<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Bendamustine and explain in detail? [/INST] Bendamustine, sold under the brand name Treanda among others, is a chemotherapy medication used in the treatment of chronic lymphocytic leukemia (CLL), multiple myeloma, and non-Hodgkins lymphoma. It is given by injection into a vein.Common side effects include low blood cell counts, fever, nausea, diarrhea, loss of appetite, cough, and rash. Other severe side effects include allergic reactions and increased risk of infection. Use in pregnancy is known to harm the baby. Bendamustine is in the alkylating agents family of medication. It works by interfering with the function of DNA and RNA.Bendamustine was approved for medical use in the United States in 2008. It is on the World Health Organizations List of Essential Medicines. The cost in the United Kingdom for the NHS is about 275.81 pounds per 100 mg vial.  It was originally made from nitrogen mustard.

Medical uses
Bendamustine has been used both as sole therapy and in combination with other agents including etoposide, fludarabine, mitoxantrone, methotrexate, prednisone, rituximab, vincristine and 90Y-ibritumomab tiuxetan.

Lymphomas
One combination for stage III/IV relapsed or refractory indolent lymphomas and mantle cell lymphoma (MCL), with or without prior rituximab-containing chemoimmunotherapy treatment, is bendamustine with mitoxantrone and rituximab. In Germany in 2012 it has become the first line treatment of choice for indolent lymphoma. After trial results released in June 2012 showed that it more than doubled disease progression-free survival when given along with rituximab. The combination also left patients with fewer side effects than the older R-CHOP treatment.

Adverse effects
Common adverse reactions are typical for the class of nitrogen mustards, and include nausea, fatigue, vomiting, diarrhea, fever, constipation, loss of appetite, cough, headache, unintentional weight loss, difficulty breathing, rashes, and stomatitis, as well as immunosuppression, anemia, and low platelet counts.
Notably, this drug has a low incidence of hair loss (alopecia) unlike most other chemotherapy drugs.

Warning
Bendamustine solution is not compatible with Closed System Transfer Devices (CSTD)
Situation: *Most CSTD vendors have adapted their system to become compatible.

FDA issued a warning on March 11, 2015, not to use bendamustine solution with CSTDs, adapters and syringes which contain either polycarbonate or acrylonitrile-butadiene-styrene (ABS) due to the incompatibility with N,N-dimethylacetamide (DMA).Background:

PhaSealR & SpirosR CSTDs contain either polycarbonate or ABS can dissolve when coming into contact with bendamustine (which contains DMA).Assessment:

This can lead to device failure, possible product contamination, and potential serious adverse health consequences, including skin reactions in health care professionals preparing and administering this product and the risk of small blood vessel blockage in patients.Recommendations:

Immediately, stop using all PhaSealR &/or SpirosR products including adapters when preparing & administering bendamustine.
Only use polypropylene syringes with bendamustine. These syringes are translucent in appearance.
Continue to use all universal PPE & safety precautions for hazardous drugs when preparing & administering bendamustine.

Pharmacology
Bendamustine is a white, water-soluble microcrystalline powder with amphoteric properties. It acts as an alkylating agent causing intra-strand and inter-strand cross-links between DNA bases.
After intravenous infusion it is extensively metabolised in the liver by cytochrome p450. More than 95% of the drug is bound to protein – primarily albumin. Only free bendamustine is active. Elimination is biphasic with a half-life of 6–10 minutes and a terminal half-life of approximately 30 minutes </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Tobramycin/dexamethasone and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Etravirine and explain in detail? [/INST] Etravirine (ETR, brand name Intelence, formerly known as TMC125) is a drug used for the treatment of HIV.  Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). Unlike the currently available agents in the class, resistance to other NNRTIs does not seem to confer resistance to etravirine.  Etravirine is marketed by Janssen, a subsidiary of Johnson & Johnson.  In January 2008, the Food and Drug Administration approved its use for patients with established resistance to other drugs, making it the 30th anti-HIV drug approved in the United States and the first to be approved in 2008. It was also approved for use in Canada on April 1, 2008.Etravirine is licensed in the United States, Canada, Israel, Russia, Australia and the European Union, and is under regulatory review in Switzerland.

Indications and dosage
Etravirine, in combination with other anti-retrovirals, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients, who have evidence of viral replication and HIV-1 strains resistant to a non-nucleoside reverse transcriptase inhibitor (NNRTI) and other antiretroviral agents.
The recommended dose of etravirine is 200 mg (2 x 100 mg tablets, or 1 x 200 mg tablet as of 03/18/2011) taken twice daily following a meal. The type of food does not affect the exposure to etravirine.

Contraindication
Each 100 mg etravirine tablet contains 160 mg of lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Mechanism of action
Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), designed to be active against HIV with mutations that confer resistance to the two most commonly prescribed first-generation NNRTIs, mutation K103N for efavirenz and Y181C for nevirapine </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Naproxen/pseudoephedrine and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Sotrovimab and explain in detail? [/INST] Sotrovimab, sold under the brand name Xevudy, is a human neutralizing monoclonal antibody with activity against severe acute respiratory syndrome coronavirus 2, known as SARS-CoV-2. It is under development by GlaxoSmithKline and Vir Biotechnology, Inc. Sotrovimab is designed to attach to the spike protein of SARS-CoV-2.The most common side effects include hypersensitivity (allergic) reactions and infusion-related reactions.

Medical uses
In the European Union, sotrovimab is indicated for the treatment of COVID-19 in people aged twelve years of age and older and weighing at least 40 kilograms (88 lb) who do not require supplemental oxygen and who are at increased risk of the disease becoming severe.Sotrovimab is given by intravenous infusion, preferably within 5 days of onset of COVID-19 symptoms.

Development and mechanism of action
Sotrovimabs development began in December 2019, at Vir Biotechnology when Vir scientists first learned of the initial COVID-19 outbreak in China. Vir subsidiary Humabs BioMed had already compiled a library of frozen blood samples from patients infected with viral diseases, including two samples from patients infected with SARS-CoV-1. Vir scientists obtained samples of the novel SARS-CoV-2 virus and mixed them with various antibodies recovered from the old SARS-CoV-1 blood samples. The objective was to identify antibodies effective against both SARS-CoV-1 and SARS-CoV-2. This would imply that the antibodies were targeting highly conserved sequences and in turn would be more likely to remain effective against future variants of SARS-CoV-2. In April 2020, Lawrence Berkeley National Laboratory conducted a X-ray crystallography study at Virs request to investigate how such antibodies bind to SARS-CoV-2 at the molecular level. The Berkeley Lab data helped Vir identify candidates for further study, and Vir eventually settled on a single candidate antibody, S309. Vir collaborated with GlaxoSmithKline to make various refinements to S309, resulting in sotrovimab.Sotrovimab has been engineered to possess an Fc LS mutation (M428L/N434S) that confers enhanced binding to the neonatal Fc receptor resulting in an extended half-life and potentially enhanced drug distribution to the lungs.Sotrovimab has demonstrated activity via two antiviral mechanisms in vitro, antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

Clinical efficacy
The pivotal COMET-ICE study is an ongoing, randomized, double-blind, placebo-controlled study to assess the safety and efficacy of sotrovimab in adults with confirmed COVID-19 (mild, early disease with less than five days of symptoms) at risk of disease progression.An interim analysis of this study reported that sotrovimab reduced the risk of hospitalization for more than 24 hours or death by 85% compared with placebo. Overall 1% of people receiving sotrovimab died or required hospitalization for more than 24 hours compared to 7% of people treated with placebo. The study is ongoing and preliminary results have been published in the New England Journal of Medicine.The full analysis of the COMET-ICE trial was published in JAMA and it showed that sotrovimab reduced risk of hospitalization for more than 24 hours or death by 79% compared to placebo (1% for sotrovoimab group and 6% for the placebo group). The trial involved 1057 participants and took place before the omicron variant was prevalent.

Manufacturing
Sotrovimab is a biologic product which takes six months to manufacture in living cells. It is produced in Chinese hamster ovary cells. At product launch in May 2021, sotrovimabs active pharmaceutical ingredient was produced by WuXi Biologics in China and sent to a GlaxoSmithKline plant in Parma, Italy for further processing into the finished product. In January 2022, the spread of the SARS-CoV-2 Omicron variant began to render other monoclonal antibodies obsolete and caused global demand for sotrovimab to skyrocket </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Alka-Seltzer and explain in detail? [/INST] Alka-Seltzer is an effervescent antacid and pain reliever first marketed by the Dr. Miles Medicine Company of Elkhart, Indiana, United States. Alka-Seltzer contains three active ingredients: aspirin (acetylsalicylic acid) (ASA), sodium bicarbonate, and anhydrous citric acid. The aspirin is a pain reliever and anti-inflammatory, the sodium bicarbonate is an antacid, and the citric acid reacts with the sodium bicarbonate and water to form effervescence.It was developed by head chemist Maurice Treneer. Alka-Seltzer is marketed for relief of minor aches, pains, inflammation, fever, headache, heartburn, stomachache, indigestion, acid reflux and hangovers, while neutralizing excess stomach acid. It was launched in 1931.Its sister product, Alka-Seltzer Plus, treats cold and flu symptoms. A wide variety of formulae, many using acetaminophen (paracetamol) instead of aspirin, are available under the sister brand.

