Advantages Of Semisynthetic Penicillins Biology Essay

Advantages Of Semisynthetic Penicillins Biology Essay Introduction Amoxycillin is a semisynthetic ÃŽ ²-lactam antibiotic derived from a common chemical nucleus of naturally occurring Penicillin G, 6-aminopenicillanic acid. Vital to Amoxycillins biological effects is the ÃŽ ²-lactam ring contained within this nucleus. Amoxicillin is bacteriolytic and bacteriocidal to susceptible gram positive and gram negative microbacteria. Today, amoxicillin is the 9th most prescribed drug in the world. Penicillin discovery Up until the early 1900s, the only treatment for bacterial infection was antiseptic which was only useful for surface wounds. In 1928, Alexander Fleming made a momentous albeit accidental discovery in St Marys Hospital in London. He noticed that a Staphylococci plate being grown in culture had been contaminated with mould of the species Penicillium notatum and that this had resulted in the inhibition of bacterial growth in the vicinity of the mould. Fleming subsequently isolated the mould and formulated an antibacterial mould broth. In 1938 at Oxford, Howard Florey and his biochemist Ernst Chain extracted penicillin from the mould and established that it was nontoxic and had chemotherapeutic effects. In 1941 an injectable form of penicillin became available for therapeutic use Advantageous of Semisynthetic Penicillins Penicillin G (naturally occurring) is poorly stable in gastric acid and broken down rapidly as it passes through the stomach. Therefore, Penicillin G must be given intramuscularly which limits its usefulness. Semisynthetic penicillins such as Amoxycillin with increased oral bioavailability were a major advancement in therapeutic antibiotics. Furthermore, while aminopenicillins and natural penicillins have similar efficacy against gram positive bacteria, semisynthetic aminopenicillins (such as Amoxycillin) are more active against certain strains of gram negative rods. Amoxycillin Discovery In Beecham Laboratories in 1957, 6-aminopenicillanic acid (6-APA) was isolate from penicillin. Through chemical modification of the ÃŽ ²-lactam thiazolidine ring side chains semisynthetic penicillins were developed. In 1961, Ampicillin was created which was quickly followed in 1964 by the introduction of a Ï -hydroxyl group in Ampicillins side chain creating amoxycillin. Amoxycillin was found to have improved absorption following oral administration and 2-2.5 times greater plasma concentrations compared to an equivalent dose of Ampicillin. In 1967 Beecham laboratories discovered that the susceptibility of Amoxycillin to ÃŽ ²-lactamase could be overcome with co-administration of clavulanic acid (a ÃŽ ²-lactamase inhibitor isolated from Streptomyces olivaceus). Chemistry Amoxycillin is a white crystalline powder that is somewhat soluble in alcohol and water. Amoxycillins chemical name is (2S,5R,6R)-6-[(R)-2amino-2-(4-hydroxyphenyl)acetamido]-3,3-dimethy;-7-oxo-4-thia-1-azabicyclo[3.2.0]heptanes-2-carboxylic acid. It has a molecular weight of 419.4. Figure 1: Chemical Structure of Amoxycillin Pharmacodynamics Amoxycillin functions by inhibiting the biosynthesis of cell wall mucopeptides of susceptible gram positive and negative microorganisms actively synthesizing peptidoglycan and undergoing multiplication. The molecular target of Amoxycillin and other ÃŽ ²-lactam antibiotics are the Penicillin Binding Proteins. Upon drug-target interaction transpeptidation is blocked and thus inhibiting the synthesis of peptidoglycan, a vital cell wall component. Subsequently, the inhibitor of autolytic enzymes in the cell wall, is removed resulting in active autolytic enzymes and bacteriolysis. Pharmacokinetics Amoxycillin complies with the two compartment model with elimination occurring from the central compartment. Figure 2 demonstrates Amoxycillins biexponential decline of serum concentration with time. Table 1 and 2 document the pharmacokinetic parameters of Amoxycillin. Figure 2: Average serum concentration versus time after 500mg IV dose of Amoxycillin. Table 1: Pharmacokinetic parameter and absolute bioavailability of a 500mg oral dose of Amoxycillin. Table 2: Pharmacokinetic parameter of a 500mg IV dose of Amoxycillin. Administration Amoxycillin is usually administered orally. The relationship between dose and extent of absorption is not linear with a plateau at higher oral concentrations. Dose adjustments need to be made in patients with renal dysfunction. Bioavailability Drug bioavailability is the proportion of drug that passes into systemic circulation after oral administration. It is dependent upon absorption across the gastrointestinal tract and first pass clearance by the liver. After oral administration of a dose of 250mg and 500mg of Amoxycillin the average peak serum concentrations (observed between 1-2 hours after administration) were 5.0mg/mL and 6.0 10.8 mg/mL respectively. The variation of plasma concentration with time is demonstrated in Figure 3. The oral bioavailability of Amoxycillin is 77.4% Amoxycillin is stable in gastric acid and is rapidly absorbed after oral administration regardless of absence or presence of food products and thus