<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Ritonavir and explain in detail? [/INST] Ritonavir, sold under the brand name Norvir, is an antiretroviral medication used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Ritonavir is a protease inhibitor and is used with other protease inhibitors. It may also be used in combination with other medications to treat hepatitis C. It is taken by mouth. Tablets of ritonavir are not bioequivalent to capsules, as the tablets may result in higher peak plasma concentrations.Common side effects include nausea, vomiting, loss of appetite, diarrhea, and numbness of the hands and feet. Serious side effects include liver problems, pancreatitis, allergic reactions, and arrythmias. Serious interactions may occur with a number of other medications including amiodarone and simvastatin. At low doses it is considered to be acceptable for use during pregnancy. Ritonavir is of the protease inhibitor class. Typically, however, it is used to inhibit the enzyme that metabolizes other protease inhibitors. This inhibition allows lower doses of these latter medications to be used.Ritonavir was patented in 1989 and came into medical use in 1996. It is on the World Health Organizations List of Essential Medicines. Ritonavir capsules were approved as a generic medication in the United States in 2020.

Medical uses
Ritonavir is indicated in combination with other antiretroviral agents for the treatment of HIV-1-infected patients.In December 2021, the combination of nirmatrelvir and ritonavir was granted emergency use authorization by the US Food and Drug Administration (FDA) for the treatment of coronavirus disease COVID-19. The co-packaged medications are sold under the brand name Paxlovid. Paxlovid is not authorized for the pre-exposure or post-exposure prevention of COVID-19 or for initiation of treatment in those requiring hospitalization due to severe or critical COVID-19. On 31 December 2021, the UK Medicines and Healthcare products Regulatory Agency (MHRA) approved the same combination "for people with mild to moderate COVID-19 who are at high risk of developing severe COVID-19".

Side effects
When administered at the initially tested higher doses effective for anti-HIV therapy, the side effects of ritonavir are those shown below.

Adverse drug reactions
Ritonavir exhibits hepatic activity.
Ritonavir induces CYP1A2 and inhibits the major P450 isoforms 3A4 and 2D6. Concomitant therapy of ritonavir with a variety of medications may result in serious and sometimes fatal drug interactions.Due to it being a strong inhibitor (that causes at least a five-fold increase in the plasma AUC values, or more than 80% decrease in clearance) of both Cytochrome P450 enzymes CYP2D6 and CYP3A4, ritonavir can severely potentiate and prolong the serious and life-threatening side-effects of the opioid painkiller Oxycodone.

Mechanism of action
Ritonavir was originally developed as an inhibitor of HIV protease, one of a family of pseudo-C2-symmetric small molecule inhibitors.Ritonavir is rarely used for its own antiviral activity but remains widely used as a booster of other protease inhibitors. More specifically, ritonavir is used to inhibit a particular enzyme, in intestines, liver, and elsewhere, that normally metabolizes protease inhibitors, cytochrome P450-3A4 (CYP3A4). The drug binds to and inhibits CYP3A4, so a low dose can be used to enhance other protease inhibitors. This discovery drastically reduced the adverse effects and improved the efficacy of protease inhibitors and HAART. However, because of the general role of CYP3A4 in xenobiotic metabolism, dosing with ritonavir also affects the efficacy of numerous other medications, adding to the challenge of prescribing drugs concurrently.

Pharmacodynamics and pharmacokinetics
The capsules of the medication do not have the same bioavailability as the tablets.Ritonavir was demonstrated to have an in vitro potency of EC50=0.02µM and highly sustained concentration in plasma after oral administration in several species.

Chemistry
Ritonavir was initially derived from a moderately potent and orally bioavailable small molecule, A-80987. The P3 and P2′ heterocyclic groups of A-80987 were redesigned to create an analogue, now known as ritonavir, with improved pharmacokinetic properties to the original.Full details of the synthesis of ritonavir were first published by scientists from Abbott Laboratories.

In the first step shown, an aldehyde derived from phenylalanine is treated with zinc dust in the presence of vanadium(III) chloride. This results in a pinacol coupling reaction which dimerizes the material to provide an intermediate which is converted to its epoxide and then reduced to (2S,3S,5S)-2,5-diamino-1,6-diphenylhexan-3-ol. Importantly, this retains the absolute stereochemistry of the amino acid precursor. The diamine is then treated sequentially with two thiazole derivatives, each linked by an amide bond, to provide ritonavir.

History
Ritonavir is sold as Norvir by AbbVie, Inc.. The US Food and Drug Administration (FDA) approved ritonavir on March 1, 1996, As a result of the introduction of "highly active antiretroviral thearap[ies]" the annual U.S. HIV-associated death rate fell from over 50,000 to about 18,000 over a period of two years.In 2014, the FDA approved a combination of ombitasvir/paritaprevir/ritonavir for the treatment of hepatitis C virus (HCV) genotype 4.In 2021, a combination of ritonavir with nirmatrelvir, an orally active 3C-like protease inhibitor, was developed for the treatment of COVID-19. Ritonavir serves to slow down metabolism of nirmatrelvir by cytochrome enzymes to maintain higher circulating concentrations of the main drug. In November that year, Pfizer announced positive phase 2/3 results, including 89% reduction in hospitalizations when given within three days after symptom onset.

Polymorphism and temporary market withdrawal
Ritonavir was originally dispensed as a capsule that did not require refrigeration. This contained a crystal form of ritonavir that is now called form I. However, like many drugs, crystalline ritonavir can exhibit polymorphism, i.e., the same molecule can crystallize into more than one crystal type, or polymorph, each of which contains the same repeating molecule but in different crystal packings/arrangements. The solubility and hence the bioavailability can vary in the different arrangements, and this was observed for forms I and II of ritonavir.During development—ritonavir was introduced in 1996—only the crystal form now called form I was found; however, in 1998, a lower free energy, more stable polymorph, form II, was discovered. This more stable crystal form was less soluble, which resulted in significantly lower bioavailability. The compromised oral bioavailability of the drug led to temporary removal of the oral capsule formulation from the market. As a consequence of the fact that even a trace amount of form II can result in the conversion of the more bioavailable form I into form II, the presence of form II threatened the ruin of existing supplies of the oral capsule formulation of ritonavir; and indeed, form II was found in production lines, effectively halting ritonavir production. Abbott (now AbbVie) withdrew the capsules from the market, and prescribing physicians were encouraged to switch to a Norvir suspension. It has been estimated that Abbott lost more than $250 million USD as a result, and the incident is often cited as a high-profile example of disappearing polymorphs.The companys research and development teams ultimately solved the problem by replacing the capsule formulation with a refrigerated gelcap. In 2000, Abbott (now AbbVie) received FDA-approval for a tablet formulation of lopinavir/ritonavir (Kaletra) which contained a preparation of ritonavir that did not require refrigeration. Ritonavir produced in a solid dispersion by melt-extrusion was found to remain in form I, and was re-introduced commercially in 2010.

Society and culture
Economics
In 2003, Abbott (AbbVie, Inc.) raised the price of a Norvir course from US$1.71 per day to US$8.57 per day, leading to claims of price gouging by patients groups and some members of Congress. Consumer group Essential Inventions petitioned the NIH to override the Norvir patent, but the NIH announced on August 4, 2004, that it lacked the legal right to allow generic production of Norvir.

Research
In 2020, the fixed-dose combination of lopinavir/ritonavir was found not to work in severe COVID-19 </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Atoltivimab/maftivimab/odesivimab and explain in detail? [/INST] Atoltivimab/maftivimab/odesivimab, sold under the brand name Inmazeb, is a fixed-dose combination of three monoclonal antibodies for the treatment of Zaire ebolavirus (Ebola virus). It contains atoltivimab, maftivimab, and odesivimab-ebgn and was developed by Regeneron Pharmaceuticals.The most common side effects include fever, chills, tachycardia (fast heart rate), tachypnea (fast breathing), and vomiting; however, these are also common symptoms of Ebola virus infection.Atoltivimab/maftivimab/odesivimab is the first FDA-approved treatment for Zaire ebolavirus. Atoltivimab/maftivimab/odesivimab was approved for medical use in the United States in October 2020. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.

Medical uses
Atoltivimab/maftivimab/odesivimab is indicated for the treatment of infection caused by Zaire ebolavirus.

Contraindications
People who receive atoltivimab/maftivimab/odesivimab should avoid the concurrent administration of a live vaccine due to the treatments potential to inhibit replication of a live vaccine virus indicated for prevention of Ebola virus infection and possibly reduce the vaccines efficacy.

Pharmacology
Mechanism of action
Atoltivimab/maftivimab/odesivimab is a combination of Zaire ebolavirus glycoprotein-directed human monoclonal antibodies. The three antibodies target the glycoprotein that is on the surface of the Ebola virus. This glycoprotein normally attaches to the cell via a receptor and fuses the viral and host cell membranes allowing the virus to enter the cell. The antibodies can bind to it simultaneously at three different locations and block attachment and entry of the virus.This combination drug targets the Zaire species of Ebola virus. The Sudan and Bundibugyo strains have also caused outbreaks, and it is unlikely that it would be effective against these strains.

History
Early development
The 2014 Ebola outbreak killed more than 11,300 people. Regeneron used its VelociGene, VelocImmune and VelociMab antibody discovery and production technologies and coordinated with the U.S. governments Biomedical Advanced Research and Development Authority (BARDA).  The therapy was developed in six months and a Phase 1 trial in healthy humans was completed in 2015.

