Discovery Of Losartan Potassium Health And Social Care Essay

Losartan is the first angiotonin II receptor antagonist drug to be marketed for usage chiefly to handle high blood force per unit area ( high blood pressure ) . Losartan was foremost discovered in March 1986 by scientists on their first assignments at a corporate research research lab, in Du Pont, as DuP 753 ( Merck 954 ) , a extremely powerful and orally active non-peptide Ang II receptor adversary. At the clip, DuPont as a company was instead new to pharmaceutical concern. The company had antecedently been covering in chemicals, but the in the 1970s when the demand for Petroleum and its related merchandises natural gas drove monetary values high, direction attempted to diversify the concern by seeking other concern avenues to cut down their dependence on chemicals in a hope of besides increasing their net income. As a consequence of making new concern, DuPont had ventured into pharmaceuticals and other life scientific disciplines concerns by the eightiess. Losartan work was one of the compounds DuPont research labs worked on. The company being rawness in this country of concern, hired Robert I. Taber, a scientist with two decennaries of research experience with Schering, to head pharmaceutical research at DuPont.It was Taber who recognized the countries of potencies and encouraged the research squad to dig farther. However, DuPont being a reasonably immature company in these countries would take to other weighty jobs, and these issues were rapidly settled by a coaction with the more experient Merck, who besides recognised the Potential of Losartan and convinced DuPont that there was more to be gained by working on Losartan. Development of Losartan was done after a series of attempts. The concluding market merchandise was Co-Developed with Scientists from both Merck & A ; DuPont. [ BHARDWAJ, G. , 2006 ]

Losartan was approved by the FDA in April 1995, and it was so launched that month as the first non-peptide anti-hypertensive drug in the new category of Ang II receptor adversaries. Merck started selling losartan under the trade names CozaarT and HyzaarT with one-year gross revenues in surplus of $ 3 Billion Dollars by 2005.

Chemical Structure

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( IUPAC ) terminology

( 2-butyl-4-chloro-1- { [ 2′- ( 1H-tetrazol-5-yl ) biphenyl-4-yl ] methyl } -1H-imidazol-5-yl ) methyl alcohol

Chemical informations

Formula C22H23ClN6O

Mol. mass 422.91

Action of Losartan

Losartan selectively inhibits all Ang II responses that have been studied and lowered blood force per unit area in several carnal theoretical accounts of renin-dependent high blood pressure. In animate beings, the antihypertensive efficaciousness of losartan has been found to be similar to that of the ACE Inhibitors ( Angiotensin Converting Enzyme inhibitors ) but, unlike ACE inhibitors, losartan is a more selective inhibitor of the renin-angiotensin system since it does non impact the metamorphosis of kinins. Compared with peptide Ang II adversaries ( e.g. saralasin ) , losartan has important advantages, including a long continuance of action, effectual unwritten soaking up and no Ang II agonist activity. [ SIEGL, P.K. , 1993 ]


High blood pressure

Losartan tablets is indicated for the intervention of high blood pressure. Losartan can be used entirely or used in combination with other antihypertensive agents, including water pills. [ Rx LIST THE INTERNET DRUG INDEX. , 2009 ]

Hypertensive Patients with Left Ventricular Hypertrophy

Losartan is besides indicated in patients with high blood pressure and left ventricular hypertrophy to cut down the hazard of shot, but at that place has been a survey to propose that Losartan is non good with Black patients in cut downing the hazard of shot. [ Rx LIST THE INTERNET DRUG INDEX.,2009 ]

In the LIFE survey, it was found out that Black patients with conditions of high blood pressure and left ventricular hypertrophy had a lower hazard of shot on Tenormin than on Losartan. However, there was some defects of the LIFE survey, as it did non supply grounds that the benefits of Losartan in hypertensive patients with left ventricular hypertrophy by cut downing the hazard of cardiovascular events applied to Black patients. [ Rx LIST THE INTERNET DRUG INDEX.,2009 ]

Nephropathy in Type 2 Diabetic Patients

Losartan is besides really utile in the intervention of patients with diabetic kidney disease, where there is an lift of serum creatinine and albuminuria ( urinary albumen to creatinine ratio a‰? 300 mg/g ) in patients that have type 2 diabetes and a history of high blood pressure. In this group, Losartan has been shown to cut down the rate of patterned advance of the kidney disease. This is measured by the happening of duplicating of serum creatinine or terminal phase nephritic disease where there is demand for dialysis or nephritic organ transplant. [ Rx LIST THE INTERNET DRUG INDEX.,2009 ]


Combination therapy:

A combination therapy is used if losartan monotherapy entirely is non sufficient to command high blood pressure. Hence, losartan is available in combination with Microzide in different strengths as follows: [ BRITISH NATIONAL FORMULARY. , 2009 ]

Losartan 50mg + Hydrochlorothiazide 12.5mg

Losartan 100mg + Hydrochlorothiazide 12.5mg

Losartan 100mg + Hydrochlorothiazide 25mg.

