<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Ethionamide and can you explain it in depth? [/INST] Ethionamide is an antibiotic used to treat tuberculosis. Specifically it is used, along with other antituberculosis medications, to treat active multidrug-resistant tuberculosis. It is no longer recommended for leprosy. It is taken by mouth.Ethionamide has a high rate of side effects. Common side effects include nausea, diarrhea, abdominal pain, and loss of appetite. Serious side effects may include liver inflammation and depression. It should not be used in people with significant liver problems. Use in pregnancy is not recommended as safety is unclear. Ethionamide is in the thioamides family of medications. It is believed to work by interfering with the use of mycolic acid.Ethionamide was discovered in 1956 and approved for medical use in the United States in 1965. It is on the World Health Organizations List of Essential Medicines.

Medical uses
Ethionamide is used in combination with other antituberculosis agents as part of a second-line regimen for active tuberculosis.Ethionamide is well absorbed orally with or without food, but is often administered with food to improve tolerance. It crosses the blood brain barrier to achieve concentrations in the cerebral-spinal fluid equivalent to plasma.The antimicrobial spectrum of ethionamide includes M. tuberculosis, M. bovis and M. segmatis. It also is used rarely against infections with M. leprae and other nontuberculous mycobacteria such as M. avium and M. kansasii. While working in a similar manner to isoniazid, cross resistance is only seen in 13% of strains, since they are both prodrugs but activated by different pathways. Resistance can emerge from mutations in ethA, which is needed to activate the drug, or ethR, which can be overexpressed to repress ethA. Mutations in inhA or the promoter of inhA can also lead to resistance through changing the binding site or overexpression.The FDA has placed it in pregnancy category C, because it has caused birth defects in animal studies. It is not known whether ethionamide is excreted into breast milk.

Adverse effects
Ethionamide frequently causes gastrointestinal distress with nausea and vomiting which can lead patients to stop taking it. This can sometimes be improved by taking it with food.Ethionamide can cause hepatocellular toxicity and is contraindicated in patients with severe liver impairment. Patients on ethionamide should have regular monitoring of their liver function tests. Liver toxicity occurs in up to 5% of patients and follows a pattern similar to isoniazid, usually arising in the first 1 to 3 months of therapy, but can occur even after more than 6 months of therapy. The pattern of liver function test derangement is often a rise in the ALT and AST.Both central neurological side effects such as psychiatric disturbances and encephalopathy, along with peripheral neuropathy have been reported. Administering pyridoxine along with ethionamide may reduce these effects and is recommended.Ethionamide is structurally similar to methimazole, which is used to inhibit thyroid hormone synthesis, and has been linked to hypothyroidism in several TB patients </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hexamethylenetetramine and can you explain it in depth? [/INST] Hexamethylenetetramine, also known as methenamine, hexamine, or urotropin, is a heterocyclic organic compound with the formula (CH2)6N4.  This white crystalline compound is highly soluble in water and polar organic solvents.  It has a cage-like structure similar to adamantane.  It is useful in the synthesis of other organic compounds, including plastics, pharmaceuticals, and rubber additives. It sublimes in vacuum at 280 °C.

Synthesis, structure, reactivity
Hexamethylenetetramine was discovered by Aleksandr Butlerov in 1859.
It is prepared industrially by combining formaldehyde and ammonia:
The reaction can be conducted in gas phase and in solution.
The molecule has a tetrahedral cage-like structure, similar to adamantane. Four vertices are occupied by nitrogen atoms, which are linked by methylene groups. Although the molecular shape defines a cage, no void space is available at the interior for binding other atoms or molecules, unlike crown ethers or larger cryptand structures.
The molecule behaves like an amine base, undergoing protonation and N-alkylation (e.g. quaternium-15).

Applications
The dominant use of hexamethylenetetramine is in the production of powdery or liquid preparations of phenolic resins and phenolic resin moulding compounds, where it is added as a hardening component. These products are used as binders, e.g. in brake and clutch linings, abrasive products, non-woven textiles, formed parts produced by moulding processes, and fireproof materials.

Medical uses
As the mandelic acid salt (methenamine mandelate) or the hippuric acid salt (methenamine hippurate), it is used for the treatment of urinary tract infection.  In an acidic environment, methenamine is believed to act as an antimicrobial by converting to formaldehyde. A systematic review of its use for this purpose in adult women found there was insufficient evidence of benefit and further research is needed.Methenamine acts as an over-the-counter antiperspirant due to the astringent property of formaldehyde.

Histological stains
Methenamine silver stains are used for staining in histology, including the following types:

Grocotts methenamine silver stain, used widely as a screen for fungal organisms.
Jones stain, a methenamine silver-Periodic acid-Schiff that stains for basement membrane, availing to view the "spiked" Glomerular basement membrane associated with membranous glomerulonephritis.

Solid fuel
Together with 1,3,5-trioxane, hexamethylenetetramine is a component of hexamine fuel tablets used by campers, hobbyists, the military and relief organizations for heating camping food or military rations.  It burns smokelessly, has a high energy density of 30.0 megajoules per kilogram (MJ/kg), does not liquify while burning, and leaves no ashes, although its fumes are toxic.
Standardized 0.149 g tablets of methenamine (hexamine) are used by fire-protection laboratories as a clean and reproducible fire source to test the flammability of carpets and rugs.

Food additive
Hexamethylene tetramine or hexamine is also used as a food additive as a preservative (INS number 239). It is approved for usage for this purpose in the EU, where it is listed under E number E239, however it is not approved in the USA, Russia, Australia, or New Zealand.

Reagent in organic chemistry
Hexamethylenetetramine is a versatile reagent in organic synthesis. It is used in the Duff reaction (formylation of arenes), the Sommelet reaction (converting benzyl halides to aldehydes), and in the Delepine reaction (synthesis of amines from alkyl halides).

Explosives
Hexamethylenetetramine is the base component to produce RDX and, consequently, C-4 as well as Octogen, hexamine dinitrate, hexamine diperchlorate and HMTD.

Historical uses
Hexamethylenetetramine was first introduced into the medical setting in 1895 as a urinary antiseptic </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Lisinopril/hydrochlorothiazide and can you explain it in depth? [/INST] Lisinopril/hydrochlorothiazide, sold under the brand name Zestoretic among others, is a fixed-dose combination medication used for the treatment of high blood pressure. It contains lisinopril, an ACE inhibitor, and hydrochlorothiazide, a diuretic </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Esomeprazole and can you explain it in depth? [/INST] Esomeprazole, sold under the brand name Nexium among others, is a medication which reduces stomach acid. It is used to treat gastroesophageal reflux disease, peptic ulcer disease, and Zollinger–Ellison syndrome. Effectiveness is similar to other proton pump inhibitors (PPIs). It is taken by mouth or injection into a vein.Common side effects include headache, constipation, dry mouth, and abdominal pain. Serious side effects may include angioedema, Clostridium difficile infection, and pneumonia. Use in pregnancy appears to be safe, while safety during breastfeeding is unclear. Esomeprazole is the (S)-(−)-isomer of omeprazole. It works by blocking H+/K+-ATPase in the parietal cells of the stomach.It was patented in 1993 and approved for medical use in 2000. It is available as a generic medication and sold over the counter in a number of countries. In 2019, it was the 127th most commonly prescribed medication in the United States, with more than 5 million prescriptions. It is also available without a prescription in the United States.

Medical use
The primary uses of esomeprazole are gastroesophageal reflux disease, treatment and maintenance of erosive esophagitis, treatment of duodenal ulcers caused by H. pylori, prevention of gastric ulcers in those on chronic NSAID therapy, and treatment of gastrointestinal ulcers associated with Crohns disease.

Gastroesophageal reflux disease
Gastroesophageal reflux disease (GERD) is a condition in which the digestive acid in the stomach comes in contact with the esophagus. The irritation caused by this disorder is known as heartburn. Long-term contact between gastric acids and the esophagus can cause permanent damage to the esophagus. Esomeprazole reduces the production of digestive acids, thus reducing their effect on the esophagus.

Duodenal ulcers
Esomeprazole is combined with the antibiotics clarithromycin and amoxicillin (or metronidazole instead of amoxicillin in penicillin-hypersensitive patients) in a 10-day eradication triple therapy for Helicobacter pylori. Infection by H. pylori is a causative factor in the majority of peptic and duodenal ulcers.

Efficacy
A 2006 meta analysis concluded that compared to other proton pump inhibitors, esomeprazole confers a modest overall benefit in esophageal healing and symptom relief. When broken down by disease severity, the benefit of esomeprazole relative to other proton pump inhibitors was negligible in people with mild disease (number needed to treat 50), but appeared more in those with severe disease (number needed to treat 8). A second meta analysis also found increases in erosive esophageal healing (>95% healing rate) when compared to standardized doses in broadly selected patient populations. A 2017 study found esomeprazole to be among a number of effective doses of PPIs.

Adverse effects
Common side effects include headache, diarrhea, nausea, flatulence, decreased appetite, constipation, dry mouth, and abdominal pain. More severe side effects are severe allergic reactions, chest pain, dark urine, fast heartbeat, fever, paresthesia, persistent sore throat, severe stomach pain, unusual bruising or bleeding, unusual tiredness, and yellowing of the eyes or skin.Proton pump inhibitors may be associated with a greater risk of hip fractures and Clostridium difficile-associated diarrhoea. Patients are frequently administered the drugs in intensive care as a protective measure against ulcers, but this use is also associated with a 30% increase in occurrence of pneumonia.Long-term use of proton pump inhibitors in patients treated for Helicobacter pylori has been shown to dramatically increase the risk of gastric cancer.Acute tubulointerstitial nephritis is a possible adverse reaction when using proton pump inhibitors.

