Drugs for Angina Pectoris PDF

Drugs for Angina Pectoris Prepared By: Princess M. Rabago, RPh Instructor I  In your own knowledge, what are the definition of the following terms? a. Heart failure WARM-UP b. Heart attack...

Drugs for Angina Pectoris Prepared By: Princess M. Rabago, RPh Instructor I  In your own knowledge, what are the definition of the following terms? a. Heart failure WARM-UP b. Heart attack ACTIVITY c. Angina pectoris d. Ischemia LEARNING INPUTS: Ischemia is a condition in which the blood flow (and thus oxygen) is restricted or reduced in a part of the body Cardiac Ischemia is the name for decreased blood flow and oxygen to the heart muscle Angina Pectoris - a characteristic chest pain (severe & crushing) caused by coronary blood flow that is insufficient to meet the oxygen demands of the myocardium - can accompany or be a precursor of a heart attack Causes: May also occur if the coronary arteries are: ✓ Injured prevalent during ✓ Inflamed arteries can narrow due to plaque physical activity due ✓ Infected deposits to heart’s increased demand for oxygen Higher risk of developing Angina Pectoris Types of Angina Pectoris Stable Angina - most prevalent type of angina, and is usually predictable as it exhibits a definite pattern - occurs because the arteries have accumulated deposits narrowing the pathway for blood to move through Types of Angina Pectoris Unstable Angina - Characterized by a sudden pain that doesn’t go away on its own or respond to rest or medication - This type is caused by a blood clot that blocks the blood vessel and it will cause a heart attack if the blockage isn’t removed - does not follow a regular predictable pattern like stable angina Types of Angina Pectoris Prinzmetal (Variant) Angina - caused by vasospasm, a narrowing of the coronary arteries caused by contraction of the smooth muscle tissue in the vessel walls rather than directly by atherosclerosis  Definition of Terms Oxygen demand is how much oxygen is needed Oxygen supply is how much oxygen is available for use Oxygen consumption is the amount of oxygen the body or a cell actually uses for energy production and metabolic processes Preload refers to the initial stretching of the heart muscle fibers at the end of diastole (before contraction) Afterload is the resistance the heart must overcome to eject blood during systole (contraction)  Definition of Terms Ejection time is the period during which the heart's ventricles contract and pump blood out into the arteries (specifically, into the aorta from the left ventricle and into the pulmonary artery from the right ventricle) Vascular tone refers to the degree of contraction or tension in the blood vessel walls particularly in the smooth muscle layer It determines how constricted or dilated the blood vessels are  Determinants of Myocardial Oxygen Consumption 1. Wall Stress (Tension) Refers to the force that stretches the myocardial fibers It is related to the pressure inside the ventricles and the size of the heart Law of Laplace: wall stress is proportional to the product of intraventricular pressure and ventricular radius, and inversely proportional to wall thickness Influence on Oxygen Consumption: Increase in ventricular pressure (dilation of the heart), increased radius, will increase wall stress and subsequently oxygen  Determinants of Myocardial Oxygen Consumption 2. Heart Rate refers to the number of heartbeats per minute Influence on Oxygen Consumption: Faster heart rates increase oxygen consumption due to more frequent contractions 3. Contractility Refers to the strength or force of the heart’s contraction Influence on Oxygen Consumption: Stronger contractions elevate oxygen demand due to increased myocardial effort  Determinants of Coronary Blood Flow 1. Coronary Perfusion Pressure The difference between the aortic pressure and the pressure in the coronary vessels Higher perfusion pressure = increased blood flow 2. Vascular Resistance Determined by the diameter of coronary arteries and vascular tone o Vasodilation (wider vessels) = more blood flow o Vasoconstriction (narrower vessels) = less blood flow 3. Heart Rate Blood flow to the coronary arteries primarily occurs during diastole (relaxation phase) Increased heart rate reduces diastolic time, decreasing blood flow  Determinants of Myocardial Oxygen Supply 1. Coronary Blood Flow More blood flow means more oxygen supply to the heart muscle 2. Oxygen Content in Blood Depends on hemoglobin levels and oxygen saturation Higher oxygen content = better oxygen supply 3. Diastolic Time Longer diastolic periods allow more time for coronary blood flow and oxygen delivery Faster heart rates reduce oxygen supply by shortening diastolic time  Determinants of Vascular Tone 1. Arteriolar tone controls arterial blood pressure and affects the heart’s workload during systole (contraction) 2. Venous tone controls how much blood returns to the heart, influencing diastolic wall stress (heart's relaxation) Key Point: When vessels constrict, vascular tone increases, leading to higher blood pressure When vessels dilate, vascular tone decreases, lowering blood pressure  Mechanisms by which Drugs may Relax Vascular Smooth Muscle 1. Increasing cGMP: cGMP facilitates the dephosphorylation of myosin light chains, preventing the interaction of myosin with actin. Nitric oxide is an effective activator of soluble guanylyl cyclase and acts mainly through this mechanism. 