<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 Bisacodyl and can you explain it in depth? [/INST] Bisacodyl (INN) is an organic compound that is used as a stimulant laxative drug.  It works directly on the colon to produce a bowel movement. It is typically prescribed for relief of episodic and chronic constipation and for the management of neurogenic bowel dysfunction, as well as part of bowel preparation before medical examinations, such as for a colonoscopy.Bisacodyl is a derivative of triphenylmethane. It was first used as a laxative in 1953 because of its structural similarity to phenolphthalein.It is on the World Health Organizations List of Essential Medicines.

Available forms
Bisacodyl is marketed under the trade names Dulcolax/Durolax, Muxol, Fleet, Nourilax, Alophen, Correctol, and Carters Little Pills (formerly Carters Little Liver Pills), as well as being available generically </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 Umbralisib and can you explain it in depth? [/INST] Umbralisib, sold under the brand name Ukoniq, is a medication for the treatment of marginal zone lymphoma (MZL) and follicular lymphoma (FL). It is taken by mouth.Umbralisib is a kinase inhibitor including PI3K-delta and casein kinase CK1-epsilon.The most common side effects include increased creatinine, diarrhea-colitis, fatigue, nausea, neutropenia, transaminase elevation, musculoskeletal pain, anemia, thrombocytopenia, upper respiratory tract infection, vomiting, abdominal pain, decreased appetite, and rash.Umbralisib was granted accelerated approval for medical use in the United States in February 2021. However, due to concerns for increased long term side effects leading to inferior overall survival which led to increased FDA scrutiny in the form of an ODAC review, it has been withdrawn from the US market.

Medical uses
On April 15, 2022, TG Therapeutics announced the voluntary withdrawal of Ukoniq (umbralisib) from sale for its approved use in the treatment of marginal zone lymphoma and follicular lymphoma. Furthermore, the company withdrew the pending Biologics License Application (BLA) and supplemental New Drug Application (sNDA) for the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) which utilized umbralisib in tandem with ublituximab, known as the "U2" regimen. The decision was based on the most recent overall survival (OS) data from the Phase 3 trial, Unity-CLL, that illustrated and increasing imbalance in OS.
Umbralisib was indicated for adults with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based regimen; and adults with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy.

Adverse effects
The prescribing information provides warnings and precautions for adverse reactions including infections, neutropenia, diarrhea and non-infectious colitis, hepatotoxicity, and severe cutaneous reactions.

History
It has undergone clinical studies for chronic lymphocytic leukemia (CLL). Three year data (including follicular lymphoma and DLBCL) was announced June 2016. It is in combination trials for various leukemias and lymphomas, such as mantle cell lymphoma (MCL) and other lymphomas.Umbralisib was granted breakthrough therapy designation by the U.S </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 Nitisinone and can you explain it in depth? [/INST] Nitisinone, sold under the brand name Nityr and Orfadin among others, is a medication used to slow the effects of hereditary tyrosinemia type 1 (HT-1).

Uses
Nitisinone is used to treat hereditary tyrosinemia type 1 (HT-1) in patients from all ages, in combination with dietary restriction of tyrosine and phenylalanine.Since its first use for this indication in 1991, it has replaced liver transplantation as the first-line treatment for this ultra rare condition.

Adverse effects
The most common adverse reactions (>1%)  for nitisinone are elevated tyrosine levels, thrombocytopenia, leukopenia, conjunctivitis, corneal opacity, keratitis, photophobia, eye pain, blepharitis, cataracts, granulocytopenia, epistaxis, pruritus, exfoliative dermatitis, dry skin, maculopapular rash and alopecia.has several negative side effects; these include but are not limited to: bloated abdomen, dark urine, abdominal pain, feeling of tiredness or weakness, headache, light-colored stools, loss of appetite, weight loss, vomiting, and yellow-colored eyes or skin.

Mechanism of action
The mechanism of action of nitisinone involves inhibition of 4-Hydroxyphenylpyruvate dioxygenase (HPPD). This is a treatment for patients with Tyrosinemia type 1 as it prevents the formation of 4-Maleylacetoacetic acid and fumarylacetoacetic acid, which have the potential to be converted to succinyl acetone, a toxin that damages the liver and kidneys. This causes the symptoms of Tyrosinemia type 1 experienced by untreated patients.Alkaptonuria is caused when an enzyme called homogentisic dioxygenase (HGD) is faulty, leading to a buildup of homogenisate. Alkaptonuria patients treated with nitisinone produce far less HGA than those not treated (95% less in the urine),  because nitisinone inhibits HPPD, resulting in less homogenisate accumulation. Clinical trials are ongoing to test whether nitisinone can prevent ochronosis experienced by older alkaptonuria patients.

