#anacin tablets

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Anacin Analgesic Tablets, 1952

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Stephen King is more readable (in a certain sense) than any writer I know – when I pick up any book he wrote, even if it’s one of his worse books or it doesn’t have a premise that’s interesting to me, within paragraphs I’m hooked enough to want the next few. I always, always want to read the next few paragraphs when I’m in a King novel.

The other notable thing about King’s writing is the gratuitous physical detail – intensely local and dated. He knows or decides what things are called and isn’t shy about listing them. No one ever picks up a paper – they pick up a specific, named paper. No one’s uncle once served in the army – they served in a specific unit in a specific war. One character intro begins with a survey of his medicine cabinet. This is one paragraph out of three, for the three shelves:

On the top shelf there’s Anacin, Excedrin, Excedrin P.M., Contac, Gelusil, Tylenol, and a large blue jar of Vicks, looking like a bit of brooding deep twilight under glass. There is a bottle of Vivarin, a bottle of Serutan (That’s “Nature’s” spelled backwards, the ads on Lawrence Welk used to say when Eddie Kaspbrak was but a wee slip of a lad), and two bottles of Phillips’ Milk of Magnesia—the regular, which tastes like liquid chalk, and the new mint flavor, which tastes like mint-flavored liquid chalk. Here is a large bottle of Rolaids standing chummily close to a large bottle of Tums. The Tums are standing next to a large bottle of orange-flavored Di-Gel tablets. The three of them look like a trio of strange piggy-banks, stuffed with pills instead of dimes.

As a teenager and aspiring writer, reading King this gave me a horrible sense of inadequacy. For god’s sake, how am I supposed to know this stuff? How am I supposed to reference specific ads?– I don’t even listen to ads! King, conversely, strikes me as someone who walks through life very awake to everything, soaking in all the random details of how the world around him worked. And when he sits down to write, he can regurgitate any of this and throw it onto the page with maximalist energy.

Possibly he got very excited about just listing things when he was on cocaine and this novel was written in cocaine era? But I definitely couldn’t list things like this on cocaine! I do not pay attention to the world around me. I don’t know the name of the company whose electricians come to fix things in my house. I don’t know what wood was used to make the legs of my kitchen chairs. I take medicine for an issue and then forget its name. I get from point A to B by train or car or bus, and then I forget what the tracks or roads were called – forget even the pattern that governs their names. I  can never make up road names because I doubt that I can model the underlying generator or distribution that names are drawn from. It’s very clear that King does not live life like me:

If, on that night of May 28th, 1985, you had wanted to find the man Time magazine had called “perhaps the most promising young architect in America” (“Urban Energy Conservation and the Young Turks,” Time, October 15, 1984), you would have had to drive west out of Omaha on Interstate 80 to do it. You’d have taken the Swedholm exit and then Highway 81 to downtown Swedholm (of which there isn’t much). There you’d turn off on Highway 92 at Bucky’s Hi-Hat Eat-Em-Up (“Chicken Fried Steak Our Specialty”) and once out in the country again you’d hang a right on Highway 63, which runs straight as a string through the deserted little town of Gatlin and finally into Hemingford Home

Stephen King, how – why – stop that! That’s just too much! I would just say “the guy was in a bar that night”. It’s hard to see what this route description adds to the story, but it’s also clear to me that the underlying tendency that made him add this paragraph is also part of what hooks me in so fast into a King novel. King’s characters are kind of samey – white and sometimes black 20th century Americans whose type he knows well – and fade quickly in my mind once I put down the book, but while I’m in it, they’re so alive and relatable and specific, bursting with the detail of who-they-are, detail that Stephen King seems to effortlessly pour onto the page.

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Revisiting Aspirin, Paracetamol and Ibuprofen: Discovery of Synthetic Procedures and Mode of Actions

Abstract

In this article, we will outline the historical background of the popular medicines Aspirin, Paracetamol and Ibuprofen which have been widely used for decades for their desired therapeutic effects as Analgesics, Antipyretics and Anti-inflammatory agents. We will discuss the synthetic procedures and mechanism of actions of these well-known drugs, achieved through systematic research on medicinal chemistry as well as cellular biology and pharmacology.

