Unit 1.B Cardiovascular, Renal, and Hematologic Pharmacology - Angina Pectoris PDF

PHARMACOLOGY II UNIT 1. Cardiovascular, Renal, and Hematologic Pharmacology Prepared by Romuelle B. Barbado, RPh Faculty, UCU College of Pharmacy Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is...

PHARMACOLOGY II UNIT 1. Cardiovascular, Renal, and Hematologic Pharmacology Prepared by Romuelle B. Barbado, RPh Faculty, UCU College of Pharmacy Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. QUIZ (30 pts) Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. OUTLINE A. Antihypertensive agents I. Sympathoplegics II. Diuretics III. Calcium Channel Blockers IV. Angiotensin Antagonists V. Vasodilators B. Drugs for Angina Pectoris and Vasodilators I. Nitrates II. Calcium Channel blockers III. Beta-blockers IV. Miscellaneous Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. DRUGS FOR ANGINA PECTORIS AND VASODILATORS Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. ANGINA PECTORIS “Angere” - strangle; “Pectus” - chest The term angina pectoris is applied to varying forms of transient chest discomfort that are attributable to insufficient myocardial oxygen It is characterized by discomfort in the chest, jaw, shoulder, back, and arms which is usually aggravated by exertion or stress and relieved by nitroglycerin It is caused by low myocardial oxygen supply due to ischemia, and high oxygen demand Ischemia is term used to describe a condition when certain parts of the body does not receive sufficient oxygen from the blood due to lack of blood flow caused by atherosclerotic lesions Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. ANGINA PECTORIS Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. ANGINA PECTORIS How does ischemia leads to myocardial infarction? Myocardial infarction is a condition in which a part of heart is completely devoid of oxygen due to blockage, causing myocardial cell death. MI can be diagnosed with the gold standard Troponin I Complete blockade of coronary arteries may due to thrombus or embolus. Thrombus - blood clot attached in the blood vessel Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. ANGINA PECTORIS Myocardial Infarction Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. ANGINA PECTORIS Etiology of Ischemic Heart Disease Hyperlipidemia - too much LDL can cause atherosclerosis Hypertension - prolonged HTN can cause myocardial hypertrophy causing an increased in oxygen demand Smoking - can damage the arteries which promotes cholesterol aggregation leading to atherosclerosis Obesity Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. ANGINA PECTORIS There different types of angina: Typical angina - caused by atherosclerosis, thrombus or embolus Stable Angina Unstable Angina Atypical angina - caused by coronary spasm Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. ANGINA PECTORIS Typical angina Stable Angina AKA Exertional angina  it can be precipitated by stress, cold temperature, exercise or heavy meals This is a predictable type of angina because the precipitants are known This is the most common type of angina This is due to a plaque in the coronary artery ~ too much oxygen demand for too long can precipitate myocardial infarction It can be managed by rest and nitroglycerin (a vasodilator) + lipid- lowering agents Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. ANGINA PECTORIS Typical angina Unstable Angina AKA Crescendo angina  it is characterized by increasing type of pain This is caused by a travelling thrombus OR emboli which might clog the coronary arteries any time hence unstable angina is considered a medical emergency due to high risk of myocardial infarction This is considered as rest angina, because symptoms can be felt even without exertion This it more severe than stable angina This is managed using anti-thrombotic agents, lipid-lowering agents, and fibrinolytics Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. ANGINA PECTORIS Atypical Angina AKA Variant angina or Prinzmetal angina This is caused by vasospasm It can happen at rest or sleep It is a rare type of angina This is managed using calcium channel blockers The use of Beta-blockers in this type of angina is contraindicated due to vasoconstriction of currently not understood mechanism Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. ANGINA PECTORIS The oxygen supply is low, and the demand of oxygen is high. Therapeutic goals: Treat the etiological conditions Increase the supply of oxygen circulating in the coronary arteries by: Vasodilation using nitrates and calcium channel blockers Increase the flow and duration of stay of blood in the coronary arteries by using nitrates, calcium channel blockers, and beta blockers Decrease the plaque by using lipid lowering agents, and prevent or remove the thrombus and embolus by using anti-thrombotic agents and fibrinolytic agents Decrease the demand of oxygen by: Decreasing the heart rate and force of contraction by using beta blockers and non-DHP calcium channel blockers Decrease the myocardial wall tension: ↓ preload by using nitrates & ↓ afterload by using DHP CCBs Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. ANGINA PECTORIS Preload is the initial Afterload is the force stretching of the or load against which cardiac myocytes the heart has to (muscle cells) prior contract to eject the to contraction. It is blood. related to ventricular filling. An increase in either of the two will result to an increased oxygen demand. Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. VASODILATORS Nitrates & Nitrites Mechanism of Action: The primary value of nitrates is venous dilation, which reduces left ventricular volume (preload) and myocardial wall tension, decreasing oxygen requirements (demand). *Nitrates undergo reduction to form nitrites and further reduced to nitric oxide. Nitric oxide → (+) guanylyl cyclase → ↑cGMP → Vasodilation Agents include: Nitroglycerin (Glyceryl trinitrate) ~ available as PO tab, SL, IV, Topical, TDDS Isosorbide dinitrate ~ available as SL, MR PO tab Erythritol tetranitrate ~ available as oral and sublingual Pentaerythritol tetranitrate Amyl nitrite ~ the only inhalational nitrite used for angina, and used for cyanide toxicity Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. VASODILATORS Nitrates & Nitrites Side effects: Reflex tachycardia and flushing Throbbing headache (transient) Monday disease ~ development of tolerance throughout therapy, it presents tachycardia, dizziness, and headache during re-exposure after a drug-free interval Indication: Euphoria and increased libido (Amyl nitrite) Primarily used in treating stable angina Used in acute angina attacks as sublingual, transmucosal (spray or buccal tablets) or IV Used as prophylaxis in angina attacks via oral or buccal tablets or patches Intravenous nitroglycerin is used in the immediate treatment of unstable angina and is used for long-term therapeutic relief. Nitrates used in combination with B-adrenergic blockers have been shown to be more effective than nitrates or B-adrenergic blockers used alone. Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. VASODILATORS Nitrates & Nitrites Drug Interaction: Nitrates + Sildenafil (Viagra®) → Excessive vasodilation + Reflex tachycardia → DEATH Sildenafil is a PDE5 inhibitor → ↑cGMP → Vasodilation Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. VASODILATORS Calcium Channel Blockers Mechanism of Action: DHPs relax the arteries leading to decreased afterload These are particularly useful and DOC for Prinzmetal angina Non-DHPs reduce the heart rate and heart contraction hence lowering the demand of oxygen in the heart Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. BETA-BLOCKERS Beta Blockers Propranolol,Metoprolol, Atenolol, Nadolol, Timolol, Acebutolol, Betaxolol, Bisoprolol, Esmolol, Labetalol B-blockers reduce oxygen demand, both at rest and during exertion, by decreasing the heart rate and myocardial contractility, which also decreases arterial blood pressure. Useful in the treatment of typical angina pectoris by prevention of exercise- induced attacks and as management of reflex tachycardia Useful in acute myocardial infarction (heart attack) by decreasing its recurrence and improving the survival rate Contraindicated in Variant or Prinzmetal Angina due to induction of coronary spasm and on patients with diabetes under strict insulin therapy because they can mask signs of hypoglycemia such as tachycardia Sudden cessation of B-blocker therapy may trigger a withdrawal syndrome that can exacerbate anginal attacks (especially in patients with IHD) or cause MI. Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. MISCELLANEOUS AGENTS Ivabradine Mechanism of action: It selectively inhibitis the "funny" channel pacemaker current (If) in the sinoatrial node in a dose-dependent fashion, resulting in a lower heart rate, increasing the perfusion time in coronary arteries thereby resulting in the lowering of oxygen demand and increasing oxygen delivery. Indications: Useful in chronic angina and heart failure Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. MISCELLANEOUS AGENTS Ranolazine Mechanism of action: Blockade of a late sodium current that facilitates calcium entry via the sodium-calcium exchanger  Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. MISCELLANEOUS AGENTS ISCHE MIA Ranolazi ↑Ca2+ in ↑Myocardial stress ne Late ↑Oxygen demand myocardial due to mechanical INa dysfunction and cells current arrhythmia ↑Na+ in Activation of myocardial Ca2+/Na+ cells exchanger Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. MISCELLANEOUS AGENTS Trimetazidine Mechanism of action: Inhibits the enzyme ketoacyl coA thiolase, an enzyme involved in the oxidation of fatty acids in the production of energy *The oxidation of fatty acids uses more O2 compared to the oxidation of glucose during the production of energy Prepared by Romuelle B. Barbado, RPh - for UCU-COP students use only. Reproduction without permission is strictly prohibited. MISCELLANEOUS AGENTS Antiplatelet Agents Aspirin Ticlopidine Clopidogrel