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Transcript
Therapy for Chronic and Acute Heart Failure Acute and Decompensated Chronic Heart Failure Aim Immediate ↑ in Cardiac Output Immediate ↓ in Cardiac Workload 1. Loop diuretic a. Furosemide 2. Nitrovasodilator a. Glyceryl trinitrate 3. Non – cardiac glycoside a. B1 agonist i. Dobutamine b. Calcium sensitizer i. Levosimendan c. Bypiridine (Phosphodiaesterase Inibitor) i. Milrinone 4. Anti-Angiotensin II Drugs a. ACE inhibitor i. Captopril b. ARB i. Losartan 5. Morphine Chronic Heart Failure Aim ↑ in Cardiac Output (Sustainable) ↓ in Cardiac Workload (Sustainable) 1. Anti-Angiotensin II Drugs a. ACE inhibitor i. Captopril b. ARB i. Losartan 2. Diuretics a. All types 3. Aldosterone antagonist a. Spironolactone 4. Cardiac glycosides a. Digoxin 5. Beta blockers a. Atenolol 6. If inhibitor a. Ivabradine Therapy for Acute and Decompensated Chronic Heart Failue Loop Diuretics Drug Name/ Infos Furosemide 1. 2. 3. Drug interaction 1. Warfarin a. Replace warfarin from protein binding 2. Ototoxicity a. ↑ incidence if given together with 4. Aminoglycosides 3. Increase toxicity a. Given with Probenecid – organic acid tansporter inhibitor Mechanism of Action Acts on Thick Ascending Limb of Henle Inhibit the Na+/K+/2Cl- cotransporter Therefore will lead to ↑ urinary excretion of a. Na b. Cl c. K d. Mg e. Ca Immediately reduce the preload, therefore less burden exerted to the failing heart improve cardiac efficiency 1. 2. 3. 4. 5. 6. 7. 8. Adverse Effects Ototoxicity Hyperuriceamia Acute hypovolumia Nephritis Hypokaleamia Hyperglycaemia Gouty arthritis Allergic reaction Nitrovasodilator Drug Name/ Infos Glyceryl Trinitrate (Prodrug) Infos 1. Fast tolerance Mechanism of Action 1. Undergoes denitration immediately upon entering into the body 2. Producing Nitric Oxide which is a very potent vasodilator a. Activate Guanylyl Cyclase b. ↑cGMP c. ↓Ca release d. ↑ smooth muscle relaxation 3. Immediately reduce afterload, therefore reducing workload improve cardiac efficiency Adverse Effects 1. Severe headache a. Due to immediate response of vasodilation 2. Severe hypotension 3. Reflex tachycardia Non-cardiac Glycosides Drug Name/ Infos B1 Agonist 1. Dobutamine (the most preferable) 2. Dopamine 3. Epinephrine Pharmacokinetic 1. Given IV 2. Immediate response 3. Only use in emergency cases, cause long term use can lead to a. Cardiac arrhythmia b. Cardiac arrest c. Mortality Drug Name/ Infos Calcium Sensitizer 1. Levosimendan 1. 2. 3. 4. 5. Mechanism of Action Binds Beta 1 receptor Activates Adenylyl Cyclase Converts ATP to cAMP This will therefore a. + chronotropic i. ↑heart rate b. + inotropic i. ↑ cardiac contractility c. + dormotrophic i. ↑impulse conduction All of these will lead to ↑ cardiac output improve efficiency of the failing heart Mechanism of Action 1. Binds to cardiac troponin C thus ↑ its sensitivity to Ca 2. This will then lead to more powerful contraction of cardiac muscle improve cardiac output 3. Opens K+ ATPase, efflux of K+ outside the peripheral smooth muscle cells relaxation of arterial and venous smooth muscle cells a. ↓afterload and preload leads to improvement of cardiac efficiency 1. 2. 3. 4. Adverse Effects Tachycardia Hypertension Atrial fibrillation Cardiac arrest Adverse Effects 1. Headache 2. Hypotension 3. Arrhythmias Drug Name/ Infos Bypiridine (Phosphodiaesterase Inhibitor) 1. Milrinone Info 1. Phosphodiaesterase Type III is an enzyme use in conversion of cAMP into AMP Mechanism of Action 1. Inhibits the Phosphodiaesterase type III leads to ↑ level of cAMP a. ↑cAMP will lead to activation of Protein Kinase A in which will further i. ↑ Ca level in the cytoplasm by 1. ↑Ca entry through Ca channel 2. ↓Ca sequestration (taking up) into the Sarcoplasmic Reticulum 2. This will then ↑ cardiac output and improve cardiac efficiency Adverse Effects 1. Cardiac arrhythmias Never been used for long time Anti-angiotensin II Drugs Drug Name/ Infos Anti-angiotensin II Drugs 1. ACE inhibitor a. Captopril 2. ARB a. Losartan Both drug should never be given to pregnant women For ARB, it is C/I in pts with 1. Angioedema due to ACEI These agents are very useful cause it will inhibit the inappropriate cardiac remodelling ↑pts survival Mechanism of Action ACE inhibitor 1. Inhibit the activity of ACE, therefore inhibit the conversion of Angiotensin I to Angiotensin II a. Leads to vasodilation b. ↓TPR ↓afterload c. ↓aldosterone release i. ↑water and Na excretion ii. ↓preload ARB 1. Blocks AT1 receptor, leads to d. Leads to vasodilation e. ↓TPR ↓afterload f. ↓aldosterone release i. ↑water and Na excretion ii. ↓preload All of these will ↓ cardiac workload thus improving cardiac 1. 