Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
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