PALM trial
During the 2018 Équateur province Ebola outbreak, a similar monoclonal antibody treatment, mAb114, was requested by the Democratic Republic of Congo (DRC) Ministry of Public Health. mAb114 was approved for compassionate use by the World Health Organization MEURI ethical protocol and at DRC ethics board. mAb114 was sent along with other therapeutic agents to the outbreak sites. However, the outbreak came to a conclusion before any therapeutic agents were given to patients.Approximately one month following the conclusion of the Équateur province outbreak, a distinct outbreak was noted in Kivu in the DRC (2018–20 Kivu Ebola outbreak). Once again, mAb114 received approval for compassionate use by WHO MEURI and DRC ethic boards and has been given to many patients under these protocols. In November 2018, the Pamoja Tulinde Maisha (PALM [together save lives]) open-label randomized clinical control trial was begun at multiple treatment units testing mAb114, REGN-EB3 and remdesivir to ZMapp. Despite the difficulty of running a clinical trial in a conflict zone, investigators have enrolled 681 patients towards their goal of 725.
This is the second largest outbreak with (as of January 2020) over 3,400 confirmed or probable cases, including more than 2,200 who have died.An interim analysis by the Data Safety and Monitoring Board (DSMB) of the first 499 patient found that mAb114 and REGN-EB3 were superior to the comparator ZMapp. Overall mortality of patients in the ZMapp and Remdesivir groups were 49% and 53% compared to 34% and 29% for mAb114 and REGN-EB3. When looking at patients who arrived early after disease symptoms appeared, survival was 89% for mAB114 and 94% for REGN-EB3.  While the study was not powered to determine whether there is any difference between REGN-EB3 and mAb114, the survival difference between those two therapies and ZMapp was significant. This led to the DSMB halting the study and PALM investigators dropping the remdesivir and ZMapp arms from the clinical trial. All patients in the outbreak who elect to participate in the trial will now be given either mAb114 or REGN-EB3.In August 2019, Congolese health officials announced it was more effective compared to two other treatments being used at the time.Among patients treated with it, 34% died; the mortality rate improved if the drug was administered soon after infection, in a timely diagnosis – critical for those infected with diseases like Ebola that can cause sepsis and, eventually, multiple organ dysfunction syndrome, more quickly than other diseases.  The survival rate if the drug was administered shortly after the infection was 89%.
Atoltivimab/maftivimab/odesivimab was evaluated in 382 adult and pediatric participants with confirmed Zaire ebolavirus infection in one clinical trial (the PALM trial) and as part of an expanded access program conducted in the Democratic Republic of the Congo (DRC) during an Ebola virus outbreak in 2018/2019. In the PALM trial, the safety and efficacy of atoltivimab/maftivimab/odesivimab was evaluated in a multi-center, open-label, randomized controlled trial, in which 154 participants received atoltivimab/maftivimab/odesivimab (50 mg of each monoclonal antibody) intravenously as a single infusion, and 168 participants received an investigational control. The trial enrolled pediatric and adult participants (including pregnant women) with Zaire ebolavirus infection. All participants received standard, supportive care for the disease. The participants and the health care providers knew which treatment was being given. The primary efficacy endpoint was 28-day mortality. The primary analysis population was all participants who were randomized and concurrently eligible to receive either atoltivimab/maftivimab/odesivimab or the investigational control during the same time period of the trial. Of the 154 participants who received atoltivimab/maftivimab/odesivimab, 33.8% died after 28 days, compared to 51% of the 153 participants who received a control. In the expanded access program, an additional 228 participants received atoltivimab/maftivimab/odesivimab.

Regulatory status
The FDA granted the application of atoltivimab/maftivimab/odesivimab-ebgn orphan drug and breakthrough therapy designations. The FDA granted the approval of Inmazeb to Regeneron Pharmaceuticals with an indication for the treatment of infection caused by Zaire ebolavirus in October 2020.The drug has also received orphan drug designation from the European Medicines Agency.

References
Further reading
External links
"Atoltivimab" </s>


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


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Muses and explain in detail? [/INST] In ancient Greek religion and mythology, the Muses (Ancient Greek: Μοῦσαι, romanized: Moûsai, Greek: Μούσες, romanized: Múses) are the inspirational goddesses of literature, science, and the arts. They were considered the source of the knowledge embodied in the poetry, lyric songs, and myths that were related orally for centuries in ancient Greek culture.
Melete, Aoede, and Mneme are the original Boeotian Muses, and Calliope, Clio, Erato, Euterpe, Melpomene, Polyhymnia, Terpsichore, Thalia, and Urania are the nine Olympian Muses.
In modern figurative usage, a Muse may be a source of artistic inspiration.

Etymology
The word Muses (Ancient Greek: Μοῦσαι, romanized: Moûsai) perhaps came from the o-grade of the Proto-Indo-European root *men- (the basic meaning of which is put in mind in verb formations with transitive function and have in mind in those with intransitive function), or from root *men- (to tower, mountain) since all the most important cult-centres of the Muses were on mountains or hills. R. S. P. Beekes rejects the latter etymology and suggests that a Pre-Greek origin is also possible.

Number and names
The earliest known records of the Muses come from Boeotia (Boeotian muses). Some ancient authorities regarded the Muses as of Thracian origin. In Thrace, a tradition of three original Muses persisted.In the first century BC, Diodorus Siculus cited Homer and Hesiod to the contrary, observing:

 Writers similarly disagree also concerning the number of the Muses; for some say that there are three, and others that there are nine, but the number nine has prevailed since it rests upon the authority of the most distinguished men, such as Homer and Hesiod and others like them.
Diodorus states (Book I.18) that Osiris first recruited the nine Muses, along with the satyrs, while passing through Aethiopia, before embarking on a tour of all Asia and Europe, teaching the arts of cultivation wherever he went.
According to Hesiods account (c. 600 BC), generally followed by the writers of antiquity, the Nine Muses were the nine daughters of Zeus and Mnemosyne (i.e., "Memory" personified), figuring as personifications of knowledge and the arts, especially poetry, literature, dance and music.
The Roman scholar Varro (116–27 BC) relates that there are only three Muses: one born from the movement of water, another who makes sound by striking the air, and a third who is embodied only in the human voice. They were called Melete or "Practice", Mneme or "Memory" and Aoide or "Song". The Quaestiones Convivales of Plutarch (46–120 AD) also report three ancient Muses (9.I4.2–4).However, the classical understanding of the Muses tripled their triad and established a set of nine goddesses, who embody the arts and inspire creation with their graces through remembered and improvised song and mime, writing, traditional music, and dance. It was not until Hellenistic times that the following systematic set of functions became associated with them, and even then some variation persisted both in their names and in their attributes:

According to Pausanias, who wrote in the later second century AD, there were originally three Muses, worshipped on Mount Helicon in Boeotia: Aoide (song or tune), Melete (practice or occasion), and Mneme (memory). Together, these three form the complete picture of the preconditions of poetic art in cult practice.
In Delphi too three Muses were worshiped, but with other names: Nete, Mese, and Hypate, which are assigned as the names of the three chords of the ancient musical instrument, the lyre.Alternatively, later they were called Cephisso, Apollonis, and Borysthenis - names which characterize them as daughters of Apollo.A later tradition recognized a set of four Muses: Thelxinoë, Aoide, Archē, and Melete, said to be daughters of Zeus and Plusia or of Ouranos.

One of the people frequently associated with the Muses was Pierus. By some he was called the father (by a Pimpleian nymph, called Antiope by Cicero) of a total of seven Muses, called Neilṓ (Νειλώ), Tritṓnē (Τριτώνη), Asōpṓ (Ἀσωπώ), Heptápora (Ἑπτάπορα), Achelōís, Tipoplṓ (Τιποπλώ), and Rhodía (Ῥοδία).

Mythology
According to Hesiods Theogony (seventh century BC), they were daughters of Zeus, king of the gods, and Mnemosyne, Titan goddess of memory. Hesiod in Theogony narrates that the Muses brought to people forgetfulness, that is, the forgetfulness of pain and the cessation of obligations.For Alcman and Mimnermus, they were even more primordial, springing from the early deities Ouranos and Gaia. Gaia is Mother Earth, an early mother goddess who was worshipped at Delphi from prehistoric times, long before the site was rededicated to Apollo, possibly indicating a transfer to association with him after that time.
Sometimes the Muses are referred to as water nymphs, associated with the springs of Helicon and with Pieris. It was said that the winged horse Pegasus touched his hooves to the ground on Helicon, causing four sacred springs to burst forth, from which the Muses, also known as pegasides, were born. Athena later tamed the horse and presented him to the Muses (compare the Roman inspiring nymphs of springs, the Camenae, the Völva of Norse Mythology and also the apsaras in the mythology of classical India).
Classical writers set Apollo as their leader, Apollon Mousēgetēs (Apollo Muse-leader). In one myth, the Muses judged a contest between Apollo and Marsyas. They also gathered the pieces of the dead body of Orpheus, son of Calliope, and buried them in Leivithra. In a later myth, Thamyris challenged them to a singing contest. They won and punished Thamyris by blinding him and robbing him of his singing ability.
According to a myth from Ovids Metamorphoses—alluding to the connection of Pieria with the Muses—Pierus, king of Macedon, had nine daughters he named after the nine Muses, believing that their skills were a great match to the Muses. He thus challenged the Muses to a match, resulting in his daughters, the Pierides, being turned into chattering jays (with κίσσα often erroneously translated as magpies) for their presumption.Pausanias records a tradition of two generations of Muses; the first are the daughters of Ouranos and Gaia, the second of Zeus and Mnemosyne. Another, rarer genealogy is that they are daughters of Harmonia (the daughter of Aphrodite and Ares), which contradicts the myth in which they were dancing at the wedding of Harmonia and Cadmus.

