Fosinopril

Last updated
Fosinopril
Fosinopril structure.svg
Clinical data
Trade names Monopril
AHFS/Drugs.com Monograph
MedlinePlus a692020
Pregnancy
category
  • AU:D
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability ~36%
Protein binding 87% (fosinoprilat)
Metabolism liver, GIT mucosa (to fosinoprilat)
Elimination half-life 12 hours (fosinoprilat)
Excretion kidney
Identifiers
  • (2S,4S)-4-cyclohexyl-1-[2-[hydroxy(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C30H46NO7P
Molar mass 563.672 g·mol−1
3D model (JSmol)
  • O=C(CP(=O)(CCCCc1ccccc1)OC(OC(=O)CC)C(C)C)N2C[C@@H](C[C@H]2C(O)=O)C3CCCCC3
  • InChI=1S/C30H46NO7P/c1-4-28(33)37-30(22(2)3)38-39(36,18-12-11-15-23-13-7-5-8-14-23)21-27(32)31-20-25(19-26(31)29(34)35)24-16-9-6-10-17-24/h5,7-8,13-14,22,24-26,30H,4,6,9-12,15-21H2,1-3H3,(H,34,35)/t25-,26+,30?,39-/m1/s1 Yes check.svgY
  • Key:BIDNLKIUORFRQP-YYTCENNOSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Fosinopril is an angiotensin converting enzyme (ACE) inhibitor [1] used for the treatment of hypertension and some types of chronic heart failure. Fosinopril is the only phosphonate-containing ACE inhibitor marketed, by Bristol-Myers Squibb 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.

Contents

It was patented in 1980 and approved for medical use in 1991. [2]

Medical uses

In congestive heart failure, the ability of the heart to pump enough blood to satisfy the physiological needs of the body is reduced. [3] This condition has a variety of causes, including damaged heart valves, myocardial infarction, 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 from the juxtaglomerular apparatus. Renin converts the inactive angiotensinogen into angiotensin I, which is converted to angiotensin II (AII) by angiotensin converting enzyme (ACE). AII can have negative effects on the cardiovascular system after events such as heart failure and myocardial infarction. AII causes arterial vasoconstriction and hypertension, resulting in an increase in afterload, increasing the resistance against which the heart works. [4] Additionally, chronic increase in production of AII is associated with structural changes to the myocardium [5] which reduces the functionality of the heart. [4]

In heart failure patients, fosinopril increases exercise tolerance and lowers the frequency of events associated with worsening heart failure, such as dyspnea, the need for supplemental diuretics, fatigue, and hospitalizations. [6]

Chemistry

Unlike other ACE inhibitors that are primarily excreted by the kidneys, fosinopril is eliminated from the body by both renal and hepatic pathways. [7] 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 [8] as fosinopril can still be eliminated by the liver, preventing accumulation of the drug in the body. [7]

Fosinopril is de-esterified by the liver or gastrointestinal mucosa and is converted to its active form, fosinoprilat. [9] 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, decreases afterload, and decreases blood pressure, [4] thus helping to alleviate the negative effects of AII on cardiac performance.

Related Research Articles

<span class="mw-page-title-main">ACE inhibitor</span> Class of medications used primarily to treat high blood pressure

Angiotensin-converting-enzyme inhibitors are a class of medication used primarily for the treatment of high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart.

<span class="mw-page-title-main">Renin</span> Aspartic protease protein and enzyme

Renin, 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 renin–angiotensin–aldosterone axis—that increases the volume of extracellular fluid and causes arterial vasoconstriction. Thus, it increases the body's mean arterial blood pressure.

<span class="mw-page-title-main">Renin–angiotensin system</span> Hormone system

The renin–angiotensin system (RAS), or renin–angiotensin–aldosterone system (RAAS), is a hormone system that regulates blood pressure, fluid and electrolyte balance, and systemic vascular resistance.

<span class="mw-page-title-main">Angiotensin</span> Group of peptide hormones in mammals

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 adrenal cortex to promote sodium retention by the kidneys.

<span class="mw-page-title-main">Captopril</span> Antihypertensive drug of the ACE inhibitor class

Captopril, sold under the brand name Capoten among others, is an angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first oral ACE inhibitor found for the treatment of hypertension. It does not cause fatigue as associated with beta-blockers. Due to the adverse drug event of causing hyperkalemia, as seen with most ACE Inhibitors, the medication is usually paired with a diuretic.