History
Nitisinone was discovered as part of a program to develop a class of herbicides called HPPD inhibitors </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 Methylscopolamine bromide 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 Trilaciclib and can you explain it in depth? [/INST] Trilaciclib, sold under the brand name Cosela, is a medication used to reduce the frequency of chemotherapy-induced bone marrow suppression.The most common side effects include fatigue; low levels of calcium, potassium and phosphate; increased levels of an enzyme called aspartate aminotransferase; headache; and infection in the lungs (pneumonia).Trilaciclib may help protect bone marrow cells from damage caused by chemotherapy by inhibiting cyclin-dependent kinase 4/6, a type of enzyme. Trilaciclib is the first therapy in its class and was approved for medical use in the United States in February 2021.Chemotherapy drugs are designed to kill cancer cells but can damage normal tissues as well. The bone marrow is particularly susceptible to chemotherapy damage. The bone marrow makes red blood cells, white blood cells, and platelets (small fragments in the blood) that transport oxygen, fight infection, and stop bleeding. When damaged, the bone marrow produces fewer of these cells, leading to fatigue, increased risk of infection, and bleeding, among other problems </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 Pancuronium bromide and can you explain it in depth? [/INST] Pancuronium (trademarked as Pavulon) is an aminosteroid muscle relaxant with various medical uses. It is used in euthanasia and is used in some states as the second of three drugs administered during lethal injections in the United States.

Mechanism of action
Pancuronium is a typical non-depolarizing curare-mimetic muscle relaxant. It competitively inhibits the nicotinic acetylcholine receptor at the neuromuscular junction by blocking the binding of acetylcholine. It has slight vagolytic activity, causing an increase in heart rate,  but no ganglioplegic (i.e., blocking ganglions) activity. It is a very potent muscle relaxant drug, with an ED95 (i.e., the dose that causes 95% depression of muscle twitch response) of only 60 µg/kg body weight. Onset of action is relatively slow compared to other similar drugs, in part due to its low dose: an intubating dose takes 3–6 minutes for full effect. Clinical effects (muscle activity lower than 25% of physiological) last for about 100 minutes. The time needed for full (over 90% muscle activity) recovery after single administration is about 120–180 minutes in healthy adults.
The effects of pancuronium can be at least partially reversed by anticholinesterasics, such as neostigmine, pyridostigmine, and edrophonium.

Development
Workers at Organon were inspired by the structure of the aminosteroid alkaloid malouetine to develop a series of aminosteroid neuromuscular blockers based on an androstane nucleus, culminating in the development of pancuronium bromide.Pancuronium is designed to mimic the action of two molecules of acetylcholine with the quaternary nitrogen atoms spaced rigidly apart by the steroid rings at a distance of ten atoms (interonium distance).
Decamethonium and suxamethonium also have this same interonium distance.

Uses in medicine
Pancuronium is used with general anesthesia in surgery for muscle relaxation and as an aid to intubation or ventilation. It does not have sedative or analgesic effects.
Side-effects include moderately raised heart rate and thereby arterial pressure and cardiac output, excessive salivation, apnea and respiratory depression, rashes, flushing, and sweating. The muscular relaxation can be dangerous in the seriously ill and it can accumulate leading to extended weakness </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 Cefalexin and can you explain it in depth? [/INST] Cefalexin, also spelled cephalexin, is an antibiotic that can treat a number of bacterial infections. It kills gram-positive and some gram-negative bacteria by disrupting the growth of the bacterial cell wall. Cefalexin is a beta-lactam antibiotic within the class of first-generation cephalosporins. It works similarly to other agents within this class, including intravenous cefazolin, but can be taken by mouth.Cefalexin can treat certain bacterial infections, including those of the middle ear, bone and joint, skin, and urinary tract. It may also be used for certain types of pneumonia and strep throat and to prevent bacterial endocarditis. Cefalexin is not effective against infections caused by methicillin-resistant Staphylococcus aureus (MRSA), most Enterococcus, or Pseudomonas. Like other antibiotics, cefalexin cannot treat viral infections, such as the flu, common cold or acute bronchitis. Cefalexin can be used in those who have mild or moderate allergies to penicillin. However, it is not recommended in those with severe penicillin allergies.Common side effects include stomach upset and diarrhea. Allergic reactions or infections with Clostridium difficile, a cause of diarrhea, are also possible. Use during pregnancy or breast feeding does not appear to be harmful to the baby. It can be used in children and those over 65 years of age. Those with kidney problems may require a decrease in dose.Cefalexin was developed in 1967. It was first marketed in 1969 and 1970 under the names Keflex and Ceporex, among others. Generic drug versions are available under other trade names and are inexpensive. It is on the World Health Organizations List of Essential Medicines. In 2019, it was the 83rd most commonly prescribed medication in the United States, with more than 9 million prescriptions. In Canada, it was the fifth most common antibiotic used in 2013. In Australia, it is one of the top 15 most prescribed medications.

Medical uses
Cefalexin can treat a number of bacterial infections including otitis media, streptococcal pharyngitis, bone and joint infections, pneumonia, cellulitis, and urinary tract infections. It may be used to prevent bacterial endocarditis. It can also be used for the prevention of recurrent urinary-tract infections.Cefalexin does not treat methicillin-resistant Staphylococcus aureus infections.Cefalexin is a useful alternative to penicillins in patients with penicillin intolerance. For example, penicillin is the treatment of choice for respiratory tract infections caused by Streptococcus, but cefalexin may be used as an alternative in penicillin-intolerant patients. Caution must be exercised when administering cephalosporin antibiotics to penicillin-sensitive patients, because cross-sensitivity with beta-lactam antibiotics has been documented in up to 10% of patients with a documented penicillin allergy.

Pregnancy and breastfeeding
It is category A in Australia meaning that no evidence of harm has been found after being taken by many pregnant women. Use during breast feeding is generally safe.

