Mechanisms of actions of ACE inhibitors, Angiotensin receptor blockers (ARBs), Beta-blockers, Aldosterone receptor antagonists (ARAs), Digoxin, Ivabradine, Angiotensin Receptor-Neprilysin Inhibitor, ARNIs (sacubitril/valsartan), Diuretics, Vasodilators. Role of RAAS, sympathetic system and natriuretic peptide system in pathophysiology of Congestive heart failure (CHF) and rational for treatment of HF.
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Heart failure is when the heart is unable to pump effectively, called systolic heart failure; or unable to fill properly, called diastolic heart failure. In both cases, blood output is reduced. Ejection fraction is reduced in systolic heart failure, but typically preserved in diastolic heart failure. The pathophysiology of heart failure involves a vicious cycle in which reduced cardiac output, as a compensatory response, activates the renin-angiotensin-aldosterone system (RAAS) and sympathetic system. However, these systems cause vasoconstriction, increase heart rate and blood pressure, making it even harder for the heart to pump. Increased aldosterone level also promotes ventricular remodeling, myocardial scarring, and vascular injury, worsening the disease. On the other hand, the natriuretic peptide system is also activated. This system is protective to the heart. It promotes vasodilation, sodium and water excretion, and inhibits cardiac remodeling. Most drugs used in heart failure therapy aim to inhibit RAAS and sympathetic activities, and/or promote the natriuretic system. Other drugs increase ventricular contractility or reduce water retention – a major heart failure symptom. First-line therapy for patients with reduced ejection fraction typically includes an angiotensin-converting enzyme (ACE) inhibitor, and a beta-blocker. - ACE inhibitors block the conversion of angiotensin-I to angiotensin-II in RAAS, thereby inhibiting RAAS activity. Common side effects include dry cough, headache, and hypotension. Rarely, ACE inhibitors may cause a swelling reaction known as angioedema. - Angiotensin receptor blockers (ARBs) inhibit the effects of angiotensin-II. Their mechanism of action is similar to that of ACE inhibitors, but they do not usually cause a cough. - Beta-blockers decrease heart rate by binding to β1-adrenergic receptor in the heart and blocking the sympathetic influences that act through these receptors. Adverse effects: hypotension, bradycardia and AV blocks. - Vasodilators reduce blood pressure and are usually used for patients who cannot tolerate ACE inhibitors or ARBs. - Diuretics are often prescribed to relieve fluid retention. Loop diuretics are most powerful and typically used for most patients. Thiazides are less effective, but they also have a vasodilation effect, and are thus preferred for patients with hypertension but only mild fluid retention. - Aldosterone receptor antagonists block the action of aldosterone. Because aldosterone’s primary function is to promote sodium and water retention, and potassium excretion; aldosterone antagonists act as potassium-sparing diuretics. However, their effect in heart failure treatment is also attributed to the inhibition of aldosterone’s damaging impact on the heart and blood vessels. - Digoxin increases cardiac contractility by inhibiting the sodium-potassium pump, causing intracellular sodium concentration to rise. This then leads to higher levels of intracellular calcium via the action of sodium-calcium exchanger. Higher calcium results in increased muscle contraction. Digoxin also decreases sympathetic activities, slowing down heart rate. - Ivabradine slows the heart rate by inhibiting the “funny” channel responsible for spontaneous firing of the SA node. Adverse effects include bradycardia, atrial fibrillation, and vision problems. - ARNIs are a new class of medications. ARNI therapy consists of a neprilysin inhibitor and an ARB.
Content
3.12 -> Heart failure is when the heart is unable to
pump effectively, called systolic heart failure;
8.52 -> or unable to fill properly, called diastolic heart
failure. In both cases, blood output is reduced.
16.62 -> Ejection fraction is reduced
in systolic heart failure,
19.5 -> but typically preserved in
diastolic heart failure.
23.22 -> The pathophysiology of heart failure involves a
vicious cycle in which reduced cardiac output,
28.62 -> as a compensatory response, activates the
renin-angiotensin-aldosterone system (RAAS) and
36 -> sympathetic system. However, these systems cause
vasoconstriction, increase heart rate and blood
42.48 -> pressure, making it even harder for the heart to
pump. Increased aldosterone level also promotes
48.48 -> ventricular remodeling, myocardial scarring,
and vascular injury, worsening the disease.
55.2 -> On the other hand, the natriuretic peptide system
is also activated. This system is protective to
61.74 -> the heart. It promotes vasodilation, sodium and
water excretion, and inhibits cardiac remodeling.
69.12 -> Most drugs used in heart failure therapy aim
to inhibit RAAS and sympathetic activities,
74.46 -> and/or promote the natriuretic system. Other drugs
increase ventricular contractility or reduce water
82.38 -> retention – a major heart failure symptom.
First-line therapy for patients with reduced
88.38 -> ejection fraction typically includes
an angiotensin-converting enzyme
92.34 -> (ACE) inhibitor, and a beta-blocker.
- ACE inhibitors block the conversion
98.4 -> of angiotensin-I to angiotensin-II in
RAAS, thereby inhibiting RAAS activity.
104.76 -> Common side effects include dry cough, headache,
and hypotension. Rarely, ACE inhibitors may
111.6 -> cause a swelling reaction known as angioedema.
- Angiotensin receptor blockers (ARBs) inhibit
119.16 -> the effects of angiotensin-II. Their mechanism
of action is similar to that of ACE inhibitors,
125.04 -> but they do not usually cause a cough. However,
they are less effective and are typically used
130.74 -> in patients who cannot tolerate ACE inhibitors.
- Beta-blockers decrease heart rate by binding to
137.82 -> β1-adrenergic receptor in the heart and blocking
the sympathetic influences that act through these
143.34 -> receptors. Common side effects are those of
hypotension. Rarer but more severe adverse
150.54 -> events include bradycardia and AV blocks.
- Vasodilators reduce blood pressure and are
157.32 -> usually used for patients who cannot tolerate ACE
inhibitors or ARBs. Side effects include nausea,
163.26 -> palpitations, joint pain, and rash.
- Diuretics are often prescribed to
169.44 -> relieve fluid retention. Loop diuretics are most
powerful and typically used for most patients.
176.28 -> Thiazides are less effective, but they also have
a vasodilation effect, and are thus preferred for
181.68 -> patients with hypertension but only mild fluid
retention. Major side effects include electrolyte
188.04 -> imbalances, metabolic alkalosis, and hypovolemia.
- Aldosterone receptor antagonists block the
195.9 -> action of aldosterone. Because aldosterone’s
primary function is to promote sodium and water
201.9 -> retention, and potassium excretion; aldosterone
antagonists act as potassium-sparing diuretics.
209.22 -> However, their effect in heart failure treatment
is also attributed to the inhibition of
214.74 -> aldosterone’s damaging impact on the heart and
blood vessels. Major adverse effects include
