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Compact CNS α 2 Vagus Nerve I-1 Preload Afterload α 1 Renin Baroreflex
GI Vasculature α 1 B1 ANP ADH B2 Renin NO Aldosterone Conductivity M2 - B1 + Na↑ HCO3↓ Na↑ K↓ ATII Na Cl↑ + K↓ PG Na↑ Ca↑ Mg↑ K↑ Na↑
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Expanded CNS α 2 Vagus Nerve I-1 Preload Afterload α 1 Renin
Baroreflex Preload Afterload GI Vasculature α 1 Expanded B1 ANP B2 NO ADH Renin Conductivity M2 - B1 + Aldosterone Na↑ HCO3↓ Na↑ K↓ ATII Na Cl↑ + K↓ PG Na↑ Ca↑ Mg↑ K↑ Na↑
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Ted Williams Pharm D Candidate OSU/OHSU College of Pharmacy
Cardiac Pharmacology Ted Williams Pharm D Candidate OSU/OHSU College of Pharmacy
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The big, scary picture
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Breaking it Down Direct Cardiac Agents Peripheral Vascular Agents
Renal Agents
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Reality Check The pharmacology really isn’t that simple, but it is a helpful framework
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Direct Cardiac Agents Beta Blockers (BB)
Non-Dihydropyridine Calcium Channel Blockers (CCB) Digitalis Glycoside (De-GOX-in) Aldosterone antagonists Well explain why this is here later
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Peripheral Vascular Agents
Nitrates Dihydropyridine CCB Phosphodiesterase Inhibitors Quinazolines (Alpha 1 Antagonists) Hydralazine Celiprolol Phentolamine
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Renal Agents ACE Inhibitors Angiotensin 2 Inhibitors Diuretics
Carbonic Anhydrase Inhibitors Loop Thiazide Diuretics Aldosterone Antagonists Potassium Sparing Diuretics
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Mixed Bag Selective I-1 Imidazoline Receptor Agonists
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Direct Cardiac Agents – BB
Selectivity Beta 1 Selective Beta 1/2 Non-Selective Alpha 1, Beta 1/2 Non-Selective Alpha 2, Beta 1/2 Non-Selective Intrinsic Sympathomimetic Activity (ISA) ISA No long term mortality benefit Post MI Non-ISA do have benefit post MI Non-ISA
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Targets of Beta Blockers
CNS α 2 Vagus Nerve I-1 Baroreflex Preload Afterload GI Vasculature α 1 B1 ANP ADH NO B2 Renin Aldosterone M2 - B1 + Conductivity Na↑ HCO3↓ Na↑ K↓ ATII Na Cl↑ + K↓ PG Na↑ Ca↑ Mg↑ K↑ Na↑
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Targets of Beta Blockers
Beta 1 blockade “Cardioselective” Inhibits sympathetic contractility, inotropy, and conductivity of the heart Inhibits sympathetic renin secretion in the kidneys Best Tolerated Beta 1 Blockers Atenolol Acebutolol Bisoprolol Metoprolol
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Targets of Beta Blocker
Beta 2 blockade Beta 2 receptors inhibit smooth muscle contractions in the lungs and GI tract Beta 2 blockade is useful for restricting hepatic blood flow for patient with Liver Cirrhosis, but generally not a therapeutic effect for CVD Commonly Used Beta 2 Blockers Propranolol Nadolol
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Targets for Non-Dihydropyridine Calcium
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Targets of Digoxin
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Targets of Aldosterone Antagonists
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Targets of Aldosterone Antagonists
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Peripheral Vascular Agents
Nitrates Dihydropyridine CCB Phosphodiesterase Inhibitors Quinazolines (Alpha 1 Antagonists) Hydralazine Celiprolol Phentolamine
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Targets of Nitrates
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Targets of Nitrates Preferential vasodilation of veins
Decreases Preload Decreases Afterload
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Targets of Dihydropyridine CCB
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Targets of Dihydropyridine CCB
Peripheral Vasodilation State dependent binding to the Inactive State Tissues more often in the inactive state have tissue selectivity Targets vascular smooth muscle, generally arterial Decreases afterload and increases stroke volume Reduces blood pressure
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Targets of Phosphodiesterase Inhibitors
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Targets of Phosphodiesterase inhibitors
Promotes vasodilation by increases cGMP Decreases Afterload Good for Heart Failure Secondary decrease in preload Reflex tachycardia via the baroreflex No so good for heart failure patients Resistance develops rapidly with continuous use, limiting therapeutic uses to acute decompensated heart failure
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Hydralazine Mechanism not well understood
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Celiprolol
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Phentolamine
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Targets for Alpha Blockers
CNS Baroreflex Preload Afterload I-1 α 2 Vagus Nerve GI Vasculature α 1 B1 ANP ADH NO B2 Renin Aldosterone M2 - B1 + Conductivity Na↑ HCO3↓ Na↑ K↓ ATII Na Cl↑ + K↓ PG Na↑ Ca↑ Mg↑ K↑ Na↑
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Targets for Alpha Blockers
Alpha 1 Blockade Peripheral Vasodilation by inhibition of Gq Signaling pathway Carvedilol (alpha-1, beta 1/2) Labetalol (alpha-1, beta 1/2) Quinazolines (Prazosin, Tamsulosin, Terasozin, Alfazosin) Alpha 2 Blockade CNS Inhibition the inhibition of the baroreflex Peripheral inhibition of the negative feedback on vagal cardiac stimulation Celiprolol (alpha-2, beta-1 blockade)
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