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.

<span class="mw-page-title-main">Amlodipine</span> Dihydropyridine calcium channel blocker used to treat cardiovascular diseases

Amlodipine, sold under the brand name Norvasc among others, is a calcium channel blocker medication used to treat high blood pressure, coronary artery disease (CAD) and variant angina. It is taken orally.

<span class="mw-page-title-main">Enalapril</span> ACE inhibitor medication

Enalapril, sold under the brand name Vasotec among others, is an ACE inhibitor medication used to treat high blood pressure, diabetic kidney disease, and heart failure. For heart failure, it is generally used with a diuretic, such as furosemide. It is given by mouth or by injection into a vein. Onset of effects are typically within an hour when taken by mouth and last for up to a day.

<span class="mw-page-title-main">Angiotensin II receptor blocker</span> Group of pharmaceuticals that modulate the renin–angiotensin system

Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals that bind to and inhibit the angiotensin II receptor type 1 (AT1) and thereby block the arteriolar contraction and sodium retention effects of renin–angiotensin system.

<span class="mw-page-title-main">Lisinopril</span> Medication used to treat high blood pressure and heart failure

Lisinopril is a medication belonging to the drug class of angiotensin-converting enzyme (ACE) inhibitors and is used to treat high blood pressure, heart failure, and heart attacks. For high blood pressure it is usually a first-line treatment. It is also used to prevent kidney problems in people with diabetes mellitus. Lisinopril is taken by mouth. Full effect may take up to four weeks to occur.

<span class="mw-page-title-main">Ramipril</span> ACE inhibitor

Ramipril, sold under the brand name Altace among others, is an ACE inhibitor type medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It can also be used as a preventative medication in patients over 55 years old to reduce the risk of having a heart attack, stroke or cardiovascular death in patients shown to be at high risk, such as some diabetics and patients with vascular disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth.

<span class="mw-page-title-main">Candesartan</span> Angiotensin II receptor antagonist

Candesartan is an angiotensin receptor blocker used mainly for the treatment of high blood pressure and congestive heart failure. Candesartan has a very low maintenance dose. Like Olmesartan, the metabolism of the drug is unusual as it is a cascading prodrug. Candesartan has good bioavailibility and is the most potent by weight of the AT-1 receptor antagonists.

<span class="mw-page-title-main">Potassium-sparing diuretic</span> Drugs that cause diuresis without causing potassium loss in the urine and leading to hyperkalemia

Potassium-sparing diuretics refers to drugs that cause diuresis without causing potassium loss in the urine. They are typically used as an adjunct in management of hypertension, cirrhosis, and congestive heart failure. The steroidal aldosterone antagonists can also be used for treatment of primary hyperaldosteronism. Spironolactone, a steroidal aldosterone antagonist, is also used in management of female hirsutism and acne from PCOS or other causes.

<span class="mw-page-title-main">Valsartan</span> Angiotensin II receptor antagonist

Valsartan, sold under the brand name Diovan among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It belongs to a class of medications referred to as angiotensin II receptor blockers (ARBs). It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combination valsartan/hydrochlorothiazide, valsartan/amlodipine, valsartan/amlodipine/hydrochlorothiazide, or valsartan/sacubitril.

<span class="mw-page-title-main">Perindopril</span> High blood pressure medication

Perindopril is a medication used to treat high blood pressure, heart failure, or stable coronary artery disease.

<span class="mw-page-title-main">Aliskiren</span> Medication

Aliskiren is the first in a class of drugs called direct renin inhibitors. It is used for essential (primary) hypertension. While used for high blood pressure, other better studied medications are typically recommended due to concerns of higher side effects and less evidence of benefit.

<span class="mw-page-title-main">Renin inhibitor</span> Compound inhibiting the activity of renin

Renin inhibitors are pharmaceutical drugs inhibiting the activity of renin that is responsible for hydrolyzing angiotensinogen to angiotensin I, which in turn reduces the formation of angiotensin II that facilitates blood pressure.

<span class="mw-page-title-main">Moexipril</span> Antihypertensive drug of the ACE inhibitor class

Moexipril an angiotensin converting enzyme inhibitor used for the treatment of hypertension and congestive heart failure. Moexipril can be administered alone or with other antihypertensives or diuretics.