Children
Calliope had two sons, Ialemus and Orpheus, with Apollo. In another version of the story, the father of Orpheus was Oeagrus, but Apollo adopted him and taught him the skill of lyre while Calliope trained him in singing.
Linus was said to have been the son of Apollo and one of the Muses, either Calliope or Terpsichore or Urania. Rhesus was the son of Strymon and Calliope or Euterpe.
The sirens were the children of Achelous and Melpomene or Terpsichore. Kleopheme was the daughter of Erato and Malos. Hyacinth was the son of Clio, according to an unpopular account.
Hymenaeus was assigned as Apollos son by one of the muses, either Calliope, or Clio, or Terpsichore, or Urania. Corybantes were the children of Thalia and Apollo.

Cult
The Muses had several temples and shrines in ancient Greece, their two main cult centres being Mount Helikon in Boiotia and Pieria in Makedonia.
Strabo wrote:

"Helikon, not far distant from Parnassos, rivals it both in height and in circuit; for both are rocky and covered with snow, and their circuit comprises no large extent of territory. Here are the temple of the Mousai and Hippukrene and the cave of the Nymphai called the Leibethrides; and from this fact one might infer that those who consecrated Helikon to the Mousai were Thrakians, the same who dedicated Pieris and Leibethron and Pimpleia [in Pieria] to the same goddesses. The Thrakians used to be called Pieres, but, now that they have disappeared, the Makedonians hold these places."The cult of the Muses was also commonly connected to that of Apollo.

Emblems
Some Greek writers give the names of the nine Muses as Kallichore, Helike, Eunike, Thelxinoë, Terpsichore, Euterpe, Eukelade, Dia, and Enope.In Renaissance and Neoclassical art, the dissemination of emblem books such as Cesare Ripas Iconologia (1593 and many further editions) helped standardize the depiction of the Muses in sculpture and painting, so they could be distinguished by certain props. These props, or emblems, became readily identifiable by the viewer, enabling one immediately to recognize the Muse and the art with which she had become associated. Here again, Calliope (epic poetry) carries a writing tablet; Clio (history) carries a scroll and books; Euterpe (song and elegiac poetry) carries a flute, the aulos; Erato (lyric poetry) is often seen with a lyre and a crown of roses; Melpomene (tragedy) is often seen with a tragic mask; Polyhymnia (sacred poetry) is often seen with a pensive expression; Terpsichore (choral dance and song) is often seen dancing and carrying a lyre; Thalia (comedy) is often seen with a comic mask; and Urania (astronomy) carries a pair of compasses and the celestial globe.

Functions
In society
The Greek word mousa is a common noun as well as a type of goddess: it literally means art or poetry. According to Pindar, to "carry a mousa" is to excel in the arts. The word derives from the Indo-European root *men-, which is also the source of Greek Mnemosyne and mania, English mind, mental and monitor, Sanskrit mantra and Avestan Mazda.

The Muses, therefore, were both the embodiments and sponsors of performed metrical speech: mousike (whence the English term music) was just "one of the arts of the Muses". Others included science, geography, mathematics, philosophy, and especially art, drama, and inspiration. In the archaic period, before the widespread availability of books (scrolls), this included nearly all of learning. The first Greek book on astronomy, by Thales, took the form of dactylic hexameters, as did many works of pre-Socratic philosophy. Both Plato and the Pythagoreans explicitly included philosophy as a sub-species of mousike. The Histories of Herodotus, whose primary medium of delivery was public recitation, were divided by Alexandrian editors into nine books, named after the nine Muses.
For poet and "law-giver" Solon, the Muses were "the key to the good life"; since they brought both prosperity and friendship. Solon sought to perpetuate his political reforms by establishing recitations of his poetry—complete with invocations to his practical-minded Muses—by Athenian boys at festivals each year. He believed that the Muses would help inspire people to do their best.

In literature
Ancient authors and their imitators invoke Muses when writing poetry, hymns or epic history. The invocation occurs near the beginning of their work. It asks for help or inspiration from the Muses, or simply invites the Muse to sing directly through the author.
Originally, the invocation of the Muse was an indication that the speaker was working inside the poetic tradition, according to the established formulas. For example:

These things declare to me from the beginning,
ye Muses who dwell in the house of Olympus,
and tell me which of them first came to be.
— Hesiod (c. 700 BCE), Theogony (Hugh G. Evelyn-White translation, 2015)

Sing to me of the man, Muse, the man of twists and turns
driven time and again off course, once he had plundered
the hallowed heights of Troy.

—Homer (c. 700 - 600 BCE), in Book I of The Odyssey (Robert Fagles translation, 1996)
O Muse! the causes and the crimes relate;
What goddess was provokd, and whence her hate;
For what offence the Queen of Heavn began
To persecute so brave, so just a man; [...]

—Virgil (c. 29 - 19 BCE), in Book I of the Aeneid (John Dryden translation, 1697)
Besides Homer and Virgil, other famous works that included an invocation of the Muse are the first of the carmina by Catullus, Ovids Metamorphoses and Amores, Dantes Inferno (Canto II), Chaucers Troilus and Criseyde (Book II), Shakespeares Henry V (Act 1, Prologue), his 38th sonnet, and Miltons Paradise Lost (openings of Books 1 and 7).

In cults and modern museums
When Pythagoras arrived at Croton, his first advice to the Crotoniates was to build a shrine to the Muses at the center of the city, to promote civic harmony and learning. Local cults of the Muses often became associated with springs or with fountains. The Muses themselves were sometimes called Aganippids because of their association with a fountain called Aganippe. Other fountains, Hippocrene and Pirene, were also important locations associated with the Muses. Some sources occasionally referred to the Muses as "Corycides" (or "Corycian nymphs") after a cave on Mount Parnassos, called the Corycian Cave. Pausanias referred to the Muses by the surnames "Ardalides" or "Ardaliotides", because of a sanctuary to them at Troezen said to have been built by the mythical Ardalus.
The Muses were venerated especially in Boeotia, in the Valley of the Muses near Helicon, and in Delphi and the Parnassus, where Apollo became known as Mousēgetēs (Muse-leader) after the sites were rededicated to his cult.
Often Muse-worship was associated with the hero-cults of poets: the tombs of Archilochus on Thasos and of Hesiod and Thamyris in Boeotia all played host to festivals in which poetic recitations accompanied sacrifices to the Muses. The Library of Alexandria and its circle of scholars formed around a mousaion (i.e., museum or shrine of the Muses) close to the tomb of Alexander the Great. Many Enlightenment figures sought to re-establish a "Cult of the Muses" in the 18th century. A famous Masonic lodge in pre-Revolutionary Paris was called Les Neuf Soeurs (The Nine Sisters, that is, the Nine Muses); Voltaire, Benjamin Franklin, Danton, and other influential Enlightenment figures attended it. As a side-effect of this movement the word museum (originally, cult place of the Muses) came to refer to a place for the public display of knowledge.
Museia (Μούσεια) was a festival dedicated to Muses which was held every fifth year on the lower slopes of Mount Helicon in Boeotia. There was also another festival which was called Museia, which was celebrated in schools.

Places named after the Muses
In New Orleans, Louisiana, there are streets named for all nine. It is commonly held that the local pronunciation of the names has been colorfully anglicized in an unusual manner by the "Yat" dialect. The pronunciations are actually in line with the French, Spanish and Creole roots of the city.

Modern use in the arts
The Muses are explicitly used in modern English to refer to an artistic inspiration, as when one cites ones own artistic muse, and also implicit in words and phrases such as amuse, museum (Latinised from mouseion—a place where the Muses were worshipped), music, and musing upon. In current literature, the influential role that the Muse plays has been extended to the political sphere.

Gallery
Genealogy
See also
Apsara
Artistic inspiration
Divine inspiration
Leibethra
Pimpleia
Saraswati
Muses in popular culture

Notes
References
West, Martin L. (2007). Indo-European Poetry and Myth. Oxford University Press </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Reslizumab and explain in detail? [/INST] Reslizumab is a humanized monoclonal antibody against human interleukin-5 (IL-5). Reslizumab binds specifically to IL-5, a key cytokine responsible for the differentiation, maturation, recruitment and activation of human eosinophils. By binding to human IL-5, it blocks its biological function; consequently survival and activity of eosinophils are reduced. The benefits with reslizumab are its ability to reduce the exacerbation rate and improve lung function and asthma-related quality of life in patients with severe eosinophilic asthma (with blood eosinophil count ≥ 400 cells/μL) and with at least one previous asthma exacerbation in the preceding year. The most common side effects are increased blood creatine phosphokinase, myalgia and anaphylactic reactions.The FDA approved reslizumab (US trade name Cinqair) for use with other asthma medicines for the maintenance treatment of severe asthma in patients aged 18 years and older on 23 March 2016. Cinqair is approved for patients who have a history of severe asthma attacks (exacerbations) despite receiving their current asthma medicines.The European Medicines Agency recommended the granting of a marketing authorisation for reslizumab (EU trade name Cinqaero) intended as add-on treatment in adult patients with severe eosinophilic asthma on 23 June 2016.Reslizumab is supplied as a refrigerated, sterile, single-use, preservative-free solution for intravenous infusion. The reslizumab solution is a slightly hazy/opalescent, slightly yellow liquid and is supplied as 100 mg in a 10 mL glass vial. Each single-use vial of reslizumab is formulated as 10 mg/mL reslizumab in an aqueous solution containing 2.45 mg/mL sodium acetate trihydrate, 0.12 mg/mL glacial acetic acid, and 70 mg/mL sucrose, with a pH of 5.5.

