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Pharmacotherapy of heart failure
- 2. BASIC PHYSIOLOGY MAP = CO X SVR HR SV ANS PRELOAD CONTRACTILITY AFTERLOAD ATRIAL CONTRACTION VENOUS RETURN LV VOLUME LV THICKNESS AORTIC PRESSURE SVR BLOOD VOLUME AT EJECTION
- 3. Questions covered 1) Describe recent advances in drug therapy of CCF/HF 2) Describe the present status of drugs used in management of CHF 3) Current and recent advances in treatment of CHF SAQ 1) Role of beta blockers in HF & individual drugs
- 4. Background & incidence • Incidence- 1.0-5.0 / 1000/ annum. • Only cardiovascular disease : increasing in incidence and prevalence. • Over 1 million patients hospitalized annually • 50,000 deaths annually • 5 yr mortality- 50%
- 5. Definition Heart failure • complex clinical syndrome • from structural or functional cardiac disorder • impairs the ventricular ability to fill with or eject blood sufficiently required to meet body’s metabolic demands Clinical manifestations dyspnea (pulmonary congestion) and fatigue (reduced exercise tolerance)
- 8. Compensatory responses… Myocardial disease (decreased contractility) (decreased stroke volume) Decreased renal perfusion RAAS activation Vasoconstriction Increased afterload Sympathetic activation Increased heart rate vasoconstriction Increased after load O2 demand Cardiac dilatation Cardiac hypertrophy Increased cardiac contractility Increased cardiac O2 demand & work
- 9. • Maintain Cardiac Output by compensatory mechanisms • In long term, increase work load and worsens cardiac performance • Compensatory mechanisms become exhausted and ineffective after a long time • TPR and after load increases-> decreasing the ejection fraction • Preload is increased due to increased blood volume and venous tone • When adaptive mechanisms fail to maintain Cardiac Output-decompensated heart failure Signs and symptoms of decompensated HF : dyspnoea with cyanosis, hepatomegaly, cardiomegaly, reflex tachycardia(?), decreased urine formation, decreased exercise tolerance and muscle fatigue
- 10. Syndrome( multiple causes) • MI/Angina • HT • Ventricular Tachycardia • Hyperthyroidism • Anaemia • Berry-berry Low CO High CO Medications Treat Cause
- 12. Classification ACC/AHA Stage NYHA Class Description A Prefailure No symptoms but risk factors present B I Symptoms with severe exercise C II/III Symptoms with marked (II) or mild (III) exercise D IV Severe symptoms at rest
- 13. Treatment of Chronic HF patients 4 ACC/AHA Stage NYHA Class Description Management A Prefailure No symptoms but risk factors present Treat obesity, HT, Diabetes, Hyperlipidemia B I Symptoms with severe exercise ACEI/ARB Β blockers diuretics C II/III Symptoms with marked (II) or mild (III) exercise Add Aldosterone antagonists, Digoxin, CRT, Hydralazine/nitrate D IV Severe symptoms at rest Transplant LVADCRT: cardiac resynchronization therapy; LVAD: left ventricular assisted device
- 15. Management of acute heart failure4 1) IV furosemide 2) IV Dopamine/Dobutamine: in HF + severe hypotension 3) IV levosimendan (alternative to β agonist) 4) Vasodilators- IV nitroprusside, nitroglycerine, nesiritide 5) Vasopressin antagonists- Conivaptan, Tolvaptan: in HF with hypovolemia( ? Is it hypervolemia)
- 17. Positive Inotropic Agent a) Cardiac Glycosides: Digoxin b) Bipyridines or PDE inhibitors: Inamrinone, Milrinone, Levosimendan, Enoximone χ) β Adrenergic Agonists: Dopamine, Dobutamine, Dopexamine
- 18. Without Inotropic effects a) Diuretics: Furosemide, Bumetanide, Hydroclorothiazide, Metolazone, Spironolactone, Eplerenone b) ACEI: Enalapril, Lisinopril, Ramipril c) AT1 receptor anatgonists: Losartan, Valsartan
- 19. d) Β blockers: Carvedilol, Bisoprolol, Metoprolol e) Vasodilators: Hydralazine, Sodium nitroprusside, Isosorbide di nitrate, Nesiritide f) Vasopressin Receptor Antagonists: Conivaptan, Tolvaptan
- 20. ACE inhibitors • First line agents in asymptomatic ventricular dysfunction • Combination with diuretics make first line therapy in HF Enalapril 2.5 mg BD ( max 10 mg BD) Lisinopril 2.5-5 mg OD ( max 20 mg OD) Ramipril 2.5 mg OD ( max 10 mg OD)
- 21. • Slow : progress of ventricular dilatation • Prolong survival : prevent pathological remodeling : heart & blood vessels • Beneficial in MI (stroke, arrhythmia) • Use : asymptomatic to severe HF • Side effects: hypotension, hyperkalaemia, cough, urticaria, angioedema, altered taste, fetopathic • Aldosterone escape is prevented by adding Spironolactone with ACEI. combination also reduces mortality.
