Download Cardiac Pharmacology

Cardiac Pharmacology
Pediatric Cardiac Care Conference  February 17, 2012
Stephanie D. Garrett, Pharm.D., BCPS
Clinical Pharmacy Specialist, Seton Healthcare Family
Clinical Assistant Professor, University of Texas College of Pharmacy
Outline
 Catecholamine and receptor overview
 Drug therapy
Epinephrine
Norepinephrine
Dobutamine
Milrinone
Nitrates
Nitroprusside
Dopamine
Digoxin
Beta blockers
ACEI
 Approach to acute and chronic heart failure
Catecholamine and Receptor
Overview
Catecholamines
Released by the adrenal medulla (triggered by
sympathetic nervous system [SNS])
 Epinephrine
 Norepinephrine
 Dopamine
Naturally occurring
catecholamines
 Sympathomimetic amines
 Naturally occurring catecholamines and drugs
that act similarly
 Adrenergic receptor antagonists
 Drugs that block the effect of sympathetic
stimulation
Catecholamine Synthesis
Beta Receptors
Contractility
And
Heart Rate
www.cvpharmacology.com
Beta Receptors in Blood Vessels
Smooth
Muscle
Relaxation
www.cvpharmacology.com
Autonomic Nerve Impulses
Receptor
Type
Adrenergic Response
Cholinergic Response
SA Node
1 and 2
 HR
 HR
Atria
1 and 2
 Contractility and
conduction velocity
 Contractility
AV Node
1 and 2
 Automaticity and
conduction velocity
 Conduction velocity
and AV block
His-Purkinje
system
1 and 2
 Automaticity and
conduction velocity
Little effect
Ventricles
1 and 2
 Contractility,
conduction velocity, and
automaticity
Slight decrease in
contractility
Goodman and Gilman’s The Pharmacological Basis of Therapeutics 2001.
Alpha Receptors
Vasoconstriction
(arteries and veins)
www.cvpharmacology.com
Alpha and Beta Receptors
Alpha and Beta Effects
Adrenoreceptors
Alpha 1
Alpha 2
Beta 1
Beta 2
(α1)
(α2)
(2)
(2)
Inhibition of
norepinephrine
release
Tachycardia
Vasodilation
Bronchodilation
Vasoconstriction
 PVR
 BP
 Contractility
Lippincott’s Pharmacology 2008
Sympathomimetics
Sympathomimetic agents could benefit the
failing heart via:
1. B1 stimulation  positive inotropic effect
2. B2 stimulation  afterload reduction
(peripheral arterial vasodilation)
3. Alpha stimulation  BP support in
hypotension
Direct Acting Adrenergic Agonists
Epinephrine
Norepinephrine
Dopamine
Dobutamine
Epinephrine and Norepinephrine
Epinephrine
 Dose related effects
 Low dose = 
 High dose = α
 Effects
 + inotropic and
chronotropic effect
  SBP > DBP
Norepinephrine
 Alpha and beta stimulation
 Effects
 Vasoconstriction
  SBP and DBP
 Reflex  in vagal activity
(bradycardia)
Dopamine
Low
• Doses ≤ 2 ug/kg/min
• D1 and D2 receptor stimulation (renal arterial beds)
• Vasodilation, natriuresis
Lancet 2000;356:2112.
Dopamine
Low
Medium
• Doses ≤ 2 ug/kg/min
• D1 and D2 receptor stimulation (renal arterial beds)
• Vasodilation, natriuresis
• Doses 2 – 5 ug/kg/min
•  receptor stimulation (cardiac)
• Increased cardiac output
Lancet 2000;356:2112.
Dopamine
Low
Medium
High
• Doses ≤ 2 ug/kg/min
• D1 and D2 receptor stimulation (renal arterial beds)
• Vasodilation, natriuresis
• Doses 2 – 5 ug/kg/min
•  receptor stimulation (cardiac)
• Increased cardiac output
• Doses 5 – 15 ug/kg/min
• Alpha receptor stimulation
• Peripheral vasoconstriction
Lancet 2000;356:2112.
Dopamine
 Can see increased SVR even at
intermediate doses
 Tachycardia may provoke ischemia
Dobutamine
 Synthetic analogue of dopamine
 “Pure” 1 agonist
 No activation of dopaminergic receptors
 Effect
 Increased contractility (positive inotropic
effect)
 Little increase in HR
 Tolerance may develop and efficacy may be
attenuated in patients on chronic beta
blockade
Summary
Drug
Receptor Effects
Clinical Effect
Epinephrine
Low dose
 1 =  2 > α1 = α2
Low dose = cardiac stimulation and
vasodilation
High Dose
α1 = α2 >  1 >  2
High doses = vasoconstriction
Norepinephrine
 1 = α1 >  2 = α2
Dopamine
 1 =  2 > α1
High doses = vasoconstriction
Also effects dopaminergic receptors
Dobutamine
 1 >  2 > α1
Cardiac stimulation with modest
vasodilation
Inotropic Response
Acute inotropic response can be achieved by:
1. Administration of exogenous
catecholamines

