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8/6/2019 Ischemic Heart Disease Revised LMK
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Dr Lateef M Khan
Assoc Prof, Pharmacology Dept, College Of Medicine,King Abdul Aziz University, Jeddah.
8/6/2019 Ischemic Heart Disease Revised LMK
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Myocardial Ischemiay R esults when there isan imbalancebetween myocardialoxygen supply anddemand
y Most occurs becauseof atheroscleroticplaque with in one ormore coronary arteries
y
Limits normal rise incoronary blood flowin response toincrease inmyocardial oxygendemand
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Process of atherosclerosis
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Oxygen Carrying Capacityy The oxygen carrying capacity relates to the content of
hemoglobin and systemic oxygenation
y
When atherosclerotic disease is present, the artery lumen is narrowed and vasoconstriction is impaired
y Coronary blood flow cannot increase in the face of increased demands and ischemia may result
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Anginay When ischemia results it is frequently accompanied by
chest discomfort: Angina Pectoris
y In the majority of patients with angina, developmentof myocardial ischemia results from a combination of fixed and vasospastic stenosis
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Chronic Stable Anginay May develop sudden increase in frequency and
duration of ischemic episodes occurring at lower
workloads than previously or even at resty Known as unstable angina: up to 70% patients sustain
MI over the ensuing 3 months
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Angina: conty Patients with mild obstruction coronary lesions can
also experience unstable angina
y >90% of Acute MI result from an acute thrombusobstructing a coronary artery with resultant prolongedischemia and tissue necrosis
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Treatment of Anginay Treatment of Chronic Angina is directed at
minimizing myocardial oxygen demand and
increasing coronary flowy Where as in the acute syndromes of unstable angina or
MI primary therapy is also directed against plateletaggregation and thrombosis
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Epidemiologyy Modifiable Factors: hyperlipidemia- ^ LDL (<130
normal) or low HDL (>60 normal), Hypertension,cigarette smoking and diabetes, obesity, BMI of >30
y Non-Modifiable Factors: advanced age, male sex,family medical history: male <55 y/o, female <65 y/o
y Other: sedentary lifestyle and stressful emotionalstress
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Homocysteiney Concentration of amino acid homocysteine is
related to incidence of coronary, cerebral, and
peripheral vascular diseasey The risk of MI is 3x > in patients with high levels of
homocysteine compared with those with thelowest levels
y Supplement of diet with foliate and other B vitamins lower levels of homocysteine but notknown where therapy improves coronary risk
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Fibrinogeny Elevated level of plasma fibrinogen is independent risk
factor for CAD in males and females
yElevated levels of coagulation factor VII is risk factor
X50 fold if with smoking or HTN
y Careful HX taking: to evaluate s/s include: quality,location, radiation, precipitating factors, frequency
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Myocardial Infarctiony R egion of myocardial necrosis due to prolonged
cessation of blood supply
yR esults from acute thrombus at side of coronary atherosclerotic stenosis
y May be first clinical manifestation of ischemic heartdisease or history of Angina Pectoris
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Precipitantsy Exertion: walking, climbing stairs, vigorous work using
arms, sexual activity
y
Vasoconstriction: extremities, increased systemic vascular resistance, increased in myocardial walltension and oxygen requirements
y Myocardial Ischemia displays a circadian rhythmthreshold for Angina it is lower in morning hours.
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Pharmacological Therapyy Therapy is aimed in restoring balance between
myocardial oxygen supply and demand
yUseful Agents: nitrates, beta-blockers and calciumchannel blockers
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Nitratesy R educe myocardial oxygen demand
y R elax vascular smooth muscle
y R educes venous return to hearty Arteriolar dilators decrease resistance against- which
left ventricle contracts and reduces wall tension andoxygen demand
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Nitrates: conty Dilate coronary arteries with augmentation of
coronary blood flow
y
Side effects: generalized warmth, transient throbbingheadache, or lightheadedness, hypotension
y ER if no relief after X2 nitro's: unstable angina or MI
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Mechanism of action of Nitrates
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Time to peak effect and duration of action for some common
organic nitrate preparations.
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P
roblems withN
itratesy Drug tolerance
y Continued administration of drug will decreaseeffectiveness
y Prevented by allowing 8 10 hours nitrate free intervaleach day.
y Elderly/inactive patients: long acting nitrates forchronic antianginal therapy is recommended
y Physical active patients: additional drugs are required
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Beta Blockersy Prevent effort induced angina
y Decrease mortality after myocardial infarction
y R educe Myocardial oxygen demand by slowing heartrate, force of ventricular contraction and decreaseblood pressure
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Beta blocking agents
From Eugene Braunwald , 5 th Edi, Heart Disease, A Textbook of Cardiovascular Medicine.
