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Compact

Compact. CNS. Baroreflex. I-1. α 2. Vagus Nerve. Preload. Afterload. α 1. GI Vasculature. B1. ANP. ADH. B2. Renin. NO. M2 -. B1 +. Aldosterone. Conductivity. Na↑ HCO3↓. Na↑ K↓. ATII. Na Cl↑ + K↓. PG. Na↑ Ca↑ Mg↑ K↑. Na↑. CNS. Baroreflex. Preload.

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Compact

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  1. Compact CNS Baroreflex I-1 α 2 Vagus Nerve Preload Afterload α 1 GI Vasculature B1 ANP ADH B2 Renin NO M2 - B1 + Aldosterone Conductivity Na↑ HCO3↓ Na↑ K↓ ATII Na Cl↑ + K↓ PG Na↑ Ca↑ Mg↑ K↑ Na↑

  2. CNS Baroreflex Preload Afterload I-1 α 2 Vagus Nerve α 1 GI Vasculature Expanded B1 ANP B2 NO ADH Renin M2 - B1 + Aldosterone Conductivity Na↑ HCO3↓ Na↑ K↓ ATII Na Cl↑ + K↓ PG Na↑ Ca↑ Mg↑ K↑ Na↑

  3. Cardiac Pharmacology Ted Williams Pharm D Candidate OSU/OHSU College of Pharmacy

  4. The big, scary picture

  5. Breaking it Down • Direct Cardiac Agents • Peripheral Vascular Agents • Renal Agents

  6. Reality Check • The pharmacology really isn’t that simple, but it is a helpful framework

  7. 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

  8. Peripheral Vascular Agents • Nitrates • Dihydropyridine CCB • Phosphodiesterase Inhibitors • Quinazolines (Alpha 1 Antagonists) • Hydralazine • Celiprolol • Phentolamine

  9. Renal Agents • ACE Inhibitors • Angiotensin 2 Inhibitors • Diuretics • Carbonic Anhydrase Inhibitors • Loop • Thiazide Diuretics • Aldosterone Antagonists • Potassium Sparing Diuretics

  10. Mixed Bag • Selective I-1 Imidazoline Receptor Agonists

  11. 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

  12. Targets of Beta Blockers CNS Baroreflex I-1 α 2 Vagus Nerve Preload Afterload α 1 GI Vasculature B1 ANP ADH NO B2 Renin M2 - Aldosterone B1 + Conductivity Na↑ HCO3↓ Na↑ K↓ ATII Na Cl↑ + K↓ PG Na↑ Ca↑ Mg↑ K↑ Na↑

  13. 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

  14. 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

  15. Targets for Non-Dihydropyridine Calcium

  16. Targets of Digoxin

  17. Targets of Aldosterone Antagonists

  18. Targets of Aldosterone Antagonists

  19. Peripheral Vascular Agents • Nitrates • Dihydropyridine CCB • Phosphodiesterase Inhibitors • Quinazolines (Alpha 1 Antagonists) • Hydralazine • Celiprolol • Phentolamine

  20. Targets of Nitrates

  21. Targets of Nitrates • Preferential vasodilation of veins • Decreases Preload • Decreases Afterload

  22. Targets of Dihydropyridine CCB

  23. 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

  24. Targets of Phosphodiesterase Inhibitors

  25. 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

  26. Hydralazine • Mechanism not well understood

  27. Celiprolol

  28. Phentolamine

  29. Targets for Alpha Blockers CNS Baroreflex Preload Afterload I-1 α 2 Vagus Nerve α 1 GI Vasculature B1 ANP ADH NO B2 Renin M2 - Aldosterone B1 + Conductivity Na↑ HCO3↓ Na↑ K↓ ATII Na Cl↑ + K↓ PG Na↑ Ca↑ Mg↑ K↑ Na↑

  30. 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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