Adverse effects
The most common adverse effects of cefalexin, like other oral cephalosporins, are gastrointestinal (stomach area) disturbances and hypersensitivity reactions.  Gastrointestinal disturbances include nausea, vomiting, and diarrhea, the latter being the most common.  Hypersensitivity reactions include skin rashes, urticaria, fever, and anaphylaxis. Pseudomembranous colitis and Clostridium difficile have been reported with use of cefalexin.Signs and symptoms of an allergic reaction include rash, itching, swelling, trouble breathing, or red, blistered, swollen, or peeling skin. Overall, cefalexin allergy occurs in less than 0.1% of patients, but it is seen in 1% to 10% of patients with a penicillin allergy.

Interactions
Like other β-lactam antibiotics, renal excretion of cefalexin is delayed by probenecid. Alcohol consumption reduces the rate at which it is absorbed. Cefalexin also interacts with metformin, an antidiabetic drug, and this can lead to higher concentrations of metformin in the body. Histamine H2 receptor antagonists like cimetidine and ranitidine may reduce the efficacy of cefalexin by delaying its absorption and altering its antimicrobial pharmacodynamics.

Pharmacology
Mechanism of action
Cefalexin is a beta-lactam antibiotic of the cephalosporin family.  It is bactericidal and acts by inhibiting synthesis of the peptidoglycan layer of the bacterial cell wall. As cefalexin closely resembles d-alanyl-d-alanine, an amino acid ending on the peptidoglycan layer of the cell wall, it is able to irreversibly bind to the active site of PBP, which is essential for the synthesis of the cell wall. It is most active against gram-positive cocci, and has moderate activity against some gram-negative bacilli. However, some bacterial cells have the enzyme β-lactamase, which hydrolyzes the beta-lactam ring, rendering the drug inactive. This contributes to antibacterial resistance towards cefalexin.

Pharmacokinetics
Cefalexin is rapidly and almost completely absorbed from the gastrointestinal tract with oral administration. Absorption is slightly reduced when it is taken with food and the medication can be taken without regard for meals. Peak levels of cefalexin occur about 1 hour after administration. Maximal levels of cefalexin increase approximately linearly over a dose range of 250 to 1,000 mg.Like most other cephalosporins, cefalexin is not metabolized or otherwise inactivated in the body.The elimination half-life of cefalexin is approximately 30 to 60 minutes in people with normal renal function. Therapeutic levels of cefalexin with oral administration are maintained for 6 to 8 hours </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 Oxiconazole 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 Doxycycline and can you explain it in depth? [/INST] Doxycycline is a broad-spectrum tetracycline class antibiotic used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus, and syphilis. It is also used to prevent malaria in combination with quinine. Doxycycline may be taken by mouth or by injection into a vein.Common side effects include diarrhea, nausea, vomiting, abdominal pain, and an increased risk of sunburn. Use during pregnancy is not recommended. Like other agents of the tetracycline class, it either slows or kills bacteria by inhibiting protein production. It kills malaria by targeting a plastid organelle, the apicoplast.Doxycycline was patented in 1957 and came into commercial use in 1967. It is on the World Health Organizations List of Essential Medicines. Doxycycline is available as a generic medicine. In 2019, it was the 90th most commonly prescribed medication in the United States, with more than 8 million prescriptions.

Medical use
In addition to the general indications for all members of the tetracycline antibiotics group, doxycycline is frequently used to treat Lyme disease, chronic prostatitis, sinusitis, pelvic inflammatory disease, acne, rosacea, and rickettsial infections.In Canada, in 2004, doxycycline was considered a first-line treatment for chlamydia and non-gonococcal urethritis and with cefixime for uncomplicated gonorrhea.

Antibacterial
Moraxella catarrhalis, Brucella melitensis, Chlamydia pneumoniae, and Mycoplasma pneumoniae are generally susceptible to doxycycline, while some Haemophilus spp., Mycoplasma hominis, and Pseudomonas aeruginosa have developed resistance to varying degrees.It is used in the treatment and prophylaxis of anthrax and Leptospirosis. It is also effective against Yersinia pestis (the infectious agent of bubonic plague), and is prescribed for the treatment of Lyme disease, ehrlichiosis, and Rocky Mountain spotted fever.Doxycycline is indicated for treatment of:
Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers caused by Rickettsia
Respiratory tract infections caused by Mycoplasma pneumoniae
Lymphogranuloma venereum, trachoma, inclusion conjunctivitis, and uncomplicated urethral, endocervical, or rectal infections in adults caused by Chlamydia trachomatis
Psittacosis
Nongonococcal urethritis caused by Ureaplasma urealyticum
Relapsing fever due to Borrelia recurrentis
Chancroid caused by Haemophilus ducreyi
Plague due to Yersinia pestis
Tularemia
Cholera
Campylobacter fetus infections
Brucellosis caused by Brucella species (in conjunction with streptomycin)
Bartonellosis
Granuloma inguinale (Klebsiella species)
Lyme diseaseWhen bacteriologic testing indicates appropriate susceptibility to the drug, doxycycline may be used to treat these infections caused by Gram-negative bacteria:
Escherichia coli infections
Enterobacter aerogenes (formerly Aerobacter aerogenes) infections
Shigella species infections
Acinetobacter species (formerly Mima species and Herellea species) infections
Respiratory tract infections caused by Haemophilus influenzae
Respiratory tract and urinary tract infections caused by Klebsiella speciesSome Gram-positive bacteria have developed resistance to doxycycline. Up to 44% of Streptococcus pyogenes and up to 74% of S. faecalis specimens have developed resistance to the tetracycline group of antibiotics. Up to 57% of P. acnes strains developed resistance to doxycycline. When bacteriologic testing indicates appropriate susceptibility to the drug, doxycycline may be used to treat these infections caused by Gram-positive bacteria:
Upper respiratory infections caused by Streptococcus pneumoniae (formerly Diplococcus pneumoniae)
Skin and soft tissue infections caused by Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus infections
Anthrax caused by Bacillus anthracis infectionWhen penicillin is contraindicated, doxycycline can be used to treat:
Syphilis caused by Treponema pallidum
Yaws caused by Treponema pertenue
Listeriosis due to Listeria monocytogenes
Vincents infection caused by Fusobacterium fusiforme
Actinomycosis caused by Actinomyces israelii
Infections caused by Clostridium speciesDoxycycline may also be used as adjunctive therapy for severe acne.The first-line treatment for brucellosis is a combination of doxycycline and streptomycin and the second-line is a combination of doxycycline and rifampicin (rifampin).

