Effects of, and Uses for Paracetamol

Effects of, and Uses for Paracetamol Paracetamol, also known as acetaminophen, is a widely used medicinal drug available over the counter The chemical name for Paracetamol is N-acetyl-p-aminophenol. Over-the-counter (OTC) Analgesic and antipyretic action with weak anti-inflammatory action Synergic effect with other analgesics, especially codeine and NSAIDs, resulting in better overall pain control Major ingredient in cold flu remedies Used in combination with opioid analgesics Oral Paracetamol has an oral bioavilabity of 63-89%. A drug given orally goes through first pass metabolism. Intravenous Intravenous administration of paracetamol has a bioavilabity of 100% Rectal Paracetamol has a rectal bioavilabity of 24-98%. Bioavailability is the amount of dose absorbed from the site of administration Oral administration has a little first pass metabolism in the liver and is well absorbed from the gastrointestinal tract First pass metabolism involves the drug being absorbed into the portal vein system via the intestine wall after which it is carried to the liver. Before the drug reaches its target site it may therefore to some extent be metabolised in the liver. A plasma concentration of 10-20mcg.ml-1 for paracetamol results in an antipyretic effect however the concentration needed to lead to an analgesia effect is not properly known. All three routes of administration have a significant difference in the time needed to reach peak plasma concentrations. Of all three routes intravenous administration reaches peak plasma concentration in the shortest amount of time and suppository takes the longest, Oral : For adults 325-650mg tablets can be taken every 4 to 6 hours 1 gram can be taken every 4 hours with a maximum of 4 doses in 24 hours. Rectal: suppositories are available in 250 and 500mg. Two 500mg suppositories can be taken by adults and children over 12 IV: The maximum dose that can be given is 3g in 24 hours For children there new dosage guidelines that put children into 7 precise age groups Since IV administration has 100% bioavilabity there is a high chance of toxicity in patients that have renal and/or hepatic problems Absorbed through the wall of the intestine and into the blood. Speed and efficiency of the absorption is determined by several factors which include the pKa, log P and molecular mass of the drug Low molecular mass and is almost completely unionised in the small intestine which allows it to be absorbed more easily Oral Bioavailability – 70%-90% Rectal Bioavailability – 30%-70% Distributed throughout the body fluids in a homogeneous way Analgesic activity is attributable to the small fraction that penetrates into the brain Binds to plasma proteins at less than 20% A high degree of protein binding makes the drug long acting The glucuronidation and sulfation pathway for paracetamol metabolism lead to the production of unharmful and on toxic products. The middle N-Hydroxylation and rearrangement pathway mediated by the isoenzyme of cytochrome p450 (CYP2E1 and CYP3A4) pathway leads to the production of toxic metabolite NAPQ1 which covalently binds to cell macromolecules in overdose. In normal cases NAPQ1 binds with glutathione resulting in an unrhamful and nontoxic product. Part A of the figure shows the metabolism of paracetamol in a healthy individual. Around 95% of the drug is conjugated with glucuronide and excreted in the urine. The leftover is conjugated with glutathione Part B shows the metabolism of paracetamol in an individual that is starved. The conjugation of glutathione does not take place adequately and its depletion results in the build of hepatotoxic NAPQ1 Excreted in urine Predominantly in the form of inactive glucuronide and sulphate conjugates A small amount of the drug is converted to a very reactive alkylating metabolite that is inactivated with reduced glutathione and is excreted in the urine as cysteine and mercapturic acid conjugates Paracetamol is absorbed from the GI tract and a peak plasma concentration occurs within 10-60 minutes after being taken orally. It has a half-life of approximately 2 hours It is distributed into the majority of body tissues Has an elimination half life ranging from 1-3 hours The volume of distribution for paracetamol is around 1L/Kg of body weight with an insignificant amount of the drug binding to plasma protein. Inhibition of cyclooxygenase (COX) – specifically COX-2 Reduces the oxidised form of the COX enzyme, preventing it from forming pro-inflammatory chemicals Peripheral anti-inflammatory activity is usually limited by high level of peroxides present in inflammatory lesions (including several other factors) Metabolites of paracetamol act upon the spinal cord via TRPA1-receptors modulates the endogenous cannabinoid system Paracetamol works inhibiting the synthesis of prostaglandins Because of its selectivity for COX-2 it does not significantly inhibit the production of the pro-clotting thromboxanes. Metabolies: suppressing the signal transduction from the superficial layers of the dorsal horn to alleviate pain. The nuclear receptor constitutive androstane receptor (CAR) can be activated by paracetamol. This induces the expression of three cytochrome P450 enzymes that lead to the transformation of paracetamol into N-acetyl-p-benzoquinone imine (NAPQI) is a reactive and toxic metabolite. It can be detoxified by conjugation with glutathione Paracetamol is a safe drug and doesn’t cause toxicity unless taken in the wrong dosage or in extreme circumstances such as starvation. Also when taken with alcol for long periods of times it enhances toxicity as the coentration of toxic metabolites such as NAPQ1 increases. NAPQ1 firstly goes through detoxification in the liver via glutathione conjugation catalysed by the enzyme GST and then goes through acetylation in the kidneys. This step is catalysed b M-acetyl transferase. It then gets excreted in the urine. The cytochrome p450 enzyme (isoenzyme CYP2E1) procures hepatoxic metabolites in small quantities. The phase 1 metabolism of paracetamol mediated by p450 gives rise to NAPQ1, that is detoxified by phase 2 conjugation with glutathione. During overdose depletion of glutathione occurs and NAPQ1 accumulates Phase 1 metabolism is where the drug molecule foes though basic structural alteration through reduction, hydrolysis, or oxidation (which is catalysed cytochrome p450 enzymes) Phase 2 metabolism involves conjugation (an ionised group attaches to the drug) making it metabolite water soluble. In the case of paracetamol overdose NAPQ1 can accumulate and can possibly lead to liver damage if left untreated It can also damage other organs that contains P450 enzymes such as the kidneys where the toxicity could result in renal dysfunction and pancreas. Liver toxicity can be prevented by blocking the activation of CAR with an antagonist or Paracetamol overdose occurs at around 7-8 g  in an adult and more than 150 mg/kg in children. Liver damage : The centrilobular zone is the first zone in the liver that gets affected by the toxicity. In extreme cases zones 1 and 2 present in the parenchyma get damaged. Kidney damage: renal dysfunction leads to the need of dialysis as a tubular necrosis table place because of the localised formation of NAPQ1.