Interactions
Esomeprazole is a competitive inhibitor of the enzyme CYP2C19, and may therefore interact with drugs that depend on it for metabolism, such as diazepam and warfarin; the concentrations of these drugs may increase if they are used concomitantly with esomeprazole. Conversely, clopidogrel (Plavix) is an inactive prodrug that partially depends on CYP2C19 for conversion to its active form; inhibition of CYP2C19 blocks the activation of clopidogrel, thus reducing its effects.Drugs that depend on stomach pH for absorption may interact with omeprazole; drugs that depend on an acidic environment (such as ketoconazole or atazanavir) will be poorly absorbed, whereas drugs that are broken down in acidic environments (such as erythromycin) will be absorbed to a greater extent than normal.

Pharmacokinetics
Single 20 to 40 mg oral doses generally give rise to peak plasma esomeprazole concentrations of 0.5-1.0 mg/L within 1–4 hours, but after several days of once-daily administration, these levels may increase by about 50%. A 30-minute intravenous infusion of a similar dose usually produces peak plasma levels on the order of 1–3 mg/L. The drug is rapidly cleared from the body, largely by urinary excretion of pharmacologically inactive metabolites such as 5-hydroxymethylesomeprazole and 5-carboxyesomeprazole. Esomeprazole and its metabolites are analytically indistinguishable from omeprazole and the corresponding omeprazole metabolites unless chiral techniques are employed.

Dosage forms
Esomeprazole is available as delayed-release capsules in the United States or as delayed-release tablets in Australia, the United Kingdom, and Canada (containing esomeprazole magnesium) in strengths of 20 and 40 mg, as delayed-release capsules in the United States (containing esomeprazole strontium) in a 49.3 mg strength (delivering the equivalent of 40 mg of esomeprazole, and as esomeprazole sodium for intravenous injection/infusion. Oral esomeprazole preparations are enteric-coated, due to the rapid degradation of the drug in the acidic conditions of the stomach. This is achieved by formulating capsules using the multiple-unit pellet system.
The combination naproxen/esomeprazole magnesium (brand name Vimovo) is used for the prevention of gastric ulcers associated with chronic NSAID therapy. Vimovo is available in two dosage strengths: 500/20 mg and 375/20 mg. Clinical trials of naproxen/esomeprazole demonstrated an incidence of GI ulcer in 24% of patients on naproxen (alone) versus 7% on naproxen/esomeprazole. The FDA has added warnings to the label for Vimovo concerning acute interstitial nephritis and risk of kidney problems in some patients.

Multiple-unit pellet system
Esomeprazole capsules, as well as Losec/Prilosec tablets, are formulated as a "multiple-unit pellet system" (MUPS). Essentially, the capsule consists of extremely small enteric-coated granules (pellets) of the esomeprazole formulation inside an outer shell. When the capsule is immersed in an aqueous solution, as happens when the capsule reaches the stomach, water enters the capsule by osmosis. The contents swell from water absorption, causing the shell to burst, and releasing the enteric-coated granules. For most patients, the multiple-unit pellet system is of no advantage over conventional enteric-coated preparations. Patients for whom the formulation is of benefit include those requiring nasogastric tube feeding and those with difficulty swallowing (dysphagia).

Society and culture
Global distribution
In 2010, AstraZeneca announced a co-promotion agreement with Daiichi Sankyo to distribute Nexium in Japan. In September 2011, Nexium was approved for sale and was launched by Daiichi Sankyo in Japan. Esomeprazole was approved for use in the United States in February 2001.

Economics
Between the launch of esomeprazole in 2001 and 2005, the drug netted AstraZeneca about $14.4 billion.

Controversy
There has been some controversy about AstraZenecas behaviour in creating, patenting, and marketing the drug. Esomeprazoles successful predecessor, omeprazole, is a mixture of two mirror-imaged molecules (esomeprazole which is the S-enantiomer, and R-omeprazole); critics said the company was trying to "evergreen" its omeprazole patent by patenting the pure esomeprazole and aggressively marketing to doctors that it is more effective than the mixture.Thomas A. Scully, head of the Centers for Medicare and Medicaid Services (CMS), also criticized AstraZeneca for their aggressive marketing of Nexium. At a conference of the American Medical Association (AMA), he said that Astra was using the new drug to overcharge consumers and insurance companies.

Brand names
Generic versions of esomeprazole magnesium are available worldwide. It is available over-the-counter under the brand name Nexium in the United States and the UK.

Other uses
Esomeprazole can be used as a parasiticide. Gokmen et al., 2016 screen for efficacy against Trichomonas vaginalis isolates from horses. They found esomeprazole to be effective as a veterinary antiparasitic.

References
Further reading
Dean L (2012). "Esomeprazole Therapy and CYP2C19 Genotype".  In Pratt VM, McLeod HL, Rubinstein WS,  et al. (eds.) </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Carbidopa/levodopa/entacapone and can you explain it in depth? [/INST] Carbidopa/levodopa/entacapone, sold under the brand name Stalevo among others, is a dopaminergic fixed-dose combination medication that contains carbidopa, levodopa, and entacapone for the treatment of Parkinsons disease. It is marketed by Swiss-based Novartis Pharmaceuticals and manufactured by Finnish drugmaker Orion Corporation.

Medical uses
Carbidopa/levodopa/entacapone was approved by the U.S. Food and Drug Administration (FDA) in June 2003, to treat adults with Parkinsons disease of unknown cause in two scenarios. First, to substitute with equivalent strength of each of the three components for immediate-release carbidopa/levodopa and entacapone previously administered as individual products. Second, to replace immediate-release carbidopa/levodopa therapy (without entacapone) when people experience the signs and symptoms of end-of-dose "wearing-off" but only for people taking a total daily dose of levodopa of 600 mg or less and not experiencing dyskinesias.It may help decrease a change of response to Parkinsons medications.In the European Union it is indicated for the treatment of adults with Parkinsons disease and end-of-dose motor fluctuations not stabilized on levodopa/dopa decarboxylase (DDC) inhibitor treatment.

Side effects
Sometimes a wearing off effect may occur at the end of the dosing interval, where a patient may feel Parkinsons symptoms. Urine, saliva, or sweat may be discolored (dark color such as red, brown, or black) after taking carbidopa/levodopa/entacapone.

Prostate cancer
On March 31, 2010, the United States Food and Drug Administration (FDA) stated it was evaluating long-term clinical data from STRIDE-PD which found that a greater number of patients taking Stalevo had prostate cancer compared to those taking carbidopa/levodopa. Other controlled clinical trials evaluating carbidopa/levodopa/entacapone or entacapone did not find an increased risk of prostate cancer. FDA is still reviewing the available information and has not concluded that carbidopa/levodopa/entacapone increases the risk of developing prostate cancer. Healthcare professionals were advised to be aware of this possible risk and follow current guidelines for prostate cancer screening. FDA recommended that healthcare professionals follow the recommendations in the drug label when prescribing carbidopa/levodopa/entacapone and Comtan. Patients were directed to not stop taking their medication unless directed to do so by their healthcare professional.

Cardiovascular risks
On August 20, 2010, the United States Food and Drug Administration stated meta-analysis of several studies "appeared to show an increase in the risk of heart attack, stroke, and cardiovascular death for people taking the drug" but also stated "findings were not clear." Heart problems are not uncommon in Parkinsons patients and the FDA will investigate the concerns.

Drug interactions
Carbidopa/levodopa/entacapone is contraindicated in patients taking a class of antidepressant drugs known as non-selective monoamine oxidase (MAO) inhibitors such as phenelzine and tranylcypromine. Combining carbidopa/levodopa/entacapone with these drugs could cause serious—possibly life-threatening—side effects. MAO inhibitors should be stopped at least two weeks before starting therapy with carbidopa/levodopa/entacapone.
Carbidopa/levodopa/entacapone may be combined with the drugs rasagiline or selegiline. These drugs are a different type of MAO inhibitor known as selective MAO inhibitors that are often prescribed for Parkinsons disease. Many drug interactions involving selegiline are theoretical, primarily based on interactions with non-selective MAO inhibitors; at oral doses the risk of these interactions may be very low. However, transdermal selegiline, known by its trade name Emsam, is still contraindicated. Transdermal selegiline results in higher plasma levels at which it behaves like a non-selective MAO inhibitor. Concominant use of entacapone, a component of carbidopa/levodopa/entacapone, with MAO inhibitors may increase toxicity of MAO inhibitors. Levodopa, also a component of carbidopa/levodopa/entacapone, in combination with MAO inhibitors may result in hypertensive reactions.

Mechanism of action
Levodopa is the immediate precursor to dopamine. Entacapone is a selective, reversible catechol-O-methyltransferase (COMT) inhibitor that prevents the degradation of levodopa </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is H5N1 vaccine and can you explain it in depth? [/INST] A H5N1 vaccine is an influenza vaccine intended to provide immunization to influenza A virus subtype H5N1.
Vaccines have been formulated against several of the avian H5N1 influenza varieties. Vaccination of poultry against the H5N1 epizootic is widespread in certain countries. Some vaccines also exist for use in humans, and others are in testing, but none have been made available to civilian populations, nor produced in quantities sufficient to protect more than a tiny fraction of the Earths population in the event of an H5N1 pandemic.
In January 2020, the U.S. Food and Drug Administration (FDA) approved Audenz, an adjuvanted influenza A (H5N1) monovalent vaccine. Audenz is a vaccine indicated for active immunization for the prevention of disease caused by the influenza A virus H5N1 subtype contained in the vaccine. Audenz is approved for use in persons six months of age and older at increased risk of exposure to the influenza A virus H5N1 subtype contained in the vaccine.Some older, egg-based H5N1 vaccines for humans that have been licensed are:

Sanofi Pasteurs vaccine approved by the United States in April 2007,
GlaxoSmithKlines vaccine Prepandrix approved by the European Union in May 2008, with reactive AS03 (containing squalene) adjuvant.  and
CSL Limiteds vaccine Panvax approved by Australia in June 2008.Other licensed H5N1 vaccines include:

