Ischemic heart diseases Ischemia : it is inadequate supply of O2 to an organ or tissue (result from inadequate blood flow) insufficient to meet the organ’s O2 demand It is accompanied by inadequate removal of local metabolic wastes. Pain is due to release of pain mediators : adenosin, substance P & lactic acid. Causes of Myocardial ischemia : 1-Decrease in blood flow: -Conroy vessel occlusion (e.g., with atherosclerotic plaque, thrombus) -Vasospasm (stress, hypertension …) 2-Decrease in amount of oxygenated blood reaching the heart: -Anemia-Carboxyhemoglobinemia-Hypotension 3-Increase in myocardial O2 demands: -Thyrotoxicosis

Ischemic heart diseases Ischemic heart diseases Angina pectoris Angina pectoris It is a clinical syndrome due to myocardial ischemia which last for short time It is a clinical syndrome due to myocardial ischemia which last for short time Myocardial infarction Myocardial infarction It is a clinical syndrome due to myocardial ischemia which last for long time mainly due to thrombus in coronary vessel (leading to myocardial necrosis or apoptosis) It is a clinical syndrome due to myocardial ischemia which last for long time mainly due to thrombus in coronary vessel (leading to myocardial necrosis or apoptosis)

Risk factors of IHD Sex,age, weight & family history. Diets: with high content of unsaturated fats and low content of natural antioxidants Smoking Lack of regular exercise Alcohol abuse Diseases as hypertension, hypotension, thyrotoxicosis, D.M.,hyperlipidemia……

ANGINA Definition : Chest pain due to a reduced perfusion to the heart which is insufficient to meet its metabolic demands Chest pain due to a reduced perfusion to the heart which is insufficient to meet its metabolic demands There are 3 types of angina: 1. Classic (effort or stable) angina (most common ) 1-Pain occur with increased work,excercise or emotional stress (which tend to increase cardiac activity). 1-Pain occur with increased work,excercise or emotional stress (which tend to increase cardiac activity). 2- It is due to presence of coronary artery disease (atherosclerosis) 2- It is due to presence of coronary artery disease (atherosclerosis) 3- There is no pain at rest, even though the coronary artery may be partially occluded. This is because the heart has the capacity to compensate for mild narrowing by increasing the resting diameter of coronary arteries. 3- There is no pain at rest, even though the coronary artery may be partially occluded. This is because the heart has the capacity to compensate for mild narrowing by increasing the resting diameter of coronary arteries. 2. Variant (vasospastic & prinzemetal ) angina 1- Less common than stable angina· 1- Less common than stable angina· 2-Pain is experienced at rest· There is no evidence of coronary artery disease. 2-Pain is experienced at rest· There is no evidence of coronary artery disease. 3-What happens is coronary vasospasm (the large coronary arteries are actively constricting). 3-What happens is coronary vasospasm (the large coronary arteries are actively constricting). 3. Unstable angina 1-Most dangerous form because it indicates that myocardial infarction is just around the corner· 1-Most dangerous form because it indicates that myocardial infarction is just around the corner· 2-Pain is experienced at rest (comes and goes) and with effort.· 2-Pain is experienced at rest (comes and goes) and with effort.· At the site of the atheroma in the coronary artery, a thrombus begins to form. As this thrombus enlarges, it totally occludes the vessel so that there is absolutely no blood flow to the heart at all. This is what causes the pain at rest· As the thrombus breaks down, the pain goes away. If the thrombus does not dissolve quickly, the myocardium is not receiving any blood flow, and so undergoes infarction (heart attack) At the site of the atheroma in the coronary artery, a thrombus begins to form. As this thrombus enlarges, it totally occludes the vessel so that there is absolutely no blood flow to the heart at all. This is what causes the pain at rest· As the thrombus breaks down, the pain goes away. If the thrombus does not dissolve quickly, the myocardium is not receiving any blood flow, and so undergoes infarction (heart attack)

Symptoms of angina Symptoms of angina 1-Sudden pain in the chest which may radiates to left arm and neck rang from mild ache to sever pain.This pain fades quickly (especially at rest=stable angina) 2-If pain is experienced at rest =variant angina 3-If frequent pain is experienced at rest (comes and goes) and with little effort =unstable angina·

Treatment of angina a-Non pharmacological Treatment of predisposing factors: hypertension,hypotension, thyrotoxicosis, hyperlipidemia, anemia…….. anemia…….. Rest –exercise program Avoid heavy work and stress Diet regulation: small frequent meals with high content of natural antioxidants and low content of unsaturated fats Stop smoking and avoid alcoholic beverages as well as stress

b- Pharmacological treatment 1-Prognostic treatment: a-Antiplatelet drugs: e.g. Aspirin 75 mg/day to prevent thrombosis (used for unstable angina). b-Lipid lowering drugs 2-Therapeutic treatment: Stable & unstable angina Stable & unstable angina The aim of therapy is to reduce the myocardial O2 demand· This is because we already have maximal blood flow - it is not possible to increase the flow any more The aim of therapy is to reduce the myocardial O2 demand· This is because we already have maximal blood flow - it is not possible to increase the flow any more 1. Decrease preload: Use nitrovasodilators 2. Reduce myocardial contractility: β blockers 3. Decrease afterload (thus decreasing the work of the heart):Ca2+ channel antagonists & Nitrovasodilator Variant angina Variant angina It is necessary to relieve the coronary vasospasm by vasodilators It is necessary to relieve the coronary vasospasm by vasodilators nitrovasodilators & Ca2+ channel blockers nitrovasodilators & Ca2+ channel blockers Never give β blockers they can actually cause coronary vasospasm· This is because if all the β receptors are blocked, the excess noradrenaline stimulates α receptors which cause vessel constriction…….Worsening the case. Never give β blockers they can actually cause coronary vasospasm· This is because if all the β receptors are blocked, the excess noradrenaline stimulates α receptors which cause vessel constriction…….Worsening the case.

