sedation, analgesia platelet aggregation

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Main classes of Adrenoceptor

• ? receptors
• ?1
• Located in vascular smooth muscle
• Mediate vasoconstriction
• ?2
• Located throughout the CNS, platelets
• Mediate sedation, analgesia platelet aggregation

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Main classes of Adrenoceptor

• ? receptors
• ?1
• Located in the heart
• Mediate increased contractility HR
• ?2
• Located mainly in the smooth muscle of bronchi
• Mediate bronchodilatation

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Main classes of Adrenoceptor

• ? receptors
• ?1
• Located in the heart
• Mediate increased contractility HR
• ?2
• Located mainly in the smooth muscle of bronchi
• Mediate bronchodilatation
• Located in blood vessels
• Dilatation of coronary vessels
• Dilatation of arteries supplying skeletal muscle

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ß1 Adrenoceptor
Adrenaline
Adenyl cyclase
G - Protein
Increased heart muscle contractility
cAMP
ATP
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Sympathomimetics

• Naturally occuring
• Epinephrine
• Norepinephrine
• Dopamine

• Synthetic
• Dobutamine
• Dopexamine
• Phenylephrine
• Metaraminol
• Ephedrine

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Sympathomimetics

• Naturally occuring
• Epinephrine
• Norepinephrine
• Dopamine

• Synthetic
• Dobutamine
• Dopexamine
• Phenylephrine
• Metaraminol
• Ephedrine

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Epinephrine

• Stimulates ? ? receptors
• Predominantly ? effects at low doses and ?
  effects at high doses
• Clinical uses
• Cardiac arrest
• Anaphylaxis
• Low cardiac output states
• Upper airway obstruction
• Combination with local anaesthetics

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Epinephrine

• Side effects
• Dysrhythmias
• Increase in myocardial oxygen consumption

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Cardiac arrest
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What is the dose of epinephrine administered
during cardiac arrest?

• 100mcg
• 1mg
• 10mg
• 100mg
• 1g

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Anaphylaxis
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What is the IM dose of epinephrine in anaphylaxis

• 100mcg
• 1mg
• 10mg
• 100mg
• 1g

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1mg of epinephrine

• 1ml of 11000
• 10ml of 110,000

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Norepinephrine

• Predominantly stimulates ?1 receptors
• Most commonly used vasopressor in critical care
• Very potent
• Administered by infusion into a central vein
• Uses
• Hypotension due to vasodilatation
• Septic shock

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Dopamine

• Effect dose dependent
• Direct
• Low dose - ?1
• High dose - ?1
• Indirect
• Stimulates norepinephrine release
• D1 receptors
• Vasodilatation of mesenteric renal circulation

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Dobutamine

• Synthetic
• Predominantly ?1
• Small effect at ?2
• Uses
• Low cardiac output states
• Cardiogenic shock

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Sympathomimetics

• Naturally occuring
• Epinephrine
• Norepinephrine
• Dopamine

• Synthetic
• Dobutamine
• Dopexamine
• Phenylephrine
• Metaraminol
• Ephedrine

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Adrenoceptor dynamics

• Desensitisation / down-regulation
• Chronic heart failure
• Prolonged use of inotrope / vasopressor
• Sespis / acidosis

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Other inotropes

• cAMP dependent
• Phosphodiesterase inhibitors
• Glucagon
• cAMP independent
• Digoxin
• Calcium
• levosimendan

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Phosphodiesterase inhibitors

• Non-selective
• Aminophylline
• Selective
• Phosphodiesterase 3
• Enoximone
• milrinone

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Phosphodiesterase inhibitors
Adrenaline
Adenyl cyclase
G - Protein
Increased heart muscle contractility
ATP
cAMP
X
PDE 3
AMP
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Digoxin
Inhibits (slows) NA/K ATPase
K
?K ?Na
NaK ATPase
Na
Na
Reduced Na gradient slows Ca removal
Na/Ca X-ch
Ca
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Other vasopressors

• Vasopressin
• Exogenous form of ADH
• Acts on kidney to retain water on peripheral
  blood vessels to cause intense vasoconstriction
• V1 receptors
• Used in severe shock
• Used in cardiac arrest in USA

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Summary

• Concept of inotropes vasopressors
• Physiological principles
• Categories
• Sympathomimetics
• cAMP dependent / independent inotropes
• Vasopressin
• Discussed clinical uses

All Figures were produced using Servier Medical
Art - www.servier.com
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