Adjupanrix, approved for medical use in the European Union in October 2009. Adjupanrix contains the flu strain A/VietNam/1194/2004 NIBRG 14 (H5N1).
Foclivia, approved for medical use in the European Union in October 2009. Foclivia contains the flu strain A/Vietnam/1194/2004 (H5N1).
Aflunov, approved for medical use in the European Union in November 2010. Aflunov contains the flu strain A/turkey/Turkey/1/2005 (H5N1)-like strain (NIBRG-23) (clade 2.2.1).
Pumarix, approved for medical use in the European Union in March 2011.In November 2013, the U.S. Food and Drug Administration (FDA) approved an experimental H5N1 bird flu vaccine to be held in stockpiles. In a clinical trial including 3,400 adults, 91% of people age 18-64 and 74% of people age 65 or older formed an immune response sufficient to provide protection. Reported adverse effects were generally mild, with pain at the injection site being the most common adverse effect.H5N1 continually mutates, meaning vaccines based on current samples of avian H5N1 cannot be depended upon to work in the case of a future pandemic of H5N1. While there can be some cross-protection against related flu strains, the best protection would be from a vaccine specifically produced for any future pandemic flu virus strain. Daniel R. Lucey, co-director of the Biohazardous Threats and Emerging Diseases graduate program at Georgetown University, has made this point, "There is no H5N1 pandemic so there can be no pandemic vaccine." However, "pre-pandemic vaccines" have been created; are being refined and tested; and do have some promise both in furthering research and preparedness for the next pandemic. Vaccine manufacturing companies are being encouraged to increase capacity so that if a pandemic vaccine is needed, facilities will be available for rapid production of large amounts of a vaccine specific to a new pandemic strain.Problems with H5N1 vaccine production include:
lack of overall production capacity
lack of surge production capacity (it is impractical to develop a system that depends on hundreds of millions of 11-day-old specialized eggs on a standby basis)
the pandemic H5N1 might be lethal to chickensCell culture (cell-based) manufacturing technology can be applied to influenza vaccines as they are with most viral vaccines and thereby solve the problems associated with creating flu vaccines using chicken eggs.
Vaccine production capacity: The protective immune response generated by influenza vaccines is largely based on viral hemagglutinin (HA) and neuraminidase (NA) antigens in the vaccine. As a consequence, the basis of influenza vaccine manufacturing is growing massive quantities of virus in order to have sufficient amounts of these protein antigens to stimulate immune responses. Influenza vaccines used in the United States and around world are manufactured by growing virus in fertilized hens eggs, a commercial process that has been in place for decades. To achieve vaccine production targets millions of 11-day-old fertilized eggs must be available every day of production.In the near term, further expansion of these systems will provide additional capacity for the U.S.-based production of both seasonal and pandemic vaccines, however, the surge capacity that will be needed for a pandemic response cannot be met by egg-based vaccine production alone, as it is impractical to develop a system that depends on hundreds of millions of 11-day-old specialized eggs on a standby basis. In addition, because a pandemic could result from an avian influenza strain that is lethal to chickens, it is impossible to ensure that eggs will be available to produce vaccine when needed.In contrast, cell culture manufacturing technology can be applied to influenza vaccines as they are with most viral vaccines (e.g., polio vaccine, measles-mumps-rubella vaccine, chickenpox vaccine). In this system, viruses are grown in closed systems such as bioreactors containing large numbers of cells in growth media rather than eggs. The surge capacity afforded by cell-based technology is insensitive to seasons and can be adjusted to vaccine demand, as capacity can be increased or decreased by the number of bioreactors or the volume used within a bioreactor. In addition to supporting basic research on cell-based influenza vaccine development, HHS is currently supporting a number of vaccine manufacturers in the advanced development of cell-based influenza vaccines with the goal of developing U.S.-licensed cell-based influenza vaccines produced in the United States. The US government has purchased from Sanofi Pasteur and Chiron Corporation several million doses of vaccine meant to be used in case of an influenza pandemic of H5N1 avian influenza and is conducting clinical trials with these vaccines. Researchers at the University of Pittsburgh have had success with a genetically engineered vaccine that took only a month to make and completely protected chickens from the highly pathogenic H5N1 virus.According to the United States Department of Health & Human Services:

In addition to supporting basic research on cell-based influenza vaccine development, HHS is currently supporting a number of vaccine manufacturers in the advanced development of cell-based influenza vaccines with the goal of developing U.S.-licensed cell-based influenza vaccines produced in the United States. Dose-sparing technologies. Current U.S.-licensed vaccines stimulate an immune response based on the quantity of HA (hemagglutinin) antigen included in the dose. Methods to stimulate a strong immune response using less HA antigen are being studied in H5N1 and H9N2 vaccine trials. These include changing the mode of delivery from intramuscular to intradermal and the addition of immune-enhancing adjuvant to the vaccine formulation. Additionally, HHS is soliciting contract proposals from manufacturers of vaccines, adjuvants, and medical devices for the development and licensure of influenza vaccines that will provide dose-sparing alternative strategies.Chiron Corporation is now recertified and under contract with the National Institutes of Health to produce 8,000–10,000 investigational doses of Avian Flu (H5N1) vaccine. MedImmune and Aventis Pasteur are under similar contracts. The United States government hopes to obtain enough vaccine in 2006 to treat 4 million people. However, it is unclear whether this vaccine would be effective against a hypothetical mutated strain that would be easily transmitted through human populations, and the shelf life of stockpiled doses has yet to be determined.The New England Journal of Medicine reported on March 30, 2006, on one of dozens of vaccine studies being conducted. The Treanor et al. study was on vaccine produced from the human isolate (A/Vietnam/1203/2004 H5N1) of a virulent clade 1 influenza A (H5N1) virus with the use of a plasmid rescue system, with only the hemagglutinin and neuraminidase genes expressed and administered without adjuvant. "The rest of the genes were derived from an avirulent egg-adapted influenza A/PR/8/34 strain. The hemagglutinin gene was further modified to replace six basic amino acids associated with high pathogenicity in birds at the cleavage site between hemagglutinin 1 and hemagglutinin 2. Immunogenicity was assessed by microneutralization and hemagglutination-inhibition assays with the use of the vaccine virus, although a subgroup of samples were tested with the use of the wild-type influenza A/Vietnam/1203/2004 (H5N1) virus." The results of this study combined with others scheduled to be completed by spring 2007 is hoped will provide a highly immunogenic vaccine that is cross-protective against heterologous influenza strains.On August 18, 2006. the World Health Organization (WHO) changed the H5N1 strains recommended for candidate vaccines for the first time since 2004. "The WHOs new prototype strains, prepared by reverse genetics, include three new H5N1 subclades. The hemagglutinin sequences of most of the H5N1 avian influenza viruses circulating in the past few years fall into two genetic groups, or clades. Clade 1 includes human and bird isolates from Vietnam, Thailand, and Cambodia and bird isolates from Laos and Malaysia. Clade 2 viruses were first identified in bird isolates from China, Indonesia, Japan, and South Korea before spreading westward to the Middle East, Europe, and Africa. The clade 2 viruses have been primarily responsible for human H5N1 infections that have occurred during late 2005 and 2006, according to WHO. Genetic analysis has identified six subclades of clade 2, three of which have a distinct geographic distribution and have been implicated in human infections:

Subclade 1, Indonesia
Subclade 2, Middle East, Europe, and Africa
Subclade 3, ChinaOn the basis of the three subclades, the WHO is offering companies and other groups that are interested in pandemic vaccine development these three new prototype strains:

An A/Indonesia/2/2005-like virus
An A/Bar headed goose/Quinghai/1A/2005-like virus
An A/Anhui/1/2005-like virus[...] Until now, researchers have been working on prepandemic vaccines for H5N1 viruses in clade 1. In March, the first clinical trial of a U.S. vaccine for H5N1 showed modest results. In May, French researchers showed somewhat better results in a clinical trial of an H5N1 vaccine that included an adjuvant. Vaccine experts arent sure if a vaccine effective against known H5N1 viral strains would be effective against future strains. Although the new viruses will now be available for vaccine research, WHO said clinical trials using the clade 1 viruses should continue as an essential step in pandemic preparedness, because the trials yield useful information on priming, cross-reactivity, and cross-protection by vaccine viruses from different clades and subclades."</ref>As of November 2006, the United States Department of Health and Human Services (HHS) had enough H5N1 pre-pandemic vaccine to treat about 3 million people (5.9 million full-potency doses) in spite of 0.2 million doses used for research and 1.4 million doses that have begun to lose potency (from the original 7.5 million full-potency doses purchased from Sanofi Pasteur and Chiron Corp.). The expected shelf life of seasonal flu vaccine is about a year so the fact that most of the H5N1 pre-pandemic stockpile is still good after about two years is considered encouraging.

Clinical trials
H5N1 clinical trials are clinical trials concerning H5N1 vaccines. They are intended to discover pharmacological effects and identify any adverse reactions the vaccines may achieve in humans.

References
Further reading
Khurana S, Suguitan AL, Rivera Y, Simmons CP, Lanzavecchia A, Sallusto F, Manischewitz J, King LR, Subbarao K, Golding H (April 2009). "Antigenic fingerprinting of H5N1 avian influenza using convalescent sera and monoclonal antibodies reveals potential vaccine and diagnostic targets" </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Tarka and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Fenoprofen and can you explain it in depth? [/INST] Fenoprofen is a nonsteroidal anti-inflammatory drug (NSAID). Fenoprofen calcium is used for symptomatic relief for rheumatoid arthritis, osteoarthritis, and mild to moderate pain </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Rifaximin and can you explain it in depth? [/INST] Rifaximin, is a non-absorbable, broad spectrum antibiotic mainly used to treat travelers diarrhea. It is based on the rifamycin antibiotics family. Since its approval in Italy in 1987, it has been licensed in over more than 30 countries for the treatment of a variety of gastrointestinal diseases like irritable bowel syndrome, and hepatic encephalopathy. It acts by inhibiting RNA synthesis in susceptible bacteria by binding to the RNA polymerase enzyme. This binding blocks translocation, which stops transcription.  It is marketed under the brand name Xifaxan by Salix Pharmaceuticals.

