Fimasartan

Last updated
Fimasartan
Fimasartan skeletal.svg
Clinical data
Trade names Kanarb
ATC code
Identifiers
  • 2-(2-Butyl-4-methyl-6-oxo-1-{[2'-(1H-tetrazol-5-yl)-4-biphenylyl]methyl}-1,6-dihydro-5-pyrimidinyl)-N,N-dimethylethanethioamide
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C27H31N7OS
Molar mass 501.65 g·mol−1
3D model (JSmol)
  • CCCCC1=NC(=C(C(=O)N1CC2=CC=C(C=C2)C3=CC=CC=C3C4=NN=NN4)CC(=S)N(C)C)C
  • InChI=1S/C27H31N7OS/c1-5-6-11-24-28-18(2)23(16-25(36)33(3)4)27(35)34(24)17-19-12-14-20(15-13-19)21-9-7-8-10-22(21)26-29-31-32-30-26/h7-10,12-15H,5-6,11,16-17H2,1-4H3,(H,29,30,31,32)
  • Key:AMEROGPZOLAFBN-UHFFFAOYSA-N

Fimasartan is a non-peptide angiotensin II receptor antagonist (ARB) used for the treatment of hypertension and heart failure. [1] [2] 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. [3] Concurrent administration of fimasartan with diuretic hydrochlorothiazide has shown to be safe in clinical trials. [1] 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. [4]

Contents

Mechanism of action

Fimasartan acts on the kidney's rennin-angiotensin cascade, which begins when renin release from the kidney causes the breakdown of angiotensinogen into angiotensin I. Angiotensin-converting enzyme (ACE) then catalyzes the reaction that forms angiotensin II, which acts on AT1 receptors on the blood vessels, heart, and kidneys. [5] On blood vessels, the AT1 receptor is coupled to an intracellular pathway that causes smooth muscle contraction (vasoconstriction) of blood vessels. [6]

In blocking the AT1 receptor, fimasartan inhibits vasoconstriction, favouring vasodilation. At the kidney and adrenal gland, AT1 blockage and prevention of aldosterone formation increase excretion of water and salt by the kidneys, which decreases overall blood volume. [7] At the heart, AT1 blockage decreases contractility and the stimulatory effects of the sympathetic nervous system. [4] Collectively, fimasartain leads to a reduction in blood pressure and alleviation of hypertensive symptoms. ARBs like fimasartan have also shown to be protective against stroke, myocardial infarction, and heart failure. [8] Fimasartan has been shown to reduce cardiac hypertrophy, fibrosis, remodelling, and unnecessary cell proliferation via blockage of AT1 activation [4] [9] conceivably through decreased Endothelin 1 production, a result of AT1 activation. [10] Fimastartan can also block TGF-β1 production (also AT1 dependent), which contributes to fibrosis and ventricular damage post-infarct. [11] After ARB administration, mice showed improved prognosis after a myocardial infarction, [9] though further studies still need to be done to assess fimasartan's specific effects on decreasing cardiovascular damage.

Side effects

Side effects In clinical trials, fimasartan was well tolerated in all patients. However, higher dosing (360 mg/day) was accompanied by increased dizziness (most likely due to the momentary decrease in blood pressure) and headaches in a low number of patients. [1] Other side effects such as diarrhea, syncope, and cold feet were also experienced in a low number of subjects, which all resolved without medical intervention. [1]

Pharmacology

Fimasartan is rapidly absorbed and has minimal accumulation in the body 7 days after administration. [1] Fimasartan possesses a half-life of 9 to 16 hours, [1] appropriate for daily dosing. Fimasartan was found to be effective in fasted or fed states, with a variety of dosing regimens. In trials, the maximum effects of the drug occurred slightly after the maximum plasma concentration (T-max) was achieved, [1] which occurs 30 minutes to 3 hours after dosing. [12] Fimasartan was found mostly in unmetabolized form in the plasma and in bile excretions. Urinary elimination of the drug was low, at less than 3% 24 hours after administration, entailing that the fimasartan does not undergo renal excretion. [1]

Society and culture

Brand names

The drug is also available in Russia as Канарб (Kanarb). [13] Fimasartan is being marketed in India under the brand name of Fimanta and Fimagen through Ajanta Pharma Ltd.

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">Beta blocker</span> Class of medications used to manage abnormal heart rhythms

Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms (arrhythmia), and to protect the heart from a second heart attack after a first heart attack. They are also widely used to treat high blood pressure, although they are no longer the first choice for initial treatment of most patients.

<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.

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">Fosinopril</span> Antihypertensive drug of the ACE inhibitor class

Fosinopril is an angiotensin converting enzyme (ACE) inhibitor 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.

<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">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">Telmisartan</span> Angiotensin II receptor antagonist

Telmisartan, sold under the brand name Micardis among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combination telmisartan/hydrochlorothiazide, telmisartan/cilnidipine and telmisartan/amlodipine.

<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">Losartan</span> Blood pressure medication

Losartan, sold under the brand name Cozaar among others, is a medication used to treat high blood pressure (hypertension). It is in the angiotensin receptor blocker (ARB) family of medication, and is considered protective of the kidneys. Besides hypertension, it is also used in diabetic kidney disease, heart failure, and left ventricular enlargement. It comes as a tablet that is taken by mouth. It may be used alone or in addition to other blood pressure medication. Up to six weeks may be required for the full effects to occur.

