PHARM CH7.pptx

CHAPTER 7 Drugs Used in Cardiovascular System Disorders INTRODUCTION High incidence of heart disease (11% of all dogs presented)  Acquired or congenital  Tx is based on cause of disease, progression & owner compliance  Poor liver & kidney function often complicate tx  Some drugs used to tx hav...

CHAPTER 7 Drugs Used in Cardiovascular System Disorders INTRODUCTION High incidence of heart disease (11% of all dogs presented)  Acquired or congenital  Tx is based on cause of disease, progression & owner compliance  Poor liver & kidney function often complicate tx  Some drugs used to tx have narrow margin of safety  ANATOMY AND PHYSIOLOGY OF THE HEART ANATOMY AND PHYSIOLOGY OF THE HEART  Phases of action  Systole – period of contraction  Diastole – period of relaxation & filling  Cardiac conduction system  Sinoatrial  AV (SA) node node  Bundle of His  Purkinje system ANATOMY AND PHYSIOLOGY OF THE HEART Impulse generated from the sinoatrial (SA) node in the right atrium  Electrical current generated by the movement of cations (Na, K, Ca) across the outer cell membrane  Resting state or polarized – cell has a slightly positive charge on the outside  Depolarization – gates in cell membrane are opened and Na & Ca flow in and K flows out  Repolarization (refractory period) – Na-K-ATPase pump restores cations to original positions  Depolarization (systole) & repolarization (diastole)  ANATOMY AND PHYSIOLOGY OF THE HEART  Influence of autonomic nervous system  Sympathetic Beta-1 receptors - positive chronotropic & inotropic effects  Alpha-1 receptors – vessel constriction  Beta-2 receptors – vessel dilation   Parasympathetic   Cholinergic receptors – negative chronotropic & inotropic effects Cardiac output – amount of blood that leaves the heart per minute  Stroke volume – amount of blood ejected with each cardiac contraction (determined by preload & afterload)  CO = SV x HR COMPENSATORY MECHANISMS OF THE HEART  Four basic mechanisms  Increasing HR  Increasing SV  Increasing the efficiency of the heart muscle  Physiologic heart enlargement COMPENSATORY MECHANISMS OF THE HEART  Disorders that usually respond to pharmacologic therapy  Valvular disease  Cardiac arrhythmias  Myocardial disease  Others : congenital defects, innervation abnormalities, vascular disease (hypertension), heartworm disease BASIC OBJECTIVES IN THE TREATMENT OF CARDIOVASCULAR DISEASE Control rhythm disturbances  Maintain or increase cardiac output   Increase strength of contraction  Decrease afterload  Arteriolar dilator  Decrease   preload Venodilator Relieve fluid accumulation  Diuretics  Dietary  salt restriction Increase the oxygenation of the blood  Bronchodilation  Ancillary treatment  Narcotics/sedatives  Oxygen POSITIVE INOTROPIC DRUGS  Pros  Improve  strength of contraction Cons  Increase  Can O2 demand of the heart potentially damage contractile tissue  Can increase the occurrence of arrhythmias POSITIVE INOTROPIC DRUGS  Cardiac glycosides (digitalis)  Beneficial effects Improve cardiac contractility  Decrease HR  Antiarrhythmic effects  Decrease signs of dyspnea   Primary actions Increase force of contraction  Decrease rate of contraction  Improve baroreceptor function   Clinical uses CHF  Atrial fibrillation  Supraventricular tachycardia   Dosage  forms Digoxin (injectable, tabs, caps, elixir)  Adverse  side effects Anorexia, V/D, arrhythmias POSITIVE INOTROPIC DRUGS  Catecholamines  Sympathomimetic drugs  Actions Increase force & rate of contractions  Constrict peripheral blood vessels  Elevate blood glucose   Short serum half-lives CATECHOLAMINES  Epinephrine  Clinical uses Cardiac resuscitation (preferred drug)  Tx of anaphylaxis   Dosage  forms 1:10000 (0.1 mg/ml) & 1:1000 (1 mg/ml)  Adverse   side effects Hypertension, arrhythmias, anxiety & excitability Dopamine  Clinical uses – adjunctive tx of acute heart failure & oliguric renal failure & supportive tx of shock  Adverse side effects – vomiting, tachycardia, dyspnea & BP variations  Dobutamine  Produces increased