Cardiovascular system pharmacology- Drugs used in Heart Failure
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| 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
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| 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
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| What are the non-pharmacologic treatments of Heart Failure? | Salt restriction
Treat the cause
Moderate exercise
Heart Transplantation
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| 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
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| 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
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| How are diuretics administered in HF? | IV
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| 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
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| 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
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| 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
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| What are the different preparations of ACEIs? | Captopril
Enalapril
Lisinopril
Quinapril
Fosinopril
All end with the suffix -pril
Careless
Evidence
Leads
Questionable
Foreigners
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| What does toxicity of ACEIs cause? | Hypotension - First dose phenomenon
Renal Impairment - Proteinurea
K+ retention
Cough
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| Examples of ARBs: | Losartan
Candesartan
Valsartan
Irbesartan(Approvel)
Telmisartan(Micardis)
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| When are ARBs used? | When patients can not tolerate ACEIs because of cough
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| 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
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| How can Beta blockers improve myocardial contractility? | Through resensitization of the down-regulated receptor
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| How are Beta blockers administered? | Started with low doses and gradually increased
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| Examples of Beta blockers: | Metoprolol
Carvedilol
Bicindolol
Bisiprolol
Many Cute Babbling Babies
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| When are beta blockers contraindicated? | In severe, refractory, or unstable cases
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| How do positive inotropic agents increase force of contraction? | By increasing intracellular cardiac Ca++ concentration
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| Examples of Cyclic AMP Independent Agents: | Digitalis
Pimobendan
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| Examples of Cyclic AMP Dependant Agents: | B-adrenergic Agonists
Phosphodiesterase Inhibitors
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| General Action of Digitalis: | Inhibits Na/K ATPase
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| Action of Pimobendan: | Sensitizes myocytes to Ca++,also inhibits PDE
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| Examples of Digitalis glycosides: | Digitalis purpura
Digitalis lanata
Strophanthus
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| Further action of Digitalis glycosides: | Positive Inotropic Effect
Vascular Muscle Contraction
Vagal Stimulation
Effects on Electrical Properties of Cardiac Tissues
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| 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
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| Pharmacological and toxic effects are greater in | Hypokalemic patients
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| Major contributing factor to digoxin toxicity | K+-depleting diuretics
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| 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
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| Therapeutic benefits of Digitalis glycosides: | Only useful in CCHF with supraventricular arrhythmia
Might decrease morbidity
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| Examples of B-adrenergic agonists (which are cAMP dependent agents): | NE
Ep
Dopamine
Dobutamine
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| Examples of phosphodiesterase inhibitors (which are cAMP dependent agents): | Amrinone
Inamrinone
Milrinone
Vesanirone
Sildenafil
Adorable Ideas Meet Slimy Verbs
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| 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
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| When is NE used? | In cardiogenic shock, but caused severe vasospasm and gangrene
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| When is Ep used? | In cardiac arrest, by intracardiac injection
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| When is dopamine used? | Widely used in cardiogenic shock
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| Low doses of dopamine cause: | Stimulation of DA1 receptors leading to renal vasodilation and improved renal function
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| Intermediate doses of dopamine cause: | Positive inotropic actions by working on B1 receptors
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| High doses of dopamine cause: | Stimulation of α receptors leading to vasoconstriction and elevation of blood pressure
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| Side effects of dopamine: | Arrhythmias
Ischemic changes
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| What is dobutamine? | Selective β1 agonist
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| When is dobutamine used? | Intermittently (IV) in CCHF
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| General function of phosphodiesterase inhibitors: | Accumulation of cAMP and cGMP leading to positive inotropic activity and peripheral vasodilation
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| Phosphodieserase inhibitors are generally used for: | Parenteral therapy of acute heart failure
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| Examples of phosphodiesterase inhibitors: | Inamrinone (PDE-3)
Milrinone (PDE-3)
Vesanirone (PDE-3)
Sildenafil (PDE-5)
Individual Men View Stars
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| Toxicity, as a result of phosphodiesterase inhibitors leads to: | Arrhythmias
Thrombocytopenia
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| 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
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| When are vasodilators used? | In acute heart failure and for short periods in CCHF
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| Action of Hydralazine-Isosorbide dinitrate combination | Decrease mortality
Reducing remodeling of the heart
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| Vasodilators can be combined with: | ACEI, diuretics and digitalis
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| Venous dilators: | Nitroglycerin
Isosorbide dinitrate
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| Mixed action vasodilators: | Nitroprusside
Captopril
Enalopril
Hydralizine + Nitrate
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| Atrial dilators: | Hydralazine
Minoxidil
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| Examples of organic nitrate vasodilators: | Nitroglycerin
Isosorbide dinitrate
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| Examples of Nitric oxide donors used for vasodilators | Nitroprusside
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| Examples of ACEIs used for vasodilators | Captopril
Enalapril
Lisinopril
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| Examples of ARBs used for vasodilators | Losartan
candesartan
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| Phosphodiesterase inhibitors used for vasodilators: | Milrinone
Inamrinon
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| Direct-acting K+ channel agonist used for vasodilators: | Hydralazine
Minoxidil
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| Adrenergic antagonists used for vasodilators: | Doxazosin
Prazosin
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| Nonselective a-adrenergic antagonists used for vasodilators: | Phentolamine
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| B1-adrenergic antagonists used for vasodilators : | Carvedilol
Labetalol
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| Ca2+ channel blockers used for vasodilators | Amlodipine
Nifedipine
Felodipine
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| 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
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| BNP is secreted by: | ventricular myocytes in response to stretch
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| Niseritide is used for the treatment of: | Acute decompensated CHF
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| Action of niseritide: | Reduces systemic and pulmonary vascular resistances, causing an indirect increase in cardiac output and diuresis
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| Why is BNP- Niseritide useful in HF? | Reduction in preload and afterload
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| Main side effect in Niseritide? | Hypotension
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| 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
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