Product information
Alka-Seltzer is a combination of sodium bicarbonate, aspirin, and anhydrous citric acid, used for the relief of heartburn, acid indigestion, and stomach aches.Alka-Seltzer is sold in foil packets, each containing two tablets. Prior to 1984, it was also available stacked in glass tubes. It is available in many different flavors.
It was once marketed as a cure-all; at one time, its ads even suggested taking it for "the blahs". Subsequent promotion has taken into consideration that aspirin is a drug that is not tolerated by everyone, and the product is no longer advertised in this fashion.

Chemistry of the effervescence
Though important to the overall effect of the medication, the aspirin (acetylsalicylic acid) is not required to produce the effervescent action of Alka-Seltzer; the effervescence is produced by the baking soda (sodium bicarbonate) and citric acid reacting to form sodium citrate and carbon dioxide gas.

Marketing
The product has been extensively advertised since its launch in the United States. It was originally marketed by Mikey Wiseman, a company scientist of Dr. Miles Medicine Company, who also helped direct its development.
Print advertising was used immediately, and in 1932 the radio show Alka-Seltzer Comedy Star of Hollywood began, with National Barn Dance following in 1933, along with many more. The radio sponsorships continued into the 1950s, with the Alka-Seltzer Time show airing from 1949 to 1957.
In 1951, the "Speedy" character was introduced. The character was conceived by creative director George Pal of the Wade Advertising agency and designed by illustrator Wally Wood. Originally named Sparky, the name was changed to Speedy by sales manager Perry L. Shupert to align with that years promotional theme, "Speedy Relief." Speedy appeared in over 200 TV commercials between 1954 and 1964. His body was one Alka-Seltzer tablet, while he wore another as a hat.
Buster Keaton appeared along with the animated Speedy Alka-Seltzer figure in a series of 1950s commercials based on the product slogan, "Relief is just a swallow away." Speedy Alka-Seltzer was voiced by Dick Beals. Speedy was revived for a "Plop, plop, fizz, fizz" song spot in 1976.
In his 1976 revival Beals proclaimed Alka-Seltzers virtues and sang the "Plop, plop, fizz, fizz, oh what a relief it is" song in his iconic high, squeaky voice. In the early 1960s, a commercial showing two tablets dropping into a glass of water instead of the usual one caused sales to double.Alka-Seltzer TV ads from the 1960s and 1970s in the US were among the most popular of the 20th century, ranking number 13, according to Advertising Age. To increase sales in a relatively flat business, Bayer  revived several of the vintage spots.Paul Margulies (father of actress Julianna Margulies) created the famous "Plop, plop, fizz, fizz" ad campaign when he worked as a Madison Avenue ad executive. The ubiquitous jingle was composed by Tom Dawes—a former member of The Cyrkle. The slogan was altered to "Plink, plink, fizz" in the United Kingdom.During the race for space in the early 1960s before the moon landing, there was a commercial with Speedy in a space suit and a jingle with the lyrics "On Mans first trip through space, I only hope that Im aboard, securely strapped in place. Theyll track our ship with radar and telescopes and soon, imagine seeing Speedy Alka-Seltzer on the moon!"George Raft starred in the 1969 Alka-Seltzer commercial "The Unfinished Lunch". It consisted of Raft incarcerated in a prison lunchroom. He takes a bite of the prison food and recoils. Suddenly he bangs his cup on the steel table. It ripples throughout the room. He starts intoning "Alka-Seltzer, Alka-Seltzer..." Soon, the other hundreds of inmates do the same. (The commercial became so popular that several weeks later, Raft appeared as a guest on The Tonight Show Starring Johnny Carson. Raft told Carson that it took more than 7 hours to tape the 30-second commercial. Raft was enraged by the end of the day, thus making his inmate portrayal that much more convincing for the final editing. The film crew gave Raft his crumpled tin cup, which he showed to Carson and the audience.An animated mid-1960s commercial, animated by R. O. Blechman, shows a man and his own stomach sitting opposite each other in chairs, having an argument moderated by their therapist in a voiceover. The stomach (voiced by Gene Wilder) accuses the man of purposely trying to irritate it. The man accuses his stomach of complaining too much about the foods he likes. The therapist suggests Alka-Seltzer, and further suggests that the two must take care of each other. The closing words are of the stomach saying to the man: "Well, Ill try — if you will."Alka-Seltzer had a series of commercials during the mid-1960s that used a song called "No Matter What Shape (Your Stomachs In)". A different version was recorded by The T-Bones and was released as a single, which became a hit in 1966. The ads featured only the midsections (no faces) of people of all shapes and sizes. A clip of the ad can be seen briefly in the 1988 motion picture The In Crowd, immediately before the movies first live broadcast of the fictitious "Perry Parkers Dance Party."
In an Alka-Seltzer commercial from 1969, an actor (played by Jack Somack) in a commercial for the fictional product "Magdalinis Meatballs" has to eat a meatball and then say "Mamma mia, thats-a spicy meat-a ball-a!" in an ersatz Italian accent. Take after take is ruined by some comedic trial or another (comedian Ronny Graham dropping the clapperboard). By the commercials end, Jack has eaten so many meatballs that its "Alka-Seltzer to the rescue." With his stomach settled, Jack does a perfect take, except that the oven door falls off. The director (off-camera) sighs and says, "OK, lets break for lunch."A 1970 commercial shows a newlywed couple in the bedroom after the woman (played by Alice Playten) has finished serving her husband (played by Terry Kiser) a giant dumpling; the implication is that her cooking skills are severely lacking, despite her husbands lament, "I cant believe I ate that whole thing!", the commercials catchphrase. She lies on the bed in delusional triumph. She offers her beleaguered husband a heart-shaped meatloaf; he disappears to take some Alka-Seltzer. When she hears the fizzy noise coming from the bathroom, he quickly covers the glass of dissolving Alka-Seltzer as she wonders aloud if it is raining </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Aspirin and explain in detail? [/INST] Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an anticoagulant. Specific inflammatory conditions which aspirin is used to treat include Kawasaki disease, pericarditis, and rheumatic fever.Aspirin is also used long-term to help prevent further heart attacks, ischaemic strokes, and blood clots in people at high risk. For pain or fever, effects typically begin within 30 minutes. Aspirin works similarly to other NSAIDs but also suppresses the normal functioning of platelets.One common adverse effect is an upset stomach. More significant side effects include stomach ulcers, stomach bleeding, and worsening asthma. Bleeding risk is greater among those who are older, drink alcohol, take other NSAIDs, or are on other blood thinners. Aspirin is not recommended in the last part of pregnancy. It is not generally recommended in children with infections because of the risk of Reye syndrome. High doses may result in ringing in the ears.A precursor to aspirin found in the bark of the willow tree (genus Salix) has been used for its health effects for at least 2,400 years. In 1853, chemist Charles Frédéric Gerhardt treated the medicine sodium salicylate with acetyl chloride to produce acetylsalicylic acid for the first time. Over the next 50 years, other chemists established the chemical structure and devised more efficient production methods.: 69–75 Aspirin is available without medical prescription as a proprietary or generic medication in most jurisdictions. It is one of the most widely used medications globally, with an estimated 40,000 tonnes (44,000 tons) (50 to 120 billion pills) consumed each year, and is on the World Health Organizations List of Essential Medicines. In 2020, it was the 36th most commonly prescribed medication in the United States, with more than 17 million prescriptions.

Brand vs. generic name
In 1897, scientists at the Bayer company began studying acetylsalicylic acid as a less-irritating replacement medication for common salicylate medicines.: 69–75  By 1899, Bayer had named it "Aspirin" and sold it around the world.Aspirins popularity grew over the first half of the 20th century, leading to competition between many brands and formulations. The word Aspirin was Bayers brand name; however, their rights to the trademark were lost or sold in many countries. The name is ultimately a blend of the prefix a(cetyl) + spir Spiraea, the meadowsweet plant genus from which the acetylsalicylic acid was originally derived at Bayer + -in, the common chemical suffix.

Chemical properties
Aspirin decomposes rapidly in solutions of ammonium acetate or the acetates, carbonates, citrates, or hydroxides of the alkali metals. It is stable in dry air, but gradually hydrolyses in contact with moisture to acetic and salicylic acids. In solution with alkalis, the hydrolysis proceeds rapidly and the clear solutions formed may consist entirely of acetate and salicylate.Like flour mills, factories producing aspirin tablets must control the amount of the powder that becomes airborne inside the building, because the powder-air mixture can be explosive. The National Institute for Occupational Safety and Health (NIOSH) has set a recommended exposure limit in the United States of 5 mg/m3 (time-weighted average). In 1989, the Occupational Safety and Health Administration (OSHA) set a legal permissible exposure limit for aspirin of 5 mg/m3, but this was vacated by the AFL-CIO v. OSHA decision in 1993.

Synthesis
The synthesis of aspirin is classified as an esterification reaction. Salicylic acid is treated with acetic anhydride, an acid derivative, causing a chemical reaction that turns salicylic acids hydroxyl group into an ester group (R-OH → R-OCOCH3). This process yields aspirin and acetic acid, which is considered a byproduct of this reaction. Small amounts of sulfuric acid (and occasionally phosphoric acid) are almost always used as a catalyst. This method is commonly demonstrated in undergraduate teaching labs.

Reaction mechanism
Formulations containing high concentrations of aspirin often smell like vinegar because aspirin can decompose through hydrolysis in moist conditions, yielding salicylic and acetic acids.

Physical properties
Aspirin, an acetyl derivative of salicylic acid, is a white, crystalline, weakly acidic substance, with a melting point of 136 °C (277 °F), and a boiling point of 140 °C (284 °F). Its acid dissociation constant (pKa) is 3.5 at 25 °C (77 °F).

