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PATHOPHYSIOLOGY OF ANGINA
Drugs for Acute Coronary Syndromes - Cardiovascular Disorders - MSD Manual Professional Edition
Industrial disease caused by chronic exposure to vasodilating concentrations of organic nitrates in the workplace; characterized by headache, dizziness, and tachycardia on return to work after 2 days absence. Nitrate tolerance, tachyphylaxis. Loss of effect of a nitrate vasodilator when exposure is prolonged beyond 10—12 h. Rapidly progressing increase in frequency and severity of anginal attacks; an acute coronary syndrome that often heralds imminent myocardial infarction.
Filling pressure of the heart, dependent on venous tone and blood volume; determines end-diastolic fiber length and tension. Impedance to ejection of stroke volume; determined by vascular resistance arterial blood pressure and arterial stiffness; determines systolic fiber tension.
Intramyocardial fiber tension. Force exerted by myocardial fibers, especially ventricular fibers at any given time; a primary determinant of myocardial O 2 requirement. Double product.
The product of heart rate and systolic blood pressure; an estimate of cardiac work. Myocardial revascularization.
Mechanical intervention to improve O 2 delivery to the myocardium by angioplasty or bypass grafting. Treatment options include lifestyle modification, pharmacologic agents, cardiac procedures, and cardiac rehabilitation. Therapeutic agents may be divided into antianginal drugs and vasoprotective drugs. While antianginals are widely used to manage both stable and unstable angina, vasoprotective agents are underprescribed.
In the U. Cardioprotective agents used in the management of angina include aspirin, heparin, and anticholesterol drugs. Combination therapy should be suggested for patients who are poorly managed. Aspirin, a relatively inexpensive form of vasculoprotective therapy, has been shown to reduce adverse clinical outcomes in patients with stable angina.
Alternatively, clopidogrel 75 mg once daily may be used in patients unable to take aspirin. The combination of aspirin and clopidogrel has not been shown to have a benefit over aspirin alone. One lifestyle modification is to engage in regular exercise, beginning at 20 to 30 minutes and increasing gradually. Patients should be advised regarding dietary modifications and smoking cessation.
Managing Unstable Angina: An attack of unstable angina is a medical emergency; because it can quickly lead to MI, the patient should be admitted to the hospital immediately. Initial therapy should focus on preventing MI or death. Antiplatelet drugs and analgesics are essential for relieving ischemia and preventing the recurrence of adverse ischemic events.
Patients treated with heparin have a decreased risk of MI and a higher incidence of minor bleeding. Following discharge, patients may require anticoagulant warfarin therapy to maintain an international normalized ratio of 2. Cardiac procedures should be performed in high-risk patients at an early stage. Because magnesium deficiency may be involved in variant angina, supplementation is recommended. If the angina does not respond to drug therapy, surgical intervention may be required.
While nitroglycerin may be life-saving, long-acting nitrates have a role in prophylaxis. Antiarrhythmic drugs are indicated for patients who develop arrhythmias during an attack. Lifestyle modifications such as weight reduction; a low-fat, low-cholesterol, low-calorie diet; carefully monitored exercise; and smoking cessation should be considered.
BBs: These agents reduce oxygen demand during both exercise and rest by blocking beta-1 receptors. This results in a lowering of HR, reduction of myocardial contractility, and attenuation of rise in systolic BP during exercise. BBs are either lipophilic or hydrophilic, and some BBs have intrinsic sympathomimetic activity.
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Irrespective of these differences, all drugs in this class seem to be equally effective for managing angina. Patients taking BBs may complain of fatigue, erectile dysfunction, sleep disturbances, and vivid dreams. Nitrates: Nitroglycerin and other organic nitrates exert their effects primarily through venous dilation that reduces left ventricular volume preload as well as myocardial-wall tension, reducing oxygen requirements demand. A smaller dilation of arterioles reduces both peripheral vascular resistance and left ventricular pressure at systole afterload. Nitrates also facilitate collateral circulation, improving regional coronary blood flow to ischemic areas and alleviating spasm.
SL, transmucosal, and IV nitrates are used to manage acute angina attacks. IV nitroglycerin is indicated for the immediate treatment of unstable angina, as well as for long-term therapeutic relief.
Oral or buccal tablets, topical ointment, or transdermal patches may be used to prevent anticipated attacks. In other patients, headaches are mild-to-moderate in severity and either resolve or diminish in intensity with continued nitrate therapy. CCBs: This class has two primary actions that are important in the management of angina: 1 CCBs prevent coronary spasm by blocking the influx of calcium, and 2 they dilate peripheral arterioles, thereby reducing oxygen demand. Additionally, they may be as effective as nitrates and BBs in stable angina.
Nifedipine has a lesser effect on the myocardium and works primarily on the blood vessels. Verapamil is a negatively inotropic CCB that reduces cardiac output, slows HR, and impairs atrioventricular conduction.
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Diltiazem has a lower negative inotropic effect than verapamil, and it rarely causes myocardial depression. The use of verapamil and diltiazem generally is not recommended in patients with left ventricular systolic dysfunction, as these drugs worsen heart failure and increase mortality. If the patient has a high degree of AV block, these agents may induce complete AV block.
CCBs should be withdrawn carefully, since sudden withdrawal has been shown to exacerbate angina. Ranolazine: This is the latest antianginal drug approved by the FDA. While its exact mechanism of action is unknown, ranolazine is thought to decrease cardiac demand by acting on cellular metabolism. This leads to decreased myocardial oxygen requirements in marginally ischemic myocytes, which can potentially reduce vascular compression, allowing more coronary blood flow to the affected area. The usual dose is mg to 1, mg twice daily.
Patients may experience dizziness, headaches, constipation, and nausea. Ranolazine is contraindicated in patients with preexisting QT prolongation or hepatic impairment, and it should not be used with other drugs that prolong the QT interval or with CYP3A inhibitors such as diltiazem. In patients with diabetes, ranolazine has the additional benefit of lowering glycosylated hemoglobin.
Other Agents: Nicorandil is a potassium channel opener with a nitrate component.