<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">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">Angiotensin II receptor type 1</span> Protein-coding gene in the species Homo sapiens

Angiotensin II receptor type 1(AT1) is a Gq/11-coupled G protein-coupled receptor (GPCR) and the best characterized angiotensin receptor. It is encoded in humans by the AGTR1 gene. AT1 has vasopressor effects and regulates aldosterone secretion. It is an important effector controlling blood pressure and volume in the cardiovascular system. Angiotensin II receptor blockers are drugs indicated for hypertension, diabetic nephropathy and congestive heart failure.

<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">Azilsartan</span> Chemical compound

Azilsartan, sold under the brand name Edarbi among others, is used for the treatment of hypertension. It is used as the prodrug azilsartan medoxomil, is an angiotensin II receptor antagonist, and was developed by Takeda.

The angiotensin receptor blockers (ARBs), also called angiotensin (AT1) receptor antagonists or sartans, are a group of antihypertensive drugs that act by blocking the effects of the hormone angiotensin II in the body, thereby lowering blood pressure. Their structure is similar to Ang II and they bind to Ang II receptors as inhibitors, e.g., [T24 from Rhys Healthcare].

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

Valsartan/hydrochlorothiazide, sold under the brand name Diovan HCT among others, is a medication used to treat high blood pressure when valsartan is not sufficient. It is a combination of valsartan, an angiotensin receptor blocker with hydrochlorothiazide, a diuretic. It is taken by mouth.

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

Forasartan, otherwise known as the compound SC-52458, is a nonpeptide angiotensin II receptor antagonist (ARB, AT1 receptor blocker).

References

  1. 1 2 3 4 5 6 7 8 Lee HY, Oh BH (July 2016). "Fimasartan: A New Angiotensin Receptor Blocker". Drugs. 76 (10): 1015–22. doi:10.1007/s40265-016-0592-1. PMID   27272555. S2CID   3067660.
  2. ↑ Pradhan A, Gupta V, Sethi R (July 2019). "Fimasartan: A new armament to fight hypertension". Journal of Family Medicine and Primary Care. 8 (7): 2184–2188. doi: 10.4103/jfmpc.jfmpc_300_19 . PMC   6691418 . PMID   31463228.
  3. ↑ DeMello WC, Re RN (2009). "Systemic versus local renin angiotensin systems. An overview.". In DeMello WC, Frohlich ED (eds.). Renin angiotensin system and cardiovascular disease. New York, NY: Humana Press. pp. 1–5. ISBN   978-1-60761-186-8.
  4. 1 2 3 "Fimasartan". American Journal of Cardiovascular Drugs. 11 (4): 249–252. 2011. doi:10.2165/11533640-000000000-00000. PMID   21740078.
  5. ↑ Burnier M (February 2001). "Angiotensin II type 1 receptor blockers". Circulation. 103 (6): 904–12. doi: 10.1161/01.cir.103.6.904 . PMID   11171802.
  6. ↑ Wynne BM, Chiao CW, Webb RC (2009). "Vascular Smooth Muscle Cell Signaling Mechanisms for Contraction to Angiotensin II and Endothelin-1". Journal of the American Society of Hypertension. 3 (2): 84–95. doi:10.1016/j.jash.2008.09.002. PMC   2704475 . PMID   20161229.
  7. ↑ Klabunde RE (15 March 2007). "Angiotensin Receptor Blockers (ARBs)". CV Pharmacology.
  8. ↑ Neal B, MacMahon S, Chapman N (December 2000). "Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Blood Pressure Lowering Treatment Trialists' Collaboration". Lancet. 356 (9246): 1955–64. doi:10.1016/s0140-6736(00)03307-9. PMID   11130523. S2CID   46148907.
  9. 1 2 Harada K, Sugaya T, Murakami K, Yazaki Y, Komuro I (November 1999). "Angiotensin II type 1A receptor knockout mice display less left ventricular remodeling and improved survival after myocardial infarction". Circulation. 100 (20): 2093–9. doi: 10.1161/01.cir.100.20.2093 . PMID   10562266.
  10. ↑ Phillips PA (July 1999). "Interaction between endothelin and angiotensin II". Clinical and Experimental Pharmacology & Physiology. 26 (7): 517–8. doi:10.1046/j.1440-1681.1999.03069.x. PMID   10405777. S2CID   27296727.
  11. ↑ Sun Y, Zhang JQ, Zhang J, Ramires FJ (August 1998). "Angiotensin II, transforming growth factor-beta1 and repair in the infarcted heart". Journal of Molecular and Cellular Cardiology. 30 (8): 1559–69. doi:10.1006/jmcc.1998.0721. PMID   9737942.
  12. ↑ Gu N, Kim BH, Lim KS, Kim SE, Nam WS, Yoon SH, Cho JY, Shin SG, Jang IJ, Yu KS (July 2012). "The effect of fimasartan, an angiotensin receptor type 1 blocker, on the pharmacokinetics and pharmacodynamics of warfarin in healthy Korean male volunteers: a one-sequence, two-period crossover clinical trial". Clinical Therapeutics. 34 (7): 1592–600. doi:10.1016/j.clinthera.2012.06.004. PMID   22727611.
  13. ↑ "Kanarb (fimasartan) film-coated tablets. Registration Certificate". Russian State Register of Medicines (in Russian). JSC R-Pharm . Retrieved 1 September 2020.
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