Ischemic Heart Disease

Ischemic Heart Disease (IHD)/ Coronary Artery Disease (CAD)

By: Dr.Abhimanyu ParasharPharm D

Definition

• Coronary artery disease is most commonly caused by obstructive atherosclerosis of epicardial coronary arteries. This leads to an inadequate perfusion of the myocardium and causes an imbalance between myocardial tissue oxygen supply and demand (myocardial ischemia).

• IHD may present as an acute coronary syndrome (acute coronary syndrome includes unstable angina, non–ST-segment elevation myocardial infarction or ST-segment elevation myocardial infarction), chronic stable exertional angina pectoris, and ischemia without clinical symptoms. Coronary artery vasospasm (variant or Prinzmetal angina)

Etiology and Pathophysiology

• The pathophysiology that underlies this disease process is dynamic, evolutionary, and complex.

• An understanding of the determinants of myocardial oxygen demand (MVO2), regulation of coronary blood flow, the effects of ischemia on the mechanical and metabolic function of the myocardium, and how ischemia is recognized are important to understanding the rationale for the selection and use of pharmacotherapy for IHD.

Risk factors for coronary artery disease: • Dyslipidemia [elevated low density lipoprotein (LDL)

cholesterol or reduced high density lipoprotein (HDL) cholesterol]

• Family history of premature myocardial infarction (MI) or sudden death

• Cigarette smoking• Hypertension• Diabetes mellitus• Males > 45 years of age and females >55 years of age. • The American Heart Association has additionally classified

obesity as a major risk factor for the development of coronary artery disease

Determinants of Oxygen Demand

• Major: Heart Rate, Contractility, Intramyocardial wall Tension during systole.

Clinical Presentation

Therapeutic Plan

• The management of ischemic heart disease involves five areas:

1. identification and treatment of concomitant conditions that may exacerbate or precipitate ischemia

2. Correction of concomitant cardiovascular risk factors

3. Lifestyle modifications4. Medical treatment5. Revascularization techniques

The ACC/AHA Practice Guidelines outline the following ABCDE mnemonic for the treatment of patients with chronic stable angina:

• A = Aspirin and Antianginal therapy • B = Beta-blocker and Blood pressure • C = Cigarette smoking and Cholesterol • D = Diet and Diabetes • E = Education and Exercise

NitratesTreatment of acute anginal attacks

Nitroglycerin sublingual tablets Sublingual 0.3–0.6 mg

repeat dose 1–3 times every 5 minutes

Nitroglycerin translingual spray Sublingual 0.4–0.8 mg

repeat dose 1–3 times every 5 minutes

ISDN chewable tablets Chewable 5–10 mg once

ISDN sublingual tablets Sublingual 2.5–10 mg

once

Prevention of acute anginal attacks

Nitroglycerin tablets Sublingual 0.15–0.6 mg

2–5 minutes before activity

Nitroglycerin spray Sublingual 0.4–0.8 mg

2–5 minutes before activity

Isosorbide dinitrate tablets Chewable 5–10 mg 5–10 minutes before activity

Isosorbide dinitrate tablets Sublingual 2.5–10 mg

5–10 minutes before activity

Nitroglycerin patch Transdermal 0.1–0.8 mg/hr

Once daily; 12-hour dosage-free interval

Contraindications: hypotension, Right ventricle infarct

Nitrate Tolerance• A decreased pharmacologic response in the presence of continuously or

frequently administered nitrates is well documented and is termed nitrate toleranceproposed mechanisms of nitrate tolerance include:

(a) depletion of sulfhydryl donors impairing the intracellular formation of nitric oxide and S-nitrosothiols, resulting in decreased formation of cGMP

(b) sympathetic activation following vasodilation producing reflex vasoconstriction and sodium retention

(c) vascular production of endothelin-1(d) plasma volume expansion, minimizing the ability of nitrates to decrease

left ventricular filling pressures

β-BlockersDrug Dose Receptor Half life (hrs)

Atenolol 50–100 mg QD β1 6–7

Bisoprolol 5–10 mg QD β1 9–12

Carvedilol 2.5–10 mg QD β1β2α1 2–6

Labetalol 200–400 mg BID β1β2α1 6–8

Metoprolol 50–100 mg BID β1 3–7

Propranolol Variable β1β2 3–5

Contraindications include: bradycardia, COPD, hypotension, CHF, pulmonary edema

Other Treatment options

• Anti platelet Agents• Calcium Channel Blockers• Other Anti Anginal's (Trimetazidine,

Ranolazine)