Module 2: Drugs for Angina Pectoris

Question 1

What is angina pectoris?

Answer 1

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

Question 2

Three families of antianginal agents

Answer 2

 Organic nitrates
* Nitroglycerin
 Beta blockers
* Example: Metoprolol
 Calcium channel blockers
* Example: Verapamil

Ranolazine
 Newer drug with limited indications
 Can be combined with other drugs

Question 3

Three forms of angina pectoris

Answer 3

 Chronic stable angina (exertional angina)
 Variant angina (Prinzmetal’s or vasospastic angina)
 Unstable angina

Question 4

Chronic Stable Angina (Exertional)

Answer 4

Pathophysiology
 Emotional excitement
 Large meals
 Cold exposure
 Coronary artery disease (CAD)

 Treatment strategy
-Increase cardiac oxygen supply
-Decrease oxygen demand

Therapeutic agents (provide symptomatic relief)
 Organic nitrates
 Beta blockers
 Calcium channel blockers
 Ranolazine

 Nondrug therapy
-Avoid factors that can precipitate angina
-Decrease risk factors

Question 5

Variant Angina
(Prinzmetal’s [Vasospastic])

Answer 5

Pathophysiology
 Coronary artery spasm

 Treatment strategy
-Increasing cardiac oxygen supply

 Therapeutic agents
-Calcium channel blockers
-Organic nitrates

Question 6

Unstable Angina:
Medical Emergency

Answer 6

Severe CAD complicated by vasospasm
 Pathophysiology
*Symptoms of angina at rest
*New-onset exertional angina
*Intensification of existing angina

Question 7

Organic Nitrates

Answer 7

**Nitroglycerin
 Stable and variant angina
 Vasodilator
 Acts directly on vascular smooth muscle (VSM) to
promote vasodilation

**Adverse effects
 Headache
 Orthostatic hypotension
 Reflex tachycardia

For Variant angina
 Relaxes or prevents spasm in coronary arteries
 Increases oxygen supply
 Does not reduce oxygen demand

Drug interactions
 Hypotensive drugs
 Phosphodiesterase type 5 inhibitors
 Beta blockers, verapamil, and diltiazem

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

Preparations and routes of administration
 Sublingual tablets
 Sustained-release oral capsules
 Transdermal delivery systems
 Translingual spray
 Topical ointment
 IV infusion

Long-acting preparations
 Discontinue slowly
 Therapeutic uses
 Acute anginal therapy
 Sustained anginal therapy
 IV for perioperative control of blood pressure and
treatment of heart failure with myocardial infarction
(MI), unstable angina, and uncontrolled exacerbations of chronic angina

Question 8

Nitroglycerin - how it works

Answer 8

Nitroglycerin is a well-known medication used primarily for the treatment and prevention of angina pectoris (chest pain usually caused by reduced blood flow to the heart). Its antianginal effects are primarily due to its ability to decrease the oxygen demand of the heart muscle.

Vasodilation:
The primary mechanism by which nitroglycerin relieves angina is through vasodilation – the widening of blood vessels.
Nitroglycerin is a vasodilator that mainly acts on the veins, but also has some effect on the arteries.

Decreasing Cardiac Preload:
By dilating the veins, nitroglycerin reduces the amount of blood returning to the heart (venous return). This reduction in venous return decreases the heart’s preload (the volume of blood in the ventricles at the end of diastole).
Lower preload means the heart has less work to do and therefore requires less oxygen.

Reducing Cardiac Workload:
With less blood to pump, the workload on the heart is reduced, leading to decreased oxygen consumption by the heart muscle.
This is particularly beneficial when the heart’s oxygen supply is already limited, such as in coronary artery disease, the most common cause of angina.

Dilating Coronary Arteries:
Nitroglycerin also helps by dilating the coronary arteries, which can increase blood flow to the heart muscle itself, enhancing oxygen delivery to areas that might be ischemic (lacking oxygen).

Relief of Coronary Artery Spasm:
In addition to its effects on preload and oxygen demand, nitroglycerin can relieve angina by relaxing spasms in the coronary arteries. This is especially useful in variant (Prinzmetal’s) angina, which is caused by spasms of the coronary arteries.

Question 9

Isosorbide mononitrate and isosorbide dinitrate

Answer 9

Actions identical to those of nitroglycerin
 Used for angina; taken orally; produce headache,
hypotension, and reflex tachycardia

Question 10

Beta Blockers

Answer 10

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

Question 11

Calcium Channel Blockers

Answer 11

Verapamil, diltiazem, nifedipine
 Block calcium channels in vascular smooth muscle
 Used for stable and variant angina
 Adverse effects
* Dilation of peripheral arterioles
* Reflex tachycardia
* Hypotension
* Beta blockers
* Bradycardia
* Heart failure
* AV block

Question 12

Ranolazine

Answer 12

Belongs to first new class of antianginal agents
approved in more than 25 years
 Benefits are modest and greater in men than in women
 Does not reduce heart rate, blood pressure, or vascular resistance
 Can prolong QT interval; multiple drug interactions
 Exact mechanism unknown
 Not a first-line therapy; combine with first-line agents for inadequate response to other first-line
medications

Question 13

Drugs Used to Prevent
Myocardial Infarction and Death

Answer 13

 Antiplatelet drugs
 Cholesterol-lowering drugs
 Angiotensin-converting enzyme (ACE) inhibitors
 Antianginal agents

Question 14

Reduction of Risk Factors

Answer 14

 Smoking
 High cholesterol
 Hypertension
 Diabetes
 Physical inactivity