Antimalarial
Doxycycline is active against the erythrocytic stages of Plasmodium falciparum but not against the gametocytes of P. falciparum. It is used to prevent malaria. It is not recommended alone for initial treatment of malaria, even when the parasite is doxycycline-sensitive, because the antimalarial effect of doxycycline is delayed.The World Health Organization (WHO) guidelines state that the combination of doxycycline with either artesunate or quinine may be used for the treatment of uncomplicated malaria due to P. falciparum or following intravenous treatment of severe malaria.

Antihelminthic
Doxycycline kills the symbiotic Wolbachia bacteria in the reproductive tracts of parasitic filarial nematodes, making the nematodes sterile, and thus reducing transmission of diseases such as onchocerciasis and elephantiasis. Field trials in 2005 showed an eight-week course of doxycycline almost eliminates the release of microfilariae.

Spectrum of susceptibility
Doxycycline has been used successfully to treat sexually transmitted, respiratory, and ophthalmic infections. Representative pathogenic genera include Chlamydia, Streptococcus, Ureaplasma, Mycoplasma, and others. The following represents MIC susceptibility data for a few medically significant microorganisms.
Chlamydia psittaci: 0.03 μg/mL
Mycoplasma pneumoniae: 0.016 μg/mL—2 μg/mL
Streptococcus pneumoniae: 0.06 μg/mL—32 μg/mL

Sclerotherapy
Doxycycline is also used for sclerotherapy in slow-flow vascular malformations, namely venous and lymphatic malformations, as well as post-operative lymphoceles.

Others
Subantimicrobial-dose doxycycline (SDD) is widely used as an adjunctive treatment to scaling and root planing for periodontitis. Significant differences were observed for all investigated clinical parameters of periodontitis in favor of the scaling and root planing + SDD group where SDD dosage regimens is 20 mg twice daily for three months in a meta-analysis published in 2011.

Contraindications
Pregnancy and lactation
Doxycycline is categorized by the FDA as a class D drug in pregnancy. Doxycycline crosses into breastmilk. Other tetracycline antibiotics are contraindicated in pregnancy and up to eight years of age, due to the potential for disrupting bone and tooth development. They include a class warning about staining of teeth and decreased development of dental enamel in children exposed to tetracyclines in utero, during breastfeeding or during young childhood. However, the FDA has acknowledged that the actual risk of dental staining of primary teeth is undetermined for doxycycline specifically. The best available evidence indicates that doxycycline has little or no effect on hypoplasia of dental enamel or on staining of teeth and the CDC recommends the use of doxycycline for treatment of Q fever and also for tick-borne rickettsial diseases in young children and others advocate for its use in malaria.

Other
Other contraindications are severe liver disease and concomitant use of isotretinoin or other retinoids, as both tetracyclines and retinoids can cause intracranial hypertension (increased pressure around the brain) in rare cases.

Adverse effects
Adverse effects are similar to those of other members of the tetracycline antibiotic group. Doxycycline can cause gastrointestinal upset. Oral doxycycline can cause pill esophagitis, particularly when it is swallowed without adequate fluid, or by persons with difficulty swallowing or impaired mobility. Doxycycline is less likely than other antibiotic drugs to cause Clostridium difficile colitis.
An erythematous rash in sun-exposed parts of the body has been reported to occur in 7.3–21.2% of persons taking doxycycline for malaria prophylaxis. One study examined the tolerability of various malaria prophylactic regimens and found doxycycline did not cause a significantly higher percentage of all skin events (photosensitivity not specified) when compared with other antimalarials. The rash resolves upon discontinuation of the drug.Unlike some other members of the tetracycline group, it may be used in those with renal impairment.Doxycycline use has been associated with increased risk of inflammatory bowel disease. In one large retrospective study, patients who were prescribed doxycycline for their acne had a 2.25-fold greater risk of developing Crohns disease.