Medical uses
Travelers’ Diarrhea (TD)
Rifaximin is used to treat travelers diarrhea caused by certain bacteria (E. coli) in adults and children at least 12 years of age. It treats travelers diarrhea by stopping the growth of the bacteria that cause diarrhea. Rifaximin will not work to treat travelers diarrhea that is bloody or occurs with fever.

Irritable Bowel Syndrome (IBS)
Rifaximin is used for the treatment of irritable bowel syndrome. It possesses anti-inflammatory and antibacterial properties, and is a nonabsorbable antibiotic that acts locally in the gut. These properties make it efficacious in relieving chronic functional symptoms of non-constipation type irritable bowel syndrome (IBS). It appears to retain its therapeutic properties for this indication, even after repeated courses. It is particularly indicated where small intestine bacterial overgrowth is suspected of involvement in a persons IBS. Symptom relief or improvement can be obtained for global IBS symptoms, including: abdominal pain, flatulence, bloating, and stool consistency. A drawback is that repeated courses may be necessary for relapse of symptoms.

Clostridium difficile Infection (CDI)
Rifaximin may also be a useful addition to vancomycin when treating patients with relapsing C. difficile infection. However, the quality of evidence of these studies was judged to be low. Because exposure to rifamycins in the past may increase risk for resistance, rifaximin should be avoided in such cases.

Hepatic Encephalopathy (HE)
Rifaximin is used to prevent episodes of hepatic encephalopathy (changes in thinking, behavior, and personality caused by a build-up of toxins in the brain in people who have liver disease) in adults who have liver disease. It treats hepatic encephalopathy by stopping the growth of bacteria that produce toxins and that may worsen the liver disease. Although high-quality evidence is still lacking, it appears to be as effective as, or more effective than, other available treatments for hepatic encephalopathy (such as lactulose), is better tolerated, and may work faster. It prevents reoccurring encephalopathy and is associated with high patient satisfaction. People are more compliant and satisfied to take this medication than any other due to minimal side effects, prolonged remission, and overall cost. The drawbacks are increased cost, and lack of robust clinical trials for HE without combination lactulose therapy.

Other uses
Other uses include treatment of: infectious diarrhea, small intestinal bacterial overgrowth, inflammatory bowel disease, and diverticular disease. It is effective in treating small intestinal bacterial overgrowth regardless of whether it is associated with irritable bowel syndrome or not. It has also shown efficacy with rosacea, ocular rosacea which also presents as dry eyes for patients with co-occurrence with small intestinal bacterial overgrowth (SIBO).

Special caution
Patients should avoid Rifaximin usage if they are allergic to Rifabutin, Rifampin and Rifapentine. It may cause attenuated vaccines (such as typhoid vaccine) to not work well. Health care professionals should be informed about its usage before having any immunizations. Pregnant or breastfeeding women should avoid taking it as it is a pregnancy category C drug and can harm the foetus. Cautious use is required in individuals with cirrhosis of the liver who have a Child-Pugh score of class C severity.

Side effects
Rifaximin has an excellent safety profile due to its lack of systemic absorption. Clinical trials did not show any serious adverse events while using the drug. There were no deaths while using it in the clinical trials.The most common side effects includes nausea, stomach pain, dizziness, fatigue, headaches, muscle tightening and joint pain. It may also cause reddish discoloration of urine.The most serious side effects of Rifaximin are:

Clostridium difficile-associated diarrhea (CDAD)
Drug-resistant bacterial superinfection
Severe allergic reactions including hives, rashes and itching

Interactions
As Rifaximin is not significantly absorbed from the gut, the great majority of these drug interactions are negligible in people with healthy liver function, so healthcare providers usually do not worry about drug interactions unless liver impairment is present. It may decrease the effectiveness of warfarin, a commonly prescribed anticoagulant, in people with liver problems.

Pharmacology
Rifaximin is a semisynthetic broad spectrum antibacterial drug, derived through chemical modification of the natural antibiotic rifamycin.  It has very low bioavailability due to its poor absorption after oral administration. Because of this local action within the gut and the lack of horizontal transfer of resistant genes, the development of bacterial resistance is rare, and most of the drug taken orally stays in the gastrointestinal tract where the infection takes place.

Mechanism of action
Rifaximin interferes with transcription by binding to the β-subunit of bacterial RNA polymerase. This results in the blockage of the translocation step that normally follows the formation of the first phosphodiester bond, which occurs in the transcription process. This in turn results in a reduction of bacteria populations, including gas-producing bacteria, which may reduce mucosal inflammation, epithelial dysfunction, and visceral hypersensitivity. Rifaximin has broad spectrum antibacterial properties against both gram positive and gram negative anaerobic and aerobic bacteria. As a result of bile acid solubility, its antibacterial action is limited mostly to the small intestine and less so the colon. A resetting of the bacterial composition has also been suggested as a possible mechanism of action for relief of IBS symptoms. Additionally, rifaximin may have a direct anti-inflammatory effect on gut mucosa via modulation of the pregnane X receptor. Other mechanisms for its therapeutic properties include inhibition of bacterial translocation across the epithelial lining of the intestine, inhibition of adherence of bacteria to the epithelial cells, and a reduction in the expression of proinflammatory cytokines.

Availability
In the United States, Salix Pharmaceuticals holds a US Patent for rifaximin and markets the drug under the name Xifaxan. In addition to receiving FDA approval for travelers diarrhea and (marketing approved for) hepatic encephalopathy, rifaximin received FDA approval for IBS in May 2015. No generic formulation is available in the US and none has appeared due to the fact that the FDA approval process was ongoing. If rifaximin receives full FDA approval for hepatic encephalopathy it is likely that Salix will maintain marketing exclusivity and be protected from generic formulations until March 24, 2017 </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Miltefosine and can you explain it in depth? [/INST] Miltefosine, sold under the trade name Impavido among others, is a medication mainly used to treat leishmaniasis and free-living amoeba infections such as Naegleria fowleri and Balamuthia mandrillaris. This includes the three forms of leishmaniasis: cutaneous, visceral and mucosal. It may be used with liposomal amphotericin B or paromomycin. It is taken by mouth.Common side effects include vomiting, abdominal pain, fever, headaches, and decreased kidney function. More severe side effects may include Stevens–Johnson syndrome or low blood platelets. Use during pregnancy appears to cause harm to the baby and use during breastfeeding is not recommended. How it works is not entirely clear.Miltefosine was first made in the early 1980s and studied as a treatment for cancer. A few years later it was found to be useful for leishmaniasis and was approved for this use in 2002 in India. It is on the World Health Organizations List of Essential Medicines.

Medical uses
Leishmaniasis
Miltefosine is primarily used for the treatment of visceral and New World cutaneous leishmaniasis, and is undergoing clinical trials for this use in several countries. This drug is now listed as a core medication for the treatment of leishmaniasis under the WHO Model List of Essential Medicines. Several medical agents have some efficacy against visceral or cutaneous leishmaniasis, however, a 2005 survey concluded that miltefosine is the only effective oral treatment for both forms of leishmaniasis.

Amoeba infections
Miltefosine has been used successfully in some cases of the very rare, but highly lethal, brain infection by the amoeba, Naegleria fowleri, acquired through water entering the nose during a plunge in contaminated water. It has orphan drug status in the United States for acanthamoeba keratitis and primary amebic meningoencephalitis (PAM).

Pregnancy and breastfeeding
Miltefosine is listed as pregnancy category D by the FDA. This means there is evidence-based adverse reaction data from investigational or marketing experience or studies in humans of harm to the human fetus.  Despite this evidence, the potential benefits of miltefosine may warrant use of the drug in pregnant women despite potential risks.  A pregnancy test should be done prior to starting treatment. Effective birth control should be used while on miltefosine and 5 months after discontinuation of treatment. Its use during breast feeding is most likely unsafe.

Contraindications
Miltefosine is contraindicated in individuals who have a hypersensitivity to this medication, pregnant women, and people who have the Sjögren-Larsson syndrome. It is embryotoxic and fetotoxic in rats and rabbits, and teratogenic in rats but not in rabbits. It is therefore contraindicated for use during pregnancy, and contraception is required beyond the end of treatment in women of child-bearing age.

Side effects
Common side effects from miltefosine treatment are nausea and vomiting, which occur in 60% of people. Other common side effects are dizziness, headache, and daytime sleepiness.Serious side effects include rash, diarrhea, and arthritis. The side effects are more severe in women and young children. The overall effects are quite mild and easily reversed.

Mechanism of action
Miltefosine primarily acts on Leishmania by affecting the speciess promastigote and amastigote stages. Miltefosine exerts its activity by interacting with lipids, inhibiting cytochrome c oxidase and causing apoptosis-like cell death. This may affect membrane integrity and mitochondrial function of the parasite.

History
Cancer
While initially studied as a cancer medication, due to side effects it was never used for this purpose.Phospholipid group alkylphosphocholine were known since the early 1980s, particularly in terms of their binding affinity with cobra venom. In 1987 the phospholipids were found to be potent toxins on leukemic cell culture. Initial in vivo investigation on the antineoplastic activity showed positive result, but then only at high dosage and at high toxicity. At the same time in Germany, Hansjörg Eibl, at the Max Planck Institute for Biophysical Chemistry, and Clemens Unger, at the University of Göttingen, demonstrated that the antineoplastic activity of the phospholipid analogue miltefosine (at the time known as hexadecylphosphocholine) was indeed tumour-specific. It was highly effective against methylnitrosourea-induced mammary carcinoma, but less so on transplantable mammary carcinomas and autochthonous benzo(a)pyrene-induced sarcomas, and relatively inactive on Walker 256 carcinosarcoma and autochthonous acetoxymethylmethylnitrosamine-induced colonic tumors of rats. It was subsequently found that miltefosine was structurally unique among lipids having anticancer property in that it lacks the glycerol group, is highly selective on cell types and acts through different mechanism.

