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CVS Pharmacology

Cardiovascular system pharmacology- Drugs used in Heart Failure

Objectives of Long Term Management of Chronic Cardiac Failure: Improve cardiac performance at rest and during exercise Relieve symptoms Improve myocardial efficiency Improve quality of life (particularly symptom-free and effort tolerance) Improve patient survival
Problems caused by HF: Reduced force of contraction Decreased CO Increased total peripheral resistance Inadequate organ perfusion Edema Decreased exercise tolerance IHD Sudden death Ventricular remodeling and decreased function
What are the non-pharmacologic treatments of Heart Failure? Salt restriction Treat the cause Moderate exercise Heart Transplantation
What drug groups are commonly used in HF? Diuretics Aldosterone receptor antagonists Angiotensin-converting enzyme inhibitors Angiotensin receptor blockers Beta blockers Cardiac glycosides Vasodilators Beta agonists Bipyridines Natriuretic peptide
What is the purpose of using diuretics in HF? They mostly treat the congestive symptoms Decrease BP and increase K+ loss Can be used in combination with digitalis
How are diuretics administered in HF? IV
What are the causes of diuretic resistance in HF? Noncompliance with regimen Excess dietary Na+ intake Decreased renal perfusion and GFR Selective reduction in glomerular perfusion pressure following initiation of ACEI therapy NSAIDs Primary renal pathology Reduced or impaired diuretic absorption
What are the pharmacological actions of ACEIs? Reduce A II levels Increase bradykinin Decreased NE release and upregulation of B1 receptors Reduction of afterload and preload Reduce myocyte & fibroblast GFs Decrease aldosterone causing decreased fluid retention, K+ loss, and arrhythmias
What is the therapeutic value of ACEIs? DOC in HF No tolerance Retard progression of HF Decrease arrhythmias Only drugs which decrease mortality, but only when the highest tolerated doses are used
What are the different preparations of ACEIs? Captopril Enalapril Lisinopril Quinapril Fosinopril All end with the suffix -pril Careless Evidence Leads Questionable Foreigners
What does toxicity of ACEIs cause? Hypotension - First dose phenomenon Renal Impairment - Proteinurea K+ retention Cough
Examples of ARBs: Losartan Candesartan Valsartan Irbesartan(Approvel) Telmisartan(Micardis)
When are ARBs used? When patients can not tolerate ACEIs because of cough
Effects of Beta Blockers: Negative inotropic Not useful in refractory HF Slowing of HR, decreased cardiac work and consequently decreased myocardial O2 consumption and enhanced efficiency lessen the frequency of ischemic events and arrhythmias
How can Beta blockers improve myocardial contractility? Through resensitization of the down-regulated receptor
How are Beta blockers administered? Started with low doses and gradually increased
Examples of Beta blockers: Metoprolol Carvedilol Bicindolol Bisiprolol Many Cute Babbling Babies
When are beta blockers contraindicated? In severe, refractory, or unstable cases
How do positive inotropic agents increase force of contraction? By increasing intracellular cardiac Ca++ concentration
Examples of Cyclic AMP Independent Agents: Digitalis Pimobendan
Examples of Cyclic AMP Dependant Agents: B-adrenergic Agonists Phosphodiesterase Inhibitors
General Action of Digitalis: Inhibits Na/K ATPase
Action of Pimobendan: Sensitizes myocytes to Ca++,also inhibits PDE
Examples of Digitalis glycosides: Digitalis purpura Digitalis lanata Strophanthus
Further action of Digitalis glycosides: Positive Inotropic Effect Vascular Muscle Contraction Vagal Stimulation Effects on Electrical Properties of Cardiac Tissues
Effects of Digitalis Toxicity: G.I.T: Anorexia, nausea, cramping, diarrhea Visual: Xanthopsia, color blindness Neurologic: Malaise, confusion, depression, vertigo Cardiac: bradycardia, Palpitations, syncope, arrhythmias, AV node block, VT Interactions
Pharmacological and toxic effects are greater in Hypokalemic patients
Major contributing factor to digoxin toxicity K+-depleting diuretics