- 22. ARBs: (AT1 receptor blockers) • Beneficial hemodynamic effects similar to ACEI • Used when ACEI are Cx (excessive cough or angioedema) or not tolerated • Side effects of ARBs : hypotension,hyperkalaemia, headache, dizziness, fetopathic Losartan: Most common ARB s in CHF T1/2: 2 hrs B.A.: 33% Dose: 50 mg OD/BD Less first dose hypotension Valsartan: T1/2 : 6-9 hrs B.A.: 23% Dose: 80-160 mg OD
- 23. Heart Failure ↓ Raised epinephrine and non-epinephrine level ↓ Cardiac Hypertrophy, Remodeling, Apoptosis Peripheral vasoconstriction
- 24. Heart Failure ↓ Raised epinephrine and non-epinephrine level ↓ Cardiac Hypertrophy, Remodeling, Apoptosis Peripheral vasoconstriction β blockers
- 25. Carvedilol • α1 + β1 + β2 antagonist • T1/2- 6-8 hrs • Dose: 3.125 mg BD for 2 weeks, if well tolerated gradual ↑ to max 25 mg BD( max) • Inhibits free radical induced lipid peroxidation, inhibits vascular smooth muscle mitogenesis and also block L type voltage gated channels-> cardioprotective in CHF β blockers
- 26. Metoprolol • T1/2: 3-6 hrs • Dose: 100 -200 mg (max) Bisoprolol • T1/2: 9-12 hrs • OD is enough • Dose: 2.5 -10 mg (max) Nebivolol • Also NO donor-vasodilatation and improve endothelial function • Dose: 5mg OD • Effective in systolic & diastolic function
- 27. • Use in mild-moderate (NYHA II/III) systolic dysfunction with cardiomyopathy • Benefit seen in symptomatic • Initiate at low doses and up titrate to max dose • 2-4 months therapy is required for clinical benefits • Do not start in decompensated HF • Sustained released metoprolol or 2-3 times daily dosing should be preferred • Clinical improvements are slight rise in ejection fraction, reduction in HR, reduction in symptoms • Long term effect: maintain hemodynamic benefits and reduction in morbidity/mortality
- 28. Side effects: • Accentuation of MI, CHF, edema (if started at high dose) • Bradycardia • Asthma/COPD precipitation • Altered carbohydrate tolerance and lipid profile • Rebound hypertension on withdrawal • fluid retention
- 29. Diuretics
- 30. Loop Diuretics Furosemide, Bumetanide • preferred in HF (symptomatic esp:edema) • Effective diuresis-> ↓ ECF -> ↓ venous return -> ↓ preload a) ↓ edema b) ↓ cardiac size(↑ CO) • Do not influence primary disease process • s/e: Hypokalaemia: precipitate digitalis toxicity & arrhythmia • T1/2 : furosemide: 1-2 hr, bumetanide: 60 mins • Dose: furosemide: 20-80 mg OD, Bumetanide: 1-5 mg OD
- 32. Aldosterone antagonists Spironolactone • Dose: 12.5-25 mg/day • Add on with ACEI & others in moderate-severe CHF • Retard disease progression (Aldosterone: fibroblast proliferation and fibrotic changes in myocardium) • Slow response • Cx in renal failure (precipitate hyperkalemia) • Eplerenone shows no gynaecomastia
- 34. • With diuretcis. Reason a) Hypokalemia prevented b) improve refractoriness of chronic diuretic use c) also improves survival • s/e: hyperkalemia, gynaecomastia • In severe CHF: ACEI+ spironolactone+ digitalis: improves survival Thiazides: Hydrochlorothiazide: used less frequently
- 35. Cardiac Glycosides Digoxin • Source: Digitalis Lanata • Ix: Low output heart failure due to HT, IHD & arrhythmias Dose: Oral route is preferred: 0.125-0.5mg/day. 1) Slow loading with 0.125-0.25 mg/day 2) Rapid method with 0.5-0.75mgevery8hrs for1dayfollowedby0.125-0.25 mg/day(rare) 3) IVis seldomrequired • Both are equally effective • Given when ACEI & Diuretics fail to control symptoms • Better results in HF with Atrial fibrillation
- 36. MOA • Raises free cytoplasmic Ca2+ -> ↑FOC -> ↑ C.O. &↓ Cardiac systole • Opposes compensatory sympathetic activity and vagal stimulation: ↓ H.R. Effects • No change or ↓ in oxygen requirement, ↓ heart size • Protection of ventricles from atrial flutter or fibrillation • ↓ in after load and preload • Diuresis • Bradycardia, improved myocardial circulation and sense of well being Subside pulmonary congestion and edema