Leishmaniasis
In the same year as the discovery of the anticancer property, miltefosine was reported by S. L. Croft and his team at the London School of Hygiene and Tropical Medicine as having antileishmanial effect as well. The compound was effective against Leishmania donovani amastigotes in cultured mouse peritoneal macrophages at a dose of 12.8 mg/kg/day in a five-day course. However, priority was given to the development of the compound for cutaneous metastases of breast cancer. In 1992 a new research was reported in which the compound was highly effective in mouse against different life cycle stages of different Leishmania species, and in fact, more potent than the conventional sodium stibogluconate therapy by a factor of more than 600. Results of the first clinical trial in humans were reported from Indian patients with chronic leishmaniasis with high degree of success and safety. This promising development promulgated a unique public–private partnership collaboration between ASTA Medica (later Zentaris GmbH), the World Health Organization (WHO) Special Programme for Research and Training in Tropical Diseases, and the Government of India. Eventually, several successful Phase II and III trials led to the approval of miltefosine in 2002 as the first and only oral drug for leishmaniasis.

Naegleria fowleri and Acanthamoeba
In 2013, the US Centers for Disease Control and Prevention recommended miltefosine for the treatment of free-living amoeba infections such as granulomatous amoebic encephalitis and primary amoebic meningoencephalitis, two fatal protozoal diseases. Historically, only four survivors have been recorded out of 138 confirmed infections in North America. One American survived the infection in 1978 and one individual from Mexico in 2003. In 2013, two children survived and recovered from primary amoebic meningoencephalitis after treatment with miltefosine. In 2016 after treatment that included miltefosine, another child became the fourth person in the United States to survive Naegleria fowleri infection.

Society and culture
Availability
Since 2017 Miltefosine is commercially available in the United States through Profounda. Previously one could only get it from the CDC for emergency use under an expanded access IND protocol for treatment of free-living amoeba (FLA) infections: primary amoebic meningoencephalitis caused by Naegleria fowleri and granulomatous amoebic encephalitis caused by Balamuthia mandrillaris and Acanthamoeba species. Miltefosine is almost exclusively produced by Profounda, a private pharmaceutical company.

Economics
In the developing world a course of treatment costs US$65 to $150. In the developed world treatment may be 10 to 50 times greater.

Further research
It is active against some bacteria and fungi, as well as human trematode Schistosoma mansoni and the snail that spreads it Biomphalaria alexandrina.

Antiprotozoal and antifungal activities
Miltefosine is being investigated by researchers interested in finding treatments for infections which have become resistant to existing drugs </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Lutetium (177Lu) oxodotreotide and can you explain it in depth? [/INST] Lutetium (177Lu) oxodotreotide (INN) or 177Lu DOTA-TATE, trade name Lutathera, is a chelated complex of a radioisotope of the element lutetium with DOTA-TATE, used in peptide receptor radionuclide therapy (PRRT). Specifically, it is used in the treatment of cancers which express somatostatin receptors.Alternatives to 177Lu-DOTATE include yttrium-90 DOTATATE or DOTATOC. The longer range of the beta particles emitted by 90Y, which deliver the therapeutic effect, may make it more suitable for large tumors with 177Lu reserved for smaller volumesThe U.S. Food and Drug Administration (FDA) considers 177Lu dotatate to be a first-in-class medication.

Clinical trials and drug approval
The European Commission approved lutetium (177Lu) oxodotreotide (trade name Lutathera) "for the treatment of unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adults" in September 2017.177Lu DOTA-TATE was approved in the United States for the treatment of SSTR positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut and hindgut neuroendocrine tumors in adults, in January 2018. This was the first time a radiopharmaceutical had been approved for the treatment of GEP-NETs in the United States.The U.S. Food and Drug Administration (FDA) approved 177Lu dotatate based primarily on evidence from one clinical trial, NETTER-1 of 229 participants with somatostatin-receptor positive midgut GEP-NETs. Enrolled participants had tumors which could not be surgically removed and were worsening while receiving treatment with octreotide.Participants were randomly assigned to receive either 177Lu dotatate with long-acting octreotide or long-acting octreotide, at a higher dose, alone. 177Lu dotatate was injected through the vein and long-acting octreotide was injected in the muscle. Both, participants and health care providers knew which treatment was given. The benefit of 177Lu dotatate was evaluated by measuring the length of time that tumors did not grow after treatment and compared it to the control group (progression free survival).The FDA considered additional data from a second study based on data from 1,214 participants with somatostatin receptor-positive tumors, including GEP-NETS, who received 177Lu dotatate at a single site in the Netherlands, Erasmus MC. All participants received 177Lu dotatate with octreotide </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Triamcinolone acetonide and can you explain it in depth? [/INST] Triamcinolone acetonide is a synthetic corticosteroid medication used topically to treat various skin conditions, to relieve the discomfort of mouth sores, and intra-articularly by proceduralists to treat various joint conditions. It is also injected intralesionally (inside a lesion) to treat inflammation in some parts of the body, particularly the skin. In nasal spray form, it is used to treat allergic rhinitis. It is a more potent derivative of triamcinolone, and is about eight times as potent as prednisone. It is used for the treatment of macular edema associated with uveitis.It is also known under the brand names Kenalog (topical) and Volon A as an injection, to treat allergies, arthritis, eye diseases, intestinal problems, and skin diseases.
In 2014, the U.S. Food and Drug Administration (FDA) made triamcinolone acetonide an over-the-counter drug in the United States in nasal spray form under the brand name Nasacort.

Medical uses
Triamcinolone acetonide as an intra-articular injectable has been used to treat a variety of musculoskeletal conditions. When applied to the skin as a topical ointment, it is used to mitigate blistering from poison ivy, oak, and sumac. When combined with nystatin, it is used to treat skin infections with discomfort from fungus, though it should not be used on the eyes. It provides relatively immediate relief and is used before using oral prednisone. Oral and dental paste preparations are used for treating aphthous ulcers.
As an intravitreal injection, triamcinolone acetonide has been used to treat various eye diseases and has been found useful in reducing macular edema. Drug trials have found it to be as efficient as anti-VEGF drugs in eyes with artificial lenses over a two-year period. A systematic review did not find any evidence of any benefit in preventing vision loss in eyes treated with triamcinolone acetonide over placebo, for patients with age-related macular degeneration.Triamcinolone acetonide is also administered via intralesional injection in the treatment of hypertrophic and keloid scars.Uncommonly, intramuscular injection of triamcinolone acetonide may be indicated for the control of severe or incapacitating allergic states for which conventional treatments have failed, such as asthma, atopic dermatitis, contact dermatitis, perennial or seasonal allergic rhinitis, serum sickness, and transfusion and drug hypersensitivity reactions.

Contraindications
Evidence suggests that usage of triamcinolone acetonide or other steroids to treat macular edema increases the risk of increasing intraocular pressure in patients.Triamcinolone acetonide should not be used by those with tuberculosis or untreated fungal, bacterial, systemic viral or herpes simplex infections without consulting a doctor first.

Pharmacology
Pharmacodynamics
Triamcinolone acetonide is a corticosteroid. It is specifically a glucocorticoid, or an agonist of the glucocorticoid receptor, that is about five times as potent as cortisol. It has very little mineralocorticoid effects. The affinities of triamcinolone acetonide for the androgen and estrogen receptors are both <0.1% (relative to testosterone and estradiol) </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Daunorubicin/cytarabine and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Caffeine/ergotamine and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Methyltestosterone and can you explain it in depth? [/INST] Methyltestosterone, sold under the brand names Android, Metandren, and Testred among others, is an androgen and anabolic steroid (AAS) medication which is used in the treatment of low testosterone levels in men, delayed puberty in boys, at low doses as a component of menopausal hormone therapy for menopausal symptoms like hot flashes, osteoporosis, and low sexual desire in women, and to treat breast cancer in women. It is taken by mouth or held in the cheek or under the tongue.Side effects of methyltestosterone include symptoms of masculinization like acne, increased hair growth, voice changes, and increased sexual desire. It can also cause estrogenic effects like fluid retention, breast tenderness, and breast enlargement in men and liver damage. The drug is a synthetic androgen and anabolic steroid and hence is an agonist of the androgen receptor (AR), the biological target of androgens like testosterone and dihydrotestosterone (DHT). It has moderate androgenic effects and moderate anabolic effects, which make it useful for producing masculinization.Methyltestosterone was discovered in 1935 and was introduced for medical use in 1936. It was made shortly after the discovery of testosterone and was one of the first synthetic AAS to be developed. In addition to its medical use, methyltestosterone is used to improve physique and performance, although it is not as commonly used as other AAS for such purposes due to its androgenic effects, estrogenic effects, and risk of liver damage. The drug is a controlled substance in many countries and so non-medical use is generally illicit.

Uses
Medical
Methyltestosterone is or has been used in the treatment of delayed puberty, hypogonadism, cryptorchidism, and erectile dysfunction in males, and in low doses to treat menopausal symptoms (specifically for osteoporosis, hot flashes, and to increase libido and energy), postpartum breast pain and engorgement, and breast cancer in women. It is specifically approved in the United States for the treatment of hypogonadism and delayed puberty in males and the treatment of advanced inoperable breast cancer in females. It was also approved in low doses in combination with esterified estrogens for the treatment of moderate to severe vasomotor symptoms associated with menopause in women in the United States, but this formulation was discontinued and hence is no longer used.Methyltestosterone is less effective in inducing masculinization than testosterone, but is useful for maintaining established masculinization in adults.The dosages of methyltestosterone used are 10 to 50 mg/day in men for common medical uses like hypogonadism and delayed puberty as well as physique- and performance-enhancing purposes and 2.5 mg/day in women for menopausal symptoms. Higher dosages of 50 to 200 mg/day have been used to treat women with inoperable breast cancer that has failed to respond to other therapies, although such dosages are associated with severe irreversible virilization.

Non-medical
Methyltestosterone is used for physique- and performance-enhancing purposes by competitive athletes, bodybuilders, and powerlifters, although it is not commonly used relative to other AAS for such purposes.