Medical uses
Eosinophilic asthma
Reslizumab was first used for eosinophilic asthma in 2008. In a 106-patient, phase II clinical trial, the researchers showed reslizumab was effective in reducing sputum eosinophils. Furthermore, the patients receiving reslizumab showed improvements in airway function, and a general trend toward greater asthma control than those receiving placebo was observed. A large, 981-patient, phase III clinical trial showed that reslizumab was effective at improving lung function, asthma control, and quality of life in comparison to placebo. These results led to the FDA approval for the maintenance treatment of severe asthma in patients aged 18 years and older, with an eosinophilic phenotype on March 23, 2016.

Adverse effects
Common adverse effects include:

oropharyngeal painLess common adverse effects include:

musculoskeletal pain
neck pain
muscle spasms
extremity pain
muscle fatigue
anaphylaxis
malignancyThe most common adverse effect of reslizumab was oropharyngeal (mouth and throat) pain. According to the phase III clinical trials data, oropharyngeal pain occurred in ≥2% of individuals along with elevated baseline creatine phosphokinase (CPK), which was more common in patients treated with reslizumab versus placebo. Myalgia was also reported more in patients in the reslizumab 3 mg/kg group versus the placebo group as well as some musculoskeletal adverse reactions. Lastly, some serious adverse reactions that occurred in subjects treated with reslizumab but not in those treated with placebo included anaphylaxis and malignancy.

Pharmacology
Mechanism of action
Reslizumab is an interleukin-5 antagonist monoclonal antibody. IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils. Eosinophils play a role in the mediation of inflammation in the airways. Eosinophilic asthma is a phenotype of asthma that is characterized by the higher than normal presence of eosinophils in the lung and sputum. It has been shown that the numbers of eosinophils in the blood and bronchial fluid can correlate with asthma severity. Reslizumab binds to IL-5 with a dissociation constant of 81 pM and inhibiting IL-5 signaling, which reduces the production and survival of eosinophils. However, the mechanism of reslizumab action in asthma has not been definitively established.

Pharmacodynamics
Reductions in blood eosinophil counts were observed following the first dose of reslizumab and maintained through 52 weeks of treatment. In phase III clinical trials, mean eosinophil counts were 696 cells/µL (n=245) and 624 cells/µL (n=244) at baseline. Following 52 weeks of reslizumab treatment, eosinophil cells were counted and were reported to be 55 cells/µL (92% reduction, n=212) and 496 cells/µL (21% reduction, n=212) for the reslizumab and placebo treatment groups, respectively. Furthermore, eosinophil count returned towards baseline in those reslizumab-treated patients who completed a follow-up assessment (n=35, 480 cells/µL), approximately 120 days after the last dose of reslizumab. Therefore, reductions of blood eosinophils were related to reslizumab serum levels.

Pharmacokinetics
The pharmacokinetic characteristics of reslizumab are similar across the children and adults. Peak serum concentrations are observed at the end of infusion and declines in a biphasic manner </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Bismuth subsalicylate and explain in detail? [/INST] Bismuth subsalicylate, sold generically as pink bismuth and under the brand names Pepto-Bismol and BisBacter, is an antacid elixir medication used to treat temporary discomforts of the stomach and gastrointestinal tract, such as nausea, heartburn, indigestion, upset stomach, and diarrhea.
Bismuth subsalicylate has the empirical chemical formula of C7H5BiO4, and it is a colloidal substance obtained by hydrolysis of bismuth salicylate (Bi(C6H4(OH)CO2)3).

Medical uses
As a derivative of salicylic acid, bismuth subsalicylate displays anti-inflammatory and bactericidal action. It also acts as an antacid.

Adverse effects
There are some adverse effects. It can cause a black tongue and black stools in some users of the drug when it combines with trace amounts of sulfur in saliva and the colon to form bismuth sulfide. Bismuth sulfide is a highly insoluble black salt, and the discoloration seen is temporary and harmless.
Long-term use (greater than six weeks) may lead to accumulation and toxicity. Some of the risks of salicylism can apply to the use of bismuth subsalicylate.Children should not take medication with bismuth subsalicylate while recovering from influenza or chicken pox, as epidemiologic evidence points to an association between the use of salicylate-containing medications during certain viral infections and the onset of Reye syndrome. For the same reason, it is typically recommended that nursing mothers not use medication containing bismuth subsalicylate because small amounts of the medication are excreted in human breast milk, and these pose a theoretical risk of Reyes syndrome to nursing children.Salicylates are very toxic to cats, and thus bismuth subsalicylate should not be administered to cats.The British National Formulary does not recommend bismuth-containing antacids (unless chelated), cautioning that absorbed bismuth can be neurotoxic, causing encephalopathy, and that such antacids tend to be constipating.

Drug interactions
There is an increased risk of bleeding when using bismuth subsalicylate and anticoagulation therapy, like Coumadin (Warfarin)

Mechanism of action
Bismuth subsalicylate is used as an antacid and antidiarrheal, and to treat some other gastrointestinal symptoms, such as nausea. The means by which this occurs is still not well documented. It is thought to be some combination of the following:
Stimulation of absorption of fluids and electrolytes by the intestinal wall (antisecretory action)
As a salicylate, reducing inflammation/irritation of stomach and intestinal lining through inhibition of prostaglandin G/H synthase 1/2
Reduction in hypermotility of the stomach
Inhibits adhesion and filmogenesis by Escherichia coli
Bactericidal action of a number of its subcomponents, including salicylic acid
Bactericidal action via a so-called oligodynamic effect in which small amounts of heavy metals such as bismuth damage many different bacteria species.
Weak antacid propertiesIn vitro and in vivo data have shown that bismuth subsalicylate hydrolyzes in the gut to bismuth oxychloride and salicylic acid and less commonly bismuth hydroxide. In the stomach, this is likely an acid-catalyzed hydrolysis. The salicylic acid is absorbed and therapeutical concentrations of salicylic acid can be found in blood after bismuth subsalicylate administration. Bismuth oxychloride and bismuth hydroxide are both believed to have bactericidal effects, as is salicylic acid for enterotoxigenic E. coli a common cause of "travelers diarrhea."Organobismuth compounds have historically been used in growth media for selective isolation of microorganisms. Such salts have been shown to inhibit proliferation of Helicobacter pylori, other enteric bacteria, and some fungi.

Structure
Despite its common usage and commercial significance, the exact structure of the pharmaceutical long remained undetermined, but was revealed, through the use of advanced electron crystallography techniques, to be a layered coordination polymer with the formula BiO(C7H5O3). In the structure, both the carboxylate and phenol groups of the salicylate coordinate towards the bismuth cations. The determination of bismuth subsalicylate had long been hindered due to the small particle size as well as defects within the structure, arising from variations in the stacking arrangement of the bismuth subsalicylate layers, which could be observed as part of the structural investigation.

History
While bismuth salts were in use in Europe by the late 1700s, the combination of bismuth subsalicylate and zinc salts for astringency with salol (phenyl salicylate) appears to have begun in the US in the early 1900s as a remedy for life-threatening diarrhea in infants with cholera. At first sold directly to physicians, it was first marketed as Bismosal in 1918.Pepto-Bismol began being sold in 1900 or 1901 by a doctor in New York </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Prednisone and explain in detail? [/INST] Prednisone is a glucocorticoid medication mostly used to suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium due to cancer and adrenal insufficiency along with other steroids. It is taken by mouth.Common side effects with long-term use include cataracts, bone loss, easy bruising, muscle weakness, and thrush. Other side effects include weight gain, swelling, high blood sugar, increased risk of infection, and psychosis. It is generally considered safe in pregnancy and low doses appear to be safe when breastfeeding. After prolonged use, prednisone needs to be stopped gradually.Prednisone is a prodrug and must be converted to prednisolone by the liver before it becomes active. Prednisolone then binds to glucocorticoid receptors, activating them and triggering changes in gene expression.Prednisone was patented in 1954 and approved for medical use in the United States in 1955. It is on the World Health Organizations List of Essential Medicines. It is available as a generic medication. In 2020, it was the 30th most commonly prescribed medication in the United States, with more than 19 million prescriptions.

Medical uses
Prednisone is used for many different autoimmune diseases and inflammatory conditions, including asthma, gout, COPD, CIDP, rheumatic disorders, allergic disorders, ulcerative colitis and Crohns disease, granulomatosis with polyangiitis, adrenocortical insufficiency, hypercalcemia due to cancer, thyroiditis, laryngitis, severe tuberculosis, hives, lipid pneumonitis, pericarditis, multiple sclerosis, nephrotic syndrome, sarcoidosis, to relieve the effects of shingles, lupus, myasthenia gravis, poison oak exposure, Ménières disease,  autoimmune hepatitis, giant-cell arteritis, the Herxheimer reaction that is common during the treatment of syphilis, Duchenne muscular dystrophy, uveitis, and as part of a drug regimen to prevent rejection after organ transplant.Prednisone has also been used in the treatment of migraine headaches and cluster headaches and for severe aphthous ulcer. Prednisone is used as an antitumor drug. It is important in the treatment of acute lymphoblastic leukemia, non-Hodgkin lymphomas, Hodgkins lymphoma, multiple myeloma, and other hormone-sensitive tumors, in combination with other anticancer drugs.
Prednisone is often also prescribed as a form of treatment for Sudden Sensorineural Hearing Loss (SSNHL).Prednisone can be used in the treatment of decompensated heart failure to increase renal responsiveness to diuretics, especially in heart failure patients with refractory diuretic resistance with large doses of loop diuretics. In terms of the mechanism of action for this purpose: prednisone, a glucocorticoid, can improve renal responsiveness to atrial natriuretic peptide by increasing the density of natriuretic peptide receptor type A in the renal inner medullary collecting duct, thereby inducing a potent diuresis.At high doses it may be used to prevent rejection following organ transplant.

