Drugs to treat angina. I. Introduction Branching off the aorta are the coronary arteries.

Drugs to treat angina

I. Introduction

• Branching off the aorta are the coronary arteries.

• They deliver blood to the muscular layer of the heart (myocardium).

• These arteries are particularly susceptible to the formation of the cholesterol filled plaques which reduce coronary blood flow (ischemia).

• A consequence of coronary artery disease (CAD) and the resulting ischemia is angina.

• Angina pectoris (chest pain) is a result of insufficient blood flow/oxygen delivery to the myocardium.

II. Classifications of Angina

• The 3 major types of angina pectoris are exertional angina, variant(Prinzmetal's) angina, and unstable angina.

A. Exertional angina

• Exertional angina is the most common type. It is usually found in people with coronary artery disease.

• There is a regular pattern to this type of angina, it is predictable in its frequency and duration.

• It often occurs during physical exertion, or emotional excitement, both increase the oxygen demand of the heart.

• With rest, the pain usually diminishes in less than 15 minutes and is relieved by medication.

B. Variant angina

• This is less common and unpredictable. It can occur at any time, even while sleeping.

• It is caused by vasospasm of one or more of the coronary arteries.

• It is relieved by medication.

• Some individuals may experience both exertional and variant angina.

C. Unstable angina

• Unstable angina is a very dangerous condition that generally occurs in patients with advanced CAD.

• It is not unpredictable, as it can occur at any time.

• It is considered a medical emergency, because it is associated with an increased risk of MI.

• It requires aggressive treatment with anticoagulant, antiplatelet, and antianginal medications.

III. Symptoms of angina

• classic presentation: sharp pain in the heart region, often moving to the left side of the neck and lower jaw, and down the left arm

IV. Treatment for angina

• 3 major classes of drugs are used to treat angina:

• nitrates

• beta blockers

• calcium channel blockers

• Of 3 classes of antianginal drugs, only the nitrates are used in the treatment of acute attacks.

• Beta blockers and calcium channel blockers are used in long term management (as are some nitrates).

A. Nitrates

• Main function of these drugs is to produce vasodilation of systemic veins and arteries.

• With venodilation, the amount of blood returning to the heart (preload) is reduced and the chambers contain less blood

• With less blood to eject cardiac output (afterload) is reduced, thus lowering oxygen demand.

• This provides relief of both ischemia and pain.

• Nitrate drugs all contain one or more nitrate group.

• This group is released from the drug and converted by enzymes in blood vessels to nitric oxide (NO).

• NO is a potent, short-acting vasodilator that relaxes vascular smooth muscle.

a. Isosorbide mononitrate (ISMO, Imdur)

• ISMO: 20 mg tablets; 30 minute onset; 6 – 8 hour duration

• Indur: 30, 60, or 120 mg extended-release tablets; 30 minute onset; 12 hour duration

b. Isosorbide dinitrate (Isordil, Sorbitrate)

• Isordil: 2 ½, 5, or 10 mg sublingual tablets with an onset of 2 – 5 minutes and a duration of 2 – 3 hours; or 5,10, 20, 30, 40 mg tablets with an onset of 30 minutes and a duration of 4 – 6 hours

• Sorbitate: 5 or 10 mg chewable tablets with a 30 minute onset and a duration of 2 – 3 hours

c. Nitroglycerin (many forms)

• Nitrostat: 0.3, 0.4, 0.6 mg sublingual tablets with an onset of 1 – 3 minutes and a duration of 30 minutes

• Nitrolingual Pump Spray: 0.4 μg per spray with an onset of 1 – 3 minutes and a duration of 30 minutes

• Nitrobid IV: 5 μg/min IV infusion with an onset of 1 – 3 minutes, duration generally until infusion is stopped

• Nitrobid 2% ointment: each inch of ointment squeezed from the tube contains about 15 mg nitroglycerin; onset of 30 minutes and a duration of 4 – 8 hours

• Transderm-Nitro: 0.2 – 0.4 mg/hour transdermal patch; onset of 30 minutes and a duration of 24 hours

• Nitrogard: 1, 2, or 3 mg extended release buccal tablets, onset of 30 minutes and a duration of 6 – 8 hours

B. Beta blockers

• Beta blockers are used in the treatment of angina to reverse the effects of sympathetic activation caused by exercise or physical exertion.

• Recall: sympathetic stimulation results in ↑ heart rate, myocardial contraction and O2 consumption

• Beta blockers: ↓ heart rate, myocardial contraction and O2 consumption

• Result in less frequent anginal attacks or delayed onset of pain during physical exertion (meaning an increased exercise tolerance)

• All beta-blockers appear to be equally effective in the treatment of angina. Only the following 4 are FDA-approved for the treatment of angina:

• Selective β1 blockers:

• atenolol (Tenormin): 50 – 100 mg

• metoprolol (Lopressor, Toprol): 100 – 400 mg

• nonselective beta blockers:

• nadolol (Corgard): 80 – 240 mg

• propranolol (Inderal): 80 – 320 mg

C. Calcium channel blockers

• These are the preferred drug for treating variant angina.

• Movement of calcium ion into smooth muscle cells lining coronary arteries is necessary for contraction

• Movement of calcium ion into smooth muscle cells lining coronary arteries is necessary for contraction.

• By inhibiting calcium influx, CCB’s produce vasodilation. The dosages used in angina primarily relax arterial smooth muscle, resulting in arteriolar vasodilation.

• CCB’s used in the treatment of angina include:

• 1. amlodipine (Norvasc)

• 2. diltiazem (Cardizem)

• 3. nicardipine (Cardene)

• 4. nifedipine (Procardia)

• 5. verapamil (Calan, Isoptin)