Available forms
Methyltestosterone is typically used as an oral medication. It is also available under the brand names Metandren and Oreton Methyl for use specifically by buccal or sublingual administration. Methyltestosterone is available in the form of 2, 5, 10, and 25 mg oral tablets. It was also available in combination with estrogens as esterified estrogens/methyltestosterone (0.625 mg/1.25 mg, 1.25 mg/2.5 mg) and conjugated estrogens/methyltestosterone (0.625 mg/5.0 mg, 1.25 mg/10 mg).

Contraindications
Methyltestosterone should be used with caution in women and children, as it can cause irreversible virilization. Due to its estrogenicity, methyltestosterone can also accelerate epiphyseal closure and thereby produce short stature in children and adolescents. It can worsen symptoms in men with benign prostatic hyperplasia. Methyltestosterone should not be used in men with prostate cancer, as androgens can accelerate tumor progression. The drug should be used with caution in patients with pre-existing hepatotoxicity, due to its own potential for hepatotoxicity.

Side effects
Adverse effects of methyltestosterone include androgenic side effects like oily skin, acne, seborrhea, increased facial/body hair growth, scalp hair loss, increased aggressiveness and sex drive, and spontaneous erections, as well as estrogenic side effects like breast tenderness, gynecomastia, fluid retention, and edema. In women, methyltestosterone can cause partially irreversible virilization, for instance voice deepening, hirsutism, clitoromegaly, breast atrophy, and muscle hypertrophy, as well as menstrual disturbances and reversible infertility. In men, the drug may also cause hypogonadism, testicular atrophy, and reversible infertility at sufficiently high dosages.Methyltestosterone can sometimes cause hepatotoxicity, for instance elevated liver enzymes, cholestatic jaundice, peliosis hepatis, hepatomas, and hepatocellular carcinoma, with extended use. It can also have adverse effects on the cardiovascular system. AAS like methyltestosterone stimulate erythropoiesis (red blood cell production) and increase hematocrit levels and at high dosages can cause polycythemia (overproduction of red blood cells), which can greatly increase the risk of thrombic events such as embolism and stroke. With long-term treatment, AAS can increase the risk of benign prostatic hyperplasia and prostate cancer. Violent and even homicidal behavior, hypomania/mania, depression, suicidality, delusions, and psychosis have all been associated with very high dosages of AAS.

Interactions
Aromatase inhibitors can be used to reduce or prevent the estrogenic effects of methyltestosterone and 5α-reductase inhibitors can be used to prevent its potentiation in so-called "androgenic" tissues and thereby improve its ratio of anabolic to androgenic activity and reduce its rate of androgenic side effects. Antiandrogens like bicalutamide and cyproterone acetate can block both the anabolic and androgenic effects of AAS like methyltestosterone.

Pharmacology
Pharmacodynamics
As an AAS, methyltestosterone is an agonist of the androgen receptor (AR), similarly to androgens like testosterone and dihydrotestosterone (DHT). It is a substrate for 5α-reductase like testosterone, and so is potentiated analogously in so-called "androgenic" tissues like the skin, hair follicles, and prostate gland via transformation into the more potent AR agonist mestanolone (17α-methyl-DHT). As such, methyltestosterone has a relatively low ratio of anabolic to androgenic activity, with a similar ratio to that of testosterone (close to 1:1), and this makes it among the most androgenic AAS. Due to efficient aromatization into the potent and metabolism-resistant estrogen methylestradiol (17α-methylestradiol), methyltestosterone has relatively high estrogenicity and hence potential for estrogenic side effects such as gynecomastia and fluid retention. The drug possesses negligible progestogenic activity.Due to its combined disadvantages of a relatively poor ratio of anabolic to androgenic activity, unusually high estrogenicity, and the potential for hepatotoxicity (as with other 17α-alkylated AAS), methyltestosterone has not been used as commonly as many other AAS either in medicine or for physique- or performance-enhancing purposes.

Pharmacokinetics
Absorption
Methyltestosterone has dramatically improved oral bioavailability and metabolic stability relative to testosterone. This difference is due to the C17α methyl group, which results in steric hindrance and prevents metabolism. The oral bioavailability of methyltestosterone is about 70%, and it is well-absorbed from the gastrointestinal tract. Methyltestosterone can also be taken buccally or sublingually. Although effective orally, methyltestosterone is more effective by these non-oral routes, which are said to approximately double its bioavailability and require half the oral dosage.Circulating levels of methyltestosterone with administration of 1.25 to 2.5 mg/day oral methyltestosterone in women are in the range of 20 to 30 ng/dL. For comparison to testosterone, methyltestosterone is at least as potent as an AAS. However, due to the large decrease in sex hormone-binding globulin (SHBG) levels and hence increase in free unbound testosterone caused by methyltestosterone, androgenic effects may be greater than reflected merely by methyltestosterone levels.

Distribution
Methyltestosterone is highly protein-bound, by approximately 98%. The medication has low but significant affinity for human serum sex hormone-binding globulin (SHBG), about 25% of that of testosterone and 5% of that of DHT.

Metabolism
The biological half-life of methyltestosterone is approximately 3 hours (range 2.5–3.5 hours). The duration of action of methyltestosterone is said to be 1 to 3 days, and is described as relatively short among AAS.

Excretion
Methyltestosterone is excreted 90% in the urine as conjugates and other metabolites, and 6% in feces.

Chemistry
Methyltestosterone, also known as 17α-methyltestosterone or as 17α-methylandrost-4-en-17β-ol-3-one, is a synthetic, 17α-alkylated androstane steroid and a derivative of testosterone differing from it only in the presence of a methyl group at the C17α position. Close synthetic relatives of methyltestosterone include metandienone (17α-methyl-δ1-testosterone) and fluoxymesterone (9α-fluoro-11β-hydroxy-17α-methyltestosterone).

Derivatives
Methyltestosterone and ethyltestosterone (17α-ethyltestosterone) are the parent structures of all 17α-alkylated AAS. Major 17α-alkylated AAS include the testosterone derivatives fluoxymesterone, metandienone (methandrostenolone), and methyltestosterone and the DHT derivatives oxandrolone, oxymetholone, and stanozolol.

Synthesis
A chemical synthesis of methyltestosterone from dehydroepiandrosterone (DHEA) with methandriol as an intermediate proceeds as follows:

History
Methyltestosterone was first synthesized in 1935 along with methandriol and mestanolone. It was the second synthetic AAS to be developed, following mesterolone (1α-methyl-DHT) in 1934, and was the first 17α-alkylated AAS to be synthesized. The drug was introduced for medical use in 1936.

Society and culture
Generic names
Methyltestosterone is the INN, USAN, USP, BAN, and JAN of the drug and its generic name in English and Japanese, while méthyltestostérone is its DCF and French name and metiltestosterone is its DCIT and Italian name. The generic name of the drug is methyltestosterone in Latin, methyltestosteron in German, and metiltestosterona in Spanish. Methyltestosterone is also known by its former developmental code name NSC-9701.

Brand names
Brand names under which methyltestosterone is or has been marketed for medical use include Afro, Agovirin, Android, Androral, Mesteron, Metandren, Methitest, Methyltestosterone, Methyl Testosterone, Oraviron, Oreton, Oreton Methyl, Testormon, Testovis, Testred, and Virilon, among others.

With an estrogen
Methyltestosterone is available at a low-dose in combination with esterified estrogens for the treatment of menopausal symptoms like hot flashes in women under the brand names Covaryx, Essian, Estratest, Menogen, and Syntest.

Availability
United States
Although it is not commonly used, methyltestosterone is one of the few AAS that remains available for medical use in the United States. The others are testosterone, testosterone cypionate, testosterone enanthate, testosterone undecanoate, oxandrolone, oxymetholone, and fluoxymesterone.

Other countries
Methyltestosterone has also been marketed in many other countries throughout the world.

Legal status
Methyltestosterone, along with other AAS, is a schedule III controlled substance in the United States under the Controlled Substances Act and a schedule IV controlled substance in Canada under the Controlled Drugs and Substances Act.

See also
Esterified estrogens/methyltestosterone
Conjugated estrogens/methyltestosterone

References
Further reading
Phillips EH, Ryan S, Ferrari R, Green C (2003). "Estratest and Estratest HS (esterified estrogens and methyltestosterone) therapy: a summary of safety surveillance data, January 1989 to August 2002". Clin Ther. 25 (12): 3027–43. doi:10.1016/s0149-2918(03)90090-7. PMID 14749144.
Kabat GC, Kamensky V, Heo M, Bea JW, Hou L, Lane DS, Liu S, Qi L, Simon MS, Wactawski-Wende J, Rohan TE (2014). "Combined conjugated esterified estrogen plus methyltestosterone supplementation and risk of breast cancer in postmenopausal women" </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Potassium chloride (medical use) and can you explain it in depth? [/INST] Potassium chloride, also known as potassium salt, is used as a medication to treat and prevent low blood potassium. Low blood potassium may occur due to vomiting, diarrhea, or certain medications. The concentrated version should be diluted before use. It is given by slow injection into a vein or by mouth.Side effects may include heart problems if given too quickly by injection into a vein. By mouth it can result in abdominal pain, peptic ulcer disease, or gastrointestinal bleeding. Greater care is recommended in those with kidney problems. As long as high blood potassium does not occur, use in pregnancy or breastfeeding is believed to be safe for the baby. Generally, the strength of the formulation for injection into a vein should not be greater than 40 mmol/L (3 mg/L).Potassium chloride came into large scale commercial use as a fertilizer in 1861 and has been used medically since the 1950s. It is on the World Health Organizations List of Essential Medicines </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Lixisenatide and can you explain it in depth? [/INST] Lixisenatide (trade name Lyxumia in the European Union and Adlyxin in the U.S. and manufactured by Sanofi) is a once-daily injectable GLP-1 receptor agonist for the treatment of type 2 diabetes.

Medical use
Lixisenatide is used as adjunct to diet and exercise to treat type 2 diabetes. In the European Union, its use is limited to complementing insulin therapy. As of 2017 it is unclear if they affect a persons risk of death.It is provided in an autoinjector containing fourteen doses and is injected subcutaneously.Lixisenatide should not be used for people who have problems with stomach emptying. Lixisenatide delays emptying of the stomach, which may change how quickly other drugs that are taken by mouth take effect.