Polymorphism
Polymorphism, or the ability of a substance to form more than one crystal structure, is important in the development of pharmaceutical ingredients. Many drugs receive regulatory approval for only a single crystal form or polymorph. For a long time, only one crystal structure for aspirin was known. That aspirin might have a second crystalline form was suspected since the 1960s. The elusive second polymorph was first discovered by Vishweshwar and coworkers in 2005, and fine structural details were given by Bond et al. A new crystal type was found during experiments after co-crystallization of aspirin and levetiracetam from hot acetonitrile. The form II is only stable at 100 K and reverts to form I at ambient temperature. In the (unambiguous) form I, two salicylic molecules form centrosymmetric dimers through the acetyl groups with the (acidic) methyl proton to carbonyl hydrogen bonds, and in the newly claimed form II, each salicylic molecule forms the same hydrogen bonds with two neighboring molecules instead of one. With respect to the hydrogen bonds formed by the carboxylic acid groups, both polymorphs form identical dimer structures.

Mechanism of action
Discovery of the mechanism
In 1971, British pharmacologist John Robert Vane, then employed by the Royal College of Surgeons in London, showed aspirin suppressed the production of prostaglandins and thromboxanes. For this discovery he was awarded the 1982 Nobel Prize in Physiology or Medicine, jointly with Sune Bergström and Bengt Ingemar Samuelsson.

Prostaglandins and thromboxanes
Aspirins ability to suppress the production of prostaglandins and thromboxanes is due to its irreversible inactivation of the cyclooxygenase (COX; officially known as prostaglandin-endoperoxide synthase, PTGS) enzyme required for prostaglandin and thromboxane synthesis. Aspirin acts as an acetylating agent where an acetyl group is covalently attached to a serine residue in the active site of the PTGS enzyme (Suicide inhibition). This makes aspirin different from other NSAIDs (such as diclofenac and ibuprofen), which are reversible inhibitors.
Low-dose aspirin use irreversibly blocks the formation of thromboxane A2 in platelets, producing an inhibitory effect on platelet aggregation during the lifetime of the affected platelet (8–9 days). This antithrombotic property makes aspirin useful for reducing the incidence of heart attacks in people who have had a heart attack, unstable angina, ischemic stroke or transient ischemic attack. 40 mg of aspirin a day is able to inhibit a large proportion of maximum thromboxane A2 release provoked acutely, with the prostaglandin I2 synthesis being little affected; however, higher doses of aspirin are required to attain further inhibition.Prostaglandins, local hormones produced in the body, have diverse effects, including the transmission of pain information to the brain, modulation of the hypothalamic thermostat, and inflammation. Thromboxanes are responsible for the aggregation of platelets that form blood clots. Heart attacks are caused primarily by blood clots, and low doses of aspirin are seen as an effective medical intervention to prevent a second acute myocardial infarction.

COX-1 and COX-2 inhibition
At least two different types of cyclooxygenases, COX-1 and COX-2, are acted on by aspirin. Aspirin irreversibly inhibits COX-1 and modifies the enzymatic activity of COX-2. COX-2 normally produces prostanoids, most of which are proinflammatory. Aspirin-modified PTGS2 (prostaglandin-endoperoxide synthase 2) produces lipoxins, most of which are anti-inflammatory. Newer NSAID drugs, COX-2 inhibitors (coxibs), have been developed to inhibit only PTGS2, with the intent to reduce the incidence of gastrointestinal side effects.Several COX-2 inhibitors, such as rofecoxib (Vioxx), have been withdrawn from the market, after evidence emerged that PTGS2 inhibitors increase the risk of heart attack and stroke. Endothelial cells lining the microvasculature in the body are proposed to express PTGS2, and, by selectively inhibiting PTGS2, prostaglandin production (specifically, PGI2; prostacyclin) is downregulated with respect to thromboxane levels, as PTGS1 in platelets is unaffected. Thus, the protective anticoagulative effect of PGI2 is removed, increasing the risk of thrombus and associated heart attacks and other circulatory problems. Since platelets have no DNA, they are unable to synthesize new PTGS once aspirin has irreversibly inhibited the enzyme, an important difference as compared with reversible inhibitors.
Furthermore, aspirin, while inhibiting the ability of COX-2 to form pro-inflammatory products such as the prostaglandins, converts this enzymes activity from a prostaglandin-forming cyclooxygenase to a lipoxygenase-like enzyme: aspirin-treated COX-2 metabolizes a variety of polyunsaturated fatty acids to hydroperoxy products which are then further metabolized to specialized proresolving mediators such as the aspirin-triggered lipoxins, aspirin-triggered resolvins, and aspirin-triggered maresins. These mediators possess potent anti-inflammatory activity. It is proposed that this aspirin-triggered transition of COX-2 from cyclooxygenase to lipoxygenase activity and the consequential formation of specialized proresolving mediators contributes to the anti-inflammatory effects of aspirin.

Additional mechanisms
Aspirin has been shown to have at least three additional modes of action. It uncouples oxidative phosphorylation in cartilaginous (and hepatic) mitochondria, by diffusing from the inner membrane space as a proton carrier back into the mitochondrial matrix, where it ionizes once again to release protons. Aspirin buffers and transports the protons. When high doses are given, it may actually cause fever, owing to the heat released from the electron transport chain, as opposed to the antipyretic action of aspirin seen with lower doses. In addition, aspirin induces the formation of NO-radicals in the body, which have been shown in mice to have an independent mechanism of reducing inflammation. This reduced leukocyte adhesion is an important step in the immune response to infection; however, evidence is insufficient to show aspirin helps to fight infection. More recent data also suggest salicylic acid and its derivatives modulate signalling through NF-κB. NF-κB, a transcription factor complex, plays a central role in many biological processes, including inflammation.Aspirin is readily broken down in the body to salicylic acid, which itself has anti-inflammatory, antipyretic, and analgesic effects. In 2012, salicylic acid was found to activate AMP-activated protein kinase, which has been suggested as a possible explanation for some of the effects of both salicylic acid and aspirin. The acetyl portion of the aspirin molecule has its own targets. Acetylation of cellular proteins is a well-established phenomenon in the regulation of protein function at the post-translational level. Aspirin is able to acetylate several other targets in addition to COX isoenzymes. These acetylation reactions may explain many hitherto unexplained effects of aspirin.

Pharmacokinetics
Acetylsalicylic acid is a weak acid, and very little of it is ionized in the stomach after oral administration. Acetylsalicylic acid is quickly absorbed through the cell membrane in the acidic conditions of the stomach. The increased pH and larger surface area of the small intestine causes aspirin to be absorbed more slowly there, as more of it is ionized. Owing to the formation of concretions, aspirin is absorbed much more slowly during overdose, and plasma concentrations can continue to rise for up to 24 hours after ingestion.About 50–80% of salicylate in the blood is bound to human serum albumin, while the rest remains in the active, ionized state; protein binding is concentration-dependent. Saturation of binding sites leads to more free salicylate and increased toxicity. The volume of distribution is 0.1–0.2 L/kg. Acidosis increases the volume of distribution because of enhancement of tissue penetration of salicylates.As much as 80% of therapeutic doses of salicylic acid is metabolized in the liver. Conjugation with glycine forms salicyluric acid, and with glucuronic acid to form two different glucuronide esters. The conjugate with the acetyl group intact is referred to as the acyl glucuronide; the deacetylated conjugate is the phenolic glucuronide. These metabolic pathways have only a limited capacity. Small amounts of salicylic acid are also hydroxylated to gentisic acid. With large salicylate doses, the kinetics switch from first-order to zero-order, as metabolic pathways become saturated and renal excretion becomes increasingly important.Salicylates are excreted mainly by the kidneys as salicyluric acid (75%), free salicylic acid (10%), salicylic phenol (10%), and acyl glucuronides (5%), gentisic acid (< 1%), and 2,3-dihydroxybenzoic acid. When small doses (less than 250 mg in an adult) are ingested, all pathways proceed by first-order kinetics, with an elimination half-life of about 2.0 h to 4.5 h. When higher doses of salicylate are ingested (more than 4 g), the half-life becomes much longer (15 h to 30 h), because the biotransformation pathways concerned with the formation of salicyluric acid and salicyl phenolic glucuronide become saturated. Renal excretion of salicylic acid becomes increasingly important as the metabolic pathways become saturated, because it is extremely sensitive to changes in urinary pH. A 10- to 20-fold increase in renal clearance occurs when urine pH is increased from 5 to 8. The use of urinary alkalinization exploits this particular aspect of salicylate elimination. It was found that short-term aspirin use in therapeutic doses might precipitate reversible acute kidney injury when the patient was ill with glomerulonephritis or cirrhosis. Aspirin for some patients with chronic kidney disease and some children with congestive heart failure was contraindicated.