Interactions
The combination of doxycycline with dairy, antacids, calcium supplements, iron products, laxatives containing magnesium, or bile acid sequestrants is not inherently dangerous, but any of these foods and supplements may decrease doxycyclines effectiveness.
Breakfast was observed to reduce doxycycline absorption significantly. Absorption of tetracycline occurs in the stomach and the upper small intestine. Absorption of tetracyclines has been reported to be impaired by milk products, aluminum hydroxide gels, sodium bicarbonate, calcium and magnesium salts, laxatives containing magnesium and iron preparations. The mechanisms responsible for decreased absorption appear to be chelation and an increase in gastric pH. ... In view of these results, it is advisable to instruct the patients to take doxycycline on an empty stomach.
Previously, doxycycline was believed to impair the effectiveness of many types of hormonal contraception due to CYP450 induction. Research has shown no significant loss of effectiveness in oral contraceptives while using most tetracycline antibiotics (including doxycycline), although many physicians still recommend the use of barrier contraception for people taking the drug to prevent unwanted pregnancy.

Pharmacology
Doxycycline, like other tetracycline antibiotics, is bacteriostatic. It works by preventing bacteria from reproducing through the inhibition of protein synthesis.Doxycycline is highly lipophilic so can easily enter cells, meaning the drug is easily absorbed after oral administration and has a large volume of distribution. It can also be re-absorbed in the renal tubules and gastrointestinal tract due to its high lipophillicity so has a long elimination half life, and does not accumulate in the kidneys of patients with kidney failure due to the compensatory excretion in faeces. Doxycycline–metal ion complexes are unstable at acid pH, therefore more doxycycline enters the duodenum for absorption than the earlier tetracycline compounds. In addition, food has less effect on absorption than on absorption of earlier drugs with doxycycline serum concentrations being reduced by about 20% by test meals compared with 50% for tetracycline.

Mechanism of action
Doxycycline is a broad-spectrum bacteriostatic antibiotic. It inhibits the synthesis of bacterial proteins by binding to the 30S ribosomal subunit, which is only found in bacteria. This prevents the binding of transfer RNA to messenger RNA at the ribosomal subunit meaning amino acids cannot be added to polypeptide chains and new proteins cannot be made. This stops bacterial growth giving the immune system time to kill and remove the bacteria.

Pharmacokinetics
The substance is almost completely absorbed from the upper part of the small intestine. It reaches highest concentrations in the blood plasma after one to two hours and has a high plasma protein binding rate of about 80–90%. Doxycycline penetrates into almost all tissues and body fluids. Very high concentrations are found in the gallbladder, liver, kidneys, lung, breast milk, bone and genitals; low ones in saliva, aqueous humour, cerebrospinal fluid (CSF), and especially in inflamed meninges. By comparison, the tetracycline antibiotic minocycline penetrates significantly better into the CSF and meninges.Doxycycline metabolism is negligible. It is actively excreted into the gut (in part via the gallbladder, in part directly from blood vessels), where some of it is inactivated by forming chelates. About 40% are eliminated via the kidneys, much less in people with end-stage kidney disease. The biological half-life is 18 to 22 hours (16±6 hours according to another source) in healthy people, slightly longer in those with end-stage kidney disease, and significantly longer in those with liver disease.

Chemistry
Expired tetracyclines or tetracyclines allowed to stand at a pH less than 2 are reported to be nephrotoxic due to the formation of a degradation product, anhydro-4-epitetracycline causing Fanconi syndrome. In the case of doxycycline, the absence of a hydroxyl group in C-6 prevents the formation of the nephrotoxic compound. Nevertheless, tetracyclines and doxycycline itself have to be taken with caution in patients with kidney injury, as they can worsen azotemia due to catabolic effects.

Chemical properties
Doxycycline, doxycycline monohydrate and doxycycline hyclate are yellow, crystalline powders with a bitter taste. The latter smells faintly of ethanol; a 1% aqueous solution has a pH of 2–3; and the specific rotation is

        [
        α

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            D

            25

    {\displaystyle [\alpha ]_{D}^{25}}
   −110° cm³/dm·g in 0.01 N methanolic hydrochloric acid.

History
After penicillin revolutionized the treatment of bacterial infections in WWII, many chemical companies moved into the field of discovering antibiotics by bioprospecting. American Cyanamid was one of these, and in the late 1940s chemists there discovered chlortetracycline, the first member of the tetracycline class of antibiotics. Shortly thereafter, scientists at Pfizer discovered terramycin and it was brought to market. Both compounds, like penicillin, were natural products and it was commonly believed that nature had perfected them, and further chemical changes could only degrade their effectiveness. Scientists at Pfizer led by Lloyd Conover modified these compounds, which led to the invention of tetracycline itself, the first semi-synthetic antibiotic. Charlie Stephens group at Pfizer worked on further analogs and created one with greatly improved stability and pharmacological efficacy: doxycycline. It was clinically developed in the early 1960s and approved by the FDA in 1967.As its patent grew near to expiring in the early 1970s, the patent became the subject of lawsuit between Pfizer and International Rectifier that was not resolved until 1983; at the time it was the largest litigated patent case in US history. Instead of a cash payment for infringement, Pfizer took the veterinary and feed-additive businesses of International Rectifiers subsidiary, Rachelle Laboratories.In January 2013, the FDA reported shortages of some, but not all, forms of doxycycline "caused by increased demand and manufacturing issues". Companies involved included an unnamed major generics manufacturer that ceased production in February 2013, Teva (which ceased production in May 2013), Mylan, Actavis, and Hikma Pharmaceuticals </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 Montelukast and can you explain it in depth? [/INST] Montelukast, sold under the brand name Singulair among others, is a medication used in the maintenance treatment of asthma. It is generally less preferred for this use than inhaled corticosteroids. It is not useful for acute asthma attacks. Other uses include allergic rhinitis and hives of long duration. For allergic rhinitis it is a second-line treatment.Common side effects include abdominal pain, cough, and headache. Severe side effects may include allergic reactions, such as anaphylaxis and eosinophilia. Use in pregnancy appears to be safe. Montelukast is in the leukotriene receptor antagonist family of medications. It works by blocking the action of leukotriene D4 in the lungs resulting in decreased inflammation and relaxation of smooth muscle.Montelukast was approved for medical use in the United States in 1998. It is available as a generic medication. In 2020, it was the fourteenth most commonly prescribed medication in the United States, with more than 31 million prescriptions.

