Gas turbine engine basics Coursework Example | Topics and Well Written Essays - 2000 words

Gas turbine engine basics - Coursework Example (Sherwin, Keith & Michael, Horsley, 1996). Fuel is mixed with air and ignited this is where energy is added to the gas stream in the combustor. The temperature increases combustion of the fuel in the high pressure environment of the combustor, the products of the combustion are forced into the turbine section. Directed through a nozzle over the turbine’s blades is the high volume and velocity of the gas flow this spins the turbine which powers the compressor and, in some other turbines, this drives their mechanical output. The reduction in the pressure and temperature of the exhaust gas comes from the energy given up to the turbine moreover, energy can also be extracted in the form of shaft power, compressed air temperature can be used to power ships, trains, aircraft, tanks, and generators. (Husain, 2010) Task 1 There are 5 basic models of a turbo fan high bypass engine. This involves the first stage compressor that is drastically enlarged for the provision of bypass airflow around that core of the engine. This also allows for a significant amount of thrust. Turbo Jet Engine Air Inlet Combustion Chambers Turbine Propelling Nozzle Compressor Diagram of turbojet engine As depicted in the diagram above, a Turbojet engine comprises of the intake, compression, combustion, turbine and exhaust sections. The compression chamber directs the incoming air into the combustion chamber at relatively a high velocity. The combustion chamber is equipped with igniters and nozzles that enable combustion. During this process of combustion, the expanding gas is then utilized in rotating the gas turbine and keeps the engine operational as the compressor is driven through the shaft (Turbine Engines). nc = T2 – T1 T2a – T1 and n4 = T3 – T4a T3 – T4 Applying the steady flow energy equation, v20 - v21 = 2(h1 – h0) Change in kinetic energy and change in enthalpy: v20 = 2cp(T1 – T0) Work output from the turbine balances the work input into the compressor, hence equating change in enthalpy results in: cp(T2a – T1) = cp(T3 – T4a) T2a – T1 = T3 – T4a [cp is constant] Airflow through the nozzle: v25 = 2cp(h4a – h5) Since velocity is constant, v4 = v1 ? 0 Exit velocity at the nozzle: v25 = 2cp(T4a – T5) Therefore, Thrust, F = mvc - mv Thrust = m(vc – v) The net exhaust speed of turbofans is much lower than that of a turbojet and as a result, this makes them much more efficient at subsonic speeds than turbojets, also they are more efficient at supersonic speeds up to Mach 1.6. Turbofans are the jet engines that are used in all currently manufactured commercial jet aircraft. During the intake phase in the turbofan engine, the pressure, temperature and volume of the gases remain constant. The fan is installed at the inlet of the engine to increase the amount of air flowing through the engine at any given time. Part of the inlet airflow is not directed toward the compressor, co mbustor, and turbine during this process, but is rather bypassed through a duct, which ends in a nozzle. This provides thrust through exchange of momentum with the airframe, because the gas leaves the nozzle at a speed that is higher than the intake velocity. Their high efficiency and relative quietness in operation is the main reason their high efficiency and relative quietness in operation is the main they use them commercially, many military jet aircraft also make use of turbofans.

