Ischemic Heart Disease Lecture Notes PDF

Ischemic Heart Diseases ▪ Coronary arteries are the BV which transport oxygenated blood to the heart tissue. (Responsible for heart O2 supply) ▪ Coronary arteries divide into two main branches, the left coronary artery (LCA) and right coronary artery (RCA) ▪ Coronary arteries are the...

Ischemic Heart Diseases ▪ Coronary arteries are the BV which transport oxygenated blood to the heart tissue. (Responsible for heart O2 supply) ▪ Coronary arteries divide into two main branches, the left coronary artery (LCA) and right coronary artery (RCA) ▪ Coronary arteries are the only arteries that filled with blood during diastole (rest) ▪ Reduced function of the coronary arteries can lead to decreased flow of blood (oxygen) and nutrients to the heart this induce a clinical situation called ischemia ▪ Ischemic heart disease: heart problems caused by narrowed coronary arteries that supply blood to the heart muscle. Atherosclerosis Vasospasm Blood Clot ▪ When the heart muscle is deprived of adequate oxygen is called angina pectoris. ▪ When the blood flow to the heart muscle is completely blocked, the heart muscle cells die, which is termed a heart attack or myocardial infarction (MI).  Angina Pectoris  Definition: ▪ Clinical syndrome characterized by sever sudden pressing chest pain due to ischemia (a lack of blood and hence O2 supply) of the heart muscle Character Site of pain Sever pressing Retrosternal radiating causing sensation to the left shoulder, of chest tightness neck, jaw & back. Precipitated by Duration Effort, emotion Usually < 15 min. and eating Relieved by if longer than 15 min Rest and/or nitrate → MI  Pathophysiology ❖ Imbalance between O2 demand (due to heart work) and O2 supply (through coronary artery) Myocardial O2 Demand Myocardial O2 supply  HR, BP and  Coronary blood flow  Contractility  Types A) Chronic stable angina (Exertional – Classic ) It is the most common type It occurs if the heart is working harder than usual and doesn’t receive adequate blood supply Narrowing of coronary BV due to formation of atheromatous plaque in coronary artery branch (subintimal deposition of lipid) Pain induced by effort and relieved by rest Aim of treatment is to decrease heart work and demand B) Unstable angina Unstable angina is very dangerous and requires emergency treatment It occurs with or without physical exertion, and it may not be relieved by rest or medicine It occurs due to rupture of atheromatous plaque and formation of thrombus Untreatable case of unstable angina developed to complete obstruction of coronary artery inducing MI Unstable angina and MI can be called (Acute coronary syndrome) c) Prinzmetal angina (Variant– Vasospastic) This type of angina is less common It occurs mainly due to coronary vasospasm leading to  heart muscle blood supply Variant angina usually happens between midnight and early morning. The pain is severe and induced at rest and relived by nitrate Aim of treatment to relax coronary artery (coronary VD)  Risk factors  Diagnosis 1. Resting ECG: ▪ This is usually normal between attacks. ▪ During an attack, transient ST depression, T-wave inversion ▪ In MI Deep Q wave and ST elevation so MI called (STEMI ) 2. Exercise ECG: ▪ Recording ECG under controlled physical effort to record ischemic changes 3. Coronary angiography (x-ray): 4. Echocardiography (ultrasound):  Treatment a. Non pharmacological 1. Diet (decrease Na intake – total fat restriction) 2. Weight (obesity is high risk factor) 3. Exercise 4. Smoking b. Pharmacological  oxygen supply  oxygen demand 1. Coronary vasodilators 1. -ve chrontropic drugs 2. -ve inotropic agents 3.  Heart work 1. Nitrate 2. β Blockers 3. CCBs 1) Organic Nitrate  Members Nitroglycerin Isosorbide Isosorbide Glyceryl trinitrate di-nitrate mono-nitrate 1. Short acting 1. Short acting ▪ Sublingual ▪ Sublingual ▪ Inhalation ▪ Onset: 1-5 min Amyl nitrite ▪ Duration: 30-60 min 2. Long acting 2. Intermediate 1. Long acting ▪ transdermal patches ▪ Oral ▪ Oral  Members Nitroglycerin Isosorbide Isosorbide Glyceryl trinitrate di-nitrate mono-nitrate 1. Short acting 1. Short acting 1. Long acting 2. Long acting 2. Intermediate  Mechanism of action Nitrates NO Nitrothiole MALDH2 SH- enzyme endothelial cell Guanylyl cyclase cGMP GTP MLC phosphatase Dephosphorylating of Myosin Relaxation  Pharmacological effect 1. CVS A. Blood vessel Veins Coronary arteries Arteries Low doses increase doses High doses Venodilatation Vasodilatation of arteriodilatation →  preload → main (large) →  afterload  cardiac work coronary arteries →  PR and demand →  coronary VD of arteries in blood flow face and neck → flushing of the B. Heart and BP face ▪ In high doses induce VD of meningeal hypotension and arteries → throbbing reflexed tachycardia headache 2. Smooth muscle ❑ Relaxation of smooth muscle (bronchial, GIT, Uterine and biliary) 3. Blood ❑ It is very rare and occurs only in high doses ❑ High dose  NO free radicle which oxidized Hb to MetHb so RBCs not able to carry O2 enough ❑ Nitrates are CI in Favism  Therapeutic uses 1- Angina Pectoris ▪ Used for treatment of all types of angina both for: a. relieving the acute attack b. Prophylaxis ▪ The mechanism is due to: Veno-dilatation →  preload →  Cardiac work →  O2 demand 2- Myocardial infarction (MI) ▪ to decrease the area of Myocardial damage 3- Acute heart failure Veno-dilatation →  preload →  Cardiac work  Adverse effects 1- Hypotension 2- Syncope 3- Reflexed tachycardia 4- Flushing of the face 5- throbbing headache 6- Nitrate Tolerance ▪  response to nitrates with continuous administration which cannot be corrected by increasing dose there are 2 theories with continuous admin.  