Discovery Of Losartan Potassium Health And Social Care Essay

Discovery Of Losartan Potassium Health And Social C atomic number 18 EssayLosartan is the for the first time angiotensin II receptor antagonist dose to be food marketed for physical exercise mainly to treat high countercurrent wedge ( high linage pressure). Losartan was first sight in March 1986 by scientists on their first assign handsts at a corporate look laboratory, in Du Pont, as DuP 753(Merck 954), a highly manly and or completelyy active non-peptide Ang II receptor antagonist. At the time, DuPont as a comp all was rather sore to pharmaceutical caudex line. The company had previously been dealing in chemicals, but the in the 1970s when the demand for Petroleum and its think products natural gas drove prices high, management attempted to diversify the business by seeking separate business avenues to reduce their dependency on chemicals in a hope of too increasing their profit. As a result of creating rude(a) business, DuPont had ventured into pharmaceuticals and untried-fashioned(prenominal) life sciences businesses by the 1980s. Losartan work was star of the compounds DuPont look into labs worked on. The company beingness inexperience in this area of business, engage Robert I. Taber, a scientist with two decades of re try experience with Schering, to head pharmaceutical research at DuPont.It was Taber who recognized the areas of capablenesss and encouraged the research team to delve further. However, DuPont being a fairly young company in these areas would lead to separate weighty problems, and these issues were quickly settled by a collaboration with the much experienced Merck, who withal recognised the Potential of Losartan and convinced DuPont that thither was more(prenominal) to be gained by working on Losartan. Development of Losartan was done afterward a series of efforts. The final market product was Co-Developed with Scientists from both Merck DuPont. BHARDWAJ, G., 2006Losartan was sanction by the FDA in April 1 995, and it was then launched that month as the first non-peptide anti-hypertensive drug in the new class of Ang II receptor antagonists. Merck started selling losartan to a write down place the trade names CozaarT and HyzaarT with annual sales in excess of $3 Billion Dollars by 2005.Chemical Structure(IUPAC) nomenclature(2-butyl-4-chloro-1-2-(1H-tetrazol-5-yl) biphenyl-4-yl methyl-1H-imidazol-5-yl) methyl alcoholChemical dataFormula C22H23ClN6OMol. mass 422.91Action of LosartanLosartan selectively inhibits all Ang II responses that suck up been studied and lowered blood pressure in several animal models of renin-dependent hypertension. In animals, the antihypertensive drug efficacy of losartan has been found to be comparable to that of the ACE Inhibitors ( angiotonin Converting Enzyme inhibitors) but, un same(p) ACE inhibitors, losartan is a more selective inhibitor of the renin-angiotensin system since it does non affect the metabolism of kinins. Compared with peptide Ang I I antagonists (e.g. saralasin), losartan has epoch-making advantages, including a long duration of action, loadive oral absorption and no Ang II agonist activity. SIEGL, P.K., 1993IndicationsHypertensionLosartan tablets is indicated for the sermon of hypertension. Losartan can be used only when or used in combination with other antihypertensive agents, including diuretics. Rx heel THE INTERNET medicate INDEX., 2009Hypertensive Patients with Left Ventricular HypertrophyLosartan is also indicated in patients with hypertension and odd ventricular hypertrophy to reduce the try of stroke, but in that respect has been a learn to suggest that Losartan is not safe with Black patients in reducing the essay of stroke. Rx distinguish THE INTERNET DRUG INDEX.,2009In the LIFE study, it was found out that Black patients with reasons of hypertension and leftover ventricular hypertrophy had a lower risk of stroke on atenolol than on Losartan. However, in that location was some short comings of the LIFE study, as it did not provide evidence that the benefits of Losartan in hypertensive patients with left ventricular hypertrophy by reducing the risk of cardiovascular events applied to Black patients. Rx LIST THE INTERNET DRUG INDEX.,2009Nephropathy in Type 2 diabetic PatientsLosartan is also very useful in the discourse of patients with diabetic nephropathy, where on that point is an elevation of serum creatinine and proteinuria (urinary albumin to creatinine ratio 300 mg/g) in patients that have type 2 diabetes and a history of hypertension. In this group, Losartan has been shown to reduce the rate of progression of the nephropathy. This is measured by the occurrence of look-a bid of serum creatinine or end stage renal disease where there is need for dialysis or renal transplantation. Rx LIST THE INTERNET DRUG INDEX.,2009 item PRODUCTS ( CONTAINING THIS DRUG) AVAILABLE FOR USE IN GIVEN CONDITIONCombination therapyA combination