Synopsis Essay Example | Topics and Well Written Essays - 750 words

Synopsis - Essay Example I felt like my heart is going to explore. A couple days later, I registered NCLEX-RN class (National Council Licensure Examination-Registered Nurse). I studied very hard. I did not feel tired. I felt like I can fly. I could not stop smiling at work, because I had a new dream. I passed the exam at first attempt. I quitted job and find an agency. I was interviewed and accepted in â€Å"A† group for which I only need to pay 25% of one-year program. I told my family at one night that I am going to America in two months. It was like having a funeral service at home. My mom and sister started crying and told me that the agency is going to sell me. My sister said if I leave for America, she was going to die. My dad and little brother were shocked. My lovely sister cried so much, so I could not persist in my plan. I folded my plan just for a while. I got a new job. Actually, I was scouted from the previous work. This was a new opening hospital. I had to teach other nurses and assistants one-on-one, because they do not had any experience in this department. It has been going really well. I was very pleased after hearing that I have strong leadership skill from the director of the department. On a very bright day, my father got a letter, which was about my grandmother land with two other people, and they wanted to sell it. As a result, we got enough money to buy a house, and paid back all the loans. I desensitized my family that America is not dangerous, as my sister said she is going to die if I leave. I opened my dream file again. I found a new agency, got a phone number from the owner of the agency, and asked her if it is okay, my mom calls you to ask questions. My mom talked with the owner for an hour, and then said I can go there. A week later, I had a dinner with my male friends, and I announced that I might go to America in four months. I got a phone call from a male friend with whom I

Critical thinking why guns wont make us safer Essay

Critical thinking why guns wont make us safer - Essay Example there are suggestions from the public that guns enable citizens to protect themselves, this is not the case because, guns continue to be used in domestic violence across the American society. To further prove the need for gun control, studies shows that countries implementing laws related to gun control have realized success in terms of reducing homicides, suicides, domestic violence and other gun related violence or crimes (Trotter 26). Sean Faircloth is correct in his argument that guns will not make the society safer. The infiltration of guns into the hands of the citizens in America, has done more harm than good. Statistics shows that gun ownership has resulted to an increase in homicide which often occur because of domestic violence. In addition guns are used to commit suicide and mentally or psychologically disturbed teenagers are using guns to kill fellow students. In essence, this statistics is an evident that there is need for gun control in the American society to protect c itizens from harm. As argued by Faircloth, it is true that most homicide committed in American homes is mainly contributed by ownership of guns by citizens. Citizens normally acquire guns for safety purposes; however, these guns pose a danger particularly in a spate of anger, either spouse can use a gun in case of an incidence of domestic violence. On the same note, it is true that domestic violence go hand in hand with gun violence and in most cases, it is women who are the victims of gun violence especially in American homes. Most people who own gun in the American society are not insane, the citizens who own guns are stable and their prior intention is to improve the safety of their homes (Faircloth). As reiterated by Faircloth: â€Å"Most citizens who own guns normally do not have an intention to turn against their wives or girlfriends, but in a spate of anger guns can become a tool of lashing out. Shooting another person only takes seconds and one only realizes after the damage

Challenges to the pharmaceutical industry's blockbuster-driven Research Paper

Challenges to the pharmaceutical industry's blockbuster-driven business model, and the effectiveness of GlaxoSmithKline's st - Research Paper Example After discussing the challenges associated with the use of the Blockbuster-Driven Business Model, the effectiveness of GSK’s strategies to meet these challenges will be tackled in details. 2. About the Company: Business Press and Analyst’s Narratives on GlaxoSmithKline (GSK) and Its Business Performance (i.e. Sales Revenue, Stock Prices, and Market Share) Based in Britain, GlaxoSmithKline (GSK) is a science-based health care company that aims to develop a wide-range of medicines through product researches and innovation (GSK, 2013a). Serving 115 countries worldwide, GSK is one of the top three biggest pharmaceutical companies around the world (GSK, 2013a ; Gilbert, Henske and Singh, 2003). To develop and innovate new drugs, GSK spent as much as ?4 billion in 2002 (GSK, 2013a). Back in July 1986, the share price of GSK was only 7.31 (Yahoo, 2013). Since January 1992, GSK’s share price has been fluctuating due to a series of merger and acquisition, expiry of patent s, heavy investment on new drug innovation, and tight competition in the market. Between 1979 to 1993, GSK filed 6 patents on Augmentin (Community Catalyst, n.d.). As a result, GSK’s share price started to increase in December 1992 at 30.75. ... It was between 1994 to 1995 when GSK contested their point-of-views with the federal appeals court concerning the legal issues behind patent infringement on one of their famous ulcer drug