a high proportion of administered dose reaches the systemic circulation.. Figure 3: Mean serum levels following oral administration of 125mg and 250mg of Amoxycillin to 11 normal volunteers. (95% confidence). Volume of Distribution Volume of distribution is defined as the volume of fluid in which the amount of drug in the body would need to be uniformly distributed to produce observed plasma concentrations. Amoxycillin distributes widely and rapidly into most body tissues and fluid. Despite this, Amoxycillin remains extracellular due to lipid insolubility and thus does not cross the blood brain barrier unless the meninges are inflamed. Volume of distribution of Amoxycillin is 20.2L (0.3 L/kg). Clearance Clearance is defined as the volume of blood cleared of drug per unit time. It is dependent on renal excretion hepatic elimination. The clearance of Amoxycillin is 221mL/min. Renal Excretion Amoxycillin is excreted predominantly via the urine in biologically active form or as penicilloic acid. 75% of a 1 gram dose is excreted in the urine within 6 hrs (60% biologically active form, 15% is in the form of penicilloic acid). Biological Half life Elimination half life is defined by the time taken for the plasma concentration of drug to reach half the steady state concentration. The biological half life is 61.3 minutes with normal renal function. Half life increases with renal dysfunction. Clinical Uses Amoxycillin is a broad spectrum ÃŽ ²-lactam antibiotic with effectiveness against many pathogenic microorganisms. It is commonly used to treat bacterial infections such as otitis media, tonsillitis, throat infections, laryngitis, bronchitis, pneumonia, urinary tract infections, gonorrhoea and skin infections. Indications for use Location of infection Microorganism Skin and skin structure E coli, Staphylococcus, nonpenicillinase producing streptococcis Respiratory (Acute and chronic) nonpenicillinase producing E coli, Streptococcus, Strep. Pneumonia, H.influenzae, staphylococcus Genitourinary tract (Complicate and uncomplicated, acute and chronic) E.Coli, P.mirabilis and Strep. Faecalis Gonorrhoea N. Gonorrhoea (nonpenicillinase producing) Prophylaxis of endocarditis Used in people at particular risk (e.g. individuals who have previously had endocarditis or with a prosthetic heart valve) Table 3: Indications for use of Amoxycillin Precautions Drug interactions Amoxycillin is rarely associated with adverse drug interactions however the following reactions have been demonstrated in some cases. Drug Interaction Oral anticoagulants (e.g. Warfarin and Acenocoumarol) Results in abnormal prolongation of prothrombin time (or international normalised ratio.) Allopurinol Results in increased rate of rash reactions. It is unknown whether this is due to Amoxycillin reacting with the allopurinol itself or the hyperuricaemia that it is treating. Combined Oral Contraceptives Like all penicillin, Amoxycillin can affect the commensal gut flora which results in decreased oestrogen absorption. This has been associated with decreased efficacy of combined oral contraceptives. Tetracyclines or other bacteriostatic drugs Bacteriostatic drugs have been known to interference with the bactericidal effects of Amoxycillin Clavulanic acid Amoxycillin therapeutic effects are inactivated by penicillinase (ÃŽ ²-lactam) producing organisms. It is possible to co-administer Amoxycillin with clavulanic acid (ÃŽ ²-lactamase inhibitor) to broaden the spectrum of susceptible bacteria (e.g.. co-amoxiclav). Probenecid Renal excretion can be delayed by administration of Probenecid as demonstrated by Figure 4. When used in conjunction there is an increased plasma concentration of Amoxycillin reached and longer duration of effect. This is a beneficial interaction. Table 4: Some common drug interactions when co-administered with Amoxycillin Figure 4: Mean serum levels following oral administration of 1 gram of Amoxycillin with and without probenicid. Pregnancy and Lactation While penicillin can cross the placenta, no teratogenic effects have been uncovered through animal studies. Similarly, Amoxycillin can be excreted in breast milk resulting in potential side effects for the nursing infant including diarrhoea or allergic response. However, Amoxycillin is generally considered safe for use in pregnant women and nursing mothers. Adverse reactions Side effects are uncommon however potentially include insomnia, diarrhoea, dizziness, confusion, heartburn, easy bruising, itching, nausea, vomiting, abdominal pain, bleeding, rash and allergic reactions. The most common adverse reaction is hypersensitivity reactions in patients with allergies to ÃŽ ² lactam antibiotics, penicillin or cephalosporins. Anaphylaxis can be fatal and occurs more frequently following parenteral administration. All penicillins have been associated with seizures when administered in excessive doses or administered intrathecally. Conclusion The discovery of penicillin by Alexander Flemming lead to the subsequent generation of the semisynthetic aminopenicillin, Amoxycillin. This ÃŽ ²-lactam antibiotic has a broad spectrum of therapeutic use, high oral bioavailability and lack of toxic effects.