History
Medicines made from willow and other salicylate-rich plants appear in clay tablets from ancient Sumer as well as the Ebers Papyrus from ancient Egypt.: 8–13  Hippocrates referred to the use of salicylic tea to reduce fevers around 400 BC, and willow bark preparations were part of the pharmacopoeia of Western medicine in classical antiquity and the Middle Ages. Willow bark extract became recognized for its specific effects on fever, pain, and inflammation in the mid-eighteenth century. By the nineteenth century, pharmacists were experimenting with and prescribing a variety of chemicals related to salicylic acid, the active component of willow extract.: 46–55

In 1853, chemist Charles Frédéric Gerhardt treated sodium salicylate with acetyl chloride to produce acetylsalicylic acid for the first time;: 46–48  in the second half of the 19th century, other academic chemists established the compounds chemical structure and devised more efficient methods of synthesis. In 1897, scientists at the drug and dye firm Bayer began investigating acetylsalicylic acid as a less-irritating replacement for standard common salicylate medicines, and identified a new way to synthesize it.: 69–75  By 1899, Bayer had dubbed this drug Aspirin and was selling it globally.: 27  The word Aspirin was Bayers brand name, rather than the generic name of the drug; however, Bayers rights to the trademark were lost or sold in many countries. Aspirins popularity grew over the first half of the 20th century leading to fierce competition with the proliferation of aspirin brands and products.Aspirins popularity declined after the development of acetaminophen/paracetamol in 1956 and ibuprofen in 1962. In the 1960s and 1970s, John Vane and others discovered the basic mechanism of aspirins effects,: 226–231  while clinical trials and other studies from the 1960s to the 1980s established aspirins efficacy as an anti-clotting agent that reduces the risk of clotting diseases.: 247–257  The initial large studies on the use of low-dose aspirin to prevent heart attacks that were published in the 1970s and 1980s helped spur reform in clinical research ethics and guidelines for human subject research and US federal law, and are often cited as examples of clinical trials that included only men, but from which people drew general conclusions that did not hold true for women.Aspirin sales revived considerably in the last decades of the 20th century, and remain strong in the 21st century with widespread use as a preventive treatment for heart attacks and strokes.: 267–269

Trademark
Bayer lost its trademark for Aspirin in the United States in actions taken between 1918 and 1921 because it had failed to use the name for its own product correctly and had for years allowed the use of "Aspirin" by other manufacturers without defending the intellectual property rights. Today, aspirin is a generic trademark in many countries. Aspirin, with a capital "A", remains a registered trademark of Bayer in Germany, Canada, Mexico, and in over 80 other countries, for acetylsalicylic acid in all markets, but using different packaging and physical aspects for each.

Compendial status
United States Pharmacopeia
British Pharmacopoeia

Medical use
Aspirin is used in the treatment of a number of conditions, including fever, pain, rheumatic fever, and inflammatory conditions, such as rheumatoid arthritis, pericarditis, and Kawasaki disease. Lower doses of aspirin have also been shown to reduce the risk of death from a heart attack, or the risk of stroke in people who are at high risk or who have cardiovascular disease, but not in elderly people who are otherwise healthy. There is some evidence that aspirin is effective at preventing colorectal cancer, though the mechanisms of this effect are unclear. In the United States, the selective initiation of low-dose aspirin, based on an individualised assessment, has been deemed reasonable for the primary prevention of cardiovascular disease in people aged between 40 and 59 who have a 10% or greater risk of developing cardiovascular disease over the next 10 years and are not at an increased risk of bleeding.

Pain
Aspirin is an effective analgesic for acute pain, although it is generally considered inferior to ibuprofen because aspirin is more likely to cause gastrointestinal bleeding. Aspirin is generally ineffective for those pains caused by muscle cramps, bloating, gastric distension, or acute skin irritation. As with other NSAIDs, combinations of aspirin and caffeine provide slightly greater pain relief than aspirin alone. Effervescent formulations of aspirin relieve pain faster than aspirin in tablets, which makes them useful for the treatment of migraines. Topical aspirin may be effective for treating some types of neuropathic pain.Aspirin, either by itself or in a combined formulation, effectively treats certain types of a headache, but its efficacy may be questionable for others. Secondary headaches, meaning those caused by another disorder or trauma, should be promptly treated by a medical provider. Among primary headaches, the International Classification of Headache Disorders distinguishes between tension headache (the most common), migraine, and cluster headache. Aspirin or other over-the-counter analgesics are widely recognized as effective for the treatment of tension headache. Aspirin, especially as a component of an aspirin/paracetamol/caffeine combination, is considered a first-line therapy in the treatment of migraine, and comparable to lower doses of sumatriptan. It is most effective at stopping migraines when they are first beginning.

Fever
Like its ability to control pain, aspirins ability to control fever is due to its action on the prostaglandin system through its irreversible inhibition of COX. Although aspirins use as an antipyretic in adults is well established, many medical societies and regulatory agencies, including the American Academy of Family Physicians, the American Academy of Pediatrics, and the Food and Drug Administration, strongly advise against using aspirin for treatment of fever in children because of the risk of Reyes syndrome, a rare but often fatal illness associated with the use of aspirin or other salicylates in children during episodes of viral or bacterial infection. Because of the risk of Reyes syndrome in children, in 1986, the US Food and Drug Administration (FDA) required labeling on all aspirin-containing medications advising against its use in children and teenagers.

Inflammation
Aspirin is used as an anti-inflammatory agent for both acute and long-term inflammation, as well as for treatment of inflammatory diseases, such as rheumatoid arthritis.

Heart attacks and strokes
Aspirin is an important part of the treatment of those who have had a heart attack. It is generally not recommended for routine use by people with no other health problems, including those over the age of 70.The 2009 Antithrombotic Trialists Collaboration published in Lancet evaluated the efficacy and safety of low dose aspirin in secondary prevention. In those with prior ischaemic stroke or acute myocardial infarction, daily low dose aspirin was associated with a 19% relative risk reduction of serious cardiovascular events (non-fatal myocardial infarction, non-fatal stroke, or vascular death). This did come at the expense of a 0.19% absolute risk increase in gastrointestinal bleeding; however, the benefits outweigh the hazard risk in this case. Data from early trials of aspirin in primary prevention suggested low dose aspirin is more beneficial for people <70 kg and high dose aspirin is more beneficial for those ≥70 kg. However, more recent trials have suggested lower dose aspirin is not more efficacious in people with a low body weight and more evidence is required to determine the effect of higher dose aspirin in people with a high body weight. The United States Preventive Services Task Force (USPSTF), in 2016, recommended initiating low-dose aspirin use for the primary prevention of cardiovascular disease and colon cancer in adults aged 50 to 59 years who have a 10% or greater 10-year cardiovascular disease (CVD) risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years. However, in 2021, the USPSTF recommended against the routine use of daily aspirin for primary prevention in adults in their 40s and 50s, citing the fact that the risk of side effects outweighs the potential benefits. In April 2022, the USPSTF said "people ages 40 to 59 who are at higher risk for CVD should decide with their clinician whether to start taking aspirin; people 60 or older should not start taking aspirin to prevent a first heart attack or stroke."The status of the use of aspirin for the primary prevention in cardiovascular disease is conflicting and inconsistent. The ASCEND study demonstrated that in high-bleeding risk diabetics with no prior cardiovascular disease, there is no overall clinical benefit (12% decrease in risk of ischaemic events v/s 29% increase in GI bleeding) of low dose aspirin in preventing the serious vascular events over a period of 7.4 years. Similarly, the results of the ARRIVE study also showed no benefit of same dose of aspirin in reducing the time to first cardiovascular outcome in patients with moderate risk of cardiovascular disease over a period of five years.Aspirin appears to offer little benefit to those at lower risk of heart attack or stroke—for instance, those without a history of these events or with pre-existing disease. Some studies recommend aspirin on a case-by-case basis, while others have suggested the risks of other events, such as gastrointestinal bleeding, were enough to outweigh any potential benefit, and recommended against using aspirin for primary prevention entirely. Aspirin has also been suggested as a component of a polypill for prevention of cardiovascular disease.Complicating the use of aspirin for prevention is the phenomenon of aspirin resistance. For people who are resistant, aspirins efficacy is reduced. Some authors have suggested testing regimens to identify people who are resistant to aspirin.After percutaneous coronary interventions (PCIs), such as the placement of a coronary artery stent, a U.S. Agency for Healthcare Research and Quality guideline recommends that aspirin be taken indefinitely. Frequently, aspirin is combined with an ADP receptor inhibitor, such as clopidogrel, prasugrel, or ticagrelor to prevent blood clots. This is called dual antiplatelet therapy (DAPT). Duration of DAPT was advised in the United States and European Union guidelines after the CURE  and PRODIGY  studies . In 2020, the systematic review and network meta-analysis from Khan et al. showed promising benefits of short-term (< 6 months) DAPT followed by P2Y12 inhibitors in selected patients, as well as the benefits of extended-term (> 12 months) DAPT in high risk patients. In conclusion, the optimal duration of DAPT after PCIs should be personalized after outweighing each patients risks of ischemic events and risks of bleeding events with consideration of multiple patient-related and procedure-related factors. Moreover, aspirin should be continued indefinitely after DAPT is complete.

Cancer prevention
Aspirin may reduce the overall risk of both getting cancer and dying from cancer. There is substantial evidence for lowering the risk of colorectal cancer (CRC), but must be taken for at least 10–20 years to see this benefit. It may also slightly reduce the risk of endometrial cancer, breast cancer, and prostate cancer.Some conclude the benefits are greater than the risks due to bleeding in those at average risk. Others are unclear if the benefits are greater than the risk. Given this uncertainty, the 2007 United States Preventive Services Task Force (USPSTF) guidelines on this topic recommended against the use of aspirin for prevention of CRC in people with average risk. Nine years later however, the USPSTF issued a grade B recommendation for the use of low-dose aspirin (75 to 100 mg/day) "for the primary prevention of CVD [cardiovascular disease] and CRC in adults 50 to 59 years of age who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years".A meta-analysis through 2019 said that there was an association between taking aspirin and lower risk of cancer of the colorectum, esophagus, and stomach.In 2021, the U.S. Preventive services Task Force raised questions about the use of aspirin in cancer prevention. It notes the results of the 2018 ASPREE (Aspirin in Reducing Events in the Elderly) Trial, in which the risk of cancer-related death was higher in the aspirin-treated group than in the placebo group.