therapy is used if losartan mon otherapy solo is not sufficient to control hypertension. Hence, losartan is operable in combination with hydrochlorothiazide in different strengths as followsBRITISH bailiwick FORMULARY., 2009Losartan 50mg + Hydrochlorothiazide 12.5mgLosartan 100mg + Hydrochlorothiazide 12.5mgLosartan 100mg + Hydrochlorothiazide 25mg.The above combination is used for treatment of high blood pressure and stroke in patients with heart disease. It is a prescription only medicine. MEDICINES AND HEALTH CARE PRODUCTS REGULATORY AGENCY., 2009EVIDENCE FOR faculty FOR THIS breedMENT.Clinical trials have shown a go efficiency of losartan as an antihypertensive by itself and a further higher efficiency in a combined state with hydrochlorothiazide. For example a double-blind, multicenter, randomized, parallel group study performed on African Americans (who are brokerrally less responsive to monotherapy from any hypertensive class), with severe hypertension have shown a significant reduction in sitting diastolic and systolic blood pressure with losartan monotherapy (45.8%) when compared with placebo (27.2%) . In the same study, the combination losartan/ hydrochlorothiazide regimen showed significant higher reductions (62.7%) in blood pressure compared with losartan monotherapy or placebo. More over, both the regimens i.e losartan monotherapy and the losartan/hydrochlorothiazide were as well tolerated as the placeboFLACK, et al., 2001. Other studies were performed on hypertensive patients who had discontinued treatment with calcium have a bun in the oven blockers and angiotensin converting enzyme inhibitors due to side centers like peripheral edema or dry expectorate independently. These patients when treated with losartan have shown as much reduction and control over blood pressure as they use to with previous therapies.GIOVANNETTI, et al., 1997. And quite interestingly it has also been observed that the clinical side fixs were minimal with losartan treatment and the haematol ogic and biochemical indites were also not disturbed. GIOVANNETTI, et al., 1997Studies performed on the pharmacokinetics and pharmacodynamic parameters of losartan on healthy male volunteers and also on special patient groups like elderly patients with renal impairment and those having liver disease, suggest that losartan is orally active and its effect lasts for over 24 hours. none of the patient groups showed any significant pharmacokinetic interactionsMcINTYRE, et al., 1997. Losartan 50mg appears to be a safe get-go and maintenance dose in most patient populations. However, when an additive effect is required, it can be easily combined with thiazide diuretics to achieve the target blood pressure. Losartan has low discontinuation rate and it has also been observed that it was not associated with cough even in patients who experience this side effect with to ACE inhibitors McINTYRE, et al., 1997.A BRIEF COMPARISON WITH OTHER MEDICINAL PRODUCT USED TO TREAT THE SAME AILMENTLosart an potassium, is an angiotensin receptor antagonist (AT1) used in the treatment of hypertension and other cardiovascular diseases. However, a comparison with other ARB(e.g. valsartan 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 efficacy in the treatment of hypertension. Losartan and valsartan when compared, acquainted a similar reduction in blood pressure at a lower concentration ,however, valsartan has a higher response rate and more useful 24hours blood pressure control rate at the dose of 160mg and 80mg respectively than losartan at 100mg and 50mg respectively.BURNIER BRUNNER 2000. Candesartan 8mg and 16mg has also demonstrated a more lasting antihypertensive effect than losartan 50mg and 100mg in ambulatory BP monitoring.LACOURCIERE ASMAR 1999A brief comparison with other medicinal products from the other class like B- adrenergic blocker(e.g. atenol ol), ACEI(e.g. enerlapril), calcium channel blocker(e.g. felodipine) and diuretics were based on the efficacy, tolerability and safety in the treatment of essential hypertension. Losartan , when compared with amilodipine has been shown to exhibit a similar clinically relevant reduction in patients with systolic blood pressure, however, losartan was better tolerated as evidenced by fewer clinically adverse effect(CAE)and discontinuation compare with amlodipine VOLPE, et al., 2003. Meanwhile, in the contrasting effect of losartan, nifedipine GIT, and fosinopril on the ambulatory blood pressure, cardiac structure and purpose, and protective function of the endothelium in patients with essential hypertension, nifedipine GIT is superior to others in plate- granule tissue layer protein (GMP), while fosinopril and losartan had a preffered action to nifedipine GIT in reversing ventricular hypertrophy, however, losartan was better tolerated than the other drugs QI XIURONG 2001. Losartan po tassium has been known to exhibit a fewer drug related adverse effect in