cardiac output but does not tend to cause arrhythmias or increase HR POSITIVE INOTROPIC DRUGS  Bipyridine derivatives  Amrinone (IV, short-term) & milrinone (orally, long- term)  Inotropic, mixed dilator  Pimobendan (Vetmedin) Clinical uses – AV insufficiency or dilated cardiomyopathy in dogs  Adverse side effects – anorexia, lethargy, diarrhea  Contraindications – hypertrophic cardiomyopathy, aortic stenosis  ANTIARRHYTHMIC DRUGS Arrhythmia – variation in normal heart rhythm  Causes – abnormality of impulse generation (increased automaticity) or abnormalities of impulse conduction  Ectopic focus  Result – reduced cardiac output due to uncoordinated pump activity  Diagnosis – ECG  ANTIARRHYTHMIC DRUGS  Factors that cause or predispose  Conditions that cause hypoxemia  Electrolyte imbalances  Increased levels of or increased sensitivity to catecholamines  Drugs – digoxin, thiobarbituates, xylazine, others  Cardiac trauma or disease resulting in altered cardiac cells  Classification  Tachyarrhythmias  Bradyarrhythmias – ventricular or atrial ANTIARRHYTHMIC DRUGS  Class IA – Na channel blockers  Quinidine Clinical uses – ventricular arrhythmias & tachycardia & atrial fib  Adverse side effects – anorexia, V/D, weakness & laminitis   Procainamide Clinical uses – premature ventricular contractions (PVCs), ventricular tachycardia & some forms of atrial tachycardia  Adverse side effects – anorexia, V/D & hypotension   Class IB – Na channel blockers  Lidocaine (IV) Clinical uses – control of PVCs & tx of ventricular tachycardia  Adverse side effects (rare) – drowsiness, depression, ataxia & muscle tremors   Tocainide & mexiletine (oral) ANTIARRHYTHMIC DRUGS  Class II – Beta-adrenergic blockers  Propranolol & atenolol Clinical uses – tx hypertrophic cardiomyopathy, arrhythmias & hypertension  Adverse side effects – bradycardia, hypotension, worsening of heart failure, bronchospasm (propranolol) and lethargy & depression   Class III  Seldom  used in veterinary medicine Class IV – Ca channel blockers  Verapamil hydrochloride Clinical uses – supraventricular tachycardia, atrial flutter & fibrillation  Adverse effects – hypotension, bradycardia, tachycardia, pulmonary edema & worsening CHF   Diltiazem  Clinical uses – supraventricular tachyarrhythmias in dogs & cats & hypertrophic cardiomyopathy in cats  Others  – amlodipine (Norvasc) Clinical uses – tx of hypertension RENIN-ANGIOTENSIN SYSTEM VASODILATOR DRUGS Dilate aa., vv. or both  Actions – direct action on smooth m., blockage of sympathetic stimulation, preventing conversion of angiotensin I to angiotensin II  Benefits – decrease afterload & preload & improve cardiac output  VASODILATOR DRUGS  Hydralazine  Arteriolar dilator  Clinical uses – reduce afterload assoc’d w/ CHF, especially when caused by mitral insufficiency  Adverse side effects – hypotension, V/D, Na & water retention & tachycardia  Nitroglycerin ointment  Venodilator  Clinical uses – reduce preload & pulmonary edema  Adverse side effects (minimal) – rashes at application site & hypotension VASODILATOR DRUGS  Prazosin  Combined vasodilator  Clinical uses – adjunctive tx of CHF, dilated cardiomyopathy in dogs, systemic & pulmonary hypertension  Adverse side effects – hypotension, syncope, V/D  Angiotensin-converting enzyme (ACE) inhibitors  Combined vasodilator  Clinical uses – tx of class II, III & IV heart failure  Dosage forms – captopril & enalapril (Enacard)  Adverse side effects – hypotension, azotemia, V/D, hyperkalemia DIURETICS  Furosemide (Laxix)  Most important & efficacious diuretic for removing edema from animals w/ heart failure  Oral & parenteral forms  Adverse side effects – hypokalemia, dehydration, hyponatremia, ototoxicity (cats), weakness & shock  Spironolactone  Typically used in combination w/ another diuretic DIETARY MANAGEMENT OF HEART DISEASE  Goals  Sodium restriction  Maintenance of good body weight and condition ANCILLARY TREATMENT OF HEART FAILURE Bronchodilators  Oxygen therapy  Sedation  Aspirin  Thoracocentesis & abdominocentesis 