called Zantac (Los Angeles Times, 1995). Since the federal appeals court supported the arguments made by GSK, Novopharm – a Canadian company was not allowed to sell the generic version of Zantac in the U.S. throughout the period when the patent right is still effective (Los Angeles Times, 1995). One of the possible reasons why GSK’s share price significantly decreased from 69.50 in December 1998 down to 48.75 in February 2000 and 35.05 in February 2003 was because of patent litigation of GSK’s Paxil (Evaluate, 2002). In relation to the expiration of GSK’s patent on Advair in 2010, GSK’s share price has also significantly decreased from 42.29 in December 14, 2009 down to the lowest point at 33.46 in May 24, 2010 (Yahoo, 2013). Because of GSK’s business strate gy, this company managed to gradually increase its share price up to 52.51 in December 2013. Since it takes 10 years for GSK to develop new patented drug (Williams et al., 2008), this company has been continuously developing other promising drug that can compete or even better than their existing â€Å"blockbuster† drugs. (See Chart I – Historical Trend of GSK’s Share Price below) Chart I – Historical Trend of GSK’s Share Price Source: Yahoo, 2013 One of GSK’s â€Å"blockbuster† drugs was the Advair Diskus – an inhaler which can be used in the treatment of chronic asthma and chronic obstructive pulmonary disease (COPD) such as bronchitis or emphysema (Kitamura, 2013; Recruiting Experts Worldwide, 2013). Costing roughly US$300 per dose, the selling of

Introduction to Law Enforcement unit 2 DB Essay Example | Topics and Well Written Essays - 250 words

Introduction to Law Enforcement unit 2 DB - Essay Example According to (BLS,2012)Police officers protect lives and property. Detectives and criminal investigators, who sometimes are called agents or special agents, gather facts and collect evidence of possible crimes. The role of the law enforcement authorities should change as the circumstances and threats surrounding a county is always unstable.For eg: Since the September 1 1th terrorist attack the role and responsibilities of law enforcement has changed for good. As per (Walsh,2009)†The field of law enforcement has changed greatly since I became involved in public safety in 1985, and my career in Wenham in 1987†. The main change I would like to make is the abuse of drugs among students and selling of drug on the street.This is because protection of young generation is the foremost duty of the law enforcement agents. According to (Bennett,2010)†Illicit drug abuse is seriously affecting our children, our schools, our workplaces and our society†. Bennett, W. J. (2010, September 4). We ignore rise in drug abuse among kids. In http://articles.cnn.com. Retrieved June 12, 2012, from http://articles.cnn.com/2010-09-24/opinion/bennett.drug.abuse_1_drug-overdose-drug-abuse-illegal-drugs?_s=PM:OPINION Walsh, K. M. (2009, February 18). Walsh: Law enforcement changes over 20 years. In .wickedlocal.com/. Retrieved June 12, 2012, from http://www.wickedlocal.com/ hamilton/news/lifestyle/ columnists/

Pategonias Expansion Strategy Essay Example for Free

Pategonias Expansion Strategy Essay 1. Patagonia’s Current Strategy: Key Processes and Customer Perception In the context of our business model our number one key process is our Rules and Norms (a complete breakdown of Patagonia’s current business model and a to-be-proposed business model are available for review in Exhibit I). This ethos that started with the founding of Chouinard Equipment continued through the creation of Lost Arrow and indeed Patagonia. Our self-proclaimed â€Å"dirtbag† culture has resulted in some unorthodox business practices over the years. We pride ourselves on our efforts to reduce the social and environmental impact of the lifetime of the goods and services we produce. This is something that our competitors recognize but do not focus efforts on; for us it is of the utmost importance. I took this liberty to draft a Customer Value Proposition (CVP) for our current model: â€Å"We provide high quality, durable outdoor athletic clothing and accessories that are produced with a high standard for environmental and social impact. We make the products that we want to use.† To extrapolate on the latter portion of our CVP, we expect our employees to not only share in the environmental and social consciousness that Mr Chouinard has weaved into the culture of Patagonia but we expect employees to be users of our products as well. This gives us an incredible insight into the functionality and durability of our products. This is exemplified in our generous sabbaticals and midday surfing breaks at our corporate headquarters. Additional insight in this regard is provided by our investment in brand ambassadors, who also provide us with the core of our visual marketing in our catalogs, our website, and social media. In order of volume we move our products through three main channels: wholesale, retail, catalog/internet. In order of profitability the channels are arranged as such retail, catalog/internet[1], and wholesale. There is an additional product repair arm of Patagonia’s structure that at the moment is not profitable. Our commitment to the ethical fiber that binds the core of what Patagonia as a brand stands for results in a product that comes at a premium price, however we believe that the money you spend on Patagonia products is a contribution to our commitment for care when it comes to the environments and social spheres within which we operate. So far we have seen success as shown below. 