Lixisenatide in neurodegenerative diseases
Results from a research work which was done by McClean PL et al. demonstrated that the GLP-1 receptor agonists liraglutide and lixisenatide which are on the market as treatments for type 2 diabetes show promise as potential drug treatments of Alzheimer disease AD. Lixisenatide was equally effective at a lower dose compared to liraglutide in some of the measured parameters after ten weeks of daily intraperitoneal injections with liraglutide (2.5 or 25 nmol/kg) or lixisenatide (1 or 10 nmol/kg) or saline of APP/PS1 mice at an age when amyloid plaques had already formed. When analyzing synaptic plasticity in the hippocampus, LTP was strongly increased in APP/PS1 mice by either drug, with more effectiveness accomplished with lixisenatide. The reduction of synapse numbers seen in APP/PS1 mice was prevented by the two drugs. The amyloid plaque load and dense-core Congo red positive plaque load in the cortex were reduced by both drugs at all doses. The chronic inflammation response (microglial activation) was also reduced by all treatments
Cai HY et al. demonstrated in a study that lixisenatide could reduce amyloid plaques, neurofibrillary tangles and neuroinflammation in the hippocampi of 12-month-old APP/PS1/tau female mice; activation of PKA-CREB signaling pathway and inhibition of p38-MAPK might be the important mechanisms in the neuroprotective function of lixisenatide. So, lixisenatide might have the potential to be developed as a novel therapy for AD
Liu Wet al found an interesting results when comparing exendin-4 (10 nmol/kg), liraglutide (25 nmol/kg) and lixisenatide (10 nmol/kg), it was found that exendin-4 showed no protective effects at the dose chosen, while both liraglutide and lixisenatide showed effects in preventing the MPTP-induced motor impairment (Rotarod, open-field locomotion, catalepsy test), reduction in tyrosine hydroxylase (TH) levels (dopamine synthesis) in the substantia nigra and basal ganglia, a reduction of the pro-apoptotic signaling molecule BAX and an increase in the anti-apoptotic signaling molecule B-cell lymphoma-2. The previous results demonstrate that both liraglutide and lixisenatide are superior to exendin-4, and both drugs show promise as a novel treatment of Parkinson disease
Another study done by Kerry Hunter et al. profiled the GLP-1 receptor agonists liraglutide and lixisenatide. The kinetics of crossing the blood brain barrier (BBB), activation of the GLP-1R by measuring cAMP levels, and physiological effects in the brain on neuronal stem cell proliferation and neurogenesis were evaluated. Both drugs were able to cross the BBB. Lixisenatide crossed the BBB at all doses tested (2.5, 25, or 250 nmol/kg ip.) when measured 30 min post-injection and at 2.5-25 nmol/kg ip. 3 h post-injection. Lixisenatide also enhanced neurogenesis in the brain. Liraglutide crossed the BBB at 25 and 250 nmol/kg ip. but no increase was detectable at 2.5 nmol/kg ip. 30 min post-injection, and at 250 nmol/kg ip. at 3 h post-injection. Liraglutide and lixisenatide enhanced cAMP levels in the brain, with lixisenatide being more effective. The previous results suggest that these novel incretin analogues cross the BBB showing physiological activity and neurogenesis in the brain, which makes them good candidates to be used as a treatment of neurodegenerative diseases.

Adverse effects
In about 0.1% of cases people have had anaphylactic reactions to lixisenatide and in about 0.2% of cases the drug has caused pancreatitis.  Use with insulin or sulfonylurea may cause hypoglycemia.  In some cases, people with no kidney disease have had acute kidney injury and in some people with existing kidney disease the condition has gotten worse. Because lixisenatide is a peptide people can and do develop an immune response to it that will eventually make the drug ineffective; people who have developed antibodies to lixisenatide tend to have more inflammation at the injection site.At least 5% of people had nausea, vomiting, diarrhea, headache, or dizziness after taking lixisenatide.

Mechanism of action
Lixisenatide is a member of the class of glucagon-like peptide-1 receptor agonist drugs, each of which activates the GLP-1 receptor. GLP-1 is a hormone that helps pancreatic beta cells to secrete insulin in response to high blood sugar.  Because it works like the normal hormone, insulin is only secreted when blood sugar is high.  Like GLP-1, it also slows gastric emptying.

Chemistry
Lixisenatide is a peptide made of 44 amino acids, with an amide group on its C terminus.has been described as "des-38-proline-exendin-4 (Heloderma suspectum)-(1–39)-peptidylpenta-L-lysyl-L-lysinamide", meaning it is derived from the first 39 amino acids in the sequence of the peptide exendin-4, that was isolated from the Gila monster venom, omitting proline at position 38 and adding six lysine residues. Its complete sequence is:
H–His–Gly–Glu–Gly–Thr–Phe–Thr–Ser–Asp–Leu–Ser–Lys–Gln–Met–Glu–Glu–Glu–Ala–Val–Arg–Leu–Phe–Ile–Glu–Trp–Leu–Lys–Asn–Gly–Gly–Pro–Ser–Ser–Gly–Ala–Pro–Pro–Ser–Lys–Lys–Lys–Lys–Lys–Lys–NH2

History
It was created by Zealand Pharma A/S of Denmark; in 2003 Zealand licensed it to Sanofi which developed the drug.  Lixisenatide was approved by the European Commission on February 1, 2013.  Sanofi submitted an NDA in the US, which was accepted for review by the US FDA in February 2013 but after discussions with the FDA about the cardiovascular safety data included in the package (starting in 2008, the FDA had required stronger CV safety data for new anti-diabetes drugs, following the controversy around the risks of Avandia) Sanofi decided to withdraw the NDA and wait for the results of a Phase III study that was scheduled to be completed in 2015 </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Oxybuprocaine and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Ibuprofen/paracetamol and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Teduglutide and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Thymoglobulin and can you explain it in depth? [/INST] Thymoglobulin (manufactured by Sanofi) is an anti-human thymocyte immunoglobulin preparation made of purified polyclonal antibodies derived from rabbits. While these antibodies have a variety of specificities, their main mechanism of immunosuppression is through depletion of T cells. Thymoglobulin is currently approved for clinical use in Europe and the United States for renal allograft rejection, prevention of graft-vs.-host disease, and conditions involving bone marrow failure, including aplastic anemia and has additional off-label uses.

History of antithymocyte globulin
Antithymocyte globulin (ATG) was originally developed as one of various tested preparations of antilymphocyte globulin (ALG) specifically generated against human lymphocytes within the thymus, or thymocytes. The purpose of this research was largely to produce an effective immunosuppressive agent safe for use in humans. Since the discovery of a link between antilymphocyte serum (ALS) and lymphocyte depletion by Metchnikoff in 1899, various studies have demonstrated the immunosuppressive ability of ALG and ATG. Experiments on ALS that confirmed its efficacy in lymphocyte depletion led to testing of different types of preparations including ALG, which were ALS produced against human lymphocytes, and ATG.A number of studies conducted in the 1960s, including studies by Starzl et al. and Mathe et al., resulted in promising data for the clinical use of ALG for preserving short-term and long-term kidney function in patients immediately after human kidney transplantation. Use of equine ALG was also found to be efficacious in preventing acute graft-vs.-host-disease in patients’ post-allogeneic bone marrow transplantation. Experimentation with ALG and ATG preparations from different sources followed, leading to testing of ATG derived from rabbit serum. Thymoglobulin was the first commercial rabbit-derived ATG to be introduced in Europe and the US in the 1980s. Due to its demonstrated efficacy as an immunosuppressive agent, it remains a commonly used ATG for induction therapy and treatment of other associated conditions, such as graft-vs.-host disease and aplastic anemia.

Mechanism of immunosuppression
As an rATG, thymoglobulin consists of polyclonal antibodies, which, unlike monoclonal antibodies, target a large variety of immune cell surface proteins, including B and T lymphocyte, natural killer cell, and plasma cell surface antigens </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Palonosetron and can you explain it in depth? [/INST] Palonosetron, sold under the brand name Aloxi, is used for the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). It is a 5-HT3 antagonist.Palonosetron is administered intravenously, or as a single oral capsule. It has a longer duration of action than  other 5-HT3 antagonists. The oral formulation was approved on August 22, 2008, for prevention of acute CINV alone, as a large clinical trial did not show oral administration to be as effective as intravenous use against delayed CINV. It is on the World Health Organizations List of Essential Medicines.The oral combination netupitant/palonosetron is approved for both acute and delayed CINV.

Adverse effects
The most common adverse effects are headache, which occurs in 4–11% of patients, and constipation in up to 6% of patients. In less than 1% of patients, other gastrointestinal disorders occur, as well as sleeplessness, first- and second-degree atrioventricular block, muscle pain and shortness of breath. Palonosetron is similarly well tolerated as other 5-HT3 antagonists, and slightly less than placebo.

Interactions
Palonosetron does not relevantly inhibit or induce cytochrome P450 liver enzymes. There are case reports about serotonin syndrome when the drug is combined with serotonergic substances such as selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs), two common types of antidepressants.

Pharmacology
Mechanism of action
Palonosetron is a 5-HT3 antagonist, commonly known as a setron. These drugs act by blocking serotonin from binding to the 5-HT3 receptor.

Pharmacokinetics
Orally taken palonosetron is absorbed well from the gut and has a bioavailability of 97%. Highest blood plasma levels are reached after 5.1±1.7 hours, independently of food intake, and plasma protein binding is 62%. 40% of the substance are eliminated in the unchanged form, and a further 45–50% are metabolized by the liver enzyme CYP2D6 and to a lesser extent by CYP3A4 and CYP1A2 </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Prothrombin complex concentrate and can you explain it in depth? [/INST] Prothrombin complex concentrate (PCC), also known as factor IX complex, is a medication made up of blood clotting factors II, IX, and X. Some versions also contain factor VII. It is used to treat and prevent bleeding in hemophilia B if pure factor IX is not available. It may also be used for reversal of warfarin therapy. It is given by slow injection into a vein.Common side effects include allergic reactions, headache, vomiting, and sleepiness. Other serious side effects include blood clots which may result in a heart attack, stroke, pulmonary embolism, or deep vein thrombosis. Antibodies may form after long term use such that future doses are less effective.Prothrombin complex concentrate came into medical use in the 1960s. It is on the World Health Organizations List of Essential Medicines. It is made from human plasma. Recombinant factor IX is also available in a stand-alone preparation. In the United States a dose of PCC costs about US$900. A number of different formulations are available globally.