- 37. Raised free cytosolic Ca2+ is due to 1) Main: Reversible inhibition of Na+ /K+ ATPase 2) Increase in Ca2+ permeability through voltage sensitive L type Ca2+ channels during plateau phase 3) Release of more Ca2+ from SR & mitochondria by activating Ryr (ryanodine) receptors 4) Inhibits SR- Ca2+ ATPase (reuptake channel)
- 39. DIGOXIN Oral absorption( %) 75-90 Administrati on Oral, iv aVd (L/kg) 6-7 Protein binding 30 Plasma T1/2 38-40 hrs Onset of action ½ hr Metabolized (%) 20(liver) Excretion Urine (unchanged) • Small mortality benefit at plasma levels <1 ng/ml • Preferred in conditions with dilated heart (helpful in restoring cardiac compensation?) • Reduces hospitalization and deaths from progressive HF but increase in sudden death4 • Shows cumulative effects: full therapeutic effects after 4 x t ½: 6-7 days • No effect on BP
- 40. Adverse effects from govind garg page 139 • Bradycardia, heart blocks. At toxic doses: extra systoles, pulsus bigeminus, ventricular fibrillation & fatal arrhythmia • Monitor serum level: digoxin & K+ and ECG • In severe toxicity- temporary cardiac pacemaker catheter +digoxin immune fab • Use of DIGIBIND Fab fragment: 40 mg neutralizes 0.6 mg digoxin • Others: GI upset, blurred vision & loss of color perception, hyperkalemia, gynaecomastiareduce dose • Cx: Hypokalemia, children<10 yrs, elderly with renal or hepatic disease, MI, hypothyroidism, WPW syndrome and myocarditis, hypercalcaemia, hypomagnesemia, A-V block, renal failure, hypo-hyper thyroidism
- 41. A pt on chronic digoxin Rx develops ventricular arrhythmia. Steps: • Withdraw digoxin • Add oral K supplements slowly & cautiously • Treat with lidocaine/B blocker • DOC: iv digibind ovine antidigoxin Fab fragments; No immunological reaction due to lack of Fc.
- 42. Drug Interactions ENHNACED digitalis toxicity 1)Loop diuretics, steroids 2) Amiodarone, quinidine, verapamil, tetracyclines, erythromycin 3) Catecholamine, Sch DECREASED digitalis effects 1) Antacids, Sucralfate, Neomycin 2)Enzyme inducers 3) Hyperthyroidism 4) Cholestyramine
- 43. • ACEI -> raised digitalis toxicity • B blockers-> reduce av conduction • Verapamil-> raised toxicity • Nifedipine- safe • Diuretics ( hypokalemia)-> raised toxicity • Quinidine, amiodarone-> toxicity
- 45. Mx of side effects
- 46. Treatment of digitalis toxicity
- 47. Explain drug interaction • Amiodarone/verapamil with digoxin
- 48. Vasodilators
- 50. Combination • Given when ACEI are not tolerated or contraindicated • Long term use can reduce damaging remodelling of the heart and prolong survival ( less than ACEI)
- 51. β agonists
- 52. Dobutamine • β1 selective • T1/2: 2 min. Steady state concentration achieved in 10 mins • IV 5-10 μg/kg/min Uses: • Short term management: acute HF • HF with MI or cardiac surgery Adverse effects • Precipitation of angina/MI (as it increases myocardial O2 demand) • Tolerance due to repeated use • Caution in atrial fibrillation (↑AV conduction) and hypertensives(↑ BP)
- 53. Dopamine • In acute HF • HF with hypotension • Low C.O. heart failure with compromised renal function Effects • ↑C.O. (β1 agonist) • Renal & splanchanic vasodilatation (D1 agonist) • Dose: 5-10 μg/kg/min • Monitor BP, HR, urinary output
- 54. PDE Inhibitors • Benefits is mostly from vasodilatation than positive inotropic effects Inamrinone and Milrinone-PDE3 inhibitors • Use in acute heart failure or severe exacerbations of chronic
- 55. Inamrinone • T1/2- 2-4 hrs • Action starts in 5 min and lasts for 2-3 hrs • Dose: 0.5 mg/kg bolus full. by 5-10 μg/kg/min infusion • s/e: thrombocytopenia, nausea, vomiting, arrhythmia, liver enzyme changes: withdrawn in some countries Milrinone • T1/2- 40-80 min • 10 times more potent than inamrinone. Preferred • Dose: 50ug/kg iv bolus foll by 0.4-1.0 ug/kg/min • s/e: less thrombocytopenia and liver effect. Same arrhytmogenic potential, headache, tremors
