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Chapter 51
Drugs for Angina Pectoris
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Drugs for Angina Pectoris

Angina pectoris



Sudden pain beneath the sternum, often radiating
to left shoulder and arm
Oxygen supply to the heart is insufficient to meet
oxygen demand
Two goals of angina drug therapy


Prevention of myocardial infarction and death
Prevention of myocardial ischemia and anginal
pain
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
2
Drugs for Angina Pectoris

Three families of antianginal agents

Organic nitrates
• Nitroglycerin
 Beta blockers
• Example: propranolol
 Calcium channel blockers
• Example: verapamil

Ranolazine

A newer drug with limited indications
 Can be combined with other drugs
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
3
Determinants of Cardiac Oxygen
Demand and Supply

Oxygen demand




Heart rate
Myocardial contractility
Intramyocardial wall tension (preload/afterload)
Oxygen supply


Myocardial blood flow
Myocardial perfusion only in diastole
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
4
Angina Pectoris:
Pathophysiology and Treatment

Three forms of angina pectoris



Chronic stable angina (exertional angina)
Variant angina (Prinzmetal’s or vasospastic
angina)
Unstable angina
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
5
Chronic Stable Angina (Exertional)

Pathophysiology





Emotional excitement
Large meals
Cold exposure
Coronary artery disease (CAD)
Treatment strategy


Increase cardiac oxygen supply
Decrease oxygen demand
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
6
Chronic Stable Angina (Exertional)

Therapeutic agents (provide symptomatic
relief)





Organic nitrates
Beta blockers
Calcium channel blockers
Ranolazine
Nondrug therapy


Avoid factors that can precipitate angina
Decrease risk factors
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
7
Fig. 51–1. Effect of exertion on the balance between oxygen supply and oxygen
demand in the healthy heart and the heart with CAD.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
8
Variant Angina
(Prinzmetal’s: Vasospastic)

Pathophysiology


Treatment strategy


Coronary artery spasm
Increasing cardiac oxygen supply
Therapeutic agents


Calcium channel blockers
Organic nitrates
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
9
Unstable Angina:
Medical Emergency


Severe CAD complicated by vasospasm
Pathophysiology




Symptoms of angina at rest
New-onset exertional angina
Intensification of existing angina
Treatment strategy


Maintain oxygen supply
Decrease oxygen demand
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
10
Unstable Angina:
Medical Emergency

Therapeutic agents for acute management



Anti-ischemic therapy
Antiplatelet therapy
Anticoagulant therapy
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
11
Anti-ischemic Therapy





Nitroglycerin
Beta blocker
Supplemental O2
IV morphine
ACE inhibitor
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
12
Antiplatelet/Anticoagulant Therapy

Aspirin (indefinitely)




Clopidogrel (Plavix)
Abciximab (ReoPro)
Eptifibatide (Integrilin)
Anticoagulant therapy

Subcutaneous LMW heparin or IV
unfractionated heparin
LMW = low-molecular-weight.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
13
Organic Nitrates

Nitroglycerin



Stable and variant angina
Vasodilator
Adverse effects



Headache
Orthostatic hypotension
Reflex tachycardia
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
14
Organic Nitrates: Nitroglycerin






Vasodilator actions
Mechanism of antianginal effects
Stable angina
Variant angina
Pharmacokinetics
Adverse effects
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
15
Organic Nitrates: Nitroglycerin




Drug interactions
Hypotensive drugs
Phophodiesterase type 5 inhibitors
Beta blockers, verapamil, and diltiazem
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
16
Organic Nitrates: Nitroglycerin

Tolerance




Can develop rapidly
Cross-tolerance to all other nitrates
To minimize, use the lowest effective dose
Long-acting formulas: 8 drug-free hours per day
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
17
Organic Nitrates: Nitroglycerin

Preparations and routes of administration






Sublingual tablets
Sustained-release oral capsules
Transdermal delivery systems
Translingual spray
Topical ointment
Intravenous infusion
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
18
Organic Nitrates: Nitroglycerin

Long-acting preparations


Discontinue slowly
Therapeutic uses summarized



Acute anginal therapy
Sustained anginal therapy
IV for perioperative control of blood pressure and
treatment of heart failure with MI, unstable angina,
and uncontrolled exacerbations of chronic angina
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
19
Organic Nitrates: Other

Isosorbide mononitrate and isosorbide
dinitrate



Actions identical to those of nitroglycerin
Used for angina, taken orally, produce headache,
hypotension, and reflex tachycardia
Amyl nitrite

Ultrashort-acting agent used to treat acute
episodes of angina pectoris
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
20
Beta Blockers

Decrease cardiac oxygen demand

Propranolol, metoprolol
• Adverse effects









Bradycardia
Decreased atrioventricular (AV) conduction
Reduction of contractility
Asthmatic effects
Use with caution in patients with diabetes
Insomnia
Depression
Bizarre dreams
Sexual dysfunction
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
21
Calcium Channel Blockers

Verapamil, diltiazem, nifedipine



Block calcium channels in vascular smooth
muscle (VSM)
Used for stable and variant angina
Adverse effects
• Dilation of peripheral arterioles
• Reflex tachycardia
• Hypotension
• Beta blockers
• Bradycardia
• Heart failure
• AV block
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
22
Ranolazine

Belongs to first new class of antianginal
agents approved in more than 25 years





Benefits modest and greater in men than in
women
Does not reduce heart rate, blood pressure, or
vascular resistance
Can prolong QT; multiple drug interactions
Exact mechanism unknown
Not a first-line therapy; combine with first-line
agents for inadequate response to other firstline medications
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
23
Revascularization Therapy



Coronary artery bypass graft (CABG) surgery
Percutaneous transluminal coronary
angioplasty (PTCA)
Comparison of CABG surgery with
percutaneous coronary intervention (PCI)
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
24
Drugs Used to Prevent
Myocardial Infarction and Death




Antiplatelet drugs
Cholesterol-lowering drugs
Angiotensin-converting enzyme (ACE)
inhibitors
Antianginal agents
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
25
Reduction of Risk Factors





Smoking
High cholesterol
Hypertension
Diabetes
Physical inactivity
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
26
Management of Variant Angina

Treatment of vasospastic angina




Initial therapy
• Calcium channel blocker or long-acting nitrate
If either of these alone is inadequate, add a nitrate
If combination fails, CABG may be indicated
Beta blockers are not effective with vasospastic
angina
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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