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Beta -1y Block myocardial receptors with less effect on
bronchial and vascular smooth muscle- patients with
asthma, intermittent claudication
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Beta-
Agonist blockers
y With partial B-agonist activity:
y Intrinsic sympathomimetic activity (ISA) have milddirect stimulation of the beta receptor while blocking
receptor against circulating catecholaminesy Agents with ISA are less desirable in patients with
angina because higher heart rates during their use may exacerbate angina
y not reduce mortality after AMI
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Esmololy Short acting administered intravenously
y Can be used to test tolerability of beta-blockage
y Used for tachydysrhythmias and unstable anginay Primary prevention trials: beta blockers decrease
incidence of first MIs with hypertensive patients
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Contraindicationsy Symptomatic CHF, history of bronchospasm,
bradycardia or AV block, peripheral vascular disease
with s/s of claudication
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Side Effectsy Bronchospasm (R AD), CHF, depression, sexual
dysfunction, AV block, exacerbation of claudication,
potential masking of hypoglycemia in IDDM patients
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Beta-Blockers: Long Term effectsy Serum lipids: decrease of HDL cholesterol and
increased triglycerides
y
Effects do not occur with beta-blockers with B-agonistactivity or alpha-blocking properties
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Calcium Channel Blockersy Anti-anginal agents prevent angina
y Helpful: episodes of coronary vasospasm
y
Decreases myocardial oxygen requirements andincrease myocardial oxygen supply
y Potent arterial vasodilators: decrease systemic vascularresistance, blood pressure, left ventricular wall stress
with decrease myocardial oxygen consumption
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Pharmacological Effect of CCB
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Nifedipine and other dihydropyridine
calcium channel blockers
y Fall in blood pressure, trigger increase heart rate
yUndesirable effect associated with increased frequency of myocardial infarction and mortality
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Amlodipine and Felodipiney Are newer CCB
y Decrease (-) inotropic effects
y Amlodipine is tolerated in patients with advancedheart failure without causing increase mortality whenadded with ace inhibitor, diuretic, and digoxin
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Contraindications forCCBs include
A. Supraventricular tachycardias
B. Hypotension
C. AV heart block
D. HypertensionE. Congestive heart failure
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Clinical Pharmacologyy Drug Selection
y
Chronic Stable Angina: beta blocker and long actingnitrate or calcium channel blocker (not verapamil:bradycardia) or both.
y If contraindication to BB a CCB is recommended
(bronchospasm, IDDM, or claudication) any of CCBapproved for angina are appropriate.
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Drugs Selection Contdy Primary coronary vasospasm: no treatment with beta
blockers, it could increase coronary constriction
y Nitrates and CCB are preferred
y Concomitant hypertension: BB or CCB are useful intreatment
y Ischemic Heart Disease & Atrial Fibrillation: treatment with BB, verapamil or Cardizem can slow ventricular
rate
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Combination Therapyy If patients do not respond to initial antianginal
therapy a drug dosage increase is recommendedunless side effects occur.
y Combination therapy: successful use of lower dosagesof each agent while minimizing individual drug sideeffects
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Combination Therapy Include:
y Nitrate and beta blocker
y Nitrate and verapamil or cardizem for similar reasons
y Long acting dihydropyridine calcium channel blocker
and beta blockery A dihydropyridine and nitrate is often not tolerated
without concomitant beta blockade because of marked vasodilatation with resultant head ache and increased
heart rate
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Combinationsy Beta blockers should be combined only very cautiously
with verapamil or cardizem because of potential of excessive bradycardia or CHF in patients with left
ventricular dysfunction
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Unstable Anginay Therapy: reduce myocardial oxygen demand with
increase coronary flow
y
Antiplatelet and anticoagulant agentsy Aspirin and IV heparin: reduces incidence of
myocardial infarction and cardiac death in unstableangina
y
Oral Antiplatelet drug: ticlopidine: used for ASA intolerance individuals
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Unstable Angina: contdy Therapy: reduce myocardial oxygen demand with
increase coronary flow
y
Antiplatelet and anticoagulant agentsy Aspirin and IV heparin: reduces incidence of
myocardial infarction and cardiac death in unstableangina
y
Oral Antiplatelet drug: ticlopidine: used for ASA intolerance individuals
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Enoxapariny Enoxaparin: low molecular weight heparin: effective in
preventing ischemic events and death at 30 days and 1 year after administration than standardized IV heparin
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Treatment of angina in patients with concomitant diseases.COPD = chronic obstructive pulmonary disease
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THANK YOU!