- 56. Enoximone • Congener of inamrinone • IV in acute heart failure • Better tolerated and improves physical quality of life (central stimulatory effect of ↑c AMP)
- 57. Levosimendan • Sensitizes troponin system to calcium & inhibits PDE • May be useful in HF • acutely decompensated congestive heart failure
- 58. Istaroxime4 • Investigational steroid derivative MOA: • Increases contractility by inhibiting Na+/K+ ATPase • Facilitates sequestration of Ca2+ by saroplasmic reticulum (may render drug less arrhythmogenic than digoxin) • In phase 2 clinical trial
- 60. Vasoactive Peptides • ↑BNP (Brain Natriuretic Peptide): diagnostic and prognostic marker in heart failure • Rapid Measurement BNP →emergency diagnosis of heart failure • released from the cardiac ventricles (response to increased wall tension)
- 62. Nesiritide • Recombinant form of human BNP • APPROVED for acute decompensated HF MOA • ↓ arteriolar and venous tone (↑ cGMP in smooth muscle cells -- smooth muscle relaxation) • Natriuresis (Inhibits Na+ absorption in collecting duct)
- 63. • Dose: 2μg/kg bolus followed by continuous IV infusion of 0.01-0.03 μg/kg/min • T1/2- 18 min • s/e- excessive hypotension, renal damage • No dose adjustment in renal insufficiency (?) C/I: syst BP< 70
- 64. he short- and long-term morbidity and mortality in acute heart failure is still unacceptably high. There is an unmet need for new therapy options with new drugs with a new mode of action Ularitide • Recombinant peptide mimics activity of urodilatin • Route of administration- IV • Under Ix for acute heart failure • Improve Cardiovascular parameter & promote diuresis without↓ creatinine clearance • In phase 3
- 65. Vasopeptidase Inhibitors MOA • ↑ANP & ↑BNP inhibition of neutral endopeptidases (enzyme metabolizing natriuretic peptides) • ↓Ang II- inhibition of ACE Effects Vasodilatation and Na+ & water excretion ↓ ↓total peripheral resistance and BP E.g.: Omapatrilat, Sampatrilat, Fasidopatrilat
- 66. Omapatrilat • Orally active long acting inhibitor of NEP Studies suggest: • ↓BP in Hypertensive animal models and in patients • ↑ cardiac functions in heart failure patients Side effects: angioedema (3 times more than ACEI), cough, dizziness Clinical status: in phase 3 trials Ecadotril:
- 67. Vasopressin Antagonists V1a : vasoconstriction V2: antidiuretic • Conivaptan • V1a & V2 antagonist • APPROVED for hyponatremia (SIADH) • Potential use in heart failure: as ↓ peripheral resistance and ↓ dilutional hyponatremia • T1/2: 5-12 hrs • Dose: 20 mg loading IV over 30 min followed by 20 mg IV over 24 hrs • Drug interactions present (CYP3A4 metabolism) • s/e: infusion site reaction, headache, hypotension, pyrexia
- 68. Tolvaptan • V2 antagonist • Oral: 15-45 mg/day • T1/2: 6-8 hrs • APPROVED to treat hyponatremia (SIADH) • Multiple drug interactions ( substrate and inhibitor of p-glycoprotein and CYP3 metabolism) • Can cause rapid Na+ reduction & may prove fatal 1)Start only in hospital setting 2)Monitor sodium level
- 69. In heart failure clinical trials (patients of CHF with low ejection fraction) Short term results:↓ body wt & ↓ dyspnoea Long term results: ↓ body wt ( ↓edema)&↑Na+ conc (normalize Na+) No effect on mortality & hospitalization s/e: g I effects, hyperglycaemia, pyrexia, DVT, DIC, hemorrhage Selective V1a antagonists potential for raised TPR state like HT and HF
- 70. Renin inhibitor Aliskiren • Recently approved for HT • In clinical trial for HF: may be efficacy similar to ACEI • Exerts beneficial effect on myocardial remodeling by ↓ left ventricular mass in HT patients--Showing salutary effects on CVS--- Trial done on CHF patients • In a trial 3 Aliskiren with β antagonist and ACEI in CHF did show no hyperkalemia and hypotension and ↓ plasma BNP levels ↓ May improve symptoms and functional capacity in CHF