How Cleanliness Can Influence Life of Kazi Zawad Badruddoza

Whereas the cleanliness is relate well to the aspects in our life. There is some reason why cleanliness is important to our life. Cleanliness influences our health, controlling our mood and then keeps the relationship with our friends. The clothes and the pants which we wear must be clean so that no more germs that can affect allergy like irritation. The food and the drink which we consume must be clean from microbes to prevent risk of illness like stomach ache, diarrhoea and many more.Then, the objects around us it should be clean from dust so we not experience the respiration illness. With kept our cleanliness so that our life must be healthy. Another reason we must watch cleanliness because the cleanliness can controlling our mood. Cleanliness makes us feel fresh and comfortable. A clean room makes us feel freshness because all of the objects are clean and free of dust so that the air is fresh. Its floor is clean so there are no bacteria or microbes and we can do the activities wi thout worried about hygiene problem.Cleanliness can be regarded as personal or environmental. These habits ensure that a person would stay fit and healthy for a long time so you will not be force to use those anti aging treatments or some sort of surgery. These habits help us in developing an ideal and healthy life style which makes our lives even more delightful and joyous. Lesser effort would result in more success if a person has healthy mind and a healthy mind can only exist in a healthyCleanliness is one of the good qualities. It is a part of our civilization. A man of dirty habits is far from civilization. So, with the progress of civilization man cleans himself more and more. He cleans his body. He cleans his mind and heart. He cleans all his action and manners. He cleans his soul. This will lead him to the highest form of civilization. But on the cleanliness of body, depend all other cleanings. Hence, cleanliness is considered so important.

The Business Structure Of Commercial Television - 901 Words

Desperate Advertisers Call for Desperate Measures Check out the boobs over here, the television beckons from the other side of the room. With all the choices available on television today, television distributors are desperate to gain the attention of audiences. In order to get advertising revenue televisions shows tap into some of our basic desires to gain our attention and loyalty. Depending on the viewer, these tactics could be having a negative impact on the viewer beyond the original intent of the content. The business structure of commercial television in America leads to the use of sexual content to increase audiences. Relationships between the television advertisers and distributors drive producers of television programs to create content that will attract an audience. Television advertisers have a product to sell and use television to broadcast commercials to attract and inform viewers about their products. The advertisers must purchase air time from television distributors in order to have access to the audience they desire. Mittell argues that â€Å"most creators of television do not enter the industry to make money, as the creative side of the industry is highly risky and unlikely to produce wealth†(Mittell, 95). Even with this argument, Mittell acknowledges that money is a factor in the creation of television programs, even if the goal is unrealized. Television content creators cannot help but be motivated and influenced by the advertisers and distributorsShow MoreRelatedAmusing Ourselves to Death by Neil Postman1180 Words   |  5 Pages Neil Postman writes, Amusing Ourselves to Death to address a television-based epistemology pollutes public communication and its surrounding landscape, not that it pollutes everything. The book was produced in 1984 in a time where television was an emerging epidemic and other forms of communication that today have taken flight, didn’t exist. 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My Utopia Essay - 823 Words

At my Utopia I feel at peace, at my Utopia I truly feel happiness. My home isn’t this god forsaken bipolar desert where the weather cant decide whether to be 120F one day or 70F the next, where rain occurs so rarely the rich lack money to acquire it. From the tallest mountain in this valley, my home is nowhere to be found, only a plane can reach my utopia but even they need a rest to reach the location, for there my home is, my utopia, but to return there, I would be at risk for there is a monster, able to destroy my family, able to destroy everything I love. My utopia remains my true home, my heaven. Near an ancient forest a village was established. The surrounding trees are giants towering over most building and so you can carve a†¦show more content†¦These bells create a sound so beautiful, every hour the 4 bells go off, all throughout the village you can hear the beautiful synchronization of tunes which would give any man a moment of ecstasy. 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