How is digitalis toxicity treated? Reduce or stop the drug Cardiac pacemeker for heart block Digitalis antibodies Arrhythmias may be converted to normal sinus rhythm by K+ Antiarrhythmic drugs, such as lidocaine, phenytoin, procainamide, or propranolol, used when K+ conc is high
Therapeutic benefits of Digitalis glycosides: Only useful in CCHF with supraventricular arrhythmia Might decrease morbidity
Examples of B-adrenergic agonists (which are cAMP dependent agents): NE Ep Dopamine Dobutamine
Examples of phosphodiesterase inhibitors (which are cAMP dependent agents): Amrinone Inamrinone Milrinone Vesanirone Sildenafil Adorable Ideas Meet Slimy Verbs
What is the general function of B-adrenergic agonists? All increase myocardial oxygen consumption, may be used (IV) for short term or in acute heart failure
When is NE used? In cardiogenic shock, but caused severe vasospasm and gangrene
When is Ep used? In cardiac arrest, by intracardiac injection
When is dopamine used? Widely used in cardiogenic shock
Low doses of dopamine cause: Stimulation of DA1 receptors leading to renal vasodilation and improved renal function
Intermediate doses of dopamine cause: Positive inotropic actions by working on B1 receptors
High doses of dopamine cause: Stimulation of α receptors leading to vasoconstriction and elevation of blood pressure
Side effects of dopamine: Arrhythmias Ischemic changes
What is dobutamine? Selective β1 agonist
When is dobutamine used? Intermittently (IV) in CCHF
General function of phosphodiesterase inhibitors: Accumulation of cAMP and cGMP leading to positive inotropic activity and peripheral vasodilation
Phosphodieserase inhibitors are generally used for: Parenteral therapy of acute heart failure
Examples of phosphodiesterase inhibitors: Inamrinone (PDE-3) Milrinone (PDE-3) Vesanirone (PDE-3) Sildenafil (PDE-5) Individual Men View Stars
Toxicity, as a result of phosphodiesterase inhibitors leads to: Arrhythmias Thrombocytopenia
What is the function of vasodilators? Affect preload and/or afterload without directly affecting contractility Consequently can decrease myocardial ischemia, enhance coronary blood flow and decrease MVO2
When are vasodilators used? In acute heart failure and for short periods in CCHF
Action of Hydralazine-Isosorbide dinitrate combination Decrease mortality Reducing remodeling of the heart
Vasodilators can be combined with: ACEI, diuretics and digitalis
Venous dilators: Nitroglycerin Isosorbide dinitrate
Mixed action vasodilators: Nitroprusside Captopril Enalopril Hydralizine + Nitrate
Atrial dilators: Hydralazine Minoxidil
Examples of organic nitrate vasodilators: Nitroglycerin Isosorbide dinitrate
Examples of Nitric oxide donors used for vasodilators Nitroprusside
Examples of ACEIs used for vasodilators Captopril Enalapril Lisinopril
Examples of ARBs used for vasodilators Losartan candesartan
Phosphodiesterase inhibitors used for vasodilators: Milrinone Inamrinon
Direct-acting K+ channel agonist used for vasodilators: Hydralazine Minoxidil
Adrenergic antagonists used for vasodilators: Doxazosin Prazosin
Nonselective a-adrenergic antagonists used for vasodilators: Phentolamine
B1-adrenergic antagonists used for vasodilators : Carvedilol Labetalol
Ca2+ channel blockers used for vasodilators Amlodipine Nifedipine Felodipine
Function of (BNP)-Niseritide: Binds to receptors in the vasculature, kidney, and other organs, producing potent vasodilation with rapid onset and offset of action by increasing levels of cGMP
BNP is secreted by: ventricular myocytes in response to stretch
Niseritide is used for the treatment of: Acute decompensated CHF
Action of niseritide: Reduces systemic and pulmonary vascular resistances, causing an indirect increase in cardiac output and diuresis
Why is BNP- Niseritide useful in HF? Reduction in preload and afterload
Main side effect in Niseritide? Hypotension
Errors in Management of HF Improper dosage of diuretics Failure to consider long term therapeutic goals Underprescribing ACEIs Use of potentially harmful drugs Failure to use hydralazine-isosorbide combination
Created by: Ulaisl



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