The above combination is used for intervention of high blood force per unit area and shot in patients with bosom disease. It is a prescription merely medical specialty. [ MEDICINES AND HEALTH CARE PRODUCTS REGULATORY AGENCY. , 2009 ]


Clinical tests have shown a better efficiency of losartan as an antihypertensive by itself and a farther higher efficiency in a combined province with Microzide. For illustration: a double-blind, multicenter, randomized, parallel – group survey performed on African Americans ( who are by and large less antiphonal to monotherapy from any hypertensive category ) , with terrible high blood pressure have shown a important decrease in sitting diastolic and systolic blood force per unit area with losartan monotherapy ( 45.8 % ) when compared with placebo ( 27.2 % ) . In the same survey, the combination losartan/ hydrochlorothiazide regimen showed important higher decreases ( 62.7 % ) in blood force per unit area compared with losartan monotherapy or placebo. More over, both the regimens i.e losartan monotherapy and the losartan/hydrochlorothiazide were every bit good tolerated as the placebo [ FLACK, et al. , 2001 ] . Other surveies were performed on hypertensive patients who had discontinued intervention with Ca channel blockers and angiotonin change overing enzyme inhibitors due to side effects like peripheral hydrops or dry cough severally. These patients when treated with losartan have shown as much decrease and control over blood force per unit area as they use to with old therapies. [ GIOVANNETTI, et al. , 1997 ] . And rather interestingly it has besides been observed that the clinical side effects were minimum with losartan intervention and the haematologic and biochemical profiles were besides non disturbed. [ GIOVANNETTI, et al. , 1997 ]

Surveies performed on the pharmacokinetics and pharmacodynamic parametric quantities of losartan on healthy male voluntaries and besides on particular patient groups like aged patients with nephritic damage and those holding liver disease, suggest that losartan is orally active and its consequence stopping points for over 24 hours. None of the patient groups showed any important pharmacokinetic interactions [ McINTYRE, et al. , 1997 ] . Losartan 50mg appears to be a safe starting and care dosage in most patient populations. However, when an linear consequence is required, it can be easy combined with thiazide water pills to accomplish the mark blood force per unit area. Losartan has low discontinuance rate and it has besides been observed that it was non associated with cough even in patients who experience this side consequence with to ACE inhibitors [ McINTYRE, et al. , 1997 ] .


Losartan K, is an angiotensin receptor adversary ( AT1 ) used in the intervention of high blood pressure and other cardiovascular diseases. However, a comparing with other ARB ( e.g. Diovan and candesartan ) shows that, these drugs have the same mechanism of action, though, their differences in pharmacokinetic profile may be responsible for their differences in efficaciousness in the intervention of high blood pressure. Losartan and Diovan when compared, exhibited a similar decrease in blood force per unit area at a lower concentration, nevertheless, Diovan has a higher response rate and more effectual 24hours blood force per unit area control rate at the dosage of 160mg and 80mg severally than losartan at 100mg and 50mg severally. [ BURNIER & A ; BRUNNER 2000 ] . Candesartan 8mg and 16mg has besides demonstrated a more permanent antihypertensive consequence than losartan 50mg and 100mg in ambulatory BP monitoring. [ LACOURCIERE & A ; ASMAR 1999 ]

A brief comparing with other medicative merchandises from the other category like B- adrenergic blocker ( e.g. Tenormin ) , ACEI ( e.g. enerlapril ) , calcium channel blocker ( e.g. felodipine ) and water pills were based on the efficaciousness, tolerability and safety in the intervention of indispensable high blood pressure. Losartan, when compared with amilodipine has been shown to exhibit a similar clinically relevant decrease in patients with systolic blood force per unit area, nevertheless, losartan was better tolerated as evidenced by fewer clinically inauspicious consequence ( CAE ) and discontinuance comparison with amlodipine [ VOLPE, et al. , 2003 ] . Meanwhile, in the contrasting consequence of losartan, nifedipine GIT, and fosinopril on the ambulatory blood force per unit area, cardiac construction and map, and protective map of the endothelium in patients with indispensable high blood pressure, nifedipine GIT is superior to others in plate- granule membrane protein ( GMP ) , while fosinopril and losartan had a preffered action to nifedipine GIT in change by reversaling ventricular hypertrophy, nevertheless, losartan was better tolerated than the other drugs [ QI & A ; XIURONG 2001 ] . Losartan K has been known to exhibit a fewer drug related inauspicious consequence in contrast to other medicative merchandises in the other categories used in the intervention of high blood pressure. [ GOLDBERG, et al. , 1995 ] In drumhead, losartan K has an first-class tolerability profile in patient with indispensable high blood pressure and, in a demographic bomber group of aged versus immature, adult females versus work forces and black versus non black ; it has been shown to hold an first-class safety profile.


