Sacubitril-Valsartan, Milrinone, Nesiritide, Ivabradine

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Pharmacology

Summary

Sacubitril/valsartan, commonly referred to as entresto, is a combination medication pivotal in managing systolic heart failure, notably for its role in diminishing the risk of cardiovascular death. This distinctive mechanism stems from sacubitril, a neprilysin inhibitor, which increases levels of the endogenous natriuretic peptides, ANP and BNP, facilitating vasodilation and sodium excretion. Sacubitril/valsartan therapy may pose several side effects including: hyperkalemia, hypotension, and symptoms of orthostatic hypotension like dizziness and syncope. Its use is contraindicated with ACE inhibitors due to the risk of angioedema, and in people with prior history of angioedema from ACE inhibitors or ARBs

Milrinone, nesiritide, and ivabradine are additional agents employed in heart failure treatment. Milrinone enhances cAMP levels, promoting cardiac contractility and arteriolar dilation, thus reducing afterload. Nesiritide, a synthetic derivative of BNP, induces vasodilation and natriuresis. Ivabradine acts by interrupting the 'funny current' (If) within the SA node, thereby moderating heart rate. Each of these drugs carries its own set of potential side effects, including hypotension with milrinone, diuresis with nesiritide, and bradycardia when using ivabradine.

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FAQs

What is the mechanism of action of sacubitril/valsartan, and when is it indicated?

Sacubitril/valsartan is a combination medication used for systolic heart failure, also known as HFrEF. Sacubitril inhibits neprilysin, an enzyme that breaks down vasoactive natriuretic peptides. By inhibiting neprilysin, levels of endogenous ANP, BNP, and bradykinin rise, resulting in arteriolar and venous dilation, and subsequently reducing preload and afterload. Valsartan, an angiotensin II receptor blocker, further assists by modulating the renin-angiotensin-aldosterone system (RAAS).

What are the potential side effects and risks associated with sacubitril/valsartan treatment?

Sacubitril/valsartan therapy may pose several side effects, including hyperkalemia, hypotension, and symptoms of orthostatic hypotension such as dizziness and fainting. Additionally, it can precipitate renal impairment or even renal failure. Sacubitril/valsartan can increase the risk of angioedema and should therefore not be combined with ACE inhibitors due to the risk of this potentially life-threatining complication. Therefore, transitioning between ACE inhibitors and sacubitril/valsartan requires a 36-hour washout period.

What is the mechanism of action of milrinone?

Milrinone, indicated for acute heart failure, acts by inhibiting the enzyme phosphodiesterase. This inhibition preserves cAMP levels, thereby increasing cardiac contractility. It also induces arteriolar dilation, which in turn reduces afterload.

What is nesiritide, and how does it function?

Nesiritide is a synthetic analogue of B-type natriuretic peptide (BNP). Its mechanism centers on elevating cGMP levels in smooth muscle, facilitating natriuresis — the process by which sodium is excreted in the urine.

What is the function of ivabradine, and what conditions is it used to treat?

Ivabradine is employed in the management of systolic heart failure or HFrEF. Its primary action disrupts the 'funny current' (If) in the sinoatrial (SA) node, culminating in a slowed heart rate, which proves advantageous in situations where it's essential to minimize cardiac workload.