Great Depression and Technology

As Albert Einstein once said â€Å"It has become appallingly obvious that our technology has exceeded our humanity. † Throughout the years our technology has become more and more advanced, creating more and more inventions. Modern technology has been created to fulfill every human’s needs. With such great advancements it has become convenient for our society to turn to technology for all our questions. We have not realized that day by day technology is taking over us. Many like to argue that it is not true, but if you were to take away every possible form of technology away from them, it would make living for them very difficult. Now a day, technology has played such an important role in our lives that it seems almost impossible for many of us to live without it. Being said, modern technology has produced more inconveniences than conveniences. To begin, with technology constantly advancing, many have become very reliant on it, making technology almost a necessity to a person’s everyday life. Almost everyone owns a car, a computer/laptop, a cell phone, and even higher advanced technology. Everywhere you go, people are either talking on their phone or texting, However, with so much technology being provided to us, it has made us profoundly lazy and too dependent on technology not allowing us to think for ourselves. So not only has modern technology made us lazy but also unintelligent. â€Å"Who can remember the days when you had to go to the library to do research for a research paper, had to pick up the morning newspaper to get the latest news, or had to buy a stamp and put a check in an envelope to pay a bill? In the last 50 years technology has undergone an amazing transformation. But with the emergence of the Internet, is our ability to access technology on a daily basis a good thing or a bad thing? † (Bradley). Bradley clearly states that we no longer do simple tasks on our own; we rely on technology to do them for us. We now use Google or other search engines to look up questions, turn on a televisions to see what is going on around us, and take a picture of a bill on our cell phones to pay it. â€Å"In another 50 years will we still be considered a lazy society? (Bradley). Furthermore, â€Å"Although the proliferation of communications technology has made it easier than to ever to have a conversation with or write a letter to another person, it has also rendered us more isolated. Computers have significantly reduced the amount of face-to-face interaction people once enjoyed. In place of the richness of human contact, many now settle for the comparatively pale pleasures of comp uter social networking† (Wolfe). With social medias like Facebook, MySpace, and Twitter, communicating with one another has become easier than ever. But this may not always be a good thing. People can easily create fake profiles and pretend to be a young man or woman when they can be a crazed rapist or murderer. Not only that but with so many social networks, cyber bullying has increased drastically. People can put whatever they want on the internet which can lower a person's self-esteem causing for them to want to kill themselves. Also, since we communicate so much over social media, it can affect our writing skills. Many people who chat online do not use proper vocabulary. For example, instead of writing okay, they abbreviate it writing OK. This causes us to begin writing in slang when we write papers for school. As a society we should learn face-to-face communication instead of over the internet. As final point, with new advanced machines being created and the machines being capable to do almost anything, there has been an increase in job elimination. Some of these jobs would include those of farm workers and factory workers. â€Å"A technology revolution is fast replacing human beings with machines in virtually every sector and industry in the global economy. Already, millions of workers have been permanently eliminated from the economic process, and whole work categories and job assignments have shrunk, been restructured, or disappeared. Global unemployment has now reached its highest level since the great depression of the 1930s. More than 800 million human beings are now unemployed or underemployed in the world. That figure is likely to rise sharply between now and the turn of the century as millions of new entrants into the workforce find themselves without jobs† (Rifkin). With modern technology taking over the jobs of farm workers, factory workers, etc, people are left jobless. And living in this economy has made it very difficult for people to find new jobs. Like Rotman said, â€Å"Rapid technological change has been destroying jobs faster than it is creating them. † With technology constantly evolving day by day our society has to be more careful than ever to not let it take over us. Although for many of us it may already have.

