ischemic heart disease revised lmk

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.



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



Process of atherosclerosis



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



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



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



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



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



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



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



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



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



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.



Pharmacological Therapyy Therapy is aimed in restoring balance between

myocardial oxygen supply and demand

yUseful Agents: nitrates, beta-blockers and calciumchannel blockers



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



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



Mechanism of action of Nitrates



Time to peak effect and duration of action for some common

organic nitrate preparations.



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



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



Beta blocking agents

From Eugene Braunwald , 5 th Edi, Heart Disease, A Textbook of Cardiovascular Medicine.



Beta -1y Block myocardial receptors with less effect on

bronchial and vascular smooth muscle- patients with

asthma, intermittent claudication



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



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



Contraindicationsy Symptomatic CHF, history of bronchospasm,

bradycardia or AV block, peripheral vascular disease

with s/s of claudication



Side Effectsy Bronchospasm (R AD), CHF, depression, sexual

dysfunction, AV block, exacerbation of claudication,

potential masking of hypoglycemia in IDDM patients



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



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



Pharmacological Effect of CCB



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



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



Contraindications forCCBs include

A. Supraventricular tachycardias

B. Hypotension

C. AV heart block

D. HypertensionE. Congestive heart failure



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.



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



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



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



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



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



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



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



Treatment of angina in patients with concomitant diseases.COPD = chronic obstructive pulmonary disease



THANK YOU!

ischemic heart disease revised lmk

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