Keywords:Aspirin; Paracetamol; Ibuprofen; Discovery; Metabolism

    Introduction

By the end of the nineteenth century, scientific approach towards development of medicine made it possible to isolate drugs like Quinine, Ipecacuanha, and Aspirin etc. which were mainly derivatives of Natural Products. In modern times, screening of synthetic drug and lead chemical identification is an extremely complex process which requires active participation of disciplines like organic chemistry, biochemistry, microbiology, physiology, pharmacology. Even after discovery, it takes ages for the candidate drug to come for marketing. It has often been seen that establishment of proper mechanism of action of therapeutic effects involves collaborations of different research groups, from different countries, even from different time periods. In this article, we will outline the developmental process of the popular medicines Aspirin, Paracetamol and Ibuprofen which have been widely used for decades for their desired therapeutic effects as Analgesics, Antipyretics and Anti-inflammatory agents. The terms Analgesics and Analgetic drugs are often used interchangeably to describe a diverse group of pain medications. Antipyretics are the drugs that lower body temperature increased by infections or other diseases but have no effect on normal body temperature. Anti-inflammatory agents are the drugs used to diminish or reduce inflammation and pain associated with it. Here we will highlight the discovery of the laboratory synthetic procedures and mechanism of actions of these well-known drugs.

    Aspirin

Willow bark extract was recognised as folk medicine from the mid-eighteenth century for treatment of fever and pain. Salicylic acid derived from willow bark is one of the oldest analgesics. However, its use can cause gastric irritation and bleeding due to the free phenolic group. This is overcome by masking the phenol as an ester. The compound acetylsalicylic acid known as Aspirin was tested and introduced into medicine by Bayer in Germany in the late 1890s. Heinrich Dreser, Arthur Eichengrün and Felix Hoffmann are recognised as pioneers in the development of acetylsalicylic acid as the drug Aspirin. Bayer’s brand name, Aspirin was named by taking a from acetyl and spirin, comes from an old name for salicylic or spiric acid, derived from its natural source of spirea plants. Synthetically, Salicylic acid is converted to its prodrug Aspirin by acetylation of the phenolic hydroxy group. In human body, Aspirin is mainly converted to salicylic acid by esterases after absorption from the GI tract. This reduces the degree of stomach irritation because lesser amount of salicylic acid encounters the gut wall lining. The drug became popular worldwide and it was sold over the counter in the form of tablets since 1915. It is a common remedy for the relief of headache, muscular pain, rheumatic states, gout, and toothache [1].

Chemical name: Acetylsalicylic acid

Common names: ASPRO, DISPRIN, CARDIPRIN

To prepare aspirin, salicylic acid is reacted with an excess of acetic anhydride. A small amount of a strong acid is used as a catalyst which speeds up the reaction (Figure 1). The product will appear as a solid mass when crystallization is complete, and crystals are collected through vacuum filtration.

Investigations were continued to understand the basic mechanism of Aspirin’s action while clinical trials and other studies in 1960s established that it reduces the risk of heart attack. In 1971, John R. Vane from the Wellcome Research Laboratories, UK discovered the mechanism by which Aspirin exerts its antiinflammatory, analgesic and antipyretic effects [2]. He proved that Aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) inhibit the activity of the enzyme now called cyclooxygenase (COX) which leads to the production of Prostaglandins (PGs), responsible for sensations of pain and processes of fever and inflammation. Aspirin acts by acetylating the hydroxyl of a serine residue in the active site of the COX enzyme. This makes Aspirin different from other NSAIDs (such as Diclofenac and Ibuprofen), which are reversible inhibitors. Moreover, Cyclooxygenase is required for synthesis of Thromboxane, responsible for the aggregation of platelets that form blood clots. So, Aspirin can also function as an efficient anti-clotting agent by irreversibly blocking the formation of Thromboxane in platelets. This entire process is depicted in Figure 2. For discoveries concerning Prostaglandin, the Nobel Prize in medicine in 1982 was awarded jointly to Sune K. Bergström, Bengt I. Samuelsson and John R. Vane.

    Paracetamol

Paracetamol is a common household drug for pain reliever and fever reducer [3]. This aniline derivative is popularly known as Paracetamol (from para-acetyl-amino-phenol) in Europe and most of the rest of the world and as Acetaminophen (from N-acetylpara- aminophenol) in the United States and Japan. The compound was first prepared in 1877 by Harmon Northrop Morse at Johns Hopkins University, but clinically tested on humans by von Mering during 1887. From a historical perspective, Acetaminophen/ Paracetamol and the related drugs such as Acetanilide (Antifebrin: 1886), Phenacetin (1887) were introduced into the market about the same time as Aspirin and the other salicylates. The sale of Aspirin was overshadowed by Phenacetin which established Bayer as a leading pharmaceutical company that time. About half a century later, it was rediscovered that Paracetamol is the active metabolite of both Phenacetin and Acetanilide [4]. After this breakthrough, Paracetamol was successfully marketed in 1953 by Sterling-Winthrop Co. as Panadol. This medicine still continues to be the most widely used analgesic antipyretics with few sideeffects and little interaction with other pharmaceutical agents.

