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Queen's University
Pharmacology and Toxicology
PHAR 100
Hisham Elbatarny

Coronary Artery Disease Coronary Artery Disease (CAD) • narrowing or blocking of coronary arteries: ◦ ↓ blood flow → ↓ O2 supply to the heart Risk Factors of CAD • non-controllable: age, male sex, family history • controllable ◦ life style: obesity, physical inactivity, smoking ◦ diseases: ▪ hypertension, ▪ atherosclerosis • most common: accumulation of lipid plaques on inside of arteries resulting in increasingly narrow lumen until totally blocked • → heart ischemia: decreased blood supply, die – muscles of heart can't regenerate ▪ diabetes mellitus: enhances condition of CAD Manifestations of CAD • asymptomatic • angina pectoris: chest pain due to myocardial ischemia • myocardial infarction: heart attack (= acute myocardial infarction) • sudden death Angina Pectoris • sudden onset of chest pain due to myocardial ischemia (↓ blood supply to the heart) • behind lower two thirds of sternum and extends to include left side of upper body ◦ lower jaw, down inside of arm, all the way to hand • pain only stays for a few minutes (more than seconds less than hours) ◦ if longer: myocardial infarction (hours) • clinical syndome Factors Affecting Anginal Pain • precipitating factors: ◦ exertion, stress, ◦ heavy meals: more blood goes to stomach and heart is compromised ◦ cold weather: blood flows to keep warm and less blood to heart • relieving factors: rest, nitrates Treatment of Angina • rest: crucial, main relieving fact, complete physical and mental rest • antianginal drugs Antianginal Drugs • organic nitrates • β blockers: also hypertention • calcium channel blockers: also hypertension Organic Nitrates Mechanism of Action • nitrates nitric oxide (NO) [active ingredient] which leads to • relaxation of smooth muscles of blood vessels → ◦ vasodilatation: ▪ venous (veins- main vessels dilated) ▪ coronary ▪ arteriolar Venous Dilatation decreases (sequence of events of nitrates on veins): • venous return (preload) • cardiac output = heart rate x stroke volume (depends on amount of blood going back to heart) • myocardial work • myocardial O demand: decreased ischemia 2 • heart size Coronary Dilatation • ↑ blood supply to the heart: improved perfusion → • ↑ O supply to ischemic myocardium 2 Arteriolar Dilatation • ↓ peripheral resistance (afterload): ↓ blood pressure Side Effects (not selective, dilate everything, unecessary • dilation of meningeal blood vessels: headache (throbbing) • flushing • hypotension (lead to heart want to pump more) • tachycardia (lead to more ischemia) • dizziness • tolerance Tolerance • due to continuous exposure • prevention: nitrate-free periods of at least eight hours (overnight) • Monday disease! ◦ condition that happens to some workers who work in factories that work w/ organic nitrates ◦ during period to exposure, develop tolerance to nitrates until weekend ◦ then coming back on Monday, have no tolerance → develop headaches, etc. b/c tolerance gone Routes of Administration Rapid onset / short duration: need quick response • sublingual tablets: very common • oral spray • intravenous: very aggressive, need to monitor BP at all times, only in emergency room Slow onset / long duration: • oral tablets: swallow
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