<span class="mw-page-title-main">Sacubitril/valsartan</span> Combination medication

Sacubitril/valsartan, sold under the brand name Entresto, is a fixed-dose combination medication for use in heart failure. It consists of the neprilysin inhibitor sacubitril and the angiotensin receptor blocker valsartan. The combination is sometimes described as an "angiotensin receptor-neprilysin inhibitor" (ARNi). In 2016, the American College of Cardiology/American Heart Association Task Force recommended it as a replacement for an ACE inhibitor or an angiotensin receptor blocker in people with heart failure with reduced ejection fraction.

<span class="mw-page-title-main">Fimasartan</span> Chemical compound

Fimasartan is a non-peptide angiotensin II receptor antagonist (ARB) used for the treatment of hypertension and heart failure. Through oral administration, fimasartan blocks angiotensin II receptor type 1 (AT1 receptors), reducing pro-hypertensive actions of angiotensin II, such as systemic vasoconstriction and water retention by the kidneys. Concurrent administration of fimasartan with diuretic hydrochlorothiazide has shown to be safe in clinical trials. Fimasartan was approved for use in South Korea on September 9, 2010, and is available under the brand name Kanarb through Boryung Pharmaceuticals, who are presently seeking worldwide partnership.

References

  1. ↑ Pilote L, Abrahamowicz M, Eisenberg M, Humphries K, Behlouli H, Tu JV (May 2008). "Effect of different angiotensin-converting-enzyme inhibitors on mortality among elderly patients with congestive heart failure". CMAJ. 178 (10): 1303–1311. doi:10.1503/cmaj.060068. PMC   2335176 . PMID   18458262.
  2. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 468. ISBN   9783527607495.
  3. ↑ Guyton AC, Hall JE (2006). Textbook of medical physiology: online access + interactive extras: studentconsult.com (11th ed.). Philadelphia, Pa: Elsevier, Saunders. ISBN   978-0-7216-0240-0.
  4. 1 2 3 Katzung BG, Masters SB, Trevor AJ (2009). Basic and Clinical Pharmacology (11th ed.). New York: McGraw-Hill. ISBN   978-0-07-160405-5.
  5. ↑ Yamagishi H, Kim S, Nishikimi T, Takeuchi K, Takeda T (November 1993). "Contribution of cardiac renin-angiotensin system to ventricular remodelling in myocardial-infarcted rats". Journal of Molecular and Cellular Cardiology. 25 (11): 1369–1380. doi:10.1006/jmcc.1993.1149. PMID   8301670.
  6. ↑ Erhardt L, MacLean A, Ilgenfritz J, Gelperin K, Blumenthal M (December 1995). "Fosinopril attenuates clinical deterioration and improves exercise tolerance in patients with heart failure. Fosinopril Efficacy/Safety Trial (FEST) Study Group". European Heart Journal. 16 (12): 1892–1899. doi:10.1093/oxfordjournals.eurheartj.a060844. PMID   8682023.
  7. 1 2 Zannad F, Chati Z, Guest M, Plat F (October 1998). "Differential effects of fosinopril and enalapril in patients with mild to moderate chronic heart failure. Fosinopril in Heart Failure Study Investigators". American Heart Journal. 136 (4 Pt 1): 672–680. doi:10.1016/s0002-8703(98)70015-8. PMID   9778071.
  8. ↑ Greenbaum R, Zucchelli P, Caspi A, Nouriel H, Paz R, Sclarovsky S, et al. (January 2000). "Comparison of the pharmacokinetics of fosinoprilat with enalaprilat and lisinopril in patients with congestive heart failure and chronic renal insufficiency". British Journal of Clinical Pharmacology. 49 (1): 23–31. doi:10.1046/j.1365-2125.2000.00103.x. PMC   2014892 . PMID   10606834.
  9. ↑ Duchin KL, Waclawski AP, Tu JI, Manning J, Frantz M, Willard DA (January 1991). "Pharmacokinetics, safety, and pharmacologic effects of fosinopril sodium, an angiotensin-converting enzyme inhibitor in healthy subjects". Journal of Clinical Pharmacology. 31 (1): 58–64. doi:10.1002/j.1552-4604.1991.tb01887.x. PMID   1646240. S2CID   24683211.
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