2. Financial Review of Current Business Model The competition analysis in Exhibit III outlines our industries averages for financial health. It would seem that our â€Å"dirtbag† approach to business has boded well for us over the last ten years. While our total market share (annual sales) is far below the industry average over all the company is making money. Our gross profit margin is over 6% higher than the industry average and our pre-tax profit margin is right in line with the industry average. While Patagonia’s ROE and ROA are below the industry average it is not my much and our debt to equity ratio is far below the industry average. So while we holds more equity and assets on hand than our competitors we has enough liquid cash flow to finance operations without having to incur much debt. Our 12 month revenue growth is trending along with the industry however our 12 month net growth income is nearly 13% higher than our competitors. Thus while we are experiencing growth that is on par with the industry we are experiencing a downward turn in our operating and/or material costs. It should be noted that the information here is of companies who compete in our industry but not exclusively. Columbia is the competitor that competes most directly with our niche in the industry and on every account except for debt/equity our numbers are favorable and even in the case of debt/equity the difference is negligible. The standards for philanthropy and an ethical purview for production and material sourcing at Patagonia are much higher than the industry average. We donate 1% of gross sales to environmental initiatives and causes, and our COGS are higher than competitors as a result of our ethical stance. However, once again (as shown in Lost Arrow: Financials, Exhibit III) we have been operating in the black for the last decade. This may also be explained by our company ethic. We focus on a curbing of consumption and that focus has limited how much we are willing to spend on advertizing. Conversely our competition holds advertisement as a high priority when establishing sales and brand. This observation is not trivial and could more than account for the balance between our costs and those of our competitors. 3. Moving Forward As discussed the current model for Patagonia works. You can be a â€Å"dirtbag† and make make money. The question is how do we continue on with the goal of 10% growth per year for the next five years? Whatever we choose we must operate within that moral fiber that helped us to achieve who we are today. Following are two suggestions for how to move forward, one uses our current business model, the other proposes a change. Please reference Exhibit I for business model analysis and Exhibit II for strategy. Strategy: Current Business Model Tactic One: A Focus on Retail – Our best margins are derived from retail sales however this accounts for just one third of our sales volume. The best type of marketing asset we have are our retail employees. Our Dirtbag Ambassadors are out there skiing, snowboarding, climbing, camping, bouldering, and living the life that Patagonia wants to be an integral part of. We must expand our retail channel and focus on those areas where dirtbags convene. A quick review of the 26 stores in the United States can be found in Exhibit V. Portland, Seattle, St. Paul, Chicago, Atlanta, DC. Sure dirtbags live in cities but where are our stores in Telluride, Tahoe, Bend, Cheyenne, or Buffalo? An expansion of our retail stream increases profitability as well as the reach of our marketing, the Patagonia way. These are the places our competitors don’t wants stores for lack of traffic, but our stores are more than commerce they are community centers for dirtbags. Tactic Two: Research and Development – Our industry ethic has produced one of the best research and development laboratories in the industry. We can leverage this in two ways. First and foremost we must fund research to produce material with the ethical and physical integrity that also helps lower our gross margins. We have pioneered ethical durable material in the industry, now we must find a way to do so cheaper. Doing so would open up the market for those dirtbags who dont have as much money and would normally go to a competitor based on price point. Second we hold patents for these materials we could offer to sell material to other outdoor companies, or begin a joint venture. In either of these cases we must make sure that the material we produced is being utilized in an end product that is up to the standards of Patagonia. Strategy Two: A New Business Model There comes a time in a business life when you have to ask: While what we are doing has worked, how long will it work? To achieve the goal of 10% growth per year we may have to think outside of our wheelhouse and think about how committed we are to our ethical and social standards. As long as we continue to produce more clothing people will buy it. As it stands our customer base has expendable income. How can we convince them to only buy what we need? Through an expansion of our clothing repair services and clothing swap market. A case is made for the business model change in Exhibit I. Tactic One: Expansion of Repair and Retail – It is not our goal to abandon what has made Patagonia the company it is today, thus once again we will need to expand retail stores however we do so in a way that will facilitate clothing repair. Each store should have a mending workshop staffed and equipped to repair what comes their way. To really take advantage of this service we must willing to mend non-Patagonia clothing. This will do two things: it will reduce the overall number of unnecessary purchases in our market and it will introduce people to the Patagonia lifestyle through our retail store. These store can also facilitate a recycling program for those articles of gear that are beyond repair. Something