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Cardiac Pharmacology Overview • Cardiovascular A & P Review • Gross Anatomy • Cellular Anatomy • Drugs that affect the cardiac system Cardiovascular Disease Cardiovascular Disease: • • Major cause of death and disability in the US 950,000 die each year, 40% before reaching a hospital • Number one reason: underlying coronary artery or Ischemic heart disease Number one presenting rhythm precipitating cardiac arrest: ventricular fibrillation • Risks: • Age • Heredity • Male • Cigarette smoker: • High lipids • Sedentary lifestyle • History • Pertinent past history of strokes, diabetes, hypertension Copy DC Dave Murphy Anatomy and Physiology Anatomy • • • • • Layers/myocardium Chambers Valves Veins Sinus Electrophysiology • • • • • • SA node AV Junction His-Purkinje Myocardial cells Electrical potential Autonomic Nervous system Myocardial Cells Action potential Depolarization Repolarization Critical electrolytes Sodium, potassium, calcium Excitability • Channels In cardiac muscle, sodium and calcium ions can enter the cell through two separate channel systems in the cell membrane: – Fast channels – Slow channels • Fast channels are sensitive to small changes in membrane potential – As the cell drifts toward threshold level (the point at which a cell depolarizes), fast sodium channels open – Results in a rush of sodium ions intracellularly and in very rapid depolarization • Slow channel selectively permeable to calcium and to a lesser extent to sodium Action Potential • The cardiac action potential can be divided into 5 phases (phases 0 through 4) • Phase 0 (rapid depolarization phase) • Phase 1 (early rapid depolarization phase) • Phase 2 (plateau phase) • Phase 3 (terminal phase of rapid repolarization) • Phase 4 Drugs That Affect the Cardiac System Overview • • • • • • • • • Cardiac Glycosides Sympathomimetics Anticholinergic Drugs Antidysrhytmics Electrolytes Thrombolytics Anticoagulants Antihypertensives Analgesics Digoxin • Cardiac Glycoside that has a positive inotropic effect on the heart • Given for: – CHF – Afib / A Flutter / PAT • Derived from the Foxglove (Digitalis) plant Digoxin • Inhibits sodium potassium ATPase (Sodium potassium exchange pump) • Results in increased quantity of Ca in sarcoplasmic reticulum • Increased Ca will result in greater contractile strength • Increased contractile strength results in increased glomerular pressure (Mild diuretic) Digitalis Toxicity • Neurological • Visual Disturbances – Flashing lights – Altered color vision • GI Disturbances • Cardiac Rhythm Disturbances • Hyperkalemia • K and Digoxin both bind to the same site on the sdoium/K pump Sympathomimetics • Adrenergic • Specific Meds: – – – – – Epi / Nor-epi Vasopressin Dopamine Isuprel Dobutamine Epinepherine (Adrenalin) • Catecholamine • Alpha, Beta 1, and Beta 2 Stimulation • Indications / Contraindications Precautions (EPI) • May be deactivated by alkaline solutions • Causes an increase in myocardial oxygen demand • IVP EPI 1:1,000 should not be administered to any person with a pulse Vasopressin • Naturally occurring antidiuretic hormone • Causes vasoconstriction • Increases circulation to brain (constriction) without Beta 1 effects • Dose: Replaces Epi 40 units IV – If no response in 10 to 20 minutes, consider returning to EPI Dopamine (Inatropin) • Pre-cursor to EPI & NorEPI with effects varying upon dosage • Indications: – Hypotensive / shock like patients in the absence of Hypovolemia Dopamine • Doses: – Renal Dose • 1 –5 micro/kg/min • Stimulation of dopaminergic receptors that result in renal, mesenteric, and cerebral vasodilation – Beta Dose • 5 - 15 micro/kg/min • Beta 1 effects Dopamine • Alpha Dose – > 15 micro/kg/min – Venous constriction