Medical uses
Montelukast is used for a number of conditions including asthma, exercise induced bronchospasm, allergic rhinitis, and urticaria. It is mainly used as a complementary therapy in adults in addition to inhaled corticosteroids, if inhaled steroids alone do not bring the desired effect. It is also used to prevent allergic reactions and asthma flare-ups during the administration of intravenous immunoglobulin. It may also be used as an adjunct therapy in symptomatic treatment of mastocytosis. It is taken by mouth, as a tablet, chewable tablet, or as granules.

Adverse effects
Common side effects include diarrhea, nausea, vomiting, mild rashes, asymptomatic elevations in liver enzymes, and fever. Uncommon side effects include fatigue and malaise, behavioral changes, paresthesias and seizures, muscle cramps, and nose bleeds. Rare (may affect up to 1 in 10,000 people taking montelukast) but serious side effects include behavioral changes (including suicidal thoughts), angioedema, erythema multiforme, and liver problems.In 2019 and 2020, concerns for neuropsychiatric reactions were added to the label in the United Kingdom and United States where the most frequently suspected were nightmares, depression, insomnia (may affect between 1 in 100 to 1 in 1,000 people taking montelukast); aggression, anxiety and abnormal behaviour or changes in behaviour (may affect between 1 in 1,000 and 1 in 10,000 people taking montelukast).

FDA investigation
In June 2009, the U.S. Food and Drug Administration (FDA) concluded a review into the possibility of neuropsychiatric side effects with leukotriene modulator drugs. Although clinical trials only revealed an increased risk of insomnia, post-marketing surveillance showed that the drugs are associated with a possible increase in suicidal behavior and other side effects such as agitation, aggression, anxiousness, dream abnormalities and hallucinations, depression, irritability, restlessness, and tremor.In September 2019, the Pediatric Advisory Committee and the Drug Safety and Risk Management Advisory Committee met to discuss a pediatric-focused safety review of neuropsychiatric events with montelukast.In March 2020, the FDA required a boxed warning for montelukast to strengthen an existing warning about the risk of neuropsychiatric events associated with the drug in the wake of an increase in case reporting of neuropsychiatric events around the time of the initial communications about the concern from FDA in 2008. The boxed warning advises health care providers to avoid prescribing montelukast for people with mild symptoms, particularly those with allergic rhinitis because there are many other effective, less-concerned allergy medicines that are also indicated for the mild cases.In the FDAs self-conducted data analysis in comparison to their received case reports which were dependent on peoples self-claims, the propensity of developing neuropsychiatric disorders after montelukast use does not outpace that of inhaled corticosteroids; and there were no statistically significant risks of new-onset neuropsychiatric disorders among males, females, patients 12 years and older, patients with a psychiatric history, or after the 2008 FDA communication and prescribing information changes that first publicized the concern. In addition, FDAs self-conducted data analysis also summarized their own findings, saying "exposure to montelukast was significantly associated with a decreased risk of treated outpatient depressive disorder and the decreased risks were seen among patients with a history of a psychiatric disorder, in patients 12 to 17 years as well as 18 years and older, and in both females and males." "Treated outpatient depressive disorder" refers to patients actions of making an appointment with psychiatrists to contend with their depressions.

Drug interactions
Montelukast has very few drug-drug interactions. This is due to the lack of off-target affinity towards other targets in the body where it might exert an effect. However, it is important to note that montelukast is an inhibitor of the drug metabolizing enzyme CYP2C8. Therefore, it is theoretically possible that the combination of montelukast with a CYP2C8 substrate (e.g. amodiaquine, an anti-malarial drug) could increase the plasma concentrations of the substrate.

Pharmacology
Montelukast is in the leukotriene receptor antagonist family of medications. It works by blocking the action of leukotriene D4 in the lungs resulting in decreased inflammation and relaxation of smooth muscle.Montelukast functions as a leukotriene receptor antagonist (cysteinyl leukotriene receptors) and consequently opposes the function of these inflammatory mediators; leukotrienes are produced by the immune system and serve to promote bronchoconstriction, inflammation, microvascular permeability, and mucus secretion in asthma and COPD. Leukotriene receptor antagonists are sometimes colloquially referred to as leukasts.
Two genes of interest are ALOX5 and LTC4S, which catalyze two major steps in the biosynthetic pathway of leukotrienes.Montelukast may affect nerve remyelination in combination with Pexidartinib and this may cause clinical benefits or side effects.