Psychiatry
Bipolar disorder
Aspirin, along with several other agents with anti-inflammatory properties, has been repurposed as an add-on treatment for depressive episodes in subjects with bipolar disorder in light of the possible role of inflammation in the pathogenesis of severe mental disorders. However, meta-analytic evidence is based on very few studies and does not suggest any efficacy of aspirin in the treatment of bipolar depression. Thus, notwithstanding the biological rationale, the clinical perspectives of aspirin and anti-inflammatory agents in the treatment of bipolar depression remain uncertain.

Dementia
Although cohort and longitudinal studies have shown low-dose aspirin has a greater likelihood of reducing the incidence of dementia, numerous randomised controlled trials have not validated this.

Other uses
Aspirin is a first-line treatment for the fever and joint-pain symptoms of acute rheumatic fever. The therapy often lasts for one to two weeks, and is rarely indicated for longer periods. After fever and pain have subsided, the aspirin is no longer necessary, since it does not decrease the incidence of heart complications and residual rheumatic heart disease. Naproxen has been shown to be as effective as aspirin and less toxic, but due to the limited clinical experience, naproxen is recommended only as a second-line treatment.Along with rheumatic fever, Kawasaki disease remains one of the few indications for aspirin use in children in spite of a lack of high quality evidence for its effectiveness.Low-dose aspirin supplementation has moderate benefits when used for prevention of pre-eclampsia. This benefit is greater when started in early pregnancy.

Resistance
For some people, aspirin does not have as strong an effect on platelets as for others, an effect known as aspirin-resistance or insensitivity. One study has suggested women are more likely to be resistant than men, and a different, aggregate study of 2,930 people found 28% were resistant.
A study in 100 Italian people found, of the apparent 31% aspirin-resistant subjects, only 5% were truly resistant, and the others were noncompliant.
Another study of 400 healthy volunteers found no subjects who were truly resistant, but some had "pseudoresistance, reflecting delayed and reduced drug absorption".
Meta-analysis and systematic reviews have concluded that laboratory confirmed aspirin resistance confers increased rates of poorer outcomes in cardiovascular and neurovascular diseases. Although the majority of research conducted has surrounded cardiovascular and neurovascular, there is emerging research into the risk of aspirin resistance after orthopaedic surgery where aspirin is used for venous thromboembolism prophylaxis. Aspirin resistance in orthopaedic surgery, specifically after total hip and knee arthroplasties, is of interest as risk factors for aspirin resistance are also risk factors for venous thromboembolisms and osteoarthritis; the sequalae of requiring a total hip or knee arthroplasty. Some of these risk factors include obesity, advancing age, diabetes mellitus, dyslipidaemia and inflammatory diseases.

Dosages
Adult aspirin tablets are produced in standardised sizes, which vary slightly from country to country, for example 300 mg in Britain and 325 mg (or 5 grains) in the United States. Smaller doses are based on these standards, e.g., 75 mg and 81 mg tablets. The 81-milligram (1+1⁄4-grain) tablets are commonly called "baby aspirin" or "baby-strength", because they were originally – but no longer – intended to be administered to infants and children. No medical significance occurs due to the slight difference in dosage between the 75 mg and the 81 mg tablets. The dose required for benefit appears to depend on a persons weight. For those weighing less than 70 kilograms (154 lb), low dose is effective for preventing cardiovascular disease; for patients above this weight, higher doses are required.In general, for adults, doses are taken four times a day for fever or arthritis, with doses near the maximal daily dose used historically for the treatment of rheumatic fever. For the prevention of myocardial infarction (MI) in someone with documented or suspected coronary artery disease, much lower doses are taken once daily.March 2009 recommendations from the USPSTF on the use of aspirin for the primary prevention of coronary heart disease encourage men aged 45–79 and women aged 55–79 to use aspirin when the potential benefit of a reduction in MI for men or stroke for women outweighs the potential harm of an increase in gastrointestinal hemorrhage. The WHI study of postmenopausal women found that aspirin resulted in a 25% lower risk of death from cardiovascular disease and a 14% lower risk of death from any cause, though there was no significant difference between 81 mg and 325 mg aspirin doses. The 2021 ADAPTABLE study also showed no significant difference in cardiovascular events or major bleeding between 81 mg and 325 mg doses of aspirin in patients (both men and women) with established cardiovascular disease.Low-dose aspirin use was also associated with a trend toward lower risk of cardiovascular events, and lower aspirin doses (75 or 81 mg/day) may optimize efficacy and safety for people requiring aspirin for long-term prevention.In children with Kawasaki disease, aspirin is taken at dosages based on body weight, initially four times a day for up to two weeks and then at a lower dose once daily for a further six to eight weeks.

Adverse effects
In October 2020, the US Food and Drug Administration (FDA) required the drug label to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid. They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy. One exception to the recommendation is the use of low-dose 81 mg aspirin at any point in pregnancy under the direction of a health care professional.

Contraindications
Aspirin should not be taken by people who are allergic to ibuprofen or naproxen, or who have salicylate intolerance or a more generalized drug intolerance to NSAIDs, and caution should be exercised in those with asthma or NSAID-precipitated bronchospasm. Owing to its effect on the stomach lining, manufacturers recommend people with peptic ulcers, mild diabetes, or gastritis seek medical advice before using aspirin. Even if none of these conditions is present, the risk of stomach bleeding is still increased when aspirin is taken with alcohol or warfarin. People with hemophilia or other bleeding tendencies should not take aspirin or other salicylates. Aspirin is known to cause hemolytic anemia in people who have the genetic disease glucose-6-phosphate dehydrogenase deficiency, particularly in large doses and depending on the severity of the disease. Use of aspirin during dengue fever is not recommended owing to increased bleeding tendency. People with kidney disease, hyperuricemia, or gout should not take aspirin because it inhibits the kidneys ability to excrete uric acid, thus may exacerbate these conditions. Aspirin should not be given to children or adolescents to control cold or influenza symptoms, as this has been linked with Reyes syndrome.

Gastrointestinal
Aspirin use has been shown to increase the risk of gastrointestinal bleeding. Although some enteric-coated formulations of aspirin are advertised as being "gentle to the stomach", in one study, enteric coating did not seem to reduce this risk. Combining aspirin with other NSAIDs has also been shown to further increase this risk. Using aspirin in combination with clopidogrel or warfarin also increases the risk of upper gastrointestinal bleeding.Blockade of COX-1 by aspirin apparently results in the upregulation of COX-2 as part of a gastric defense. Several trials suggest that the simultaneous use of a COX-2 inhibitor with aspirin may increase the risk of gastrointestinal injury. However, currently available evidence has been unable to prove that this effect is consistently repeatable in everyday clinical practice. More dedicated research is required to provide greater clarity on the subject. Therefore, caution should be exercised if combining aspirin with any "natural" supplements with COX-2-inhibiting properties, such as garlic extracts, curcumin, bilberry, pine bark, ginkgo, fish oil, resveratrol, genistein, quercetin, resorcinol, and others.In addition to enteric coating, "buffering" is the other main method companies have used to try to mitigate the problem of gastrointestinal bleeding. Buffering agents are intended to work by preventing the aspirin from concentrating in the walls of the stomach, although the benefits of buffered aspirin are disputed. Almost any buffering agent used in antacids can be used; Bufferin, for example, uses magnesium oxide. Other preparations use calcium carbonate. Gas-forming agents in effervescent tablet and powder formulations can also double as a buffering agent, one example being sodium bicarbonate found in Alka-Seltzer.Taking it with vitamin C has been investigated as a method of protecting the stomach lining. Taking equal doses of vitamin C and aspirin may decrease the amount of stomach damage that occurs compared to taking aspirin alone.

Retinal vein occlusion
It is a widespread habit among eye specialists (ophthalmologists) to prescribe aspirin as an add-on medication for patients with retinal vein occlusion (RVO), such as central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). The reason of this widespread use is the evidence of its proven effectiveness in major systemic venous thrombotic disorders, and it has been assumed that may be similarly beneficial in various types of retinal vein occlusion.
However, a large-scale investigation based on data of nearly 700 patients showed "that aspirin or other antiplatelet aggregating agents or anticoagulants adversely influence the visual outcome in patients with CRVO and hemi-CRVO, without any evidence of protective or beneficial effect". Several expert groups, including the Royal College of Ophthalmologists, recommended against the use of antithrombotic drugs (incl. aspirin) for patients with RVO.

Central effects
Large doses of salicylate, a metabolite of aspirin, cause temporary tinnitus (ringing in the ears) based on experiments in rats, via the action on arachidonic acid and NMDA receptors cascade.

Reyes syndrome
Reyes syndrome, a rare but severe illness characterized by acute encephalopathy and fatty liver, can occur when children or adolescents are given aspirin for a fever or other illness or infection. From 1981 to 1997, 1207 cases of Reyes syndrome in people younger than 18 were reported to the US Centers for Disease Control and Prevention (CDC). Of these, 93% reported being ill in the three weeks preceding the onset of Reyes syndrome, most commonly with a respiratory infection, chickenpox, or diarrhea. Salicylates were detectable in 81.9% of children for whom test results were reported. After the association between Reyes syndrome and aspirin was reported, and safety measures to prevent it (including a Surgeon Generals warning, and changes to the labeling of aspirin-containing drugs) were implemented, aspirin taken by children declined considerably in the United States, as did the number of reported cases of Reyes syndrome; a similar decline was found in the United Kingdom after warnings against pediatric aspirin use were issued. The US Food and Drug Administration recommends aspirin (or aspirin-containing products) should not be given to anyone under the age of 12 who has a fever, and the UK National Health Service recommends children who are under 16 years of age should not take aspirin, unless it is on the advice of a doctor.