Stimulation of beta receptor (i.e., beta agonists)
2. Inhibition of breakdown of cyclic AMP

Phosphodiesterase inhibitors
Phosphodiesterase Inhibitors
 Milrinone inhibits
breakdown of cAMP in
cardiac and peripheral
vascular smooth muscle
 Increased contractility
 Balanced vasodilation
www.cvpharmacology.com
Preload / Afterload Reduction
Vasodilator Summary
Arterial
Venous
Hydralazine
Nitroglycerin
Isosorbide dinitrate
Mixed or Balanced
Nitroprusside
Phentolamine
Prazosin
Angiotensin converting enzyme inhibitors (i.e., captopril, lisinopril)
Calcium channel blockers (verapamil, diltiazem, nifedipine)
Nitroprusside and Nitrates
www.cvpharmacology.com
Approach to Pharmacologic
Management
Stroke Volume
Hemodynamic Subsets
Normal
Congestion
Hypoperfusion
Congestion and
Hypoperfusion
Ventricular Filling Pressure
Goodman and Gilman’s The Pharmacological Basis of Therapeutics 2001
Pharmacotherapy: A Pathophysiologic Approach 2002
.
Stroke Volume
Hemodynamic Subsets
Normal
Congestion
Hypoperfusion
Congestion and
Hypoperfusion
Ventricular Filling Pressure
Goodman and Gilman’s The Pharmacological Basis of Therapeutics 2001
Pharmacotherapy: A Pathophysiologic Approach 2002
.
Stroke Volume
Hemodynamic Subsets
Normal
Congestion
Hypoperfusion
Congestion and
Hypoperfusion
Ventricular Filling Pressure
Goodman and Gilman’s The Pharmacological Basis of Therapeutics 2001
Pharmacotherapy: A Pathophysiologic Approach 2002
.
Approach to Treatment
Fluid Overload
Hypoperfusion
Pulmonary
Congestion
Low or
Normal SVR
Elevated SVR
Venodilators
Diuretics
Dopamine
Dobutamine
Nitroprusside
Milrinone
IV vs Oral
Inotrope
Vasodilator
Dopamine
Nitroprusside
Digoxin
ACEI
Chronic Management
ACEI
(Angiotensin Converting Enzyme Inhibitors)
 Mixed vasodilation
 Reduced hypertrophy
 Decreased Na and
water retention
 Decreased mortality
Beta Blockers
1 Selective
Metoprolol
Atenolol
Esmolol
Bisoprolol
NonSelective
Propranolol
Nadolol
Alpha and
Beta Blockers
Carvedilol
Labetalol
Beta Blockers in Heart Failure
1 Selective
Metoprolol
Bisoprolol
Alpha and
Beta Blockers
Carvedilol
Digoxin
www.cvpharmacology.com
Cardiac Pharmacology
Pediatric Cardiac Care Conference  February 17, 2012
Stephanie D. Garrett, Pharm.D., BCPS
Clinical Pharmacy Specialist, Seton Healthcare Family
Clinical Assistant Professor, University of Texas College of Pharmacy