ANTIANGINAL DRUGS Syed Tajamul BHCNMT ANGINA PECTORIS • Chest pain or discomfort that occurs when the heart muscle doesn't receive enough oxygen-rich blood results from narrowed or blocked coronary arteries, often due to atherosclerosis/ (CAD) or Ischemic Heart Diseases and is characterized by: • squeezing, tightness, or pressure-like pain in the chest, although it can also radiate to the arms, neck, jaw, shoulder, or back. • Pathophysiology: • Heart utilizes approx about 75% of available oxygen— heart muscles favors energy from from fatty acids that requires more O2 for per unit ATP— this demand of oxygen increases during any heavy work load of heart muscles and decreases in any compromised vasculature of coronary arteries— imbalance of O2 delivery and O2 demand to the heart muscles — leads to ischemia of heart muscles—triggers pressure, squeezing or burning sensations of heart muscles & is perceived as chest pain known as Angina Pectoris. • Treatment: supplemental Oxygen, pharmacological and Surgery. Types of Angina Pectoris • Classic Angina: also Known as Stable Angina/ Atherosclerotic angina or Angina-of-Effort —occurs during physical exertion, stress or other situations that increase hearts workload. • Unstable Angina: acute coronary syndrome—present at rest—can occur after increased episodes of unstable angina— Plaque and Clots. • Variant Angina or Prinzmetal’s Angina: silent or ambulatory ischemia followed by temporary spasm or narrowing of coronary arteries • Others: Noctural Angina, micro vascular Angina and Mixed Angina Agents Used in Treatment of Angina • 1. Nitrates/ Nitric Acid and Nitrites ( Vasodilators) • 2. Calcium Channel Blockers • 3. Beta Blockers 1. Vasodilators- Nitric acid and Nitrous Acid Mechanism Of Action • NTG is denitrated by Glutathione S-transferase— nitric oxide in endothelial smooth muscles—activation of guanylyl cyclase— increase in cGMP— dephosphorylation of Myocin light chains— causes smooth muscle relaxation— increases blood flow Mechanism Of Action Clinical Uses and Adverse Effects of NTGs
Clinical Uses Adverse Effects
• Angina : —relaxing of epicardial • Vasodilation: Orthostatic coronary Arteries hypotension, tachycardia, throbbing • Smooth Muscles: Relaxation— headach. Bronchi, GI tract & GU system • Continuous exposure in high levels of • Vascular Smooth Muscles: nitrates I chemical industry can Vasodilation of large Arteries > Veins produce Monday disease/Syndrome— > arterioles > pre-capillary sphincters tachycardia, headach, and dizziness • Platelets: Decrease platelet • Tolerance: tolerance to NTGs can aggregation develop soon after few hours of continuous exposure. • Other: topical use for Erectile • Carcinogenicity : Hypothetical Dysfunction; Cyanide Poisoning Other Vasodilators PDE inhibitors pFOX inhibitors & Bradycardia Drugs • Sildenafil (viagra) 50-100mg PO • Ronalazine 500 mg PO • Tadalafil 25-125mg Po • MAO: inhibit fatty acid oxidation • Alprotadil 1.25-60mcg Intracavernous pathways in myocardial cells— decreases oxygen demand for production ATPs • Uses: were primarily used for treatment • Ivabradine: Selective Sodium channel of Angina and Hypertension but evolved blocker – prevents action potential across into a revolutionary for the treatment of membranes –bradycardia Erectile dysfunction. • MaO: increase cGMP by inhibiting its • MOA: inhibit hyperpolarization activated breakdown by phosphodiesterase PDE Na channels in SA node • Side Effects: gastritis, Tachycardia, Hot flushes and Headache CALCIUM CHANNEL BLOCKERS • Calcium Channels are integral membrane proteins that allows the selective passage of calcium ionsCa2+ across cell membranes. They are essential for various physiological processes including muscle contraction, nerve impulse signaling, Activation of glands and regulation of gene expression. • Types: • Voltage Gating Ca+ Channels: open and close in response to changes in membrane voltage • Ligand Gating Ca+ Channels: Dominant, open and close in response to the binding of specific Molecules (ligands). Has receptors å, ß, g, ∂, • L-type Calcium Channel Blockers are exclusively currently used in cardiovascular conditions, others are under study. Agents- Pharmacokinetics • Cardiac muscle is highly dependent on calcium influx into the excitable cell during each action potential for normal function.
Mechanism of • Calcium channel blockers decrease myocardial contractile force, which
reduces myocardial oxygen requirements. • Calcium channel- blocking agents also relieve and prevent focal coronary
action artery spasm in variant angina.
• Agents Verapamil > Dilitiazem > dihydropyridines decreases conduction in SA and AV nodal tissue, Nifedipine does not effect AV conduction can be safely used in AV conduction abnormalities. Clinical Uses and Adverse effects
Clinical Uses Adverse Effects
• Anti angina • Cardiac Depression— Bradycardia • Hypertension • AV Block, Cardiac Arrest and • Supraventricular Heart Failure tachyarrythmias • Flushing, nausea, Constipation • Cardiomyopathy, and peripheral edema • Migraine and • Raynaud’s disease Beta Adrenergic Blockers and others. • The beneficial effects of β-blocking agents are related to their hemodynamic effects— decreased heart rate, blood pressure, and contractility—which decrease myocardial oxygen requirements at rest and during exercise. • Beta blockers may also be valuable in treating silent or ambulatory ischemia because of no pain. • Anti-platelet agents— Aspirin and Clopidogrel to prevent Myocardial infarction and death • Lipid Lowering Agents— Statins— to reduce severity of the incidence of ischemia. • First line of therapy of (CAD) depends on : Modification of risk factors: Smoking, Alcohol, Diet, Obesity, Hyperlipidemia and Hypertension.