Skin
For a small number of people, taking aspirin can result in symptoms including hives, swelling, and headache. Aspirin can exacerbate symptoms among those with chronic hives, or create acute symptoms of hives. These responses can be due to allergic reactions to aspirin, or more often due to its effect of inhibiting the COX-1 enzyme. Skin reactions may also tie to systemic contraindications, seen with NSAID-precipitated bronchospasm, or those with atopy.Aspirin and other NSAIDs, such as ibuprofen, may delay the healing of skin wounds. Earlier findings from two small, low-quality trials suggested a benefit with aspirin (alongside compression therapy) on venous leg ulcer healing time and leg ulcer size, however larger, more recent studies of higher quality have been unable to corroborate these outcomes. As such, further research is required to clarify the role of aspirin in this context.

Other adverse effects
Aspirin can induce swelling of skin tissues in some people. In one study, angioedema appeared one to six hours after ingesting aspirin in some of the people. However, when the aspirin was taken alone, it did not cause angioedema in these people; the aspirin had been taken in combination with another NSAID-induced drug when angioedema appeared.Aspirin causes an increased risk of cerebral microbleeds having the appearance on MRI scans of 5 to 10 mm or smaller, hypointense (dark holes) patches.A study of a group with a mean dosage of aspirin of 270 mg per day estimated an average absolute risk increase in intracerebral hemorrhage (ICH) of 12 events per 10,000 persons. In comparison, the estimated absolute risk reduction in myocardial infarction was 137 events per 10,000 persons, and a reduction of 39 events per 10,000 persons in ischemic stroke. In cases where ICH already has occurred, aspirin use results in higher mortality, with a dose of about 250 mg per day resulting in a relative risk of death within three months after the ICH around 2.5 (95% confidence interval 1.3 to 4.6).Aspirin and other NSAIDs can cause abnormally high blood levels of potassium by inducing a hyporeninemic hypoaldosteronic state via inhibition of prostaglandin synthesis; however, these agents do not typically cause hyperkalemia by themselves in the setting of normal renal function and euvolemic state.Use of low-dose aspirin before a surgical procedure has been associated with an increased risk of bleeding events in some patients, however, ceasing aspirin prior to surgery has also been associated with an increase in major adverse cardiac events. An analysis of multiple studies found a three-fold increase in adverse events such as myocardial infarction in patients who ceased aspirin prior to surgery. The analysis found that the risk is dependent on the type of surgery being performed and the patient indication for aspirin use.On 9 July 2015, the US Food and Drug Administration (FDA) toughened warnings of increased heart attack and stroke risk associated with nonsteroidal anti-inflammatory drugs (NSAID). Aspirin is an NSAID but is not affected by the new warnings.

Overdose
Aspirin overdose can be acute or chronic. In acute poisoning, a single large dose is taken; in chronic poisoning, higher than normal doses are taken over a period of time. Acute overdose has a mortality rate of 2%. Chronic overdose is more commonly lethal, with a mortality rate of 25%; chronic overdose may be especially severe in children. Toxicity is managed with a number of potential treatments, including activated charcoal, intravenous dextrose and normal saline, sodium bicarbonate, and dialysis. The diagnosis of poisoning usually involves measurement of plasma salicylate, the active metabolite of aspirin, by automated spectrophotometric methods. Plasma salicylate levels in general range from 30 to 100 mg/L after usual therapeutic doses, 50–300 mg/L in people taking high doses and 700–1400 mg/L following acute overdose. Salicylate is also produced as a result of exposure to bismuth subsalicylate, methyl salicylate, and sodium salicylate.

Interactions
Aspirin is known to interact with other drugs. For example, acetazolamide and ammonium chloride are known to enhance the intoxicating effect of salicylates, and alcohol also increases the gastrointestinal bleeding associated with these types of drugs. Aspirin is known to displace a number of drugs from protein-binding sites in the blood, including the antidiabetic drugs tolbutamide and chlorpropamide, warfarin, methotrexate, phenytoin, probenecid, valproic acid (as well as interfering with beta oxidation, an important part of valproate metabolism), and other NSAIDs. Corticosteroids may also reduce the concentration of aspirin. Other NSAIDs, such as ibuprofen and naproxen, may reduce the antiplatelet effect of aspirin. Although limited evidence suggests this may not result in a reduced cardioprotective effect of aspirin. Analgesic doses of aspirin decrease sodium loss induced by spironolactone in the urine, however this does not reduce the antihypertensive effects of spironolactone. Furthermore, antiplatelet doses of aspirin are deemed too small to produce an interaction with spironolactone. Aspirin is known to compete with penicillin G for renal tubular secretion. Aspirin may also inhibit the absorption of vitamin C.

Research
The ISIS-2 trial demonstrated that aspirin at doses of 160 mg daily for one month, decreased the mortality by 21% of participants with a suspected myocardial infarction in the first five weeks. A single daily dose of 324 mg of aspirin for 12 weeks has a highly protective effect against acute myocardial infarction and death in men with unstable angina.

Bipolar disorder
Aspirin has been repurposed as an add-on treatment for depressive episodes in subjects with bipolar disorder. However, meta-analytic evidence is based on very few studies and does not suggest any efficacy of aspirin in the treatment of bipolar depression. Thus, notwithstanding the biological rationale, the clinical perspectives of aspirin and anti-inflammatory agents in the treatment of bipolar depression remain uncertain.

Infectious diseases
Several studies investigated the anti-infective properties of aspirin for bacterial, viral and parasitic infections. Aspirin was demonstrated to limit platelet activation induced by Staphylococcus aureus and Enterococcus faecalis and to reduce streptococcal adhesion to heart valves. In patients with tuberculous meningitis, the addition of aspirin reduced the risk of new cerebral infarction [RR = 0.52 (0.29-0.92)]. A role of aspirin on bacterial and fungal biofilm is also being supported by growing evidence.

Cancer prevention
Aspirin might weakly reduce the risk of breast cancer per a 2020 meta-analysis.

In gardening
There are a many anecdotal reportings that aspirin can improve plants growth and resistance though most research involved salicylic acid instead of aspirin.

Veterinary medicine
Aspirin is sometimes used in veterinary medicine as an anticoagulant or to relieve pain associated with musculoskeletal inflammation or osteoarthritis. Aspirin should only be given to animals under the direct supervision of a veterinarian, as adverse effects—including gastrointestinal issues—are common. An aspirin overdose in any species may result in salicylate poisoning, characterized by hemorrhaging, seizures, coma, and even death.Dogs are better able to tolerate aspirin than cats are. Cats metabolize aspirin slowly because they lack the glucuronide conjugates that aid in the excretion of aspirin, making it potentially toxic if dosing is not spaced out properly. No clinical signs of toxicosis occurred when cats were given 25 mg/kg of aspirin every 48 hours for 4 weeks, but the recommended dose for relief of pain and fever and for treating blood clotting diseases in cats is 10 mg/kg every 48 hours to allow for metabolization.

References
Further reading
McTavish, Jan R. (Fall 1987). "Whats in a name? Aspirin and the American Medical Association". Bulletin of the History of Medicine. 61.3: 343–366 </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Yonsa and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is BC Powder and explain in detail? [/INST] BC Powder is an American brand of over-the-counter analgesic pain reliever owned by Prestige Consumer Healthcare and manufactured in Washington, DC.

Ingredients
Originally produced at the Hepolscheiemer Clinic in Graz, Austria, it contains 845 mg of aspirin and 65 mg of caffeine. BC readily promotes the fact that, due to its powder form, it dissolves faster than pain-relief tablets, and thus gets to work faster. It can be taken in a variety of ways, most commonly mixed into water or soda.
In 2009 BC Powder removed the 195 mg of Salicylamide from the "Blue Box Original Formula BC Powder".  The original formula consisted of 650 mg aspirin, 195 mg salicylamide and 33.3 mg caffeine. The New packaging states "New Formula" and "Same Fast Relief!" on the front of the box.  The new formula has 845 mg aspirin and 65 mg caffeine.

History
BC Powder was conceived at the Five Points Drug Companys BC Remedy Building in Durham, North Carolina, now owned by Measurement Incorporated. It was developed in 1906 by C.T. Council, in the Durham, NC pharmacy of Germain Bernard </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Anacin and explain in detail? [/INST] Anacin is an American brand of analgesic that is manufactured by Prestige Consumer Healthcare. Its product contains aspirin and caffeine.

History
Anacin was invented by William Milton Knight and was first to be used circa 1916 as stated in the patent. Anacin is one of the oldest brands of pain relievers in the United States, first being sold in the 1930s. Anacins mascot at the time was Ana Anacin, who was found in a number of ads for this product by Bayer.
It was originally sold by the Anacin Co. ("Pharmaceutical Chemists") in Chicago, Illinois. American Home Products, now known as Wyeth, purchased the manufacturing rights in 1930. Anacin was reportedly their most popular product. Insight Pharmaceuticals acquired the brand in 2003. In 2014, Prestige Brands signed an agreement with Insight to acquire the company; it was Prestige Brands largest acquisition to that point.