Side effects
Short-term side effects, as with all glucocorticoids, include high blood glucose levels (especially in patients with diabetes mellitus or on other medications that increase blood glucose, such as tacrolimus) and mineralocorticoid effects such as fluid retention. The mineralocorticoid effects of prednisone are minor, which is why it is not used in the management of adrenal insufficiency, unless a more potent mineralocorticoid is administered concomitantly.
It can also cause depression or depressive symptoms and anxiety in some individuals.Long-term side effects include Cushings syndrome, steroid dementia syndrome, truncal weight gain, glaucoma and cataracts, diabetes mellitus type 2, and depression upon dose reduction or cessation. Long-term steroids can also increase the risk of osteoporosis, but research has found that few of these people were taking medications to protect bones. Prednisone also results in leukocytosis.When used as treatment for sudden deafness or sudden sensorineural hearing loss, it can cause or exacerbate Tinnitus or a ringing in the ears.

Major
Source:

Minor
Source:

Dependency
Adrenal suppression will begin to occur if prednisone is taken for longer than seven days. Eventually, this may cause the body to temporarily lose the ability to manufacture natural corticosteroids (especially cortisol), which results in dependence on prednisone. For this reason, prednisone should not be abruptly stopped if taken for more than seven days; instead, the dosage should be gradually reduced. This weaning process may be over a few days if the course of prednisone was short, but may take weeks or months if the patient had been on long-term treatment. Abrupt withdrawal may lead to an Addisonian crisis. For those on chronic therapy, alternate-day dosing may preserve adrenal function and thereby reduce side effects.Glucocorticoids act to inhibit feedback of both the hypothalamus, decreasing corticotropin-releasing hormone (CRH), and corticotrophs in the anterior pituitary gland, decreasing the amount of adrenocorticotropic hormone (ACTH). For this reason, glucocorticoid analogue drugs such as prednisone down-regulate the natural synthesis of glucocorticoids. This mechanism leads to dependence in a short time and can be dangerous if medications are withdrawn too quickly. The body must have time to begin synthesis of CRH and ACTH and for the adrenal glands to begin functioning normally again.
Prednisone may start to result in the suppression of the hypothalamic-pituitary-adrenal (HPA) axis if used at doses 7–10 mg or higher for several weeks. This is approximately equal to the amount of endogenous cortisol produced by the body every day. As such, the HPA axis starts to become suppressed and atrophy. If this occurs the patient should be tapered off prednisone slowly to give the adrenal gland enough time to regain its function and endogenous production of steroids. Supplemental doses, or "stress doses" may be required in those with HPA axis suppression who are experiencing a higher degree of stress (e.g., illness, surgery, trauma, etc.). Failing to do so in such situations could be life-threatening.

Withdrawal
The magnitude and speed of dose reduction in corticosteroid withdrawal should be determined on a case-by-case basis, taking into consideration the underlying condition being treated, and individual patient factors such as the likelihood of relapse and the duration of corticosteroid treatment. Gradual withdrawal of systemic corticosteroids should be considered in those whose disease is unlikely to relapse and have:

received more than 40 mg prednisone (or equivalent) daily for more than 1 week
been given repeat doses in the evening
received more than 3 weeks of treatment
recently received repeated courses (particularly if taken for longer than 3 weeks)
taken a short course within 1 year of stopping long-term therapy
other possible causes of adrenal suppressionSystemic corticosteroids may be stopped abruptly in those whose disease is unlikely to relapse and who have received treatment for 3 weeks or less and who are not included in the patient groups described above.
During corticosteroid withdrawal, the dose may be reduced rapidly down to physiological doses (equivalent to prednisolone 7.5 mg daily) and then reduced more slowly. Assessment of the disease may be needed during withdrawal to ensure that relapse does not occur.

Pharmacology
Prednisone is a synthetic glucocorticoid used for its anti-inflammatory and immunosuppressive properties. Prednisone is a prodrug; it is metabolised in the liver by 11-β-HSD to prednisolone, the active drug. Prednisone has no substantial biological effects until converted via hepatic metabolism to prednisolone.

Pharmacokinetics
Prednisone is absorbed in the gastrointestinal tract and has a half life of 2–3 hours. it has a volume of distribution of 0.4–1 L/kg. The drug is cleared by hepatic metabolism using cytochrome P450 enzymes. Metabolites are excreted in the bile and urine.

Lodotra
"Lodotra" is the brand name of an oral formulation, which releases prednisone four hours after ingestion. It is indicated for rheumatoid arthritis with morning stiffness </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Benzoyl peroxide and explain in detail? [/INST] Benzoyl peroxide is a chemical compound (specifically, an organic peroxide) with structural formula  (C6H5−C(=O)O−)2, often abbreviated as (BzO)2.  In terms of its structure, the molecule can be described as two benzoyl (C6H5−C(=O)−, Bz) groups connected by a peroxide (−O−O−).  It is a white granular  solid with a faint odour of benzaldehyde, poorly soluble in water but soluble in acetone, ethanol, and many other organic solvents. Benzoyl peroxide is an oxidizer, which is principally used as in the production of polymers.As a bleach, it has been used as a medication and a water disinfectant. In specialized contexts, the name may be abbreviated as BPO.
As a medication, benzoyl peroxide is mostly used to treat acne, either alone or in combination with other treatments. Some versions are sold mixed with antibiotics such as clindamycin. It is on the WHO List of Essential Medicines, and, in the US, it is available as an over-the-counter and generic medication. It is also used in dentistry for teeth whitening.
Benzoyl peroxide is also used in the plastics industry and for bleaching flour, hair, and textiles. It is also used to remove stubborn stains from dolls and other plastic toys, although some users have claimed that the product has unwanted long-term effects of discolouring the item, particularly with the My Little Pony brand.

History
Benzoyl peroxide was first prepared and described by Liebig in 1858.  It was the first organic peroxide prepared intentionally.In 1901, J. H. Kastle and his graduate student A. S. Loevenhart observed that the compound made the tincture of guaiacum tincture turn blue, a sign of oxygen being released.  Around  1905, Loevenhart reported on the successful use of BPO to treat various skin conditions, including burns, chronic varicose leg tumors, and tinea sycosis. He also reported animal experiments that showed the relatively low toxicity of the compound.Treatment with benzoyl peroxide was proposed for wounds by Lyon and Reynolds in 1929, and for sycosis vulgaris and acne varioliformis by Peck and Chagrin in 1934. However, preparations were often of questionable quality.  It was officially approved for the treatment of acne in the US in 1960.

Medical uses
Acne treatment
Benzoyl peroxide is effective for treating acne lesions. It does not induce antibiotic resistance. It may be combined with salicylic acid, sulfur, erythromycin or clindamycin (antibiotics), or adapalene (a synthetic retinoid).  Two common combination drugs include benzoyl peroxide/clindamycin and adapalene/benzoyl peroxide, adapalene being a chemically stable retinoid that can be combined with benzoyl peroxide unlike tezarotene and tretinoin. Combination products such as benzoyl peroxide/clindamycin and benzoyl peroxide/salicylic acid appear to be slightly more effective than benzoyl peroxide alone for the treatment of acne lesions. The combination tretinoin/benzoyl peroxide was approved for medical use in the United States in 2021.
Benzoyl peroxide for acne treatment is typically applied to the affected areas in gel, cream, or liquid, in concentrations of 2.5% increasing through 5.0%, and up to 10%. No strong evidence supports the idea that higher concentrations of benzoyl peroxide are more effective than lower concentrations.

Mechanism of action
Classically, benzoyl peroxide is thought to have a three-fold activity in treating acne. It is sebostatic, comedolytic, and inhibits growth of  Cutibacterium acnes, the main bacterium associated with acne.  In general, acne vulgaris is a hormone-mediated inflammation of sebaceous glands and hair follicles. Hormone changes cause an increase in keratin and sebum production, leading to blocked drainage. C. acnes has many lytic enzymes that break down the proteins and lipids in the sebum, leading to an inflammatory response. The free-radical reaction of benzoyl peroxide can break down the keratin, therefore unblocking the drainage of sebum (comedolytic). It can cause nonspecific peroxidation of C. acnes, making it bactericidal, and it was thought to decrease sebum production, but  disagreement exists within the literature on this.Some evidence suggests that benzoyl peroxide has an anti-inflammatory effect as well. In micromolar concentrations it prevents neutrophils from releasing reactive oxygen species, part of the inflammatory response in acne.

Side effects
Application of benzoyl peroxide to the skin may result in redness, burning, and irritation. This side effect is dose-dependent.Because of these possible side effects, it is recommended to start with a low concentration and build up as appropriate, as the skin gradually develops tolerance to the medication. Skin sensitivity typically resolves after a few weeks of continuous use. Irritation can also be reduced by avoiding harsh facial cleansers and wearing sunscreen prior to sun exposure.One in 500 people experience hypersensitivity to BPO and are liable to experience burning, itching, crusting, and possibly swelling.  About one-third of people experience phototoxicity under exposure to ultraviolet (UVB) light.

Dosage
In the U.S., the typical concentration for benzoyl peroxide is 2.5% to 10% for both prescription and over-the-counter drug preparations that are used in treatment for acne.

Other medical uses
Benzoyl peroxide is used in dentistry as a tooth whitening product.