1-Nitrovasodilator ( Organic Nitrates): Gylcerol trinitrate (GTN) Isosorbide mono- & di-ntrate They are used sublingually especially before exertion They are used sublingually especially before exertion Mechanism of action: Mechanism of action: 1-These drugs are all prodrugs which ultimately form NO, a powerful vasodilator· NO is capable of dilating all blood vessels. 1-These drugs are all prodrugs which ultimately form NO, a powerful vasodilator· NO is capable of dilating all blood vessels. 2-GTN dilates the blood vessels reduces (preload) + reduces (after load ) making thus reducing the O2 demand (stable angina) 2-GTN dilates the blood vessels reduces (preload) + reduces (after load ) making thus reducing the O2 demand (stable angina) 3-Also, they dilate collateral arterioles, increased perfusion to the ischemic area of the heart (This is their main effect in case of variant angina). 3-Also, they dilate collateral arterioles, increased perfusion to the ischemic area of the heart (This is their main effect in case of variant angina).

Anti-anginal Drugs

Adverse effects of Nitrates: Adverse effects of Nitrates: · Postural hypotension (due to venous pooling) · Tachycardia (mild and brief, resolves quickly or they can be given with β blockers) · Headache (cerebral VD) · Flushing of the face. Tolerance (treated by stop taking the drug at night).

Ca++ channel blockers: These group of drugs is useful in treatment of All types of angina and also when angina is accompanied with other disorders as asthma, COPD, PVD,D.M. or arrhythmia. These group of drugs is useful in treatment of All types of angina and also when angina is accompanied with other disorders as asthma, COPD, PVD,D.M. or arrhythmia. · Nifedipine (greatest effect on relaxing arterioles) · Diltiazem (cardiac selective) · Verapamil (cardiac selective) Mechanism of action Mechanism of action Block the L- & T - type voltage operated Ca2+ channel which is present on smooth muscle and cardiac muscle· By blocking these channels, Ca2+ is prevented from entering and thus causing smooth muscle relaxation. Block the L- & T - type voltage operated Ca2+ channel which is present on smooth muscle and cardiac muscle· By blocking these channels, Ca2+ is prevented from entering and thus causing smooth muscle relaxation. Nifedipine is used as a vasodilator· It is used to decrease TPR (and hence after load…..O2 demand is reduced), by decreasing the tone of the arterioles and arteries (relieve vasospasm …..important in variant angina). Verapamil & diltiazem are used to decrease contractility of the heart, reducing the force and rate of contraction by inhibiting the entry of Ca2+ into the cardiac muscle( decrease O2 demands…….stable & unstable) The choice of drug depends on the patients underlying cardiovascular problems. E.g. · If angina + hypertension use nifedipine · If angina + arrhythmia use verapamil Verapamil must never be used in conjunction with β blockers because of the possibility of too much myocardial depression.

Adverse effects of Ca channel blockers : · Hypotension · Bradycardia, AV block, heart arrest (espically if given with β blockers ) · Headache · Flushing.Ankle edema

3-β blockers These group of drugs is useful in treatment of stable and unstable angina BUT NEVER USE IT IN VARIANT ANGINA……………Why????· Propranolol Propranolol · Atenolol. Nadolol. Metaprolol Mechanism of action Mechanism of action Decrease cardiac contractility (decrease force and rate of contraction =decrease O2 demands)· Decrease cardiac contractility (decrease force and rate of contraction =decrease O2 demands)· Adverse effects: Adverse effects: Standard adverse effects of blocking β receptors (e.g. don’t use in asthmatics) Should not use β blockers with verapamil Don’t use if there is any evidence of heart disease (they cause bradycardia & may lead to heart block). Also,they increase triglycerides They are contraindicated in diabetic patients because they mask symptoms of hypoglycemia (tachycardia) NOT taken by patients with PVD

4-Potassium channel activators Ex. Nicorandil It is an opener for K channels in both arteries & veins hyper polarization VD pre- & after load O2 demand Side effects: HeadacheFlushingDizziness

Myocardial infarction It is a clinical syndrome due to myocardial ischemia which last for long time mainly due to blocking of coronary vessel with large thrombus (leading to myocardial necrosis or apoptosis) It is a clinical syndrome due to myocardial ischemia which last for long time mainly due to blocking of coronary vessel with large thrombus (leading to myocardial necrosis or apoptosis) Symptoms of MI: Sever pain suddenly occur last for long period Sweating, pale( due to hypoxia), breathlessness Nausea &vomiting Moderate fever (due to cell necrosis) Tachycardia

Treatment of Myocardial Infarction Treatment of Myocardial Infarction

Treatment of MI Thrombolytic & antiplatelet drugs to open the blocked artery Oxygen Opioids to reduce pain & increased sympathetic activity. ACEI drugs & β blockers to decrease cardiac work and load.