for more lecture notes Antianginal Agents Dr.Shadi-Sarahroodi Pharm.D & PhD Qom University of Medical sciences Iran PUBLISHED BY

for more lecture notes Angina Pectoris (Chest Pain) When the supply of oxygen and nutrients in the blood is insufficient to meet the demands of the heart, the heart muscle aches. When the supply of oxygen and nutrients in the blood is insufficient to meet the demands of the heart, the heart muscle aches.

for more lecture notes Types of Angina Atherosclerotic angina (also called classic or effort angina) Atherosclerotic angina (also called classic or effort angina) Vasospastic angina (also called Prinzmetal’s or variant angina) Vasospastic angina (also called Prinzmetal’s or variant angina) Unstable angina (also called preinfarction or crescendo angina) Unstable angina (also called preinfarction or crescendo angina)

for more lecture notes Antianginal Agents: Therapeutic Objectives Increase blood flow to ischemic heart muscle Increase blood flow to ischemic heart muscleand/or Decrease myocardial oxygen demand Decrease myocardial oxygen demand

for more lecture notes Antianginal Agents Nitrates Nitrates Beta blockers Beta blockers Calcium channel blockers Calcium channel blockers

for more lecture notes intracellular conversion to nitrite ions, and then to nitric oxide intracellular conversion to nitrite ions, and then to nitric oxide activates guanylate cyclase and increases the cells' cyclic guanosine monophosphate (cGMP). activates guanylate cyclase and increases the cells' cyclic guanosine monophosphate (cGMP). Elevated cGMP ultimately leads to dephosphorylation of the myosin light chain, resulting in vascular smooth muscle relaxation Elevated cGMP ultimately leads to dephosphorylation of the myosin light chain, resulting in vascular smooth muscle relaxation

for more lecture notes Organic Nitrates Ferid Murad

for more lecture notes Antianginal Agents: Nitrates Available forms: SublingualOintments BuccalTransdermal patches Chewable tabletsInhalable sprays CapsulesIntravenous solutions

for more lecture notes BENEFITS OF NITRATES Reduce myocardial oxygen demand by dilating veins and increase venous pooling of blood Reduce myocardial oxygen demand by dilating veins and increase venous pooling of blood Increase systemic arteriolar vasodilation (intravenous forms only) Increase systemic arteriolar vasodilation (intravenous forms only) Directly dilate undiseased coronary arteries, helping restore blood flow deep within myocardial tissues Directly dilate undiseased coronary arteries, helping restore blood flow deep within myocardial tissues Decrease ventricular wall tension due to increased venous pooling Decrease ventricular wall tension due to increased venous pooling Improve exercise tolerance Improve exercise tolerance

for more lecture notes Antianginal Agents: Nitrates Nitroglycerin Prototypical nitrate Prototypical nitrate Large first-pass effect with PO forms Large first-pass effect with PO forms Used for symptomatic treatment of ischemic heart conditions (angina) Used for symptomatic treatment of ischemic heart conditions (angina) IV form used for BP control in perioperative hypertension, treatment of CHF, ischemic pain, and pulmonary edema associated with acute MI IV form used for BP control in perioperative hypertension, treatment of CHF, ischemic pain, and pulmonary edema associated with acute MI

for more lecture notes Antianginal Agents: Nitrates isosorbide dinitrate (Isordil, Sorbitrate, Dilatrate SR) isosorbide dinitrate (Isordil, Sorbitrate, Dilatrate SR) isosorbide mononitrate (Imdur, Monoket, ISMO) isosorbide mononitrate (Imdur, Monoket, ISMO) Used for: Acute relief of angina Acute relief of angina Prophylaxis in situations that may provoke angina Prophylaxis in situations that may provoke angina Long-term prophylaxis of angina Long-term prophylaxis of angina

for more lecture notes

Antianginal Agents: Nitrates Side Effects Headache Headache –Usually diminish in intensity and frequency with continued use Tachycardia, postural hypotension Tachycardia, postural hypotension Tolerance may develop Tolerance may develop facial flushing, and tachycardia facial flushing, and tachycardia