Side consequence ; In the intervention of high blood pressure, losartan has exhibited fewer drug related side consequence when it was compared with other category of antihypertensive agents. [ GOLDBERG, et al. , 1995 ]

Tolerance ; when compared in patients with indispensable high blood pressure, losartan was better tolerated than other agents from the other category and hence an first-class tolerability profile.

Safety profile ; It has a good safety profile in a demographic bomber groups.

It does n’t bring forth bounce high blood force per unit area when it is withdrawn.


1 Losartan has been associated with some detrimental consequence on the fetus which may include reduced organic structure weight, decease and kidney hurts hence it is contraindicated in gestation. [ GOLDBERG, et al. , 1995 ]

Analysis of the market potency for the development of new drug campaigners to handle the given status

Development of new drug merchandises has ever been a ambitious undertaking. Growth in engineering resulted in an development in pharmaceutical universe and has paved manner for research and development to run into demands for more efficient merchandises. About one billion people have been affected by high blood pressure – universe broad and studies besides says that in US entirely 65 1000000s people are affected by high blood force per unit area. [ SMITH & A ; ASHIYA 2007 ] . This indicates the degree of demand of antihypertensives universe broad. Attempts have been made and many possible drugs have been developed boulder clay day of the month.

However the termination of patents of angiotonin receptor blockers ( ARB ) opened doors for reaching of inexpensive generic merchandises which resulted in a menace to the planetary pharmaceutical market. Data monitoring of the gross revenues of antihypertensives in seven major planetary markets ( i.e UK, France, US, Italy, Spain, Germany and Japan ) predicted gross revenues of upto $ 29.5 one million millions by 2018, which would be a bead of $ 6 billion when compared to that of 2008. Sing above menaces, the large pharmaceutical companies are under an feeling that it is non deserving to pass on research and development of fresh therapies and they appear to be traveling off from puting in research and development to develop more efficient antihypertensive therapies. [ THE MEDICAL NEWS. , 2009 ]

Merchandise Name

Patent Number

Patent Termination

Merck ‘s COZAAR ( losartan K )

5,138,069*PEDA A

11 Feb,2010

Merck ‘s COZAAR ( losartan K )


06 Apr, 2010

Merck ‘s COZAAR ( losartan K )

5,210,079*PEDA A

11 Nov,2010

Table demoing the termination of patent of COZAAR ( losartan K ) – Angiotensin receptor blocker. [ DRUG PATENT WATCH. , 2010 ]

Short approachs of the bing intervention to warrant new drug development

Though antihypertensive agents were able to accomplish important control over high blood pressure induced morbidity and mortality, still there is much to be done. For illustration: letdowns associated with coronary arteria disease, hazard of cardiovascular events even after intervention with antiphyertensive agents and relatively higher possibility of cardiovascular events in hypertensive patients compared to normotensive patients. These effects are thought to be due to inability of bing antihypertensives to change by reversal other associated factors like left ventricular hypertrophy, negative metabolic effects and hazard associated with overtreatment. [ HANSSON, L. , 1991 ] . Hence there is a demand for an ideal hypertensive agent which may be able to command blood force per unit area to normotensive degrees whilst being free of negative metabolic effects. Furthermore, it should besides be able to reverss cardiovascular alterations like cardiac hypertrophy and control tissue harm in instance of possible vascular complications. [ HANSSON, L. , 1991 ] .

Analysis of informations available on hunt engines indicates the promising function of upcoming cistron – therapy and nano-technology to bring forth new drug campaigners. For illustration: Exploring countries like cistron transcripton, molecular familial ordinance of blood force per unit area ( aiming familial hazard factors as in instances of indispensable high blood pressure ) appears to be a new hope for future developments of antihypertensives. [ KURTZ & A ; GARDNER 1998 ]

Possible potency for new therapy.

Research is presently being carried out to research the potency of upcoming cistron – therapy and nano-technology to bring forth new drug campaigners. For illustration: Areas like cistron transcripton, molecular familial ordinance of blood force per unit area ( aiming familial hazard factors as in instance of indispensable high blood pressure ) appears to be a new hope for future developments of antihypertensives. [ KURTZ & A ; GARDNER 1998 ] . However instead, combination merchandises incorporating antihypertensives and lipid-lowering medicines could be a new hope for future developments. aˆ¦aˆ¦aˆ¦aˆ¦aˆ¦aˆ¦aˆ¦



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