as simple as an in store credit can get people who would otherwise go to Nike experience Patagonia CA. Additionally the expanded retail presence will be an opportunity to create a network for clothing swaps Tactic Two: Expansion of Internal Repair – Expand the repair infrastructure behind retail presence. That is to say, as opposed to expanding retail and having repair work centers in-store, invest in larger repair facilities that stores can send garments to. In our current business model we are reaching critical mass with regard to how much clothing repair we can handle. If we strategically place lager facilities near our exiting stores we can handle this work load our selves. This also ensures that the materials and process of clothing repair is within the ethical conduct of our company without having to do audits of our outsourced partners. The clothing repair infrastructure for our market is basically nonexistent at this point and with research and development focused on this new business model we can create and dominate this market. This will once again involve repairing more than just Patagonia products but in the end that’s what this business model is about. To survive and grow into the next decade we must not just reduce the consumption of our customer base but we must reduce the consumption of our competitors as well. When a dirtbag holds on to a coat for another year he helps reduce Patagonias impact on the earth and its inhabitants. When Patagonia repairs a Columbia or North Face coat and it lasts for another year we have slowed the consumption of unethically produced clothes and possibly created another dirtbag. Exhibit I: Four Components of Business Model Framework (Johnson, Christensen, Kagerman) Customer value proposition (CVP): Current: Providing high quality durable outdoor athletic clothing and accessories (CA) produced with a high standard for environmental and social impact. Proposed: In addition to production, engage the consumer in the environmental and social impact of their outdoor athletic CA by involving them in the maintenance/repair/swap of CA. Profit formula: Revenue model: Current: Standard industry mark up on goods sold. Proposed: Lower the price of goods sold and charge a small fee for repairs or continue with current price structure charge cost for repairs of Patagonia clothing/accessories, charge premium repair rates for non-Patagonia clothing and accessory repair. Cost structure: Current: COGS = 80% materials 20% parts with a wholesale margin of 45% and a retail margin of 65% Proposed: A modified cost structure that emphasizes retail sales and profits off of repairs Margin model: Current: Largest channel of sales in wholesale 44%, second retail 33%, and finally Catalog/internet 23% Proposed: Shift focus from wholesale to retail/catalog/internet sales, add additional emphasis on repair cost structure for maximum profitability Resource velocity: Current: In general keeping inventory exhausts resources, something which Patagonia wants to minimize. Thus production should match as close to demand as possible. Assets should be available, although they do not need to be incredibly liquid. Proposed: Same as current model. Key resources. Current: People: There is a certain type of person who works for Patagonia. Ideally a person who works at Patagonia is the ideal consumer of their goods. Brand: With a strong brand associated with high environmental and social standards combined with a strong dislike of standard advertising channels for the industry the reputation Patagonias brand has gained is remarkable (this is achieved through the people they employ as well). Technology: Their ethical commitment to responsible sourcing and production has resulted in some profitable patents of great CA material. Proposed: The current Key Resources should not be lost but the Technology will shift to the new business model – a focus on materials , threads, and substances for repair. Additionally there would be a re-purposing of Facilities to reflect this model change as well. Key processes. Current: Rules and Norms: Patagonias Rules and Norms inform every aspect of their business and it is no different when it comes to their Key Processes. So while manufacturing, service, and training are all important, it all comes down to the Rules and Norms. Propsed: This would not change. When a new business model is needed. 1. The opportunity to address through disruptive innovation the needs of large groups of potential customers who are shut out of a market entirely because existing solutions are too expensive or complicated for them. The product repair market is just this. As it stands now such jackets tend to be luxury purchases as they hobbies they are designed for are not generally cheap ones to keep. 2. The opportunity to capitalize on a brand new technology by wrapping a new business model around it or the opportunity to leverage a tested technology by bringing it to a whole new market Patagonia isn’t capitalizing on a new technology when it comes to CA per se but the market could motivate their RD department to develop a technology that could be incorporated into the repair model. 3. The opportunity to bring a job-to-be done focus where one does not yet exist The expansion of clothing repair for Patagonia and other non-Patagonia CA provides a real opportunity for an existing market that consumers may not know they need. It creates a job to be done (clothing repair as opposed to replacement). 4. The need to fend off low-end disrupters. Patagonia would be a low end disrupter in the repair market; repair is cheaper than replacement. 5. The need to respond to a shifting basis of competition. Patagonia would be shifting the basis of competition.