free radicle → oxidation depletion of SH group and inhibition of MALDH2 responsible for enzyme responsible for transformation of NO to transformation of nitrate nitrothiole which cause VD into vasoactive NO through increasing CGMP ❑ Prevention of this case (Drug holiday – Nitrate free interval) Make a daily nitrate free interval (10-12h) to give chance for enzymes to be regenerated. During this period, give another antianginal drug e.g. beta blocker or CCBs. If patch put the patch 12 hour and remove the other 12 h  Β-Blockers ▪ They are considered first line in long term treatment of classic angina ▪ Mechanism of B blocker in angina: 1.  contractility and HR →  myocardial work →  O2 demand 2.  diastole filling time to increase O2 supply 3. Cause redistribution of blood from normal to ischemic regions where they prevent coronary blood steal 4. They produce metabolic switch from myocardial fat utilization to carbohydrate utilization (improve myocardium metabolism) ▪ All β-blockers are effective in angina except ISA β- blocker e.g. pindolol ▪ β- blockers are contraindicated in Prinzemetal angina?????? Coronary arteries contain both α1 (VC) and β2 (VD) receptors. Because of unopposed α-adrenoceptor mediated more coronary vasoconstriction. ▪ Combination of B blockers with nitrate has several effects??? a- overcome nitrate tolerance b- increase nitrate efficacy and decreased adverse effect tachycardia c- b blocker increased diastole filling time that allow enhancing increase blood supply  Calcium channel blockers CCBs ❑ They considered the first line treatment for Prinzmetal angina (long acting dihydropyridine) ❑ They are considered the second line treatment after β-blocker in chronic stable angina if B blocker cannot be used (verapamil) ❑ Amlodipine is the CCBs of best choice for symptomatic treatment of angina and/ or hypertension in patient with chronic heart failure 2) Newer anti-anginal drugs 1. pFox inhibitor (Metabolic modifiers) : Trimetazidine They don't affect HR, BP or coronary blood flow They partially inhibit fatty acid oxidation in the myocardium In normal: fatty acid uptake by myocardium cells and oxidized in mitochondria to produce high energy where heart utilize 65% of its energy from fats  In diseased: heart tissue → fatty acid not oxidized in mitochondria and accumulated in cytoplasm →  acidosis →  releasing of Ca from SR → induce necrosis and heart contraction pFox inhibitor  fatty acid influx →  acidosis →  Ca release → prevent necrosis  2. K+ Channel opener Nicorandil ❑Is a new anti-anginal drug with 2 proposed mechanisms of action 1. it opens ATP-dependent K channel in the vascular wall leading to VD of peripheral and coronary arteries 2. Nitrate like activity: it has nitrate component and  cGMP ❑ Like nitrate should not be used with sildenafil  3. Late Na+ Channel blocker: Ranolazin ▪ It  intracellular Ca+2 indirectly by reducing Na+ ion influx that facilitate Ca+2 entry into myocardial cell ▪ The reduction of intracellular Na+ and Ca+2 →  cardiac contractility and work  4. Funny Channel blocker: Ivabradine ▪ The main action of this drug is to induce bradycardia through blocking funny channel present in SA node responsible for heart stimulation ▪ If β-blocker not sufficient to induce bradycardia they may be combined with Ivabradine  5. Platelet inhibiting agents ❑ Aspirin in low doses (75-100 mg/day orally) reduces the incidence of acute myocardial infarction in patients with coronary artery disease. ❑ Clopidogrel  6. Statins ❑ Statins are drugs used to lower blood cholesterol. Acute Myocardial Infarction ▪ It is commonly known as a heart attack ,occurs due to stopping of blood flow to a part of the heart, causing damage to the heart muscle and cell death ▪ Characterized by sever chest pain that sustained > 15 min and not removed by rest or medication ▪ Diagnosed by ECG or biochemical parameters (troponin - CK-MB) ▪ Troponin I, this is a contractile protein that normally is not found in serum. It is released only when myonecrosis occurs ▪ All cases must be hospatilized in a specialized ICU Complication: 1. Lethal arrhythmias 2. Cardiogenic shock: This is characterized by a  cardiac output Pharmacologic therapy The aim: 1. To relieve the pain and anxiety 2. To limit infarct size 3. To prevent complication and reduce mortality rate.