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Drug Treatment of Ischemic Heart Disease

Ischemic Heart Disease

When the demand of oxygen by heart is more than the supply, it is known as ischemia. Any factor which increases the work load, stress of oxygen consumption, if not met by concomitant increase in blood flow, results is ischemic heart disease.

Related Physiological Aspects

1. Heart is unlike other tissues, it has to work 24/7, throughout the life span

2. Coronary circulation is by two coronary arteries, the left supplies the anterior and lateral surface of left ventricle, while the right supplies the right ventricle and the posterior surface of left ventricle.

3. Normal coronary blood flow is 225 ml, which makes 4-5% of total cardiac output.

4. During exercise, cardiac output increases 4-6 times (can go up to 30l), work load becomes even more than this because of:

a. Increased contractility

b. Increased heart rate

c. Increased blood pressure (heart has to pump blood against greater blood pressure)

There is about 6-8 times increase in work load and oxygen demand, but the coronary blood flow increases only 3-4 times. There is, thus, relative deficiency of oxygen supply to heart in strenuous exercise.

Normally the problem is resolved by efficient use of energy. Problem arises when the coronary artery is affected by atherosclerosis. Due to deficiency of blood flow, lactic acid accumulates leading to precipitation of symptoms, including:

    1. Feeling of compression
    2. Discomfort
    3. Constriction of chest
    4. Pain occurs only in a minority of cases
    5. Hand at heart, complete hand placed on heart (if pointing with one finger, then not ischemia)

5. Under normal resting conditions, heart prefers to utilize fatty acids to ATP generation. The amount of energy used for fatty acids breakdown is much more than that for carbohydrates.

Drugs which can convert to glucose metabolism are effective, as less oxygen is consumed.

6. Large coronary arteries do not have anastomosis, while smaller arteries have some collaterals. If chronic heart disease occurs, some collaterals do develop in ischemia.

7. Phasic changes –of all the organs, the heart receives blood supply during diastole. During systole, coronary arteries are compressed, contrary to any other place in the body.

 Symptoms
  1. Typical symptoms
  2. Atypical symptoms –pain in right arm, epigastric region, jaw or back.
Angina Pectoris
a. Stable angina  

Atherosclerotic plaque is formed which is stable. It is also known as exercise induced angina or angina of effort (classical angina). No symptoms are seen at rest, which appear under stress. These symptoms are the typical presentation of angina.

b. Unstable angina

Most deaths occur due to MI in unstable angina. The symptoms appear even at rest and the character may change.

Stable angina may change into unstable angina due to rupture of atherosclerotic plaque releasing fatty acids, fatty cells, etc.

Platelet aggregation may lead to non occlusive type of angina. Sometimes resolution appears later on.

c. Variant angina (Prinzmetal) or Vasospastic

Momentary spasm of vessel, recovering after some time, but enough to produce symptoms or even MI. Might occur due to stress, underlying atherosclerosis

d.  Silent ischemia

Patient does not complain of symptoms, but changes visible only on ECG are suggestive of ischemia. This is unusual and may have episodes of symptomatic angina with it.

Occurs in diabetics, as they do not complain of any symptoms.

e. Angina of autonomic dysfunction/ Orthostatic Angina

On changing posture, the blood pressure decreases, producing angina. If person is only suffering from this type of angina, the treatment is different. Treatment involves increasing the blood volume by increasing minerocorticoids (Na+ rich diet).

Percutaneous Coronary Intervention (PCI)

PCI has revolutionized the treatment. In good hospitals it is applied straight away.

Drugs are still important because:

    1. there is need of drugs before intervention
    2. even after operation, drugs are needed

 Classification of Antianginal Drugs

1. Organic Nitrates
  • isosorbide dinitrate
  • glyceryl trinitrate
  • erythrityl tetranitrate
  • pentaerythritol tetranitrate
2. Beta adrenergic receptor blockers (devoid of intrinsic sympathetic activity)
3. Calcium channel blockers
4. Potassium channel opener

nicorandil

5. pfox inhibitors (fatty acid oxidation inhibitors)
  • trimetazidine
  • ranolazine
6. Direct Bradycardiac agents

Ivabradine

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