Compact

B1

ATII

ADH

Aldosterone

α 1

Na↑ K↓

Na↑ Ca↑Mg↑ K↑

Na↑HCO3↓

NO

PG

B2

Na↑

Na Cl↑+ K↓

ANP

AfterloadPreload

Conductivity

M2 - B1+

CNS α 2

Vagus Nerve

I-1

BaroreflexBaroreflex

Renin

B1

ATII

ADH

Aldosterone

α 1

Na↑ K↓

Na↑ Ca↑Mg↑ K↑

Na↑HCO3↓

NO

PG

B2

Na↑

Na Cl↑+ K↓

ANP

AfterloadPreload

Conductivity

M2 - B1+

CNS α 2

Vagus Nerve

I-1

BaroreflexBaroreflex

Renin

Expanded

Cardiac Pharmacology

Ted WilliamsPharm D Candidate

OSU/OHSU College of Pharmacy

The big, scary picture

Breaking it Down

• Direct Cardiac Agents• Peripheral Vascular Agents• Renal Agents

Reality Check

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

Direct Cardiac Agents

1. Beta Blockers (BB)2. Non-Dihydropyridine Calcium Channel

Blockers (CCB)3. Digitalis Glycoside (De-GOX-in)4. Aldosterone antagonists – Well explain why this is here later

Peripheral Vascular Agents

1. Nitrates2. Dihydropyridine CCB3. Phosphodiesterase Inhibitors4. Quinazolines (Alpha 1 Antagonists)5. Hydralazine6. Celiprolol7. Phentolamine

Renal Agents

1. ACE Inhibitors2. Angiotensin 2 Inhibitors3. Diuretics

i. Carbonic Anhydrase Inhibitorsii. Loopiii. Thiazide Diureticsiv. Aldosterone Antagonistsv. Potassium Sparing Diuretics

Mixed Bag

• Selective I-1 Imidazoline Receptor Agonists

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

Targets of Beta Blockers

B1

ATII

ADH

Aldosterone

α 1

Na↑ K↓

Na↑ Ca↑Mg↑ K↑

Na↑HCO3↓

NO

PG

B2

Na↑

Na Cl↑+ K↓

ANP

AfterloadPreload

Conductivity

M2 - B1+

CNS α 2

Vagus Nerve

I-1

BaroreflexBaroreflex

Renin

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

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

Targets for Non-Dihydropyridine Calcium

Targets of Digoxin

Targets of Aldosterone Antagonists

Targets of Aldosterone Antagonists

Peripheral Vascular Agents

1. Nitrates2. Dihydropyridine CCB3. Phosphodiesterase Inhibitors4. Quinazolines (Alpha 1 Antagonists)5. Hydralazine6. Celiprolol7. Phentolamine

Targets of Nitrates

Targets of Nitrates

• Preferential vasodilation of veins– Decreases Preload– Decreases Afterload

Targets of Dihydropyridine CCB

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

Targets of Phosphodiesterase Inhibitors

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

Hydralazine

• Mechanism not well understood

Celiprolol

Phentolamine

Targets for Alpha Blockers

B1

ATII

ADH

Aldosterone

α 1

Na↑ K↓

Na↑ Ca↑Mg↑ K↑

Na↑HCO3↓

NO

PG

B2

Na↑

Na Cl↑+ K↓

ANP

AfterloadPreload

Conductivity

M2 - B1+

CNS α 2

Vagus Nerve

I-1

BaroreflexBaroreflex

Renin

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)