2. Decreasing intracellular Ca2+: Calcium channel blockers predictably cause vasodilation because they reduce intracellular Ca 2+ , a major modulator of the activation of myosin light chain kinase. 3. Stabilizing or preventing depolarization of the vascular smooth muscle cell membrane: The membrane potential of excitable cells is stabilized near the resting potential by increasing potassium permeability. 4. Increasing cAMP in vascular smooth muscle cells: An increase in cAMP increases the rate of inactivation of myosin light chain kinase, the enzyme responsible for triggering the interaction of actin with myosin in these cells. Figure 1. Mechanism of action of nitrates, nitrites, and other substances that increase the concentration of nitric oxide (NO) in vascular smooth muscle cells. Steps leading to relaxation are shown with blue arrows. MLCK: activated myosin light-chain kinase GC: activated guanylyl cyclase PDE: phosphodiesterase eNOS: endothelial nitric oxide synthase  3 Major Classes of Drugs Used to Treat Angina: A. Nitrites and Nitrates Vasodilators Main effect: To produce a general vasodilation of veins and arteries which reduces the work of oxygen consumption of the heart. MOA: relax vascular smooth muscle by NO3, which is chemically released from the drug, binding to and stimulating the nitrate receptor located in vascular smooth muscle 1. Nitroglycerin - the most widely used antianginal drug - can be administered in several different forms a. Sublingual Nitroglycerin (Nitrostat) - DOC in the treatment of acute angina attacks - Effects usually occur within 1-3 minutes with peak effect occurring at about 5 minutes b. Nitroglycerin Ointment 2% - applied topically to an area of the chest or abdomen - Absorption occurs through the skin with an onset of action of 15 minutes and a duration of 4-8 hour c. Nitroglycerin Extended-Release (Nitrogard) Capsules = 2.6 mg, 6.5 mg, 9.0 mg  d. Transdermal Nitroglycerin - Nitroglycerin is contained within an adhesive patch which is applied on the torso 2. Nitric Acid Nitrite (Amyl Nitrite) - used by inhalation to relieve the pain of angina attacks Isosorbide Mononitrate (Ismo) = 20 mg Isosorbide Dinitrate (Isordil) = 5mg, 10 mg Adverse Effects: ❖ Cutaneous flushing, dizziness, headache, weakness and fainting ❖ Blood pressure usually decreases ❖ Tolerance to nitrites and nitrates ❖ Contraindicated in patients with glaucoma ❖ Higher Doses – nitrates and nitrites oxidize hemoglobin to methemoglobin B. β-adrenergic Blockers Antagonize or reverse the effects of sympathetic activation caused by exercise and other physical or mental exertions Therapeutic action in the treatment of angina lies in the ability of these drugs to decrease heart rate and force of contraction Indicated for the long term management of angina pectoris Propranolol (Inderal) - β-blocker most widely used in the treatment of angina usual dose: 10-90mg PO,BID,TID or QID - can be used in combination with nitrates in patient who require more than one drug to control angina C. Calcium Antagonists interfere with the movement of Ca+ through cell membranes dilate larger coronary arteries which increases coronary blood flow 1. Verapamil (Calan, Isoptin) - widely used to treat supraventricular arrhythmias due its vasodilating properties allow it to be considered for the treatment of angina - dose: 80-120 mg PO, TID or QID 2. Diltiazem (Cordizem) - potent dilator of the coronary arteries and usually produces a modest fall in B.P. causes less effects on the heart than verapamil, - dose: 30-90mg TID or QID 3. Nifedipine (Procardia,Calcibloc) - very potent vasodilator and usually lowers B.P. - has minor effects on heart rate and myocardial contraction - dose: 10-30 mg PO,TID or QID Adverse Effects: ❖ headache ❖ facial flushing ❖ dizziness ❖ hypotension ❖ minor GI disturbance Summary of Drugs Used in the Treatment of Angina Summary of Drugs Used in the Treatment of Angina Get in Touch With Us Send us a message or visit us City of Batac, Ilocos Norte, Philippines (63) 77-600-0459 [email protected] Follow us for updates facebook.com/MMSUofficial www.mmsu.edu.ph