Advertising
In 1939, Anacin sponsored a daytime serial called Our Gal Sunday. Their sponsorship spanned 18 of the programs 23 years on the air. Early Anacin radio commercials appeared in radio shows and dramas of the 1940s and 50s. These "formulaic" commercials usually claimed that Anacin was being actively prescribed by doctors and dentists at the time, treated "headaches, neuritis and neuralgia", and that it contained "a combination of medically proven ingredients, like a doctors prescription", without specifying those ingredients. Sometimes the announcer would mention that there were four active ingredients in Anacin, one of which was the medicine the consumer was already taking </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Radio-renal syndrome and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Placenta and explain in detail? [/INST] The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate maternal and fetal circulations, and is an important endocrine organ producing hormones that regulate both maternal and fetal physiology during pregnancy. The placenta connects to the fetus via the umbilical cord, and on the opposite aspect to the maternal uterus in a species-dependent manner. In humans, a thin layer of maternal decidual (endometrial) tissue comes away with the placenta when it is expelled from the uterus following birth (sometimes incorrectly referred to as the maternal part of the placenta). Placentas are a defining characteristic of placental mammals, but are also found in marsupials and some non-mammals with varying levels of development.Mammalian placentas probably first evolved about 150 million to 200 million years ago. The protein syncytin, found in the outer barrier of the placenta (the syncytiotrophoblast) between mother and fetus, has a certain RNA signature in its genome that has led to the hypothesis that it originated from an ancient retrovirus: essentially a virus that helped pave the transition from egg-laying to live-birth.The word placenta  comes from the Latin word for a type of cake, from Greek πλακόεντα/πλακοῦντα plakóenta/plakoúnta, accusative of πλακόεις/πλακούς plakóeis/plakoús, "flat, slab-like", with reference to its round, flat appearance in humans. The classical plural is placentae, but the form placentas is more common in modern English.

Phylogenetic diversity
Although all mammalian placentas have the same functions, there are important differences in structure and function in different groups of mammals. For example, human, bovine, equine and canine placentas are very different at both the gross and the microscopic levels. Placentas of these species also differ in their ability to provide maternal immunoglobulins to the fetus.

Structure
Placental mammals, such as humans, have a chorioallantoic placenta that forms from the chorion and allantois. In humans, the placenta averages 22 cm (9 inch) in length and 2–2.5 cm (0.8–1 inch) in thickness, with the center being the thickest, and the edges being the thinnest. It typically weighs approximately 500 grams (just over 1 lb).  It has a dark reddish-blue or crimson color. It connects to the fetus by an umbilical cord of approximately 55–60 cm (22–24 inch) in length, which contains two umbilical arteries and one umbilical vein.  The umbilical cord inserts into the chorionic plate (has an eccentric attachment). Vessels branch out over the surface of the placenta and further divide to form a network covered by a thin layer of cells. This results in the formation of villous tree structures. On the maternal side, these villous tree structures are grouped into lobules called cotyledons. In humans, the placenta usually has a disc shape, but size varies vastly between different mammalian species.The placenta occasionally takes a form in which it comprises several distinct parts connected by blood vessels. The parts, called lobes, may number two, three, four, or more. Such placentas are described as bilobed/bilobular/bipartite, trilobed/trilobular/tripartite, and so on. If there is a clearly discernible main lobe and auxiliary lobe, the latter is called a succenturiate placenta. Sometimes the blood vessels connecting the lobes get in the way of fetal presentation during labor, which is called vasa previa.

Gene and protein expression
About 20,000 protein coding genes are expressed in human cells and 70% of these genes are expressed in the normal mature placenta. Some 350 of these genes are more specifically expressed in the placenta and fewer than 100 genes are highly placenta specific. The corresponding specific proteins are mainly expressed in trophoblasts and have functions related to female pregnancy. Examples of proteins with elevated expression in placenta compared to other organs and tissues are PEG10 and the cancer testis antigen PAGE4 and expressed in cytotrophoblasts, CSH1 and KISS1 expressed in syncytiotrophoblasts, and PAPPA2 and PRG2 expressed in extravillous trophoblasts.

Physiology
Development
The placenta begins to develop upon implantation of the blastocyst into the maternal endometrium, very early on in pregnancy at about week 4.The outer layer of the late blastocyst, is formed of trophoblasts, cells that form the outer layer of the placenta. This outer layer is divided into two further layers: the underlying cytotrophoblast layer and the overlying syncytiotrophoblast layer. The syncytiotrophoblast is a multinucleated continuous cell layer that covers the surface of the placenta. It forms as a result of differentiation and fusion of the underlying cytotrophoblasts, a process that continues throughout placental development. The syncytiotrophoblast contributes to the barrier function of the placenta.The placenta grows throughout pregnancy. Development of the maternal blood supply to the placenta is complete by the end of the first trimester of pregnancy week 14 (DM).

Placental circulation
Maternal placental circulation
In preparation for implantation of the blastocyst, the endometrium undergoes decidualization. Spiral arteries in the decidua are remodeled so that they become less convoluted and their diameter is increased. The increased diameter and straighter flow path both act to increase maternal blood flow to the placenta. There is relatively high pressure as the maternal blood fills intervillous space through these spiral arteries which bathe the fetal villi in blood, allowing an exchange of gases to take place. In humans and other hemochorial placentals, the maternal blood comes into direct contact with the fetal chorion, though no fluid is exchanged. As the pressure decreases between pulses, the deoxygenated blood flows back through the endometrial veins.
Maternal blood flow is approximately 600–700 ml/min at term.
This begins at day 5–12.

Fetoplacental circulation
Deoxygenated fetal blood passes through umbilical arteries to the placenta. At the junction of umbilical cord and placenta, the umbilical arteries branch radially to form chorionic arteries. Chorionic arteries, in turn, branch into cotyledon arteries. In the villi, these vessels eventually branch to form an extensive arterio-capillary-venous system, bringing the fetal blood extremely close to the maternal blood; but no intermingling of fetal and maternal blood occurs ("placental barrier").Endothelin and prostanoids cause vasoconstriction in placental arteries, while nitric oxide causes vasodilation. On the other hand, there is no neural vascular regulation, and catecholamines have only little effect.The fetoplacental circulation is vulnerable to persistent hypoxia or intermittent hypoxia and reoxygenation, which can lead to generation of excessive free radicals. This may contribute to pre-eclampsia and other pregnancy complications. It is proposed that melatonin plays a role as an antioxidant in the placenta.This begins at day 17–22.

Birth
Placental expulsion begins as a physiological separation from the wall of the uterus. The period from just after the child is born until just after the placenta is expelled is called the "third stage of labor". The placenta is usually expelled within 15–30 minutes of birth.
Placental expulsion can be managed actively, for example by giving oxytocin via intramuscular injection followed by cord traction to assist in delivering the placenta. Alternatively, it can be managed expectantly, allowing the placenta to be expelled without medical assistance. Blood loss and the risk of postpartum bleeding may be reduced in women offered active management of the third stage of labour, however there may be adverse effects and more research is necessary.The habit is to cut the cord immediately after birth, but it is theorised that there is no medical reason to do this; on the contrary, it is theorised that not cutting the cord helps the baby in its adaptation to extrauterine life, especially in preterm infants.

Microbiome
The placenta is traditionally thought to be sterile, but recent research suggests that a resident, non-pathogenic, and diverse population of microorganisms may be present in healthy tissue. However, whether these microbes exist or are clinically important is highly controversial and is the subject of active research.

Functions
Nutrition and gas exchange
The placenta intermediates the transfer of nutrients between mother and fetus. The perfusion of the intervillous spaces of the placenta with maternal blood allows the transfer of nutrients and oxygen from the mother to the fetus and the transfer of waste products and carbon dioxide back from the fetus to the maternal blood. Nutrient transfer to the fetus can occur via both active and passive transport. Placental nutrient metabolism was found to play a key role in limiting the transfer of some nutrients. Adverse pregnancy situations, such as those involving maternal diabetes or obesity, can increase or decrease levels of nutrient transporters in the placenta potentially resulting in overgrowth or restricted growth of the fetus.

Excretion
Waste products excreted from the fetus such as urea, uric acid, and creatinine are transferred to the maternal blood by diffusion across the placenta.

Immunity
The placenta functions as a selective barrier between maternal and fetal cells, preventing maternal blood, proteins and microbes (including bacteria and most viruses) from crossing the maternal-fetal barrier.
Deterioration in placental functioning, referred to as placental insufficiency, may be related to mother-to-child transmission of some infectious diseases.
A very small number of viruses including rubella virus, Zika virus and cytomegalovirus (CMV) can travel across the placental barrier, generally taking advantage of conditions at certain gestational periods as the placenta develops. CMV and Zika travel from the maternal bloodstream via placental cells to the fetal bloodstream.Beginning as early as 13 weeks of gestation, and increasing linearly, with the largest transfer occurring in the third trimester, IgG antibodies can pass through the human placenta, providing protection to the fetus in utero.
This passive immunity lingers for several months after birth, providing the newborn with a carbon copy of the mothers long-term humoral immunity to see the infant through the crucial first months of extrauterine life. IgM antibodies, because of their larger size, cannot cross the placenta, one reason why infections acquired during pregnancy can be particularly hazardous for the fetus.