Isoproteronol (Isuprel) • Synthetic catecholimine that stimulates Beta 1 & Beta 2 (no alpha) receptors • Increases Inotropic & Chronotropic activity • Indications: • Torsades de Points • Symptomatic bradycardias unresponsive to Atropine Dobutamine (Dobutrex) • Synthetic catacholamine with Beta 1 stimulating effects • Primary inotropic effect • Indications: – CHF • Drip format Anticholinergic • Atropine – Parsympatholytic – Inhibits Ach at postganglionic parasympathetic receptor sites (Muscarininc) – Used for symptomatic bradycardias and to antagonize excess muscarinic receptor stimulation from OPP / Nerve agents Atropine Sulfate • Concerns: • Glaucoma • GI Problems • May increase the size of infarct Antidysrhymthmics • Sodium Channel Blockers • Beta Blockers • K+ Channel Blockers • Ca Channel Blockers Antidysrhythmics • Treat & prevent cardiac rhythm disturbances • General mechanism of action: • Act directly on cardiac cell membrane • Indirect action that affects the cardiac cells Antidysrhythmics • Cardiac rhythm disturbances: – – – – – – – Ischemia Hypoxia H ion derangements Electrolyte imbalances Excessive catecholimine release Scarred / diseased tissue Drug toxicity Antidysrhythmics • Impulse Formation •Impulse Conduction Antidysrhythmics • All have some ability to suppress automaticity – – – – Class I – Sodium Channel Blockers Class II – Beta Blockers Class III – Potassium Channel Blocking Class IV – Calcium Channel Blocking Class I – Sodium Channel Blocking • Mechanism of action: Slow conduction • Class Ia – Procainamide • Class Ib – Have no effect on conduction velocity – Lidocaine & Dilantin • Class Ic – Profound slowing of conduction – Life threatening dysrhythmias only Procainamide • Suppresses phase 4 depolarization • Reduces automaticity of ectopic foci • Indications: • PVCs refractory to Lidocaine • VT with a pulse refractory to lidocaine • Wide complex PSVTs • Dose: 20 mg/min infusion Lidocaine • • • • • Antidysrhythmic Decreases phase 4 diastolic depolarization Decreases ectopy & the fibrillation threshold Indications Contraindications – Hypersensitive – 2nd & 3rd Degree Heart Block Class II – Beta Blockers • Reduce stimulation of Beta receptors • Primary use in HTN - Class III – K Channel Blockers • Block K channels • Increase contractility with no effect on automaticity & conduction velocity • Includes: – Bretylium – Amiodorone Amiodarone • Antidysrhythmic • Multiple mechanisms of action: • Prolongs duration of the action potential • Indications – Recurring VF & VT – Tachycardias Amiodarone • Contraindications: – Pulmonary edema – Hypotension • Precautions: • May precipitate hypotension & bradycardia when given with Beta Blockers & Ca Channel Blockers Bretylium • Used for patients who fail to respond to Lidocaine • Exact mechanism unsure Class IV – Calcium Channel Blocking • Blocking the flow of Ca across the cell membrane may affect the automaticity & conductivity of cardiac cells Calcium 2 Roles: Muscle Contraction Impulse propagation (Slow channels) Calcium Channel Blocker • Works to block some of the calcium channels in smooth muscle….Dilated Vessels • Blocks the slow Ca channels of Cardiac cells…decreased conduction velocity Common Generic Ca Channel Blockers • • • • • • • Amlodipine (Norvasc, Lotrel) Bepridil (Vascor) Diltiazem (Cardizem) Felodipine (Plendil, Lexxel) Isradapine (Dynacirc) Nifedipine (Adalat, Procardia) Verapamil (Calan, Isoptin) Diltiazem (Cardizem) Indications Symptomatic A-Fib and A-Flutter Contraindications Hypotension less than 90mmHg 2nd or 3rd degree AV Block Hypersensitivity Cardizem Dosage • .25 mg/kg slow IV push ( over 2 minutes) • Repeat in 15 minutes @ .35mg/kg • Consider 5 – 10 mg slow push for older patients & borderline blood pressure Verapamil (Isoptin) • • • • Effects localized to SA & AV node Decreases atrial automaticity Reduces smooth muscle vascular tone Decreases contractility Adenosine • Formed by the breakdown of ATP • Slows SVTs by slowing conduction through AV node • Can be used diagnostically in wide complex tachycardias of unknown origin • Can be effective with WPW Adenosine • Not effective with A-fib, A-flutter, or V Tach • Adverse reactions • Techniques Antihypertensives • The Ideal Antihypertensive: – – – – – Maintain adequate BP Maintain perfusion Reduce workload of heart No undesirable effects Allow for long term administration Antihypertensives • • • • • Diuretics Sympathetic Blocking Agents Vasodilators ACE Inhibitors Calcium Channel Blockers Diuretics • Renal excretion – Thiazides (HCTZ) – Lasix • K+ Sparing Agents – Prevent loss of K+ – Spironolactone Beta Blockers • Control of Hypertension through blocking of Beta receptors • Beta Blockades – Inotropic effects – Chronotropic effects – Dromotropic effects Common Beta Blockers • • • • • • • Atenolol (Tenormin) Labetalol (Tandate) Levobunolol Metoprolol (Betaloc, Lopressor) Nadolol (Corgard) Propranolol (Inderal) Timolol maleate (Timoptol) The Beta Blocker OD • Through the production of cAMP, increased Glucagon levels in the body will result in increased myocardial contractile strength (Positive Inotropic response) • cAMP is a second messenger that causes a release of catecholamines, and therefore vasoconstriction ACE Inhibitors • Angiotensin Co-enzyme Inhibitors • Angiotensinogen & Renin = Angiotensin I • Angiotensin I is converted to Angiotensin II • Angiotensin II causes the release of Aldosterone (hormone) from adrenal cortex • Aldosterone causes the retention of sodium in the proximal and distal tubules Common ACE Inhibitors • • • • • • • • Captopril (Capoten) Enalopril maleate (Innovace) Fosinopril (Staril) Lisinopril (Zestril) Perindopril (Coversyl) Quinopril (Accupro) Ramipril (Tritace) Trandolapril (Gopten, Odrik) Other Antihypertensives • Calcium Channel Blockers may be used for HTN if other treatments are unsuccessful • MAO Inhibitors may be used Vasodilator Drugs • Act on smooth muscle of vasculature Vasodilators • Decrease peripheral vascular resistance, preload, (or both) and therefore drop BP • Some dilate arterioles – Decreases PVR (afterload) – Hydralazine • Some dilate both arterioles and veins – Decreases both afterload and preload – Sodium nitroprusside Anticoagulants • Platelets and fibrin clots repair damaged vessels • 3 Major risk factors: – Stasis – Localized trauma – Hypercoagulable states The Basics of Clots • Clotting factors: Created in liver (Vitamin K) • Plasminogen – Trapped in a clot as well as many other plasma proteins • Plasmin – Form when natural t-PA is released form endothelial cells and digest clots Anticoagulant • Prevent thrombus by decreasing coagulability • Examples: – Warfarin – Heparin Warfarin Sodium • Coumadin – Interferes with the hepatic synthesis of Vitamin K dependent clotting factors – Results in the depletion of clotting factors • Indications: – A-Fib – Unlabeled: MI Heparin • Inhibits the formation of fibrin clots Antiplatelet Agents • ASA – Salicylate – Inhibits synthesis of prostaglandins (mediators of inflammation) – Inhibits platelet aggregation Thrombolytic Agents • Dissolve clots by promoting the digestion of fibrin • Goal: Establish re-perfusion Thrombolytics • Alteplase & reteplase • Human tissue enzyme • Converts plasminogen into fibrinolysin • Streptokinase • Enzyme isolated from streptococci bacteria • Converts plasminogen to plasmin • Urokinase • Isolated from human urine • Converts plasminogen to plasmin Thrombolytics Review • • • • • Cardiac A & P Review Cardiac Glycosides Antidysrhythmics Antihypertensives Anticoagulation