IOP Spike Control after Intravitreal Anti-VEGF

IOP Spike Control after Intravitreal Anti-VEGF In ophthalmology many ophthalmic procedures are there in which there is a spike of intraocular pressure after the procedures. Cataract surgery, argon laser trabulectomy (ALT), yag laser capsulotomy, yag laser iridotomy, trabulectomy, pars plana vitrectomy are few to be named. The new anti VEGF therapy is an addition to the prior list. Many IOP lowering drugs have been used in different procedures to stop these spikes. For ALT 1% apraclonidine, an alpha agonist has been found to be the most effective against the IOP spikes, but 0.5% has also been found to be equally effective. Brimonidine an alpha 2 adrenergic agonist has also been shown to be effective and safe choice. For cataract surgery different drugs have been used treat the postoperative increase in IOP. These include carbonic anhydrase inhibitors, prostaglandin analogs like latanoprost, alpha agonists like apraclonidine and brimonidine, beta-blockers and miotics (intracameral carbachol and acetylcholine). Similarly intravitreal injection of triamcinolone has been complicated with a rise of IOP and have been controlled effectively by beta blockers, but some may need aggressive treatment. Different researchers have worked on the control of acute spikes after the intravitreal injection of anti-VEGF, showing varied result. Some have advocated the use of IOP lowering medicine while other negating the need all together. Lim Young et al showed that the prophylactic use of fixed dorsolamide/timolol combination eye drops before the intravitreal anti-VEGF injection was a safe method of preventing IOP spikes occurring immediately after the intravitreal injection of anti-VEGF. He showed that the mean IOP at 5 minutes and 30 minutes postoperative was 14.12 Â ± 4.18 mm Hg and 10.87 Â ± 1.58 mm Hg in group 1 using IOP lowering medication while it was 28.21 Â ± 3.16 mm Hg and 17.48 Â ± 2.34 mm Hg in control group 2, respectively.9 He showed that there was a significant lowering of mean IOP at each reading at 5 minutes of interval. Frenkel et al showed the use of IOP-lowering medication prior to injection of pegaptanib, ranibizumab, or bevacizumab had little effect on the IOP spike. The failure of lowering the IOP spike was implicated to be due to the inability of these medications to counteract the volume-related mechanism of the IOP spikes after anti-VEGF injections. However, it was stated that there might be benefit to lower the IOP before intravitreal injection. In their study 2 cases of sudden loss of vision were reported due to the high IOP spike which prompted them to do anterior chamber paracentesis.8 It was also stated that the prophylactic use of medication in patients with advanced glaucoma receiving pegaptanib intravitreal injection or patients receiving 0.1 ml of bevacizumab could be considered because their study showed that it lowered IOP at the 3- to 10-minute interval in these patients. In another study done in 2013 the IOP lowering effect of Dorzolamide/Timolol and Brinzolamide/Timolol were compared with a control group. They measured the IOP after every 5 minutes for the first half hour and the next day and week after that. For all the 3 groups, the changes relative to the baseline at 5 and 30 minutes after intravitreal injection was found to be significant. Also when the groups were broken down as to whether receiving bevacizumab or ranibizumab, again the mean decrease of IOP compared to the control group was found significant. El Chehab et al have also found that the prophylactic use of fixed combination of timolol with brimonidine or dorzolamide and of 1% apraclonidine could not only reduce the IOP spikes but also their duration; and both the combination and 1% apraclonidine had equal effect. However the use of oral acetzolamide 20 minutes prior to the intravitreal injection was not proven to be effective. Evaluating the efficacy of timolol 0.5 % and brimonidine 0.2 % eye drops as a fixed combination in preventing IOP spikes Theoulakis et al found that twice a day instillation on the day before and before the time of injection in eyes which were scheduled for intravitreal ranibizumab was a safe and also effective in controlling the IOP spikes. IOP LOWERING MEDICATIONS Most of the IOP lowering medicines are administered topically. They are