▪ Congestive heart failure introduction
▪ Classification of drugs used
▪ Pharmacology of drug
▪ Treatment of CHF
CONGESTIVE HEART FAILURE
The function of heart is to pump an adequate amount of blood to various tissues. In CHF (Congestive heart failure), there is an inadequate or inefficient contraction of heart leading to reduced cardiac output.
In initial stages of CHF, the compensatory mechanisms try to maintain the proper cardiac output which are :
• increased sympathetic activity.
• increased renin-angiotensin aldosterone activity.
• myocardial hyertrophy and remodelling.
The basic haemodynamic disturbances seen in congestive cardiac failure are :
• increased pulmonary capillary pressure termed as backward failure, which is characterised by dysnoea and orthopnoea.
• decreased cardiac output termed as forward failure, leading to decreased oxygen supply to the peripheral tissue.
CLASSIFICATION
1) Diuretics.
a. Loop diuretics : furosemide, bumetanide, torsemide.
b. Thiazide diuretics : chlorothiazide, hydrochlorothiazide.
c. K+ sparing diuretics : spironolactone, amiloride.
2) Cardiac glycosides : digoxin, digitoxin.
3) Vasodilator :
a. Arteriolar dilators : hydralazine, minoxidil, nicorandil.
b. Venodilators : nitrates.
c. Arteriolar and venodilators : ACE inhibitors, sodium nitroprusside.
4) beta-blockers : metoprolol, bisoprolol, carvedilol.
5) sympathomimetic amines : dopamine, dobutamine.
6) phosphodiesterase inhibitors : amrinone, milrinone.
b. Thiazide diuretics : chlorothiazide, hydrochlorothiazide.
c. K+ sparing diuretics : spironolactone, amiloride.
2) Cardiac glycosides : digoxin, digitoxin.
3) Vasodilator :
a. Arteriolar dilators : hydralazine, minoxidil, nicorandil.
b. Venodilators : nitrates.
c. Arteriolar and venodilators : ACE inhibitors, sodium nitroprusside.
4) beta-blockers : metoprolol, bisoprolol, carvedilol.
5) sympathomimetic amines : dopamine, dobutamine.
6) phosphodiesterase inhibitors : amrinone, milrinone.
TREATMENT OF CONGESTIVE HEART FAILURE
There are two distinct goals of drug therapy in CHF :
a) Relief of congestive/low output symptoms and restoration of cardiac performance :
Drugs used in this are : digoxin, dobutamine, dopamine, amrinone, furosemide, thiazides, ACE inhibitors, hydralazine, nitrates, metoprolol, bisoprolol, carvedilol.
b) Arrest/reversal of disease progression and prolongation of survival :
Drugs used in this are : ACE inhibitors, Beta blockers, spironolactone.
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CARDIAC GLYCOSIDES
Chemistry :
The glycosides consist of an aglycone (steroid nucleus with an attached lactone ring) with one or more sugar moieties attached to it. They have potent action on the heart, hence referred to as cardiac glycosides.
Mechanism of action of Digitalis :
Na+ K+ -ATPase is a membrane bound enzyme which is called digitalis receptor. It is also called sodium pump.
PHARMACOLOGICAL ACTION
1.Cardiac
2. Extracardiac
Cardiac actions :
Digitalis has direct and indirect actions on heart.
▪ direct action by inhibiting Na+ K+ -ATPase.
▪ indirect action by stimulating vagus.
1. Myocardial contractility :
- digitalis increases the forces of contraction of the myocardium (positive inotropic effect).
- The positive inotropic effect causes complete emptying of ventricles during systole and increases the cardiac output.
- This decreases pulmonary congestion and systemic venous pressure.
- Diastolic size of heart is reduced and hence size of the muscle fibre length also reduced, thereby, decreases the oxygen requirement of myocardium.
- The digitalised heart, now can do more work for the same energy.
2. Heart rate :
- digitalis reduces the heart rate by direct and indirect action, in small doses, it causes decreased heart rate.
3. Electrophysiological action :
- at therapeutic concentration, digoxin decreases automaticity and increases membrane potential by vagal action in atria and AV node.
Extra cardiac :
1. Gasrtointestinal tract : digitalis can produce anorexia, nausea, vomiting, and diarrhoea.
2. Kidney : causes diuresis.
3. Central nervous system : in high doses, it can causes central sympathetic stimulation, confusion, blurring of vision, disorientation.
PHARMACOKINETICS
Digoxin is the commonly used glycoside and administered by oral route.
widely distributed in body, concentrated in the heart, liver, kidneys, and skeletal muscle.
crosses the BBB and is mainly excreted in urine.
ADVERSE EFFECT
1. Extra cardiac :
i) GIT : anorexia, nausea, vomiting.
ii) CNS : headache, confusion, restlessness, disorientation, weakness, visual disturbances, altered mood and hallucination.
iii) Skin rashes and gynaecomastia : it can occur occasionally.
2. Cardiac : digitalis can causes any type of arrhythmia. The most common are ventricular premature beats, pulses bigeminy and ventricular tachycardia. Also cause A-V block , atrial tachycardia, atrial fibrillation, atrial flutter, even severe bradycardia.
DIURETICS
Thiazides are used in mild to moderate cardiac failure. They inhibits Na+ -Cl- symport in the cortical diluting sigment.
Loop diuretics inhibits Na+ - K+ -2Cl- cotransport, mainly in the thick ascending limb of the loop of henle.
Loop diuretcs are mainly used in severe cardiac failure, pulmonary oedema and refractory heart failure.
Causes : Hypokalaemia.
ACE INHIBITORS
These are the first line drugs in treatment of chronic heart failure. They inhibit the conversion of angiotensin-I to angiotensin-II.
Beta BLOCKER
Metaprolol, bisoprolol, are useful in mild to moderate heart failure.
Long term therapy with these drugs improves symptoms, reduces hospitalization and decreases mortality in patients with mild to moderate heart failure.
DOPAMINE
At low concentration, dopamine selectively dilates renal, mesenteric and coronary blood vessels by acting on D1 receptors. Thus dopamine increases GFR and urine output.
At moderate concentration, stimulates Beta receptors of heart, increases myocardial contractility and cardiac output.
At high concentration, it causes generalized vasoconstriction. This increases afterload and reduces blood flow to renal, mesenteric and other vital organs. So the beneficial effects seen with low to moderate doses of dopamine are lost at higher concentration.
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😊 I hope you've got help, if you have any suggestion or any question regarding this article "Congestive heart failure,, please comment i will be very happy.
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