The drug inhibits COX activities in the central nervous system, but it lacks an anti-inflammatory effect because it cannot inhibit COX in the peripheral tissues. So, unlike Aspirin and salicylates, it does not cause gastrointestinal problems or prolonged bleeding time. This family of drug is on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in a health system. Doses of Paracetamol greater than the recommended ones can cause severe liver damage [5].

Common names: ANACIN-3, CALPOL, CROCINE, PANADOL, TYLENOL

For production of Paracetamol, phenol is used as the starting material which is reacted with sodium nitrate giving a mixture of two isomers of which the desired nitration product, 4-nitrophenol (BP: 279°C) can easily be separated by steam distillation. The nitro group is then reduced to amine, giving 4-aminophenol. Industrially direct hydrogenation is used, but in the laboratory scale sodium borohydride serves. Finally, the amine is acetylated with acetic anhydride. The synthesis reaction is shown in Figure 3.

    Ibuprofen

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) belonging to the family of synthetic 2-arylpropionic acids (Profens) that is used for treating pain, fever and inflammation. It is mainly effective for the pain and swelling associated with arthritis. It is a reversible, non-selective COX inhibitor, lowering the level of Prostaglandins via blocking the metabolism of Arachidonic acid in the body. Ibuprofen is administered as a racemic mixture. The human body can convert the inactive (R) form into the active (S) form, so eventually 100% of the Ibuprofen taken becomes active.

Chemical name: [(±)-2-(4-isobutylphenyl)] propionic acid

Common names : BRUFEN, FENLONG, NOVAPRIN, EMFLAM. ADVIL, MOTRIN

The two most popular ways to obtain ibuprofen are the Boot process and the Hoechst process. The Boot process is an older commercial process developed by the Boot Pure Drug Company and patented in 1960s [6]. This synthesis consists of six steps and resulted in unwanted by products as shown in Figure 4. The Boots- Hoechst-Celanese (BHC) synthesis serves as a model that has genuinely contributed to green chemistry [7]. In 1992, the BHC Company developed a new, sustainable synthesis that reduced the number of synthetic steps to half (total three steps) of that in the original Boots Company method (Figure 4). It is noteworthy that the synthesis began with the same first step, e.g. acylation of isobutylbenzene, but utilized anhydrous hydrogen fluoride as both a catalyst and solvent. The reduced amount of unwanted waste due to the generation of only one molecule of water as the byproduct is another achievement of the BHC method. Ibuprofen is the first pharmaceutical compound that was recognized by the U.S. Environmental Protection Agency Presidential Green Chemistry Challenge Awards in 1997.

    Conclusion

During the past century, Aspirin and Paracetamol have occupied a central role in the treatment of fever and pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) have proved to be highly efficient for getting instant relief from pain and inflammation and Ibuprofen remains the first choice for this. With evolving research on biological activity, traditional role of Aspirin has been re-defined leading to the appropriate use of this agent in clinical practice. The green synthesis of Ibuprofen has emerged resulting improved and economical yield. We can conclude that the field of medicinal chemistry based on the studies on cellular biology and pharmacology has covered a long journey to understand the mode of operation and metabolism of these synthetic drugs in the body.

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Boost Your Business With Advertising - Chl Worldwide

Advertising is considered multidimensional. Help in a series of marketing activities. It is a sales promotion technique. Sales volume increases with advertising. Help and support the seller in the sale of the products. Consumer knowledge about the product increases with advertising. Advertising helps consumers save time on purchase.

It also helps manufacturers sell their products. Therefore, fast selling is possible, which leads to higher production at lower cost. The relationship between wholesalers and retailers is improved through advertising. Advertising introduces new products, stimulates markets with respect to the existing product and repeated sales.

Advantages for manufacturers:

1. Increase sales volume:

Advertising increases the sales volume of the product. Therefore, mass production is possible. This leads to a reduction in the cost of production.