absorbed through the cornea and conjunctiva; mainly acting locally on the eye. Many anti glaucoma medicines have been used. The main groups of drugs are as following: BETA- ADRENERGICANTAGONISTS They are the most prescribed drugs of IOP control. There are a total of five topical beta-adrenergic antagonists which are currently FDA approved for managing high intra ocular pressure. They are timolol betaxolol, carteolol, metipranolol, levobunolol. Betaxolol is selective beta1 selective antagonist, and is safe to use this drug in patients with pulmonary and cardiac problems. The mechanism of action is to reduce IOP by decreasing the production of aqueous by inhibiting the production of cyclic adenosine monophosphate (cAMP) in ciliary epithelium. The IOP reduction is upto 20 to 35%. The effects of beta blockers occur within an hour after its instillation. Timolol is available in the market in concentrations of 0.1%, 0.25% and 0.5%. The recommended dosage is 1 drop two times a day. Burning, allergy and corneal epithelial erosions are the main ocular side effects. It can be absorbed systemically and can cause systemic side effects like bronchospasm, bradycardia, hypotension, respiratory failure. Timolol maleate has a molecular weight of 432.50. It is an odorless, white, crystalline powder that is soluble in methanol, water and alcohol. It is compounded as an isotonic, sterile, buffered solution available in two strengths: 0.25% Timolol maleate eye drops contains 2.5 mg of timolol (about 3.4 mg of timolol maleate). It has a pH of approximately 7.0, and an osmolarity of 274-328 milliosmole. And each ml of 0.5% Timolol Maleate eye drops contains 5 mg of timolol (about 6.8 mg of timolol maleate). The Inactive ingredients are usually monobasic and dibasic sodium phosphate and sodium hydroxide to adjust pH. Preservative used is Benzalkonium chloride 0.01%. PARA SYMPATHOMIMETIC AGENTS They act by stimulating sphincter pupillae and ciliary body by acting on the muscarinic receptors. They cause the contraction of the ciliary muscles which thus increases the aqueous outflow through the trabecular meshwork. Pilocarpine is the commercially available drug in this group and is compounded in concentration of 1%, 2%, 3%, and 4% and the recommended dosage is 1 drop 4 times per day. Ocular side effects are miosis, induced myopia with brow ache, retinal detachment, and cataract. Systemic side effects after its absorption can be of diarrhea, vomiting, abdominal cramps and bronchial spasm. CARBONIC ANHYDRASE INHIBITORS (CAIs) The enzyme required for aqueous formation is carbonic anhydrase. The CAIs cause inhibition of this enzyme and thus cause a decrease in the aqueous humor secretion by the ciliary epithelium. Carbonic anhydrase is required for catalyzing the reaction of CO2 to H2CO3 which further splits into HCO3 _ and H+. The bicarbonate ions are pumped along with sodium ions into the posterior chamber along with diffusion of water for the formation of aqueous humor. Carbonic anhydrase is present in ciliary body in excess. 99.9 % of the enzyme must be inhibited before a significant decrease in IOP can occur. Dorzolamide and brinzolamide are the commercially available eye drops in market. They have a good corneal penetration, and are also water soluble. These agents are able to reduce IOP upto 14-17%. Adverse effects of topical CAIs are burning and stinging of eyes on instillation, conjunctivitis, blephritis, corneal allergy, corneal punctuates keratitis and can also cause bitter taste. The systemic used CAIs are methazolamide and acetazolamide. They also cause inhibition of carbonic anhydrase in ciliary epithlium thus reducing the reduction of aqueous humor. As it is taken orally systemic side effects of CAIs include metabolic acidosis, leading to alkaline diuresis which result in hypokalemia. So potassium levels should be regularly checked in patients using CAIs on long term basis and oral potassium supplement should be recommended to all these patients. Other side effects include renal stones formation and central nervous system side effects like numbness and tingling of hands and feet, depression, anorexia, and nausea. Dorzolamide hydrochloride has a molecular weight of 360.91. It is a white to off-white in colour, in a crystalline powder form, which is also soluble in water, methanol and ethanol. ADRENERGIC AGONISTS