Discovery Of Losartan Potassium Health And Social Care Essay

Discovery Of Losartan Potassium Health And Social Care EssayLosartan is the first angiotensin II receptor antagonist medicate to be marketed for use mainly to treat high railway line press (hypertension). Losartan was first discovered in March 1986 by scientists on their first assignments at a corporate research laboratory, in Du Pont, as DuP 753(Merck 954), a highly potent and orally ready non-peptide Ang II receptor antagonist. At the time, DuPont as a federation was rather new to pharmaceutical business. The company had previously been dealing in chemicals, but the in the 1970s when the demand for Petroleum and its related products natural particle accelerator drove prices high, management attempted to diversify the business by seeking former(a) business avenues to reduce their dependency on chemicals in a anticipate of also increasing their profit. As a result of creating new business, DuPont had ventured into pharmaceuticals and other life sciences businesses by the 1980s . Losartan work was one of the compounds DuPont research labs worked on. The company being tenderness in this area of business, hired Robert I. Taber, a scientist with two decades of research experience with Schering, to head pharmaceutical research at DuPont.It was Taber who recognized the areas of potentials and encouraged the research aggroup to delve unless. However, DuPont being a fairly young company in these areas would lead to other weighty problems, and these issues were quickly settled by a collaborationism with the more experienced Merck, who also 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(prenominal) a series of efforts. The final market product was Co-Developed with Scientists from both Merck DuPont. BHARDWAJ, G., 2006Losartan was approved by the FDA in April 1995, and it was then launched that month as the first non-peptide anti-hypertensive do drugs in the new class of Ang II receptor antagonists. Merck started selling losartan under 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) methanolChemical dataFormula C22H23ClN6OMol. mass 422.91Action of LosartanLosartan selectively inhibits all Ang II responses that have been analyse and lowered lineage pressure in several animal models of renin-dependent hypertension. In animals, the antihypertensive drug efficacy of losartan has been found to be similar to that of the aste danger Inhibitors (Angiotensin Converting Enzyme inhibitors) but, un care ACE inhibitors, losartan is a more selective inhibitor of the renin-angiotensin system since it does not affect the metabolism of kinins. Compared with peptide Ang II antagonists (e.g. saralasin), losartan has significant advantages, including a long duration of action, effective oral density and no Ang II agonist activity. SIEGL, P.K., 1993IndicationsHypertensionLosartan tablets is indicated for the treatment of hypertension. Losartan can be used alone or used in combination with other antihypertensive agents, including diuretics. Rx LIST THE INTERNET DRUG INDEX., 2009Hypertensive Patients with Left Ventricular HypertrophyLosartan is also indicated in patients with hypertension and left ventricular hypertrophy to reduce the danger of stroke, but there has been a study to suggest that Losartan is not beneficial with Black patients in reducing the risk of stroke. Rx LIST THE INTERNET DRUG INDEX.,2009In the LIFE study, it was found out that Black patients with conditions of hypertension and left ventricular hypertrophy had a lower risk of stroke on atenolol than on Losartan. However, there was some shortcomings of the LIFE study, as it did not provide evidence that the benefits of Losartan in hypertensive patients with left ventricular hypertrophy by reducin g 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 treatment of patients with diabetic nephropathy, where there 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 doubling of serum creatinine or end stage renal infirmity where there is need for dialysis or renal transplantation. Rx LIST THE INTERNET DRUG INDEX.,2009SPECIFIC PRODUCTS ( CONTAINING THIS DRUG) AVAILABLE FOR USE IN GIVEN CONDITIONCombination therapyA combination therapy is used if losartan monotherapy alone is not sufficient to control hypertension. Hence, losartan is available in combination with hydrochlorothiazide in different strengths as followsBRIT ISH NATIONAL 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 tho medicine. MEDICINES AND HEALTH CARE PRODUCTS REGULATORY AGENCY., 2009EVIDENCE FOR EFFICACY FOR THIS TREATMENT.Clinical trials have shown a better 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 mainly less responsive to monotherapy from any hypertensive class), with severe hypertension have shown a significant drop-off 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/ hydrochlorothia zide 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 channel blockers and angiotensin converting enzyme inhibitors due to side set up like peripheral edema or dry cough respectively. 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 notice that the clinical side effects were minimal with losartan treatment and the haematologic and biochemical profiles were also not disturbed. GIOVANNETTI, et al., 1997Studies performed on the pharmacokinetics and pharmacodynamic parameters of losartan on healthy male volunteers an d 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 starting and maintenance dose in to the highest degree 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 apply TO TREAT THE SAME AILMENTLosartan 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. v alsartan 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, exhibited a similar reduction in blood pressure at a lower concentration ,however, valsartan has a higher response rate and more effective 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 observe.LACOURCIERE ASMAR 1999A brief comparison with other healthful products from the other class like B- adrenergic blocker(e.g. atenolol), 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 hypertens ion. 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 less 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 function, and restrictive function of the endothelium in patients with essential hypertension, nifedipine GIT is superior to others in plate- granule membrane 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 potassium 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. GOLDBE RG, 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 thusly an excellent tolerability profile.Safety profile It has a good safety profile in a demographic sub groups.It doesnt hold rebound high blood pressure when it is withdrawn.DISADVANTAGES OF LOSARTAN POTASSIUM.1 Losartan has been associated with some damaging effect on the foetus which may include reduced body weight, death and kidney injuries hence it is contraindicated in pregnancy. GOLDBERG, et al., 1995 synopsis 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. development in technology resulted in an evolution in pharmaceutical world and has paved way for research and development to meet demands for more efficient products. intimately one billion deal 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 arrival of cheap generic products which resulted in a threat to the global pharmaceutical market. Data monitoring of the sales of antihypertensives in seven major global market s (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 pornographic 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 forth from investing in research and development to develop more efficient antihypertensive therapies. THE MEDICAL NEWS., 2009Product NamePatent NumberPatent tipMercks 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 comings of the existing treatment to justify new drug developmentThough antihypertensive agents were able to achieve significant control over hypertension indu ced 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 free of negative metabolic effects. Moreover, it should also be able to reverss cardiovascular changes like cardiac hypertrophy and control tissue damage in nerve of possible vascular complications. HANSSON, L., 1991.Analysis of data available on search engines indicates the promising role of u pcoming 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 antihypertensives and statins could be a new hope for future developments.