Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 45 Calcium Channel...

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Chapter 45

Calcium Channel Blockers

2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.


Drugs that prevent calcium ions from entering cells

Greatest impact on heart and blood vessels Used to treat hypertension, angina pectoris,

and cardiac dysrhythmias Controversy: safety for patients with

hypertension and diabetes Also known as calcium antagonists and slow

channel blockers



Calcium channels: physiologic functions and consequences of blockade

Calcium channel blockers: classification and sites of action

Verapamil and diltiazem: agents that act on vascular smooth muscle and the heart

Dihydropyridines: agents that act mainly on vascular smooth muscle


Physiologic Functions and Consequences of Blockade

Vascular smooth muscle Calcium channels open = Contractile process Calcium channels blocked = Vasoconstriction

Therapeutic doses Selectively on peripheral arterioles and arteries

and arterioles of the heart No significant effect on veins


Physiologic Functions and Consequences of Blockade

Heart Myocardium Sinoatrial (SA) node Atrioventricular (AV) node Coupling of cardiac calcium channels to beta1-

adrenergic receptors


Fig. 45–1. Coupling of cardiac calcium channels with beta1-adrenergic receptors.


Classification and Sites of Action

Classification Dihydropyridines—nifedipine Phenylalanine—verapamil Benzothiazepine—diltiazem

Sites of action Dihydropyridines act primarily on arterioles Verapamil and diltiazem act on arterioles and on

the heart


Verapamil and Diltiazem

Agents that act on vascular smooth muscle and the heart

Hemodynamic effects Direct effects on the heart and blood vessels Indirect (reflex) effects Net effects


Verapamil and Diltiazem: Hemodynamic Effects

Five direct hemodynamic effects Blockade at peripheral arterioles

• Reduces arterial pressure Blockade at arteries and arterioles of heart

• Increases coronary perfusion Blockade at SA node

• Reduces heart rate Blockade at AV node (most important)

• Decreases AV nodal conduction Blockade in the myocardium

• Decreases force of contraction


Verapamil and Diltiazem: Hemodynamic Effects

Indirect (reflex) hemodynamic effects Baroreceptor reflex

Net effects Little or no net effect on cardiac performance Vasodilation accompanied by reduced arterial

pressure and increased coronary perfusion


Verapamil (Calan, Covera-HS, Isoptin, Verelan)

Therapeutic uses Angina pectoris

• Vasospastic angina and angina of effort Essential hypertension

• First-line agent Cardiac dysrhythmias

• Atrial flutter, atrial fibrillation, paroxysmal supraventricular tachycardia

Migraine



Adverse effects Constipation

• Most common complaint• Results from blockade of calcium channels in smooth

muscle of the intestine• Especially severe for the elderly• Can be decreased by increasing dietary fiber and fluids



Adverse effects (cont’d) Dizziness Facial flushing Headache Edema of ankles and feet Gingival hyperplasia Heart block



Drug interactions Digoxin Beta-adrenergic blocking agents

Toxicity Severe hypotension Bradycardia and AV block Ventricular tachydysrhythmias



IV verapamil for dysrhythmias can cause severe cardiovascular effects. Blood pressure and ECG should be monitored

with resuscitation equipment immediately available.


Diltiazem (Cardizem, Dilacor-XR, Tiazac, Others)

Actions and uses Blocks calcium channels in the heart and blood

vessels (similar to verapamil) Lowers blood pressure

• Arteriolar dilation• Direct suppressant/reflex cardiac stimulation = Little net

effect on heart



Therapeutic uses Angina pectoris Hypertension Cardiac dysrhythmias

• Atrial flutter, atrial fibrillation, paroxysmal tachycardia



Adverse effects Similar to verapamil, except for less constipation Dizziness Flushing Headache Edema of ankles and feet Exacerbates bradycardia, sick sinus syndrome,

heart failure, second- or third-degree heart block



Drug interactions Digoxin Beta-adrenergic blocking agents


Dihydropyridines

Agents that act mainly on vascular smooth muscle Nifedipine (Adalat, Nifedical, Nifediac, Procardia)

Significant blockade of calcium channels in blood vessels

Minimal blockade of calcium channels in the heart

Similar to verapamil in some respects and quite different in others


Nifedipine (Adalat, Nifedical, Nifediac, Procardia)

Vasodilation by blocking calcium channels Blocks in vascular smooth muscle Very little blockade of heart Ca channels Cannot be used to treat dysrhythmias Less likely than verapamil to exacerbate pre-

existing cardiac disorders



Direct effects Limited to blockade of Ca channels in vascular

smooth muscle (VSM)• No direct suppressant effects on:

Automaticity, AV conduction, or contractile force Indirect effects

Lowered blood pressure (BP) activates baroreceptor reflex

Primarily with fast-acting vs. sustained-release



Vasodilation by blocking calcium channels Net effect

• Lowered blood pressure• Increased heart rate• Increased contractile force



Therapeutic uses Angina pectoris Hypertension Investigational basis to relieve migraine headache

and to suppress preterm labor



Adverse effects Flushing Dizziness Headache Peripheral edema Gingival hyperplasia Chronic eczematous rash in older patients



Adverse effects (cont’d) Reflex tachycardia Increases cardiac oxygen demand Can increase pain for anginal patients Can be combined with a beta blocker for

prevention of reflex tachycardia• Note: Beta blockers decrease the adverse cardiac

effects of nifedipine, but can intensify the adverse cardiac effects of verapamil and diltiazem



Adverse effects (cont’d) Rapid-acting nifedipine (not sustained)

• Has been associated with increased mortality in patients with MI and unstable angina

• Other rapid-acting calcium channel blockers also associated

• No cause-and-effect relationship established• National Heart, Lung, and Blood Institute (NHLBI)

recommends these be used with great caution


Dihydropyridines

Seven other dihydropyridines available All similar to nifedipine Produce greater blockade of Ca channels in

the VSM than in the heart Nicardipine, amlodipine, isradipine, felodipine,

nimodipine, nisoldipine, and clevidipine

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 45 Calcium Channel...

Documents

Transcript of Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 45 Calcium Channel...