Adrenergic agonists act by increasing the uveoscleral and trabecular meshwork outflow thus causing decrease in IOP. Epinephrine has a mixed action of being an alpha and a beta agonist. Its effect usually begins at 1 hour and reaches a maximum at 2-6 hours. Topical epinephrine drops usage has been stopped due to frequent systemic side effects of headache, palpitation and cardiac arrhythmias. The main ocular side effect is cystoid macular edema and black pigmentation of conjunctiva. Commercially available topical form is dipivefrin hydrochloride 0.1%eye drops, which is a prodrug of epinephrine. It is converted by the enzyme esterase into epinephrine in the cornea. Because of its high lipid solubility and corneal penetration a low dose is required as compared to epinephrine and thus has less side effects. The selective alpha 2 agonist apraclonidine and brimonidine are indirect acting adrenergic agonist which act by decreasing aqueous production and also the episcleral venous pressure and thus improving the trabecular outflow. Apraclonidine is associated with tachyphylaxis while brimonidine has less of this problem. Brimonidine tartrate is available commercially in 0.25 and 0.15% eye drops. Its reduces IOP by 26% at 2 hour of interval. PROSTAGLANDIN ANALOGUES Prostaglandin analogues are relatively a new class of IOP lowering drugs. Four prostaglandin analogues have been approved by the FDA for clinical use. Latanoprost was the pioneer drug to be developed and used in this group. Others are travoprost, bimatoprost, and unoprostone. Latanoprost is a pro drug which penetrates the cornea and then is turned into active form. It enhances the uveoscleral outflow and thus lowers the IOP upto 25-35%. The dosage is one drop per day which makes the compliance of the patient better. The main ocular side effect is darkening of the iris and the periocular skin, by increase in the number of melanosomes in the melanocytes. Other side effects include conjunctival hyperemia, hypertrichosis, uveitis and cystoid macular edema. Systemic side effects are flu like symptoms, skin rash and uterine bleeding. OSMOTIC AGENTS Osmotic agents act by decreasing the vitreous volume by removing the liquid out of the eye into the circulation. The osmotic agents can be given orally or intravenously. Oral agent is glycerin while urea and mannitol are given intravenously. The osmotic activity is dependent upon the number of particles in the solution which cannot cross over and maintains the osmotic gradient between the compartments. Mannitol is given intravenously because it cannot be absorbed from the gastro-intestinal tract. A rebound increase in IOP and local tissue necrosis limit the use of urea. Glycerin is most commonly used oral osmotic agent which is given along with cracked ice to dilute its nauseating feeling. In patients with diabetes a non-metabolized sugar isosorbide can be used instead. Several fixed combinations have been developed which are available in markets used for IOP-lowering. Most of these fixed combinations contain timolol (dosed once or twice daily) combined with either adrenergic agonists, prostaglandin analogs, and CAIs. COMBINATION Fixed combination timolol maleate 0.5% with dorzolamide hydrochloride 2% was first introduced in market in 1998. Each milliliter of drug consisting of 6.83 mg timolol maleate and 22.26 mg dorzolamide hydrochloride. Timolol inhibits aqueous humor production by down-regulating adenylate cyclase by inhibiting ÃŽ ²2-adrenergic receptor sites on the ciliary process . While dorzolamide acts as a selective inhibitor of Carbonic anhydrase II enzyme, present on the ciliary process. The local bicarbonate production is slowed down, which as a result decreases sodium and fluid transport and, finally, decreases the aqueous humor production thus lowering the IOP. Because the mechanisms of action of both the drugs differ, they provide an additive effect when used together. Fixed combinations of drugs have been found to improve the compliance of the patient by reducing the number of eye drops used daily. Moreover the IOP-lowering effect of fixed combination timolol and dorzolamide was found to be greater than that of either drug instilled as monotherapy. In addition the load of preservative is also reduced along with any wash out of drug when the drugs in monotherapy are instilled one after the other.