Non-medical uses
Bleaching
Like most peroxides, it is a powerful bleaching agent. It has been used for the bleaching of flour, fats, oils, waxes, and cheeses, as well as a stain remover.

Polymerization
Benzoyl peroxide is also used as a radical initiator to induce chain-growth polymerization reactions, such as for polyester and poly(methyl methacrylate) (PMMA) resins and dental cements and restoratives. It is the most important among the various organic peroxides used for this purpose, a relatively safe alternative to the much more hazardous methyl ethyl ketone peroxide.  It is also used in rubber curing and as a finishing agent for some acetate yarns.

Safety
Explosion hazard
Concentrated benzoyl peroxide is potentially explosive like other organic peroxides, and can cause fires without external ignition. The hazard is acute for the pure material, so the compound is generally used as a solution or a paste. For example, cosmetics contain only a small percentage of benzoyl peroxide and pose no explosion risk.

Toxicity
Benzoyl peroxide breaks down in contact with skin, producing benzoic acid and oxygen, neither of which is very toxic.The carcinogenic potential of benzoyl peroxide has been investigated. A 1981 study published in the journal Science found that although benzoyl peroxide is not a carcinogen, it does promote cell growth when applied to an initiated tumor. The study concluded, "caution should be recommended in the use of this and other free radical-generating compounds".A 1999 IARC review of carcinogenicity studies found no convincing evidence linking BPO acne medication to skin cancers in humans.  However, some animal studies found that the compound could act as a carcinogen and enhance the effect of known carcinogens.

Skin irritation
In a 1977 study using a human maximization test, 76% of subjects acquired a contact sensitization to benzoyl peroxide. Formulations of 5% and 10% were used.The U.S. National Institute for Occupational Safety and Health has developed criteria for a recommended standard for occupational exposure to benzoyl peroxide.

Cloth staining
Contact with fabrics or hair, such as from still-moist acne medication, can cause permanent color dampening almost immediately. Even secondary contact can cause bleaching, for example, contact with a towel that has been used to wash off benzoyl peroxide-containing hygiene products.

Reactivity
The original 1858 synthesis by Liebig reacted benzoyl chloride with barium peroxide, a reaction that probably follows this equation:

2 C6H5C(O)Cl + BaO2 → (C6H5CO)2O2 + BaCl2Benzoyl peroxide is usually prepared by treating hydrogen peroxide with benzoyl chloride under alkaline conditions.

2 C6H5COCl + H2O2 + 2 NaOH → (C6H5CO)2O2 + 2 NaCl + 2 H2OThe oxygen–oxygen bond in peroxides is weak </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Amiloride and explain in detail? [/INST] Amiloride, sold under the trade name Midamor among others, is a medication typically used with other medications to treat high blood pressure or swelling due to heart failure or cirrhosis of the liver. Amiloride is classified as a potassium-sparing diuretic. Amiloride is often used together with another diuretic, such as a thiazide or loop diuretic. It is taken by mouth. Onset of action is about two hours and it lasts for about a day.Common side effects include high blood potassium, vomiting, loss of appetite, rash, and headache. The risk of high blood potassium is greater in those with kidney problems, diabetes, and those who are older. Amiloride blocks the epithelial sodium channel (ENaC) in the late distal tubule, connecting tubule, and collecting duct of the nephron, which both reduces absorption of sodium ion from the lumen of the nephron and reduces excretion of potassium ion into the lumen.Amiloride was developed in 1967. It is on the World Health Organizations List of Essential Medicines.

Medical uses
Amiloride may be used in combination with a thiazide diuretic for treatment of high blood pressure or (less commonly) in combination with a loop diuretic for treatment of heart failure. The potassium-sparing effects of amiloride offset the low blood potassium (hypokalemia) that is often induced by thiazides or loop diuretics, which is of particular importance in people for whom maintaining a normal level of potassium is critically important. For example, people that are taking Digitalis (i.e. digoxin) are at higher risk for changes in heart rhythm if their potassium levels get too high. The 2017 clinical practice guidelines of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines list amiloride as a "secondary" oral antihypertensive, with minimal efficacy. For people with resistant hypertension, already taking a thiazide diuretic, an angiotensin converting enzyme inhibitor (ACE-i) or an angiotensin II receptor blocker (ARB), and a calcium channel blocker, the addition of amiloride (or spironolactone) was better at reducing blood pressure than adding a beta-blocker (bisoprolol) or an alpha-1 blocker (doxazosin). When combined with hydrochlorothiazide, the addition of amiloride had positive effects on blood pressure and blood sugar tolerance. Amiloride may therefore be useful for preventing the metabolic side effects of thiazide diuretics, allowing for the use of higher thiazide doses (in line with how they were originally studied).Amiloride is the treatment of choice for Liddle phenotype, which is characterized by high blood pressure, low blood potassium, and metabolic alkalosis in conjunction with a low plasma renin activity and a low aldosterone. Some people with the Liddle phenotype have Liddle syndrome, which involves a genetic mutation resulting in upregulation of the epithelial sodium channel (ENaC), located in the apical membrane of polarized epithelial cells in the late distal tubule and collecting duct of the kidney. Because Liddle phenotype usually involves an upregulation of ENaC channels, leading to retention of sodium and water and to hypokalemia, amiloride is useful as an ENaC channel inhibitor due to its promotion of sodium excretion and its potassium-sparing effects, restoring potassium to normal levels.Amiloride can be used as a monotherapy (single-drug therapy) or an adjunctive therapy alongside other diuretics (e.g. hydrochlorothiazide, furosemide) for the treatment of ascites and edema (swelling) due to cirrhosis of the liver. The 2012 clinical practice guidelines by the American Association for the Study of Liver Diseases (AASLD) states that amiloride can be used to treat ascites in place of spironolactone if it isnt tolerated (e.g. due to the side effect of gynecomastia), though amiloride isnt a preferred drug due to cost and lack of efficacy.

Specific populations
Diabetics
People with diabetes are at higher risk for kidney problems, which increases their risk for hyperkalemia (high blood potassium). The use of amiloride in people with diabetes requires careful potassium and kidney function monitoring to prevent toxicity. Amiloride must be discontinued for at least 3 days prior to glucose tolerance testing, due to the risk for fatal hyperkalemia.

Poor kidney function
People with poor kidney function (e.g. blood urea nitrogen >30 mg/dL, or serum creatinine >1.5 mg/dL) are at high risk for hyperkalemia.

Lactation
There is no data on the use of amiloride in women that are breastfeeding. While diuretics can make lactation difficult, it is unlikely that amiloride would induce this effect in the absence of other diuretics.

Pregnancy
Data from the use of amiloride in animals suggests that it does not pose a risk to the developing fetus. However, when used in combination with the drug acetazolamide during the process of organ formation, amiloride increases the risk for kidney and ureter abnormalities. Limited human data from use during pregnancy suggests an association with a specific congenital penis abnormality if taken during the first trimester, as well as a risk for mild intrauterine growth restriction if taken throughout pregnancy.

Contraindications
Amiloride is contraindicated in people with kidney problems (e.g. anuria, acute or chronic kidney disease, or diabetic nephropathy), elevated blood potassium (≥5.5 mEq/L), or people that are hypersensitive to amiloride or any ingredients within the specific formulation. Use is also contraindicated in people that are already taking potassium-sparing drugs (e.g. spironolactone and triamterene) or whom are taking potassium supplements (e.g. potassium chloride) in most circumstances.

Adverse effects
Amiloride is generally well tolerated. Common adverse effects to the use of amiloride include elevated blood potassium, mild skin rashes, headaches, and gastrointestinal side effects (nausea, vomiting, diarrhea, decreased appetite, flatulence, and abdominal pain). Mild symptoms of high blood potassium concentrations include unusual skin sensations, muscle weakness, or fatigue, but more severe symptoms such as flaccid paralysis of the limbs, slow heart rate, and even shock can occur.

Overdose
There exists no overdose data on amiloride in humans, though it is expected than an overdose would produce effects consistent with its therapeutic effects; e.g. dehydration due to over-diuresis, and electrolyte disturbances related to hyperkalemia. It is unknown if amiloride can be dialyzed off, and no specific antidote against it exists. Treatment is generally supportive, though hyperkalemia can be treated.

Interactions
Amiloride may have important drug-drug interactions when combined with other medications that also increase potassium levels in the blood, leading to hyperkalemia. For example, the combination of amiloride with angiotensin-converting enzyme (ACE) inhibitors like lisinopril, or angiotensin II receptor type 1 (AT1) antagonists like losartan, may lead to high levels of potassium in the blood, requiring frequent monitoring.

Pharmacology
Mechanism of action
Diuresis
Amiloride works by directly blocking the epithelial sodium channel (ENaC) with an IC50 around 0.1 μM, indicating potent blockade. Antagonism of ENaC thereby inhibits sodium reabsorption in the late distal convoluted tubules, connecting tubules, and collecting ducts in the nephron. This promotes the loss of sodium and water from the body, and reduces potassium excretion. The drug is often used in conjunction with a thiazide diuretic to counteract with a potassium-losing effect. Due to its potassium-sparing capacities, hyperkalemia (elevated potassium concentration in the blood) can occur. The risk of developing hyperkalemia is increased in patients who are also taking ACE inhibitors, angiotensin II receptor antagonists, other potassium-sparing diuretics, or any potassium-containing supplements.