Marginal Benefits And Marginal Costs Essay

The first rule can be summarized with the undermentioned phrase â€Å"There’s ne'er a free lunch† every clip that you need something you have to give something in return. One illustration is an employee that needs a peculiar twenty-four hours off. He could merely lose work and non acquire paid or inquire for a alteration of agenda and non miss work. This allows flexibleness or via media between parties. Previous to doing any determinations on the trade off you should ever see the cost. At times the cost of some actions may non be evident at a glimpse. The cost of any given undertaking may reflect on the result of your determination. Never assume that everybody is rational. Rational people seldom decide in black and white but for the most portion their determinations are in the grey country. As you go deeper into economic sciences. you will meet houses that decide how many workers to engage and how much of their merchandise to fabricate and sell to maximise net incomes. Incentives. who doesn’t like a positive inducements? Keep in head that if there is positive inducement there can besides be negative 1s. Rational people will ever maintain in head the cost and benefits of a undertaking and they will react to the inducements provided for the completions of given undertaking. An illustration of fringy benefits and the fringy costs of consider an air hose make up one's minding how much to bear down riders who fly standby. Suppose that winging a 200 – rider plane across the United States costs the air hose $ 100. 000. In this instance. the mean cost of each place is $ 100. 000/200. which is $ 500. One might be tempted to reason that the air hose should ne'er sell a ticket for less than $ 500. In fact. nevertheless. the air hose can raise its net incomes by believing at the border. Imagine that a plane is about to take off with 10 empty seats. and a standby rider waiting at the gate will pay $ 300 for a place. The air hose in this illustration will inquire itself should I sell the staying seats at the cost of $ 300 per rider is cost effectual. The reply is yes it will be profitable to sell the staying place at this monetary value. While the rider pays more than the fringy cost of the place. An inducement that could take to another determination would be a rival air hose supplying the same trip for less or the same monetary value. Persons are prone to incentives if you provide them with pecuniary. intervention or any other benefits that will honor them for their attempts. The cardinal lessons about the economic system as a whole are that productiveness is the ultimate beginning of life criterions. that money growing is the ultimate beginning of rising prices. and that society faces a short-term tradeoff between rising prices and unemployment. In a market economic system. the determinations of a authorities are replaced by the determinations of companies and persons. Companies decide how many people to engage and what merchandise to fabricate. Persons decide which industries to work for and what points to purchase with their wages. A centrally planned economic system is when a authorities decides what points to bring forth and how much. Determine the allotment of scarce resources and who will bring forth and devour these goods and services. When the market economic system and the centrally planned economic system are combined and influenced by the control of the private and authorities sector. In decision economic sciences play an intrical portion of our day-to-day lives. It allows a state to turn or a company to drop. Decicion devising is an of import facet of the economic system and all decicions sing this topic has to be treated as a delicate subject. MentionsGregory. N. ( 2009 ) . Principles of Economics ( 5th ed. ) . Mason. Oh: South-Western Cengage Learning. Hubbard. R. & A ; O’Brien. A. ( 2010 ) . Economicss ( 3rd ed. ) . Boston. MA: Pearson Hall.

Questions On Google s Article On Facebook - 1181 Words

4 Must-Dos to Improve Your Innovation Capabilities By Christelle Espinasse | Submitted On June 04, 2015 Recommend Article Article Comments Print Article Share this article on Facebook Share this article on Twitter Share this article on Google+ Share this article on Linkedin Share this article on StumbleUpon Share this article on Delicious Share this article on Digg Share this article on Reddit Share this article on Pinterest Expert Author Christelle Espinasse I would rather make the mistake of moving too fast than make no mistake and move too slow - Larry Page, Google s CEO Despite a plethora of business literature on how to improve innovation, it remains an elusive endeavour for many executives. Strategic advice ranges from how to come up with better ideas (e.g. opened innovation, crowdsourcing, etc), how to set it up (e.g. cross-functional teams, separate exploratory units, etc), how to establish funding mechanisms (e.g. venture capital arms, separate funding, etc), how to sharpen execution (rapid prototyping, gate-funding, etc) to name just a few - but all assume that all businesses face the same obstacles. In reality, any improvements to innovation are contingent upon company specific factors to be identified first before ways can be developed to address them. 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