- 71. Endothelin antagonists Bosentan • Oral, non –selective • Approved for use in pts with pulmonary hypertension. • Not shown efficacy in heart failure • Failed to show benefit in mortality and morbidity Tezosentan • nonselective ET receptor antagonist Darunsentan
- 72. Adrenomedullin • Potent vasodilator peptide • Experimental therapeutic intervention in rats by transfer of the AM gene or of recombinant AM inhibit the progression of cardiac hypertrophy and remodeling • Promotes maintenance or improvement in renal function • Counter the activation or actions of vasoconstricting and sodium-retaining hormone systems • Potential therapeutic agents for Heart failure.
- 73. Steroids in HF
- 74. Statins
- 75. Allopurinol
Editor's Notes
- inherited or acquired abnormalities of cardiac structure or function unable to meet metabolic demands of the body, at rest and during exercise
- High CO patients rarely present with congestion Low CO patients also rarely present with congestion at the initial stage or on follow ups after treatment
- Other classification way is left side and right side HF but it is not a clear cut demarcation
- NYHA nt used nowadays as its based on symptoms so its patient specific
- CRT: left ventricular or bi ventricular pacing: reduce mortality pts of HF with normal sinus rhythm and wide QRS interval (&gt;120 ms) have impaired right and left ventricular contraction and so poor synch which leads to reduce CO
- Acute heart failure or decompensated heart failure
- ACEI cant replace Digoxin in pts receiving digoxin bcos pts withdrawn from digoxin deteriorate while on ACEI therapy Lisinopril has long duration of action (OD) and less hepatic metabolism so preferred All are prodrugs except captopril and lisinopril
- Duration of action oflisinopril and ramipril is more so once a day dose is enough Enalapril’s absorption not affected by food, onset is slow so no first dose hypotension Long duration of action, rashes and loss of taste are less
- Excessive tachycardia and high catecholamin levels leads to downward course of HF Initiate cautiously at low doses, as acutely blocking the supportive efffects of catecholamines can worsen the HF
- Excessive tachycardia and high catecholamin levels leads to downward course of HF Initiate cautiously at low doses, as acutely blocking the supportive efffects of catecholamines can worsen the HF
- Most common at home test to check b blockers effect is wt measurement. Reduced CO due to b blockers causes less renal perfusion, urine formation is less and low urine output-&gt;edema and thus weight gain Better than metoprolol and bisoprolol (selective β1 antagonists) 6.25 mg to 12.5 mg BD for HT, angina More β blocking action than alpha Max dose of carvedi: 50, meto: 200, biso: 10 Not all β blockers are effective in HF
- K and H+ loss is due to Na + water loss due to furosemide Other s/e are hyponatremia, hyper uric acis level, hyper glycemia, hyper lipids, hypo calcium and magnesium
- 12.5-25 mg/day: avoid hyperkalemia Can combined with ACEI…though causes hyperkalemia but low dose spironolactone can be added
- Spironolactone prevents myocardial and vascular fibrosis- prevent pathological remodeling of heart as spironolactone receptors present on cardiac myocyte Severe HF: after long term furosemide, add thiazide (chlorthalidone) spirono or metolazone Mild Hf: spirono + thiazide is sufficient
- Rapid method is given in acute HF Digoxin is not termed as inodilator though reduces preload and afterload bcos there is no direct vasodilatation but indirectly due to inhibition of sympathetic overactivity Digoxin and phenytoin not combined as it increases convulsion s/e digoxin: mc is anorexia, others are yellow vision,
- Less cardiac systole will give more time for ventricular rest and filling Reduction in HR is due to inhibition of Na+-K+ activity No change in o2 requirement is due to neutralization of ↓ hr by raise foc Decreases conduction velocity of avnode and his-purkinje system and prolongs ERP by vagal and extra vagal inhibition (Na+-K+ ATP ase) Due to inhibitonof compensatory SYMP activity-vasodilatation, diuresis( RAAS inhibition)