contrast to other medicinal products in the other classes used in the treatment of hypertension. GOLDBERG, et al., 1995 In summary, losartan potassium has an excellent tolerability profile in patient with essential hypertension and, in a demographic sub group of elderly versus young, women versus men and black versus non black it has been shown to have an excellent safety profile.ADVANTAGES OF LOSARTAN POTASSIUM.Side effect In the treatment of hypertension, losartan has exhibited fewer drug related side effect when it was compared with other class of antihypertensive agents .GOLDBERG, et al., 1995Tolerance when compared in patients with essential hypertension, losartan was better tolerated than other agents from the other class and hence an excellent tolerability profile.Safety profile It has a good safety profile in a demographic sub groups.It doesnt produce rebound high blood pressure when it is withdrawn.DIS ADVANTAGES OF LOSARTAN POTASSIUM.1 Losartan has been associated with some damaging effect on the foetus which may accommodate reduced body weight, death and kidney injuries hence it is contraindicated in pregnancy. GOLDBERG, et al., 1995Analysis of the market potential for the development of new drug candidates to treat the given conditionDevelopment of new drug products has always been a challenging task. maturation in technology resulted in an evolution in pharmaceutical piece and has paved way for research and development to meet demands for more good products. About one billion people have been affected by hypertension world wide and reports also says that in US alone 65 millions people are affected by high blood pressure.SMITH ASHIYA 2007. This indicates the level of demand of antihypertensives world wide. Efforts have been made and many potential drugs have been developed till date.However the expiry of patents of angiotensin receptor blockers (ARB) opened doors for arri val of cheap generic products which resulted in a curse to the global pharmaceutical market. Data monitoring of the sales of antihypertensives in 7 major global markets (i.e UK, France, US, Italy, Spain, Germany and Japan ) predicted sales of upto $ 29.5 billions by 2018, which would be a drop of $6 billion when compared to that of 2008. Considering above threats, the big pharmaceutical companies are under an impression that it is not worth to spend on research and development of novel therapies and they appear to be moving away from place in research and development to develop more efficient antihypertensive therapies. THE MEDICAL NEWS., 2009Product NamePatent NumberPatent designMercks COZAAR (losartan potassium)5,138,069*PED11 Feb,2010Mercks COZAAR (losartan potassium)5,153,197*PED06 Apr, 2010Mercks COZAAR (losartan potassium)5,210,079*PED11 Nov,2010Table showing the expiry of patent of COZAAR (losartan potassium) Angiotensin receptor blocker. DRUG PATENT WATCH., 2010Short co mings of the existing treatment to justify new drug developmentThough antihypertensive agents were able to achieve significant control over hypertension induced morbidity and mortality, still there is much to be done. For example disappointments associated with coronary artery disease, risk of cardiovascular events even after treatment with antiphyertensive agents and comparatively higher possibility of cardiovascular events in hypertensive patients compared to normotensive patients. These effects are thought to be due to inability of existing antihypertensives to reverse other associated factors like left ventricular hypertrophy, negative metabolic effects and risk associated with overtreatment.HANSSON, L., 1991. Hence there is a need for an ideal hypertensive agent which may be able to control blood pressure to normotensive levels whilst being turn of negative metabolic effects. Moreover, it should also be able to reverss cardiovascular changes like cardiac hypertrophy and contro l tissue damage in solecism of possible vascular complications. HANSSON, L., 1991.Analysis of data available on search engines indicates the promising role of forthcoming gene therapy and nano-technology to produce new drug candidates. For example Exploring areas like gene transcripton, molecular genetic regulation of blood pressure ( targeting genetic risk factors as in cases of essential hypertension) appears to be a new hope for future developments of antihypertensives.KURTZ GARDNER 1998Possible potential for new therapy.Research is currently being carried out to explore the potential of upcoming gene therapy and nano-technology to produce new drug candidates. For example Areas like gene transcripton, molecular genetic regulation of blood pressure ( targeting genetic risk factors as in case of essential hypertension) appears to be a new hope for future developments of antihypertensives.KURTZ GARDNER 1998. However alternatively, combination products containing antihypertensi ves and statins could be a new hope for future developments.