for more lecture notes Tolerance blood vessels become desensitized to vasodilation blood vessels become desensitized to vasodilation daily “nitrate-free interval” daily “nitrate-free interval” typically 10 to 12 hours, usually at night, because demand on the heart is decreased at that time typically 10 to 12 hours, usually at night, because demand on the heart is decreased at that time variant angina worsens early in the morning, perhaps due to circadian catecholamine surges variant angina worsens early in the morning, perhaps due to circadian catecholamine surges

for more lecture notes Antianginal Agents: Beta Blockers

for more lecture notes Antianginal Agents: Beta Blockers Mechanism of Action Decrease the HR, resulting in decreased myocardial oxygen demand and increased oxygen delivery to the heart Decrease the HR, resulting in decreased myocardial oxygen demand and increased oxygen delivery to the heart Decrease myocardial contractility, helping to conserve energy or decrease demand Decrease myocardial contractility, helping to conserve energy or decrease demand

for more lecture notes Propranolol is the prototype: not cardioselective Propranolol is the prototype: not cardioselective metoprolol or atenolol, are preferred metoprolol or atenolol, are preferred

for more lecture notes All β-blockers are nonselective at high doses and can inhibit β 2 receptors. All β-blockers are nonselective at high doses and can inhibit β 2 receptors. Important in asthmatics. Important in asthmatics.

for more lecture notes contraindication Asthma Asthma Diabetes Diabetes severe bradycardia severe bradycardia peripheral vascular disease peripheral vascular disease chronic obstructive pulmonary disease. chronic obstructive pulmonary disease.

for more lecture notes Do not discontinue β-blocker therapy abruptly. Do not discontinue β-blocker therapy abruptly. The dose should be gradually tapered off over 5 to 10 days to avoid rebound angina or hypertension.] The dose should be gradually tapered off over 5 to 10 days to avoid rebound angina or hypertension.]

for more lecture notes Antianginal Agents: Calcium Channel Blockers

for more lecture notes Mechanism of Action Calcium influx is increased in ischemia because of the membrane depolarization that hypoxia produces Calcium influx is increased in ischemia because of the membrane depolarization that hypoxia produces In turn, this promotes the activity of several adenosine triphosphate– consuming enzymes, thereby depleting energy stores and worsening the ischemia In turn, this promotes the activity of several adenosine triphosphate– consuming enzymes, thereby depleting energy stores and worsening the ischemia

for more lecture notes Antianginal Agents: Calcium Channel Blockers Cause peripheral arterial vasodilation Cause peripheral arterial vasodilation Reduce myocardial contractility (negative inotropic action) Reduce myocardial contractility (negative inotropic action) Result: decreased myocardial oxygen demand Result: decreased myocardial oxygen demand

for more lecture notes Nifedipine a dihydropyridine derivative a dihydropyridine derivative arteriolar vasodilator arteriolar vasodilator Oral Oral Usually: extended-release tablets. Usually: extended-release tablets. Hepatic metabolism Hepatic metabolism Eliminate in both urine and the feces Eliminate in both urine and the feces

for more lecture notes Side Effects Flushing Flushing Headache Headache Hypotension Hypotension peripheral edema as peripheral edema as all calcium-channel blockers are with constipation is a problem all calcium-channel blockers are with constipation is a problem

for more lecture notes Verapamil Slows AV conduction Slows AV conduction decreases heart rate, contractility, blood pressure, and oxygen demand decreases heart rate, contractility, blood pressure, and oxygen demand contraindicated in patients with preexisting depressed cardiac function or AV conduction abnormalities contraindicated in patients with preexisting depressed cardiac function or AV conduction abnormalities

for more lecture notes Diltiazem slow AV conduction slow AV conduction decrease the rate of firing of the sinus node pacemaker decrease the rate of firing of the sinus node pacemaker metabolized by the liver metabolized by the liver

for more lecture notes PUBLISHED BY PUBLISHED BY