Medical uses
Prothrombin complex concentrate reverses the effects of warfarin and other vitamin K antagonist anti-coagulants and is used in cases of significant bleeding in people with a coagulopathy. It is also used when such a person must undergo an emergency operation. Other uses include a deficiency of one of the included clotting factors, either congenital or due to liver disease, and hemophilia. Several guidelines, including those from the American College of Chest Physicians, recommend prothrombin complex concentrate for warfarin reversal in people with serious bleeding.For rapid anticoagulation reversal for surgery, four-factor prothrombin complex concentrate reduces international normalized ratio (INR) and decreases bleeding during surgery when compared with administration of fresh frozen plasma. No differences in thromboembolic event was found.

Contraindications
The package insert states that prothrombin complex concentrate is contraindicated in patients with disseminated intravascular coagulation, a pathological activation of coagulation, because giving clotting factors would only further fuel this process </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Sulfasalazine and can you explain it in depth? [/INST] Sulfasalazine (SSZ), sold under the trade name Azulfidine among others, is a medication used to treat rheumatoid arthritis, ulcerative colitis, and Crohns disease. It is considered by some to be a first-line treatment in rheumatoid arthritis. It is taken by mouth.Significant side effects occur in about 25% of people. Commonly these include loss of appetite, nausea, headache, and rash. Severe side effects include bone marrow suppression, liver problems, Stevens–Johnson syndrome, and kidney problems. It should not be used in people allergic to aspirin or sulfonamide. Use during pregnancy appears to be safe for the baby.Sulfasalazine is in the disease-modifying antirheumatic drugs (DMARDs) family of medications. It is unclear exactly how it works. One proposed mechanism is the inhibition of prostaglandins, resulting in local anti-inflammatory effects in the colon. The medication is broken down by intestinal bacteria into sulfapyridine and 5-aminosalicylic acid. That which is absorbed is excreted by the kidneys and in the bile.Sulfasalazine was approved for medical use in the United States in 1950. It is on the World Health Organizations List of Essential Medicines. Sulfasalazine is available as a generic medication.

Medical uses
Sulfasalazine is used in the treatment of inflammatory bowel disease, including ulcerative colitis and Crohns disease. It is also indicated for use in rheumatoid arthritis and used in other types of inflammatory arthritis (e.g. psoriatic arthritis and reactive arthritis).It is usually not given to children under two years of age.

Side effects
Use of sulfasalazine is contraindicated in people with sulfa allergies and in those with urinary tract obstructions, intestinal obstructions, and severe liver or kidney problems.Sulfasalazine metabolizes to sulfapyridine. Serum levels should be monitored every three months, and more frequently at the outset. Serum levels above 50 μg/L are associated with side effects. In rare cases, sulfasalazine can cause severe depression in young males </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Praziquantel and can you explain it in depth? [/INST] Praziquantel (PZQ), sold under the brandname Biltricide among others, is a medication used to treat a number of types of parasitic worm infections in mammals, birds, amphibians, reptiles, and fish. In humans specifically, it is used to treat schistosomiasis, clonorchiasis, opisthorchiasis, tapeworm infections, cysticercosis, hydatid disease, and other fluke infections. It should not be used for worm infections of the eye. It is taken by mouth.Side effects in humans may include poor coordination, abdominal pain, vomiting, headache, and allergic reactions. While it may be used during pregnancy, it is not recommended for use during breastfeeding. Praziquantel is in the anthelmintic class of medications. It works partly by affecting the function of the worms sucker.Praziquantel was approved for medical use in the United States in 1982. It is on the World Health Organizations List of Essential Medicines.

Medical uses
Praziquantel is used to treat diseases caused by infection with several types of internal/gastrointestinal, and external parasites, including:

Hydatid disease caused by infection of various organs with larval stages of tapeworms of the genus Echinococcus
Cysticercosis caused by infection of the brain and/or muscles with the eggs and larvae of the pork tapeworm Taenia solium (though it has been judged less effective than albendazole in treatment of neurocysticercosis)
In dogs and cats, whose gastrointestinal tracts are infected with the tapeworms Dipylidium caninum or Taenia taeniaeformis, respectively; praziquantel is also often used in fixed combination with pyrantel embonate against the roundworms (ascarids): Toxocara cati and Toxascaris leonina. Praziquantel is also effective against Echinococcus multilocularis.
Schistosomiasis caused by trematodes of the genus Schistosoma: As of 2005, praziquantel is the primary treatment for human schistosomiasis, for which it is usually effective in a single dose.
Clonorchiasis brought on by the Chinese liver fluke Clonorchis sinensis
Paragonimiasis caused by infection with lung flukes, mostly of the species Paragonimus westermani
Fasciolopsiasis caused by intestinal fluke Fasciolopsis buski

Side effects
The majority of side effects develop due to the release of the contents of the parasites as they are killed and the consequent host immune reaction. The heavier the parasite burden, the heavier and more frequent the side effects normally are.

Central nervous system (CNS): Frequently occurring side effects are dizziness, headache, and malaise. Drowsiness, somnolence, fatigue, and vertigo have also been seen. Almost all patients with cerebral cysticercosis experience CNS side effects related to the cell-death of the parasites (headache, worsening of pre-existing neurological problems, seizures, arachnoiditis, and meningism). These side effects may be life-threatening and can be reduced by coadministration of corticosteroids. All patients with cerebral cysticercosis are strongly recommended to be  hospitalized during treatment.
Gastrointestinal tract: About 90% of all patients have abdominal pain or cramps with or without nausea and vomiting. Diarrhea may develop and may be severe with colic. Sweating, fever, and sometimes bloody stools may occur together with diarrhea.
Liver: Asymptomatic and transient increases of liver enzymes (AST and ALT) are noted frequently (up to 27%). No case of symptomatic liver damage has been seen so far.
Sensitivity reactions: Urticaria, rash, pruritus and eosinophilia in white blood cell counts
Other locations/body as a whole: Lower back pain, myalgia, arthralgia, fever, sweating, various cardiac arrhythmias, and hypotension

Pregnancy
The WHO states praziquantel is safe during pregnancy. Animal studies have failed to reveal evidence of fetal harm. Praziquantel is effective in reducing schistosomiasis during pregnancy. Another trial found that treatment with praziquantel did not increase the rates of low birthweight, fetal death, or congenital anomalies.

Drug interactions
The antibiotic rifampicin decreases plasma concentrations of praziquantel.Carbamazepine and phenytoin are reported to reduce the bioavailability of praziquantel. Chloroquine also reduces its bioavailability.The drug cimetidine heightens praziquantel bioavailability.

Mechanism of action
The drugs mode of action is not exactly known at present, but experimental evidence indicates praziquantel increases the permeability of the membranes of schistosome cells towards calcium ions. The drug thereby induces contraction of the parasites muscle, resulting in paralysis in the contracted state. The dying parasites are dislodged from their site of action in the host organism and may enter systemic circulation or may be destroyed by host immune reaction (phagocytosis). Additional mechanisms including focal disintegrations and disturbances of oviposition (laying of eggs) are seen in other types of sensitive parasites.
Another hypothesis regarding the mechanism of action is that it interferes with adenosine uptake in worms. This effect may have therapeutical relevance given that the schistosome, as the Taenia and the Echinococcus (other praziquantel-sensitive parasites), is unable to synthesize purines, such as adenosine, de novo.
Bayers Animal Health Division website states, "Praziquantel is active against cestodes (tapeworms). Praziquantel is absorbed, metabolized in the liver, and excreted in the bile. Upon entering the digestive tract from the bile, cestocidal activity is exhibited. Following exposure to praziquantel, the tapeworm loses its ability to resist digestion by the mammalian host. Because of this, whole tapeworms, including the scolices (plural of "scolex"), are very rarely passed after administration of praziquantel. In many instances, only disintegrated and partially digested pieces of tapeworms will be seen in the stool. The majority of tapeworms are digested and are not found in the feces."Praziquantel is administered as a racemate, but only the (R)-enantiomer is biologically active; the enantiomers may be separated using a resolution of an amine obtained from praziquantel.

Pharmacokinetics
Praziquantel is well absorbed (about 80%) from the gastrointestinal tract. However, due to extensive first-pass metabolism, only a relatively small amount enters systemic circulation. Praziquantel has a serum half-life of 0.8 to 1.5 hours in adults with normal renal and liver function. Metabolites have a half-life of 4 to 5 hours. In patients with significantly impaired liver function (Child-Pugh score B and C), the serum half-life is increased to 3 to 8 hours. Praziquantel and its metabolites are mainly excreted renally; within 24 h after a single oral dose, 70 to 80% is found in urine, but less than 0.1% as the unchanged drug. Praziquantel is metabolized through the cytochrome P450 pathway via CYP3A4.  Agents that induce or inhibit CYP3A4 such as phenytoin, rifampin, and azole antifungals will affect the metabolism of praziquantel.
Praziquantel has a particularly dramatic effect on patients with schistosomiasis. Studies of those treated have shown that within six months of receiving a dose of praziquantel, up to 90% of the damage done to internal organs due to schistosomiasis infection can be reversed.

History
Praziquantel was developed in the laboratories for parasitological research of Bayer AG and Merck KGaA in Germany (Elberfeld and Darmstadt) in the mid-1970s.

Society and culture
Brand names
Biltricide (Bayer) Tablets (for human use)
Cesol (Merck) Tablets
Cestoved (Vedco) both tablets and injectable for veterinary use
Cysticide (Merck) Tablets
Distocide (Shin Poong Pharm </s>