أ. م . د. وحدة اليوزبكيHead of Department of Pharmacology- College of Medicine- University of Mosul-2014
Management of Heart Failure 2
Objectives- At the end of this lecture, students should be able to : 1- Define Heart failure (CHF) 2- State Underlying causes of CHF 3- Enumerate groups of Drug Therapy of CHF. 4- Identify action of diuretic in CHF. 5- Identify action, clinical uses and side effects of ACEIs in CHF. 6- Discuss Positive Inotropic Drugs - At a level accepted to the quality assurance standards for the College of Medicine/ University of Mosul.
Management of Heart Failure
Definition: CHF: It is a condition in which the heart is unable to pump sufficient blood to meet the metabolic requirement of the body (peripheral system). Underlying causes of CHF include: 1- Atherosclerosis (most common). 2- Hypertension. 3- Valvular heart diseases. 4- Dilated cardiomyopathy. 5- Congenital heart diseases.Compensatory physiological responses in CHF
Management of CHF
I- General Measures: 1- Physical activity. 2- Low dietary intake of Na(<1500ug/day). 3- Avoid drugs that may precipitate CHF, E.g. NSAIDs, B Blocker, Calcium channel blocker, Some antiarrhythmic drugs, Alcohol.II- Drug Therapy
1- Vasodilators, include: ACE Inhibitors (captopril). 2- Diuretics. 3- Inotropic Drugs: a- Digitalis. b- B adrenergic agonist (Dobutamine). c- Phosphdiesterase inhibitors (Dipyridines) Eg. Amrinone, Milirinone.I- Vasodilators in CHF
-Vasodilators are useful in reducing excessive preload & afterload in CHF. - ACE Inhibitors (Captopril) are the agents of choice in CHF. Action: These drugs block the enzyme that cleaves angiotensin I to form the potent vasoconstrictor angiotensin II, this will lead to: 1- Vasodilatation of vascular sm.m , lead to reduction of peripheral resistance (PR) and thereby reduce afterload. 2- Reducing aldosterone secretion: This lead to reduce salt and water retention and in this way reduce the preload. 3- The reduction of the sympathetic output and activity. 4- Decrease the rate of Bradykinin degradationand so this will lead to increase bradykinin level ( which is potent vasodilator).Action of ACE Inhibitors in CHF
Indication of ACE inhibitors
1- Single agent therapy in patient with mild dyspnea on exertion. 2- Patient with recent MI. Side Effects of ACE Inhibitors: - First dose postural hypotension, hyperkalaemia, renal insufficiency, persistent dry cough, skin rash, taste disturbance, leucopenia, angioneurotic edema & protein urea. Note: ACE Inhibitors should not be given to pregnant.2- Diuretic in CHF
Action: Diuretic by plasma volume: 1- venous return to the heart (preload) & & this results in reduction of edema and its symptoms, and reduction of cardiac size, which leads to improved pump efficiency.. 2- Bdp & so afterload. Note: The diuretic used in CHF is Thiazide group which is mild & loose efficacy if patient creatinine clearance is less than 50 ml/ min in this case use loop diuretic (in case of renal insufficiency).3-Positive Inotropic Drugs
These drugs enhance & improve cardiac contractility & thus increase C.O. 2 Groups of inotropic drugs: A- Digitalis Glycosides. The cardiac glycosides are often called digitalis because most of the drug come from digitalis (foxglove plant).Mechanism of Action of Digoxin
Cardiac glycosides affect: A- Cardiac effect : 1- Directly: By inhibition of the membrane bound (Na-K activated Atpase). 2- In directly: By enhancement of vagal (PS) B- Extra cardiac effect:
Mechanism of Action of Digoxin
2- In directly: By enhancement of vagal (PS) by complex peripheral & central mechanism, & so slow the conducting tissue (SA &AV node) Negative chronotropic effect ( HR). B- Extra cardiac effect: Digitalis by increase cardiac output renal blood flow & urine volume ( diuretic effect) edema & preload.Extensive in liver & excreted in faeces
85% excreted unchanged (kidney)Metabolism
< Vd
>
Protein binding
More rapid
Onset of action
Up to 2 days
36 h
t 1/2
90-100%
40-75%
Absorption
Digitoxin
Digoxin
Pharmacokinetic of Digitalis
Indications of Digoxin1- CHF: mainly severe LV function. 2- Atrial fibrillation & some cases of Atrial Flutter. Dose (Digitalization): - Maintenance & slow loading (0.125-0.5 mg) - Rapid digitalization ( 0.5-0.75 mg / 8h for 3 doses).
Side Effects of Digoxin
Digoxin has low therapeutic index ( 0.5-2 ng / ml), so has low margin of safety & toxicity occur if serum conc. of digoxin rise > 2 ng / ml: 1- GIT effect: 2- CNS effect: 3- Cardiac effects: 4- Gynaecomastia in men & breast enlargement in women with long use.Factors predisposing to digitalis toxicity
1- Electrolyte Disturbance: a- Hypokalaemia ( K ). b- Hypercalcaemia ( Ca). c- Hypomagnesaemia ( Mg). 2- Diseases : a- Renal impairment ( excretion of digoxin). b- Hypothyroidism ( metabolism of digoxin). c- Diarrhea ( K ). 3- Drugs: a- diuretic therapy. b- Quinidin. c- Verapamil. d- NSAI drugs & Ca channel blocking agents. e. Antibiotic. f- Steroids.Management of Digoxin Toxicity
1- Discontinued digoxin & K depleting agents. 2- Kcl given orally or by slow IV infusion. 3- Mg replacing therapy may be given. 4- Phenytoin may be given for treatment of ectopic. 5- Lidocain for Ventricular tachycardia. 6- Atropin for sinus bradycardia. 7- In severe acute poisoning ( suicidal overdose), 8- (Digoxin immune fab) used. 9- Cardioversion (DC) reserved for VF.B- Second Group of positive inotropic Phosphodiesterase inhibitors ( Amrinone & Milirinone)
Action: These drugs by inhibiting phosphdiesterase enzyme prevent hydrolysis & decrease inactivation of CAMP to AMP CAMP level IC Ca improve cardiac muscle contractility. Side Effects: Cardiac arrhythmia < digitalis, BM & liver toxicity & even mortality.