Patents
Singulair was covered by U.S. Patent No. 5,565,473 which expired on 3 August 2012. The same day, the FDA approved several generic versions of montelukast.The United States Patent and Trademark Office launched a reexamination of the patent covering Singulair on 28 May 2009.  The decision was driven by the discovery of references that were not included in the original patent application process.  The references were submitted through Article One Partners, an online research community focused on finding literature relating to existing patents.  The references included a scientific article produced by a Merck employee on the active ingredient in Singulair </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 Amlodipine/benazepril and can you explain it in depth? [/INST] Amlodipine/benazepril, sold under the brand name Lotrel among others, is a medication used to treat high blood pressure. It is a combination of amlodipine, a calcium channel blocker and benazepril, an angiotensin converting enzyme inhibitor. It may be used if a single agent is not sufficient </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 Pegfilgrastim and can you explain it in depth? [/INST] Pegfilgrastim, sold under the brand name Neulasta among others, is a PEGylated form of the recombinant human granulocyte colony-stimulating factor (GCSF) analog filgrastim </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 Aluminium chloride and can you explain it in depth? [/INST] Aluminium chloride, also known as aluminium trichloride, is an inorganic compound with the formula AlCl3. It forms hexahydrate  with the formula [Al(H2O)6]Cl3, containing six water molecules of hydration. Both are colourless crystals, but samples are often contaminated with iron(III) chloride, giving a yellow color.
The anhydrous material is important commercially. It has a low melting and boiling point. It is mainly produced and consumed in the production of aluminium metal, but large amounts are also used in other areas of the chemical industry. The compound is often cited as a Lewis acid. It is an example of an inorganic compound that reversibly changes from a polymer to a monomer at mild temperature.

Structure
Anhydrous
AlCl3 adopts three structures, depending on the temperature and the state (solid, liquid, gas). Solid AlCl3 has a sheet-like layered structure with cubic close-packed chloride ions. In this framework, the Al centres exhibit octahedral coordination geometry. Yttrium(III) chloride adopts the same structure, as do a range of other compounds. When aluminium trichloride is in its melted state, it exists as the dimer Al2Cl6, with tetracoordinate aluminium. This change in structure is related to the lower density of the liquid phase (1.78 g/cm3) versus solid aluminium trichloride (2.48 g/cm3). Al2Cl6 dimers are also found in the vapour phase. At higher temperatures, the Al2Cl6 dimers dissociate into trigonal planar AlCl3 monomer, which is structurally analogous to BF3. The melt conducts electricity poorly, unlike more ionic halides such as sodium chloride.
Aluminium chloride monomer belongs to the point group D3h in its monomeric form and D2h in its dimeric form.

Hexahydrate
The hexahydrate consists of octahedral [Al(H2O)6]3+ cation centers and chloride anions (Cl−) as counterions. Hydrogen bonds link the cation and anions.
The hydrated form of aluminium chloride has an octahedral molecular geometry, with the central aluminium ion surrounded by six water ligand molecules. Being coordinatively saturated, the hydrate is of little value as a catalyst in Friedel-Crafts alkylation and related reactions.

Uses
Alkylation and acylation of arenes
AlCl3 is a common Lewis-acid catalyst for Friedel-Crafts reactions, both acylations and alkylations. Important products are detergents and ethylbenzene. These types of reactions are the major use for aluminium chloride, for example, in the preparation of anthraquinone (used in the dyestuffs industry) from benzene and phosgene. In the general Friedel-Crafts reaction, an acyl chloride or alkyl halide reacts with an aromatic system as shown:
The alkylation reaction is more widely used than the acylation reaction, although its practice is more technically demanding. For both reactions, the aluminium chloride, as well as other materials and the equipment, should be dry, although a trace of moisture is necessary for the reaction to proceed. Detailed procedures are available for alkylation and acylation of arenes.
A general problem with the Friedel-Crafts reaction is that the aluminium chloride catalyst sometimes is required in full stoichiometric quantities, because it complexes strongly with the products. This complication sometimes generates a large amount of corrosive waste. For these and similar reasons, the use of aluminium chloride has often been displaced by zeolites.Aluminium chloride can also be used to introduce aldehyde groups onto aromatic rings, for example via the Gattermann-Koch reaction which uses carbon monoxide, hydrogen chloride and a copper(I) chloride co-catalyst.

Other applications in organic and organometallic synthesis
Aluminium chloride finds a wide variety of other applications in organic chemistry. For example, it can catalyse the "ene reaction", such as the addition of 3-buten-2-one (methyl vinyl ketone) to carvone:
It is used to induce a variety of hydrocarbon couplings and rearrangements.Aluminium chloride combined with aluminium in the presence of an arene can be used to synthesize bis(arene) metal complexes, e.g </s>


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<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 Trospium chloride and can you explain it in depth? [/INST] Trospium chloride is used to treat overactive bladder.It has side effects typical of drugs like it, namely dry mouth, stomach upset, and constipation; these side effects cause problems with people taking their medicine as directed.  However it doesnt cause central nervous system side effects like other drugs of its class.  It is pregnancy category C and is excreted somewhat in breast milk.Chemically it is a quaternary ammonium cation which causes it to stay in periphery rather than crossing the blood-brain barrier.  It works by causing the smooth muscle in the bladder to relax.It was patented in 1966 and approved for medical use in 1974. It was first approved in the US in 2004, and an extended release version with once-daily dosing was brought to market in 2007.  It became generic in Europe in 2009 and in the US the first extended-release generic was approved in 2012.