- Level less than 0.9 mg/l will reduce mortality and more than 1.5 will increase Measurement of plasma digoxin level is must 50% pts with normal sinus rhythm will have relief of HF from digitalis and more better result in hf with atrial fib Preferred in conditions with dilated heart (helpful in restoring cardiac compensation ?) Cumulative effect: when maintenance dose started in the beginning, steady state level and therapeutic benefit seen in 6-7 days
- Reason of extra systole, pulses bigeminus and vent fib is due to raised automaticity & contractility, shortening of ERP of atrial muscles and ventricles Rx for arrhythmia: correction of calcium, magnesium and potassium Treatment for bigeminus: oral k, withdrawal of digoxin, parenteral k, lidocaine Ppnl for ventricular & supravent tachycardia, atropine for bradycardia & av block… Do nt give ppnl if vent tachy is with av block Max effect of digitalis at av node as vagal fibres are innervated till av node Hyperkalemia is due to skeltal muscles and tissue potassium loss Hyperkalemia prevent binding of digitalis to na k atpase so reduces digitalis toxicity Digitalis induced arrhythmia increased by hypokalemia, hypercalcemia and hypomagnesemia (low dose can be given in elderlies Hypothyroidim causes slow elimination of drug In myocarditis chances of arrhythmia are high In wpw, digitalis enhances the conduction through accessory pathway and cause s ventricular fib
- At toxic doses: arrhythmia: antiarrhytmic drugs can be fatal as athigher doses automaticity gets depressed due to lowering of negative threshold potential…so at usual digoxin doseautomaticity increase but at higher dose it reduces
- Choice of agent depends on signs, symptoms, hemodynamics In african-american pts-already receiving ACEI, addition of BiDil reduces mortality(5)
- Choice of agent depends on signs, symptoms, hemodynamics In african-american pts-already receiving ACEI, addition of BiDil reduces mortality(5) Secere chf will have both dypnea nd fatifue Only veno/arterio are given in acute HF Long acting nitrates are: isosorbide dinitrate, glceryl tri nitrate
- Activation of protein kinase. Active pk phosphorylates ca channel and increase in flow
- Dobutamine increase CO and decrease venticular filling pressure Leads to tachycardia, and increase in myocardial oxygen consumption so ppt angina and arrhyth. Given in cardiogenic shock
- Dobutamine has additional b2 agonist Reason of adding dobutamine with dopamine
- Non glycoside non sympathomimetic inotropics Are bipyridines Inodilators Infusion in normal saline nt dextrose (drugs are unstable in dextrose)
- Milrinone is clinically given in children
- Milrinone is safer, maintain patients awaiting cardiac transplantation, low co hf with hypoperfusion, and those who fail to respond to iv diuretics
- for inotropic support However, the drug was proven to be superior to dobutamine for treating patients with a history of CHF or those on beta-blocker therapy when they are hospitalized with acute decompensations.[3](SURVIVE STUDY)
- BNP is synthesized in the heart Given in acute decompensated failure with dyspnea at rest
- Greater effect than nitroglycerine
- Urodilatin is an endogenous peptide similar to ANP which is synthesized in the kidney and function ther causing vasodilatation and natriuresis
- NEP inhibitor inhibit neutral endopeptidase which are responsible for degradation of ANP, BNP and adrenomedullin and bradikinin.
- Status of vasopepti
- Search clinical staus of newer drugs
- Expressed in cardiovascular tissues such as those of the cardiac atria and ventricles Exert inhibitory actions on myocyte hypertrophy & and on proliferation and collagen production of cardiac fibroblasts
- Ccbs cause depressant effect on the heart and worsen HF( WHY NT B BLOCEKRS THEN)