Miscellaneous
A fraction of the effects of amiloride is inhibition of cyclic GMP-gated cation channels in the inner medullary collecting duct.Amiloride has a second action on the heart, blocking Na+/H+ exchangers sodium–hydrogen antiporter 1 or NHE-1.
Amiloride also blocks the Na+/H+ antiporter on the apical surface of the proximal tubule cells in the nephron, abolishing more than 80% of the action of angiotensin II on the secretion of hydrogen ions in proximal tubule cells. Note that amiloride is not an angiotensin II receptor blocker (like losartan, for example). The Na-H transporter is also found in the Jejunum of the small intestine, as a result, amiloride also blocks the reabsorption of Na, and thereby water in the intestines.Amiloride is considered to be a reversible, pan-acid-sensing ion channel (ASIC) inhibitor that prevents the transient flow of ions but not the sustained flow of ions. ASICs are members of the ENaC family of protein channels, and are found in the nervous system, the cardiovascular system, the gastrointestinal system, and  the skin. Broadly, ASICs are involved in harm detection, chemosensation (pH changes specifically), and touch.

Pharmacokinetics
Absorption
Amiloride has an oral bioavailability of 50%, meaning that about 50% of an oral dose is absorbed into the blood stream. Coadministration with food reduces the amount of amiloride that is absorbed by the body by about 30%, though it does not affect the rate of absorption. However, taking amiloride with food helps to reduce the incidence of its gastrointestinal side effects. After being taken, amilorides diuretic effect occurs within 2 hours, with peak diuresis within 6–10 hours. The diuretic effects of amiloride persist for about 24 hours after administration.

Distribution
Amiloride cross the placenta and distributes into breast milk in vivo.

Metabolism
Amiloride is not metabolized by the liver. In comparison, the ENaC inhibitor triamterene is metabolized by the liver.

Excretion
About 50% of amiloride is excreted unchanged by the kidneys, while around 40% is excreted in the feces (likely drug that wasnt absorbed). The half-life of amiloride in humans is between 6 and 9 hours, which may be prolonged in people with poor kidney function.

Pharmacogenomics
A single nucleotide polymorphism (SNP) in the protein NEDD4L may impact how amiloride affects a persons blood pressure in people with high blood pressure.

Chemistry
Amiloride is a pyrazinoylguanidine, composed of a substituted pyrazine ring structure with a carbonylguanidinium substituent. Amilorides pKa is 8.67, which is due to the guanidinium group. In high pH (alkaline, low hydrogen concentration) environments, the guanidinium group is deprotonated and the compound is rendered neutral, depleting its activity on sodium channels. Amiloride, as a pure substance, is highly fluorescent, with excitation wavelengths at 215, 288, and 360 nm, emitting light at 420 nm.

History
Amiloride was first synthesized and discovered by the Merck Sharp and Dohme Research Laboratories in the late 1960s. The drug was discovered as part of a screening process of chemicals that reversed the effects of mineralocorticoids in vivo. Amiloride was the only drug in the screen that was capable of causing the excretion of sodium (natriuresis) without a concomitant urinary excretion of potassium (kaliuresis). Thousands of amiloride analogues have been studied since its initial discovery, which have been used to study the effects of sodium transporters.Amiloride was approved by the U.S. Food and Drug Administration (FDA) on October 5, 1981.

Society and culture
It is on the World Health Organizations List of Essential Medicines.Amiloride is on the World Anti-Doping Agencys list of banned substances, as it is considered a masking agent. Diuretics like amiloride act as masking agents by reducing the concentration of other doping agents due to promoting diuresis, increasing the total volume of the urine. The list includes other potassium-sparing diuretics, such as triamterene and spironolactone. In 2008, amiloride and the potassium-sparing diuretic triamterene were found in 3% of positive diuretic doping samples.

Formulations and trade names
Amiloride hydrochloride
Midamor (U.S.)
Co-amilozide (amiloride hydrochloride with hydrochlorothiazide)
Co-amilofruse (amiloride hydrochloride with furosemide)
Amiloride hydrochloride with cyclopenthiazide
Amiloride hydrochloride with bumetanide

Research
Amiloride is an inhibitor of NHE-1, which helps to maintain normal pH within cells. Cancer cells in leukemia, a type of blood cancer, have higher pH compared to normal cells. Amiloride affects the splicing and regulation of multiple genes involved in cancer, though they do not appear to be directly related to its effects on pH. Amiloride has been tested in vitro as an adjunct to the anticancer drug imatinib, which appeared to show a synergistic effect </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Moxetumomab pasudotox and explain in detail? [/INST] Moxetumomab pasudotox, sold under the brand name Lumoxiti, is an anti-CD22 immunotoxin medication for the treatment of adults with relapsed or refractory hairy cell leukemia (HCL) who have received at least two prior systemic therapies, including treatment with a purine nucleoside analog. Moxetumomab pasudotox is a CD22-directed cytotoxin and is the first of this type of treatment for adults with HCL. The drug consists of the binding fragment (Fv) of an anti-CD22 antibody fused to a toxin called PE38. This toxin is a 38 kDa fragment of Pseudomonas exotoxin A.
Hairy cell leukemia (HCL) is a rare, slow-growing cancer of the blood in which the bone marrow makes too many B cells (lymphocytes), a type of white blood cell that fights infection. HCL is named after these extra B cells which look “hairy” when viewed under a microscope. As the number of leukemia cells increases, fewer healthy white blood cells, red blood cells and platelets are produced.

Medical uses
Moxetumomab pasudotox as monotherapy is indicated for the treatment of adults with relapsed or refractory hairy cell leukemia (HCL) after receiving at least two prior systemic therapies, including treatment with a purine nucleoside analogue (PNA).

Adverse effects
Common side effects include infusion-related reactions, swelling caused by excess fluid in body tissue (edema), nausea, fatigue, headache, fever (pyrexia), constipation, anemia and diarrhea.The prescribing information for moxetumomab pasudotox includes a boxed warning about the risk of developing capillary leak syndrome, a condition in which fluid and proteins leak out of tiny blood vessels into surrounding tissues. Symptoms of capillary leak syndrome include difficulty breathing, weight gain, hypotension, or swelling of arms, legs and/or face. The boxed warning also notes the risk of hemolytic uremic syndrome, a condition caused by the abnormal destruction of red blood cells.Other serious warnings include: decreased renal function, infusion-related reactions and electrolyte abnormalities.Women who are breastfeeding should not be given moxetumomab pasudotox.

Discovery and ownership background
On 1 November 2005, Cambridge Antibody Technology (CAT) announced it was acquiring two anti-CD22 immunotoxin products from Genencor, namely GCR-3888 and GCR-8015. Genencor is the biotechnology division of Danisco and the acquisition meant CAT would hire certain former Genencor key employees to be responsible for the development of the programmes.GCR-3888 and GCR-8015 were discovered and initially developed by the National Cancer Institute, which is part of the U.S. National Institutes of Health.  Genencor licensed the candidates for hematological malignancies and entered into a Cooperative Research and Development Agreement (CRADA) with the NIH, which will now be continued by CAT.  Under the original
license agreement with the NIH, CAT gained the rights to a portfolio of intellectual property associated with the programs and would pay future royalties to the NIH.
CAT intended to file an Investigational New Drug (IND) application for GCR-8015 in various CD22 positive B-cell malignancies, including Non-Hodgkin lymphoma and chronic lymphocytic leukemia, following a period of manufacturing development which is expected to be complete by the end of 2006 and to support the NCIs ongoing development of GCR-3888 in Hairy cell leukemia (HCL) and pediatric acute lymphoblastic leukemia (pALL).CAT-8015 exhibited a greater affinity for CD22 than its predecessor, CAT-3888 and CATs language such as "CAT will support the NCIs ongoing development of CAT-3888..." suggested at the time that their focus was on the second generation candidate.CAT was acquired by AstraZeneca, who also acquired MedImmune, combining the two into a biologics division. MedImmune renamed CAT-8015 to moxetumomab pasudotox.On 16 May 2013, AstraZeneca announced that CAT-8015 had started Phase III clinical trials.

History
On 5 December 2008, orphan designation (EU/3/08/592) was granted by the European Commission to Medimmune Limited, United Kingdom, for murine anti-CD22 antibody variable region fused to truncated Pseudomonas exotoxin 38 for the treatment of hairy cell leukaemia. It was renamed to Moxetumomab pasudotox. The sponsorship was transferred to AstraZeneca AB, Sweden, in January 2019.On 17 July 2013, orphan designation (EU/3/13/1150) was granted by the European Commission to MedImmune Ltd, United Kingdom, for moxetumomab pasudotox for the treatment of B-lymphoblastic leukaemia / lymphoma. The sponsorship was transferred to AstraZeneca AB, Sweden, in January 2019.Moxetumomab pasudotox was approved for use in the United States in September 2018.The efficacy of moxetumomab pasudotox was studied in a single-arm, open-label clinical trial of 80 subjects who had received prior treatment for hairy cell leukemia with at least two systemic therapies, including a purine nucleoside analog. The trial measured durable complete response (CR), defined as maintenance of hematologic remission for more than 180 days after achievement of CR. Thirty percent of subjects in the trial achieved durable CR, and the overall response rate (number of subjects with partial or complete response to therapy) was 75 percent.The US Food and Drug Administration (FDA) granted the application for moxetumomab pasudotox fast track, priority review, and orphan drug designations. The FDA granted the approval of a Biologics License Application for Lumoxiti to AstraZeneca Pharmaceuticals. This was subsequently transferred to Innate Pharma in March 2020.On 10 December 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization under exceptional circumstances for the medicinal product Lumoxiti, intended for the treatment of relapsed or refractory hairy cell leukemia after two prior systemic therapies including a purine nucleoside analog. The orphan designation for Lumoxiti for treatment of hairy cell leukaemia was also maintained </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Motofen and explain in detail? [/INST] Motofen is the brand name for an antiperistaltic anti-diarrheal medication, containing 1.0 mg difenoxin HCl and 0.025 mg atropine (U.S. Food and Drug Administration: Schedule IV Combination). It was invented by Kendra Clark. Atropine is purposely added at 25 micrograms per tablet, or 1/24 to 1/40 of the usual therapeutic dose for atropine to minimize the potential of misuse by swallowing large numbers of tablets or preparing them for injection since difenoxin is chemically related to the pethidine-piritramide subgroup of the opioid family, and could theoretically be misused.  Although unlikely, physical and mental withdrawal symptoms (from both anticholinergic rebound caused by atropine, and opiate withdrawal caused by the difenoxin) are possible if taken for long periods of time.  However, both of these compounds are responsible for the medicinal effects of the medicine (both atropine and difenoxin slow gut movement).
This combination medication should not be confused with Lomotil (2.5 mg diphenoxylate and 0.025 mg atropine – a Schedule V combination), because the active ingredients in the two medications are different compounds, except for the inclusion of atropine.  Motofen is approximately 2 to 4 times more effective in treating symptoms than Lomotil.

