Compact

1
Compact
Afterload
Preload
a 1
GI Vasculature
B1
ANP
ADH
B2
NO
Renin
Aldosterone
Na? K?
Na? HCO3?
ATII
Na Cl? K?
PG
Na? Ca? Mg? K?
Na?
2
Expanded
Afterload
Preload
a 1
GI Vasculature
B1
ANP
B2
NO
ADH
Renin
Aldosterone
Na? K?
Na? HCO3?
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 isnt 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

8
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

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

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Targets of Beta Blockers
Afterload
Preload
a 1
GI Vasculature
B1
ANP
ADH
NO
B2
Renin
Aldosterone
M2 -
B1
Conductivity
Na? K?
Na? HCO3?
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

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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
19
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
Afterload
Preload
I-1
a 2
a 1
Vagus Nerve
GI Vasculature
B1
ANP
ADH
NO
B2
Renin
Aldosterone
M2 -
B1
Conductivity
Na? K?
Na? HCO3?
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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