Medical uses
Trospium chloride is used for the treatment of overactive bladder with symptoms of urge incontinence and frequent urination.It shouldnt be used with people who retain urine, who have severe digestive conditions, myasthenia gravis, narrow-angle glaucoma, or tachyarrhythmia.It should be used in caution with people who have problems with their autonomous nervous system (dysautonomia) or who have gastroesophageal reflux disease, or in whom fast heart rates are undesirable, such as people with hyperthyroidism, coronary artery disease and congestive heart failure.Trospium chloride is rated Pregnancy Category C, as there are no adequate and well-controlled studies of trospium chloride in pregnant women and there were signs of harm to the fetus in animal studies. The drug was excreted somewhat in the milk of nursing mothers.  The drug was studied in children.

Side effects
Side effects are typical of gastrointestinal effects of anticholinergic drugs, and include dry mouth, indigestion, and constipation.  These side effects lead to problems with adherence, especially for older people.
The only CNS side effect is headache, which was very rare.  Tachycardia is a rare side effect.

Mechanism of action
Trospium chloride is a muscarinic antagonist. Trospium chloride blocks the effect of acetylcholine on muscarinic receptors organs that are responsive to the compounds, including the bladder. Its parasympatholytic action relaxes the smooth muscle in the bladder.  Receptor assays showed that trospium chloride  has negligible affinity for nicotinic receptors as compared to muscarinic receptors at concentrations obtained from therapeutic doses.

Pharmacokinetics
After oral administration, less than 10% of the dose is absorbed. Mean absolute bioavailability of a 20 mg dose is 9.6% (range: 4.0 to 16.1%). Peak plasma concentrations (Cmax) occur between 5 and 6 hours post-dose. Mean Cmax increases greater than dose-proportionally; a 3-fold and 4-fold increase in Cmax was observed for dose increases from 20 mg to 40 mg and from 20 mg to 60 mg, respectively. AUC exhibits dose linearity for single doses up to 60 mg. Trospium chloride exhibits diurnal variability in exposure with a decrease in Cmax and AUC of up to 59% and 33%, respectively, for evening relative to morning doses.Administration with a high fat meal resulted in reduced absorption, with AUC and Cmax values 70 to 80% lower than those obtained when trospium chloride was administered while fasting. Therefore, it is recommended that trospium chloride should be taken at least one hour prior to meals or on an empty stomach.Protein binding ranged from 50 to 85% when concentration levels of trospium chloride (0.5 to 50 ng/mL) were incubated with human serum in vitro. The 3H-trospium chloride ratio of plasma to whole blood was 1.6:1. This ratio indicates that the majority of 3H-trospium chloride is distributed in plasma. The apparent volume of distribution for a 20 mg oral dose is 395 (± 140) liters.The metabolic pathway of trospium in humans has not been fully defined. Of the 10% of the dose absorbed, metabolites account for approximately 40% of the excreted dose following oral administration. The major metabolic pathway is hypothesized as ester hydrolysis with subsequent conjugation of benzylic acid to form azoniaspironortropanol with glucuronic acid. Cytochrome P450 is not expected to contribute significantly to the elimination of trospium. Data taken from in vitro human liver microsomes investigating the inhibitory effect of trospium on seven cytochrome P450 isoenzyme substrates (CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4) suggest a lack of inhibition at clinically relevant concentrations.The plasma half-life for trospium chloride following oral administration is approximately 20 hours. After oral administration of an immediate-release formulation of 14C-trospium chloride, the majority of the dose (85.2%) was recovered in feces and a smaller amount (5.8% of the dose) was recovered in urine; 60% of the radioactivity excreted in urine was unchanged trospium. The mean renal clearance for trospium (29 L/hour) is 4-fold higher than average glomerular filtration rate, indicating that active tubular secretion is a major route of elimination for trospium. There may be competition for elimination with other compounds that are also renally eliminated.

Chemical properties
Anticholinergic drugs used to treat overactive bladder were all amines as of 2003. Quaternary ammonium cations in general are more hydrophilic than other amines and dont cross membranes well, so they tend to be poorly absorbed from the digestive system, and to not cross the blood-brain barrier.  Oxybutynin, tolterodine, darifenacin, and solifenacin are tertiary amines while trospium chloride and propantheline are quaternary amines.

History
The synthesis of trospium was described by scientists from Dr. Robert Pfleger Chemische Fabrik GmbH,  Heinz Bertholdt, Robert Pfleger, and Wolfram Schulz, in US. Pat. No. 3,480,626 (the US equivalent to DE119442), and its activity was first published in the literature in 1967.The first regulatory approval was granted in Germany in August 1999 to Madaus AG for Regurin 20 mg Tablets.: 13  Madaus is considered the originator for regulatory filings worldwide. The German filing was recognized throughout Europe under the Mutual Recognition Procedure.: 13 Madaus licensed the US rights to trospium chloride to Interneuron in 1999 and Interneuron ran clinical trials in the US to win FDA approval.  Interneuron changed its name to Indevus in 2002 Indevus entered into a partnership with Odyssey Pharmaceuticals, a subsidiary of Pliva, to market the drug in April 2004, and won FDA approval for the drug, which it branded as Sanctura, in May 2004.  The approval earned Indevus a milestone payment of $120M from Pliva, which had already paid Indevus $30 million at signing; the market for overactive bladder therapies was estimated to be worth $1.1 billion in 2004 </s>