Indications and uses
Although Motofen is officially indicated by the U.S. Food and Drug Administration (FDA) for diarrhea, it has also been successfully used by physicians for irritable bowel syndrome (IBS), and hyperhidrosis (chronic, severe sweating).

Side effects, interactions, and misuse potential
Side effects include drowsiness, nausea, vomiting, burning eyes, blurred vision, dry eyes, dizziness, dry mouth, epigastric distress, and constipation.  Side effects attributed to the atropine content (especially when taken in excess doses, or in children), include: flushing, dryness in many areas, urinary retention, insomnia, headache, anxiety, hyperthermia, and tachycardia.  It is these side effects that make it undesirable for most patients to take higher amounts of the medicine.

Dosing and administration
The recommended initial dosing is two tablets, and one tablet to be taken after each loose stool thereafter.  The therapeutic dosage for Motofen should not exceed 8 tablets (8 milligrams of Difenoxin).  There are currently no instructions indicating usage for irritable bowel syndrome (IBS) and Hyperhidrosis, although as stated above, it has been used successfully in treating symptoms of both disorders (which can accompany each other).  There was a "Motofen half-strength" tablet, containing only 0.5 milligram of difenoxin, but it has since been discontinued.  Only standard 1.0 milligram strength tablets are available by prescription.

Availability, price, and supply
There is currently only one manufacturer of Motofen tablets: Valeant Pharmaceuticals. It acquired the drug from Amarin Pharmaceuticals in 2004.  Valeants tablets are pentagonal shaped, impressed with a "V" on one side, and vertically scored on the other side.  In addition, the number "0500" is impressed bisecting the score line perpendicularly.  The aforementioned bisection renders "05" and "00" on the left and right side of the score, respectively.  Amarins version were also pentagonal shaped, but impressed with an "A" on one side with "74" on the opposing.
Motofen is higher priced than both Imodium and Lomotil, does not have a generic equivalent, and is only available by prescription in the United States.  Many United States insurance companies do not include Motofen as one of their formulary drugs, causing consumers to pay the highest copay, if it is covered by their health insurance at all.  This is most likely due to the high cost of the medication itself, and the fact that similar lower-priced medicines can help ease symptoms of diarrhea.  The United States is currently the only country where Motofen tablets are prescribed, approved by the government, and sold.

Miscellaneous information
Strangely, Motofen is only included in the Physicians Desk Reference (PDR) for the years 2005 and 2006 as a literal snippet entry.  Nothing is said about the indications and usage, only the ingredients, current appearance (at the time of publishing), NDC#, and the quantities in which it is supplied.  As of August 1, 2008, Motofen appears to have been discontinued by Valeant Pharmaceuticals </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Tamsulosin and explain in detail? [/INST] Tamsulosin, sold under the brand name Flomax among others, is a medication used to treat symptomatic benign prostatic hyperplasia (BPH) and chronic prostatitis and to help with the passage of kidney stones. The evidence for benefit with a kidney stone is better when the stone is larger. It is taken by mouth.Common side effects include dizziness, headache, sleeplessness, nausea, blurry vision, and sexual problems. Other side effects may include feeling lightheaded with standing and angioedema. Tamsulosin is an alpha blocker and works by relaxing muscles in the prostate. Specifically it is an α1 adrenergic receptor blocker.Tamsulosin was approved for medical use in the United States in 1997. It is available as a generic medication. In 2020, it was the 24th most commonly prescribed medication in the United States, with more than 24 million prescriptions.

Medical uses
Tamsulosin is primarily used for benign prostatic hyperplasia and to help with the passage of kidney stones. Tamsulosin, however, appears to be effective only for stones over 4 mm and less than 10 mm in size.Tamsulosin is also used as an add-on treatment for acute urinary retention. People may void more successfully after catheter removal if they are taking tamsulosin. People taking tamsulosin also are less likely to need re-catheterization.Tamsulosin does not decrease the overall size of the prostate in men with benign prostatic hyperplasia (BPH), and is not recommended for prevention of prostate cancer.

Combination therapy
The results of the CombAT (combination of dutasteride (Avodart) and tamsulosin, under the brand name Duodart) trial in 2008 demonstrated that treatment with the combination of dutasteride and tamsulosin provides greater symptom benefits compared to monotherapy with either agent alone for treatment of benign prostatic hyperplasia.
The CombAT trial became the medication Jalyn.  It was approved by the FDA on 14 June 2010.  This combination can be useful because it may take up to six months for symptomatic relief to be found when using 5-alpha-reductase inhibitors such as dutasteride compared to alpha-1 receptor blockers, which can provide relief in some cases within 48 hours.

Adverse effects
Eyes: People taking tamsulosin are prone to a complication known as floppy iris syndrome during cataract surgery. Adverse outcomes of the surgery are greatly reduced by the surgeons prior knowledge of the persons history with this drug, and thus having the option of alternative techniques.
Severe hypotension.
Persons with cardiac conditions including hypotension, mechanical heart failure (valvular, pulmonary embolism, pericarditis), and congestive heart failure should be monitored carefully while taking tamsulosin.
Alpha blockers, including prazosin, terazosin, doxazosin, or tamsulosin, do not appear to affect all-cause mortality in heart failure re-hospitalization in those also receiving β-blockers.
Tamsulosin can also cause retrograde ejaculation, which occurs when semen is redirected to the urinary bladder instead of being ejaculated normally. This is because tamsulosin relaxes the muscles of the urethral sphincters, which are normally closed during ejaculation. This side effect can be mitigated by regular pelvic floor (Kegel) exercise and contracting the pelvic floor during ejaculation.

Mechanism
Tamsulosin is a selective α1 receptor antagonist that has preferential selectivity for the α1A receptor in the prostate versus the α1B receptor in the blood vessels.When alpha 1 receptors in the bladder neck, the prostate, the ureter, and the urethra are blocked, a relaxation in smooth muscle tissue results. This mechanism decreases resistance to urinary flow, reduces discomfort associated with BPH, and facilitates passage of kidney stones.Selective action of tamsulosin in alpha 1A/D receptors is controversial and over three quarters of tamsulosin registered human studies are unpublished.

Brand names
Tamsulosin was first marketed in 1996 under the trade name Flomax. The U.S. patent expired in October 2009. The U.S. Food and Drug Administration (FDA) approved generics in March 2010. In 2010, tamsulosin was available as OTC medication in UK.It is marketed by various companies under licence, including Boehringer Ingelheim and CSL. Tamsulosin hydrochloride extended-release capsules are marketed under the trade names Urimax 0.4(India), Flomax, Flomaxtra, Contiflo XL, bestflo, Mecir LP (France), Urimax, Pamsvax, and Pradif, although generic, non-modified-release capsules are still approved and marketed in many countries (such as Canada). Generic extended-release tablets are marketed in most countries of the EEA </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Oxacillin and explain in detail? [/INST] Oxacillin (trade name Bactocill) is a narrow-spectrum beta-lactam antibiotic of the penicillin class developed by Beecham.It was patented in 1960 and approved for medical use in 1962.

Medical uses
Oxacillin is a penicillinase-resistant β-lactam. It is similar to methicillin, and has replaced methicillin in clinical use.  Other related compounds are nafcillin, cloxacillin, dicloxacillin, and flucloxacillin.  Since it is resistant to penicillinase enzymes, such as that produced by Staphylococcus aureus, it is widely used clinically in the US to treat penicillin-resistant Staphylococcus aureus.   However, with the introduction and widespread use of both oxacillin and methicillin, antibiotic-resistant strains called methicillin-resistant and oxacillin-resistant Staphylococcus aureus (MRSA/ORSA) have become increasingly prevalent worldwide.  MRSA/ORSA can be treated with vancomycin or other new antibiotics.

Contraindications
The use of oxacillin is contraindicated in individuals that have experienced a hypersensitivity reaction to any medication in the penicillin family of antibiotics. Cross-allergenicity has been documented in individuals taking oxacillin that experienced a previous hypersensitivity reaction when given cephalosporins and cephamycins.

Adverse effects
Commonly reported adverse effects associated with the use of oxacillin include skin rash, diarrhea, nausea, vomiting, hematuria, agranulocytosis, eosinophilia, leukopenia, neutropenia, thrombocytopenia, hepatotoxicity, acute interstitial nephritis, and fever. High doses of oxacillin have been reported to cause renal, hepatic, and nervous system toxicity </s>