2. 3. 4. Adverse Effects Dry cough (ACEI only) Angioedema Hyperkaleamia Acute renal failure a. Pts with renal artery stenosis Therapy for Chronic Heart Failure Anti-angiotensin II Drugs Drug Name/ Infos Anti-angiotensin II Drugs 3. ACE inhibitor a. Captopril 4. ARB a. Losartan Both drug should never be given to pregnant women For ARB, it is C/I in pts with 2. Angioedema due to ACEI These agents are very useful cause it will inhibit the inappropriate cardiac remodelling ↑pts survival Mechanism of Action ACE inhibitor 1. Inhibit the activity of ACE, therefore inhibit the conversion of Angiotensin I to Angiotensin II a. Leads to vasodilation b. ↓TPR ↓afterload c. ↓aldosterone release i. ↑water and Na excretion ii. ↓preload ARB 1. Blocks AT1 receptor, leads to d. Leads to vasodilation e. ↓TPR ↓afterload f. ↓aldosterone release i. ↑water and Na excretion ii. ↓preload All of these will ↓ cardiac workload thus improving cardiac 5. 6. 7. 8. Adverse Effects Dry cough (ACEI only) Angioedema Hyperkaleamia Acute renal failure a. Pts with renal artery stenosis Diuretics 1. 2. 3. 4. Drug Name/ Infos Loop diuretics a. Furosemide Thiazide diuretics a. Hydrochlorothiazide Potassium Sparing Diuretic a. Spironolactone Carbonic Anhydrase Inhibitor a. Acetozolamide Mechanism of Action 1. Reducing cardiac preload by a. ↑diuresis water and Na excretion from urine 2. After several periods of usage, diuretic will start to mobilize accumulated fluid in the interstitium (edema) into the blood vessel, this will then lead to improve Cardiac Output Adverse Effects Numerous side effects of diuretics Aldosterone Receptor Antagonist Drug Name/ Infos Spironolactone Infos Aldosterone roles in cardiac failure 1. ↑ Na and water retention a. ↑preload (↑cardiac burden) 2. ↑formation of fibrous tissue in heart a. Cardiac remodelling (↓efficiency) 3. Hypokaleamia and hypomagnesimia a. Cardiac arrest Mechanism of Action 1. This weak diuretic exerts its important role not thru diuretic but thru the inhibition of aldosterone receptor 2. Inhibition of aldosterone effect is very important as it will inhibit inappropriate cardiac remodelling 3. This will improve pts survival Adverse Effects 1. Gyneacomastia 2. Hyperkaleamia Cardiac Glycosides (Digitalis) Drug Name/ Infos Digoxin Mechanism of Action Direct effect 1. Irreversible blocks the Na+/K+ ATPase pump Pharmacokinetics a. ↑intracellular Na 1. Oral absorption 65% b. ↓transmembrane potential 80% c. Activate Na+/Ca2+ exchanger 2. Plasma protein binding d. ↑Ca level in the cell e. ↑cardiac contractility increase cardiac 25% 3. Large volume of output distribution Indirect effect a. 400L 1. ↓catecholamine release b. Stored in skeletal 2. ↑parasympathetic activity muscle 3. ↓RAAS activity 4. 2/3 excreted unchanged In which all these will ↓ preload and afterload thru urine (↓cardiac workload) 5. Half life 36 hours 6. Late onset Major effects of Digoxin a. 4-5 days 1. + inotropic b. Not preferable for a. ↑ cardiac contractility acute attack 2. + tonotropic 7. Narrow therapeutic a. ↓size of the heart index 3. + bathmotropic a. Major limitation a. ↑cardiac excitability 4. – chronotropic a. ↓ heart rate 5. – dromotropic a. ↓impulse conduction 1. 2. 3. 4. Adverse Effects Arrhythmias Headache Fatigue Electrolyte imbalances a. Hypokalemia b. Hypomagnesimia c. Hypercalceamia Beta Adrenergic Blocker Drug Name/ Infos Atenolol Beta blocker is the standard therapy for chronic heart failure for pts 1. Heamodynamically stable 2. No dyspnea during resting 3. Not C/I to use this agent Mechanism of Action 1. Cardiovascular system a. (-) in : i. Inotropic ii. Chronotropic b. Causing in: i. ↓cardiac output ii. ↓cardiac work iii. ↓oxygen consumption 2. Improve cardiac efficiency Adverse Effects 1. Rebound hypertension If Inhibitor Drug Name/ Infos Ivabradine Mechanism of Action 1. Block the HCN channel/ Funny channel a. ↓pacemaking activity of SA node b. ↓heart rate c. ↓cardiac workload d. ↓cardiac oxygen demand 2. There is no effect on cardiac contractility Adverse Effects 1. Luminous phenomena 2. Headache 3. Bradycardia