Fosinopril is an angiotensin converting enzyme (ACE) inhibitor used for the treatment of

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

and some types of chronic

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...

. Fosinopril is the only phosphonate-containing ACE inhibitor marketed, by

Bristol-Myers Squibb The Bristol-Myers Squibb Company, doing business as Bristol Myers Squibb (BMS), is an American multinational pharmaceutical company. Headquartered in Princeton, New Jersey, BMS is one of the world's largest pharmaceutical companies and consist ...

under the trade name Monopril. Fosinopril is a cascading pro-drug. The special niche for the medication that differentiates it from the other members of the ACE Inhibitor drug class is that was specifically developed for the use for patients with renal impairment. This was through manipulation of the metabolism and excretion, and is seen that fifty percent of the drug is hepatobiliary cleared, which can compensate for diminished renal clearance. The remaining fifty percent is excreted in urine. It does not need dose adjustment. It was patented in 1980 and approved for medical use in 1991.

Medical uses

congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF typically pr ...

, the ability of the heart to pump enough blood to satisfy the physiological needs of the body is reduced. This condition has a variety of causes, including damaged heart valves,

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

, hypertension, vitamin B₁ deficiency, and genetic mutations. When subsequent blood flow to the kidneys is reduced, the kidneys respond by increasing the secretion of

renin Renin ( etymology and pronunciation), also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin-angiotensin-aldosterone system (RAAS)—also known as the reni ...

from the

juxtaglomerular apparatus The juxtaglomerular apparatus (also known as the juxtaglomerular complex) is a structure in the kidney that regulates the function of each nephron, the functional units of the kidney. The juxtaglomerular apparatus is named because it is next to ...

. Renin converts the inactive

angiotensinogen Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adr ...

into

angiotensin I Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adren ...

, which is converted to

angiotensin II Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the ...

(AII) by

angiotensin converting enzyme Angiotensin-converting enzyme (), or ACE, is a central component of the renin–angiotensin system (RAS), which controls blood pressure by regulating the volume of fluids in the body. It converts the hormone angiotensin I to the active vasocon ...

(ACE). AII can have negative effects on the cardiovascular system after events such as heart failure and myocardial infarction. AII causes arterial

vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...

and hypertension, resulting in an increase in

afterload Afterload is the pressure that the heart must work against to eject blood during systole (ventricular contraction). Afterload is proportional to the average arterial pressure. As aortic and pulmonary pressures increase, the afterload increases on ...

, increasing the resistance against which the heart works. Additionally, chronic increase in production of AII is associated with structural changes to the

myocardium Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall o ...

which reduces the functionality of the heart. In heart failure patients, fosinopril increases exercise tolerance and lowers the frequency of events associated with worsening heart failure, such as

dyspnea Shortness of breath (SOB), known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing discomfort that ...

, the need for supplemental

diuretic A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics ...

s, fatigue, and hospitalizations.

Chemistry

Unlike other ACE inhibitors that are primarily excreted by the kidneys, fosinopril is eliminated from the body by both

renal In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and right in the retrop ...

and

hepatic The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

pathways. This characteristic of fosinopril makes the drug a safer choice than other ACE inhibitors for heart failure patients with impaired kidney function resulting from poor

perfusion Perfusion is the passage of fluid through the circulatory system or lymphatic system to an organ (anatomy), organ or a tissue (biology), tissue, usually referring to the delivery of blood to a capillary bed in tissue. Perfusion may also refer t ...

as fosinopril can still be eliminated by the liver, preventing accumulation of the drug in the body. Fosinopril is de-esterified by the liver or gastrointestinal mucosa and is converted to its active form, fosinoprilat. Fosinoprilat competitively binds to ACE, preventing ACE from binding to and converting angiotensin I to angiotensin II. Inhibiting the production of AII lowers

peripheral vascular resistance Vascular resistance is the resistance that must be overcome for blood to flow through the circulatory system. The resistance offered by the systemic circulation is known as the systemic vascular resistance or may sometimes be called by another ter ...

, decreases afterload, and decreases blood pressure, thus helping to alleviate the negative effects of AII on cardiac performance.

References

{{Angiotensin receptor modulators ACE inhibitors Carboxamides Enantiopure drugs Phosphinates Prodrugs Pyrrolidines Cyclohexyl compounds