Endocrine function
The first hormone released by the placenta is called the human chorionic gonadotropin (hCG) hormone. This is responsible for stopping the process at the end of menses when the corpus luteum ceases activity and atrophies. If hCG did not interrupt this process, it would lead to spontaneous abortion of the fetus. The corpus luteum also produces and releases progesterone and estrogen, and hCG stimulates it to increase the amount that it releases. hCG is the indicator of pregnancy that pregnancy tests look for. These tests will work when menses has not occurred or after implantation has happened on days seven to ten. hCG may also have an anti-antibody effect, protecting it from being rejected by the mothers body. hCG also assists the male fetus by stimulating the testes to produce testosterone, which is the hormone needed to allow the sex organs of the male to grow.
Progesterone helps the embryo implant by assisting passage through the fallopian tubes. It also affects the fallopian tubes and the uterus by stimulating an increase in secretions necessary for fetal nutrition. Progesterone, like hCG, is necessary to prevent spontaneous abortion because it prevents contractions of the uterus and is necessary for implantation.
Estrogen is a crucial hormone in the process of proliferation. This involves the enlargement of the breasts and uterus, allowing for growth of the fetus and production of milk. Estrogen is also responsible for increased blood supply towards the end of pregnancy through vasodilation. The levels of estrogen during pregnancy can increase so that they are thirty times what a non-pregnant woman mid-cycles estrogen level would be.
Human placental lactogen (hPL) is a hormone used in pregnancy to develop fetal metabolism and general growth and development. Human placental lactogen works with growth hormone to stimulate Insulin-like growth factor production and regulating intermediary metabolism. In the fetus, hPL acts on lactogenic receptors to modulate embryonic development, metabolism and stimulate production of IGF, insulin, surfactant and adrenocortical hormones. hPL values increase with multiple pregnancies, intact molar pregnancy, diabetes and Rh incompatibility. They are decreased with toxemia, choriocarcinoma, and Placental insufficiency.

Immunological barrier
The placenta and fetus may be regarded as a foreign body inside the mother and must be protected from the normal immune response of the mother that would cause it to be rejected. The placenta and fetus are thus treated as sites of immune privilege, with immune tolerance.
For this purpose, the placenta uses several mechanisms :

It secretes neurokinin B-containing phosphocholine molecules. This is the same mechanism used by parasitic nematodes to avoid detection by the immune system of their host.
There is presence of small lymphocytic suppressor cells in the fetus that inhibit maternal cytotoxic T cells by inhibiting the response to interleukin 2.However, the placental barrier is not the sole means of evading the immune system, as foreign fetal cells also persist in the maternal circulation, on the other side of the placental barrier.

Other
The placenta also provides a reservoir of blood for the fetus, delivering blood to it in case of hypotension and vice versa, comparable to a capacitor.

Clinical significance
Numerous pathologies can affect the placenta.

Placenta accreta, when the placenta implants too deeply, all the way to the actual muscle of uterine wall (without penetrating it)
Placenta praevia, when the placement of the placenta is too close to or blocks the cervix
Placental abruption, premature detachment of the placenta
Placentitis, inflammation of the placenta, such as by TORCH infections.

Society and culture
The placenta often plays an important role in various cultures, with many societies conducting rituals regarding its disposal. In the Western world, the placenta is most often incinerated.Some cultures bury the placenta for various reasons. The Māori of New Zealand traditionally bury the placenta from a newborn child to emphasize the relationship between humans and the earth. Likewise, the Navajo bury the placenta and umbilical cord at a specially chosen site, particularly if the baby dies during birth. In Cambodia and Costa Rica, burial of the placenta is believed to protect and ensure the health of the baby and the mother. If a mother dies in childbirth, the Aymara of Bolivia bury the placenta in a secret place so that the mothers spirit will not return to claim her babys life.The placenta is believed by some communities to have power over the lives of the baby or its parents. The Kwakiutl of British Columbia bury girls placentas to give the girl skill in digging clams, and expose boys placentas to ravens to encourage future prophetic visions. In Turkey, the proper disposal of the placenta and umbilical cord is believed to promote devoutness in the child later in life </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Mechanical hemolytic anemia and explain in detail? [/INST] Mechanical hemolytic anemia is a form of hemolytic anemia due to mechanically induced damage to red blood cells. Red blood cells, while flexible, may in some circumstances succumb to physical shear and compression </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Enchondromatosis and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Stimulant use disorder and explain in detail? [/INST] Stimulant use disorder is a type of substance use disorder that involves the non-medical use of stimulants. It is defined in the DSM-5 as "the continued use of amphetamine-type substances, cocaine, or other stimulants leading to clinically significant impairment or distress, from mild to severe". These psychoactive drugs, known as stimulants, are the most widely used drugs in the world today. Approximately 200 million Americans have used some type of stimulant in the past year alone.

Definition
A psychoactive drug, such as a stimulant, is a chemical or substance that affects one’s behavior, mind, and body. A stimulant can be smoked, injected, snorted, taken in pill form, chewed, and even ingested in the form of a drink. Synthetic stimulants are becoming increasingly popular as users attempt to alter the chemicals in drugs to create different reactions, and ultimately steer clear of jail time, legal penalties, and detection in drug screening efforts.If a substance is used over a long period of time and the user becomes dependent upon it, a substance use disorder may develop. Substance use may lead to substance dependence and with time, addiction. Both mental and physiological dependence requires the development of tolerance leading to withdrawal symptoms. Stimulants come in a very large variety of subtypes and among the most common are caffeine, nicotine, cocaine, methamphetamine, amphetamines, amphetamine congeners, electronic cigarettes, diet pills, plant stimulants, energy drinks, and the ever-evolving designer stimulants such as bath salts. Caffeine and nicotine are the most popular stimulants used today, with roughly 400 million cups of coffee consumed daily and 36.5 million current cigarette smokers, according to a 2015 study conducted by the Centers for Disease Control and Prevention. Nicotine, however, is treated separately psychiatrically under tobacco use disorder. Conversely, caffeine misuse does not qualify as an addictive disorder; thus it can not be diagnosed as a stimulant use disorder or any other substance use disorder. Certain isolated conditions related to caffeine are recognized in the DSM-5’s "substance-related" section, however: caffeine intoxication, caffeine withdrawal and other caffeine-induced disorders (e.g., Anxiety and Sleep Disorders).

Signs and symptoms
Short-term effects
Even in small doses, stimulants cause a decrease in appetite, an increase in physical activity and alertness, convulsions, an elevated body temperature, increased respiration, irregular heartbeat, and increased blood pressure; some of which can cause sudden death depending upon the medical history of the user, even among first-time users.

Long-term effects
The long-term use of stimulants can ultimately cause very serious medical issues, including addiction. Stimulant addiction, similar to other kinds of addiction, involves neurobiological changes that cause sensitization of the reward system to the stimulus in question (stimulants, in this case). People who use stimulants for a prolonged period frequently experience physiological changes that can be detrimental to their quality of life and require long-term treatment.

Symptoms of the disorder
The symptoms of stimulant use disorder include failure to control usage and frequency of use, an intense craving for the drug, increased use over time to obtain the same effects, known as a developed tolerance, and continued use despite negative repercussions and interference in one’s everyday life and functioning. Furthermore, a disorder is noted when withdrawal symptoms occur because of a decrease in the drug amount and frequency, as well as stopping the use of the drug entirely. These withdrawal symptoms can last for days, weeks, months, and on rare occasions, years, depending on the frequency and dosages used by the individual. These symptoms include, but are not limited to, increased appetite, decreased energy, depression, loss of motivation and interest in once pleasurable activities, anxiety, insomnia, agitation, and an intense craving for the drug. Unless intensive medical and psychological treatment is sought after, there is a very high likelihood of relapse among the user.

Epidemiology
The use of stimulants in humans causes rapid weight loss, cardiovascular effects such as an increase in heart rate, respiration, and blood pressure, emotional or mental side effects such as paranoia, anxiety, and aggression, as well as a change in the survival pathway known as the reward/reinforcement pathway in our brain. An increase in energy, a reduced appetite, increased alertness and a boost in confidence are all additional side effects of stimulant use when introduced to the body.

Medical
Currently, stimulants are used medically to treat certain types of asthma, the common cold, depression, obesity, and a wide variety of physical pain and ailments. Most commonly, stimulants such as Adderall, Ritalin, and Vyvanse are prescribed for both children and adults diagnosed with attention deficit hyperactivity disorder (ADHD).

Recreational
Recreationally speaking, stimulants are used to change one’s state of mind and users report feeling a "rush" as the central nervous system is flooded with dopamine and epinephrine, and norepinephrine. This rush is caused by the sudden change in both the electrical and chemical activity in the brain. This alteration occurs when a stimulant is introduced, as it causes a manipulation in the natural energy chemicals which are forced out and released into the body when they are not needed. In terms of recreational use, it is common for the user to smoke, inject, snort, and ingest stimulants, all of which create different effects on the body.

History
Certain types of stimulants are found in plants and grow naturally. The tobacco plant, the cocoa shrub, yohimbe, the betel nut, and the ephedra bush are just a few of the naturally occurring stimulants. Other forms of stimulants are man-made, with no naturally occurring plant base, and are instead created using synthetic chemicals.
Often, this involves using prescription or over-the-counter pharmaceutical products as precursor materials.Stimulants were first introduced to the medical community with the isolation of cocaine from the coca leaf in 1855, which is not only a stimulant but also a topical anesthetic.
In 1879, Vassili von Anrep of the University of Würzburg conducted an experiment in which he applied cocaine to one side of a frog’s limbs before attempting an invasive medical procedure. Cocaine proved to be extremely effective as both an anesthetic and pain reducer.In World War II, soldiers were medicated using a type of stimulant called amphetamines to keep both pilots and soldiers alert, full of energy, and ready to fight </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Generalized granuloma annulare and explain in detail? [/INST]  </s>