2. Increase net profit:

Increase net profit by higher sales volume. It leads to a higher production volume. Therefore, the average cost of production is lower and the profit will increase.

3. Stabilize the sales volume:

The stabilization of sales volume is possible through advertising through the repetition process. Regular and frequent advertising leads to a regular flow of sales. It often gives the public the name, location, products and services of the houses they sell. During the fall period, advertising tends to guarantee a permanent class of customers to buy the product.

4. Control the product price:

The control of the wholesale and retail price is possible through advertising. Needy retailers are overloaded by some greedy wholesalers. Retailers charge higher prices for products. Therefore, consumers do not want to buy such products. This will lead to a reduction in sales. Therefore, manufacturers print on the cover or announce the retail price of the product.

5. Help to open a new market:

Advertising is useful for opening or creating new markets. It helps to gain leadership in the market. It helps manufacturers to decide whether or not to expand the market share. It also helps them sell new products or an improved variety of products.

Advantages for the seller:

1. Create a fund:

The domain and skill of sellers satisfy customers. The work of an active and well trained tactical salesperson facilitates distribution work. The ad, which is the background, will help sellers a lot. Customers know the product through advertising. When the seller contacts them with the product, customers buy the product without hesitation.

2. Reduces the workload of the seller:

If the advertising is done by the manufacturer, the work of the seller is reduced. Otherwise, you have to advertise about the product and then try to sell it. The seller's function is compatible and complemented by advertising. Sale and advertising are words of "cup and saucer" or "key and lock". The work of sellers is made easier and more encouraging thanks to advertising.

3. Less effort:

The advertised product can be sold very easily. The seller's time is saved and you can contact more customers in a shorter period. You can meet many customers with the least effort.

4. The need of the consumer can be studied:

The confidence of a seller increases through advertising by educating and stimulating consumers. Demand and customer needs are studied by him correctly. Manufacturers are informed of this. They will supply the products according to the demand of the customers and thus match the demand and supply of their products.

5. Create enthusiasm:

Advertising reduces the work of the seller. You can do your job in a better way to sell the products, crossing the fixed fee. Therefore, create enthusiasm and trust in him.

Advantages for wholesalers and retailers:

1. Create easy sales:

The announcement informs consumers about the quality of the product. Therefore, they know about the product. Selling that product is easy for wholesalers and retailers.

2. Increase turnover:

Advertising helps the rapid sale of the product, which in turn increases the turnover rate of the product. Therefore, it is not about old stocks. Reduce overhead expenses.

3. Attract more customers:

Advertising provides detailed information about the product and product availability in a particular store. As such, it attracts more customers in that particular store.

4. Increase the prestige of the store:

Customers know the store through advertising. "The goodwill or reputation earned by the manufacturer is also shared by the stores they sell. This increases the prestige of the company.

5. Advertising:

In advertising, the advertising of the product and the advertising of the wholesale or retail store are carried out simultaneously. Therefore, retailers are also known to the public and, therefore, also increase their sales.

Advantages for customers:

1. Easy purchase:

Advertising helps customers easily buy products. The ad offers useful information about the reasonableness of the price and the quality of the product. There are many headache tablets, such as anacin, aspro, coldarin, etc. Good advertising can help you buy the best one.

2 Connection links:

Advertising is the link between the manufacturer and customers. Eliminate intermediaries. There are no profits for intermediaries. Therefore, the price is low.

3. Fair:

Help customers get the product at a fair price.

4. Time saving:

Help customers by providing information about product availability, that is, where and when. Customers can select the best product in a particular store. Therefore, reduce your purchase time. ‘

5. Best quality product:

Advertising generally represents a quality product. Manufacturers advertise their product just to sell it. If the product is not good, customers will switch to other products (brand). Manufacturers maintain their quality to retain the market. As such, it is advantageous for customers. The benefits of standardization are assured to customers through advertising.

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Learn how to pronounce Tylenol in English correctly - pronunciation of Tylenol ★ http://Learn2Pronounce.com ★ Click show more for definition of Tylenol ___________ TYLENOL Pronunciation: /'taɪlʌnɔl/ - Definition: (noun) an analgesic for mild pain but not for inflammation; also used as an antipyretic; (Datril, Tylenol, Panadol, Phenaphen, Tempra, and Anacin III are trademarks of brands of acetaminophen tablets) Tylenol pronunciation and definition: https://youtu.be/dadz-N6uV7g

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Anacin Analgesic Tablets, 1970