<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Rho(D) immune globulin and can you explain it in depth? [/INST] Rho(D) immune globulin (RhIG) is a medication used to prevent RhD isoimmunization in mothers who are RhD negative and to treat idiopathic thrombocytopenic purpura (ITP) in people who are Rh positive. It is often given both during and following pregnancy. It may also be used when RhD-negative people are given RhD-positive blood. It is given by injection into muscle or a vein. A single dose lasts 12 weeks.Common side effects include fever, headache, pain at the site of injection, and red blood cell breakdown. Other side effects include allergic reactions, kidney problems, and a very small risk of viral infections. In those with ITP, the amount of red blood cell breakdown may be significant. Use is safe with breastfeeding. Rho(D) immune globulin is made up of antibodies to the antigen Rho(D) present on some red blood cells. It is believed to work by blocking a persons immune system from recognizing this antigen.Rho(D) immune globulin came into medical use in the 1960s. It is on the World Health Organizations List of Essential Medicines. It is made from human blood plasma.

Medical uses
In a pregnancy where the mother is RhD negative and the father is RhD positive, the probability of the fetus having RhD positive blood is dependent on whether the father is homozygous for RhD (i.e., both RhD alleles are present) or heterozygous (i.e., only one RhD allele is present). If the father is homozygous, the fetus will necessarily be RhD positive, as the father will necessarily pass on a Rh D positive allele. If the father is heterozygous, there is a 50% chance that the fetus will be RhD positive, as he will randomly pass on either the RhD positive allele or not.If a fetus is RhD positive and the mother is RhD negative, the mother is at risk of RhD alloimmunization, where the mother mounts an immune response (develops antibodies) to fetal red blood cells. This usually has minimal effect on the first such pregnancy; but, in a second such pregnancy, pre-existing maternal antibodies to RhD antigens on fetal red blood cells often leads to erythroblastosis fetalis, a condition which can be fatal to the fetus. In countries without Rh immune globulin (RhIG) protocols, as many as 14% of affected fetuses are stillborn and 50% of live births result in neonatal death or brain injury.Because of this severe complication, the American College of Obstetricians and Gynecologists (ACOG) recommends that all RhD negative mothers, regardless of fetal blood type, receive RhIG at about 28 weeks gestation, and again shortly after delivery in the case of an RhD positive or RhD unknown baby. It should be given within 3 days of a potential exposure to Rh positive blood from the baby such as may occur during second or third trimester miscarriage, amniocentesis, cordocentesis, chorionic villus sampling, external cephalic version, trauma, or delivery. It should be considered after first trimester miscarriage. The 28 weeks recommendation comes from the fact that 92% of women who develop an anti-D during pregnancy do so at or after 28 weeks gestation. It is given by intramuscular injection as part of modern routine antenatal care. Despite excellent results, the medication retains an FDA Pregnancy Category C.RhIG is recommended in the UK after antenatal pathological events that are likely to cause a feto–maternal hemorrhage. Applicable pathologic events include accidents which may induce fetomaternal hemorrhage (motor vehicle accidents, falls, abdominal trauma), following obstetric/gynecologic procedures during pregnancy, and at the time of threatened- or spontaneous-/elective abortions, regardless of gestational age.
There is insufficient evidence that the use of Rho(D) immune globulin after a spontaneous miscarriage is needed and a Cochrane review recommends that local practices be followed.In an RhD negative mother, RhIG can prevent temporary sensitization of the maternal immune system to RhD antigens, which can cause rhesus disease in the current or in subsequent pregnancies. With the widespread use of RhIG, Rh disease of the fetus and newborn has almost disappeared in the developed world. The risk that an RhD negative mother can be alloimmunized by a RhD positive fetus can be reduced from approximately 16% to less than 0.1% by the appropriate administration of RhIG.Rh immune globulin is composed of IgG antibodies and therefore is able to cross the placenta. In rare cases this can cause a baby to have a weakly positive direct antiglobulin test (DAT) due to sensitization of fetal cells from mothers who have received multiple doses of RhIG. However, no treatment is necessary as the clinical course is benign.

Following delivery
A D-negative mother who is not alloimmunized to D should also receive an appropriate dose of RhIG after delivery of a D-positive infant. After delivery, a cord blood sample from infants born to D-negative mothers should be tested for the D antigen.  If the neonate is D-negative, no further RhIG is needed.  However, if the infant is D-positive, the mother should have a postpartum blood sample screened for fetomaternal hemorrhage in order to determine the appropriate dosage of RhIG to be administered.  (The presence of residual anti-D from antepartum RhIG administration does not indicate ongoing protection from alloimmunization- repeat administration of RhIG is necessary.)The rosette test is a sensitive method to detect fetomaternal hemorrhage of 10 cc or more.  This qualitative (not quantitative) test will be positive if fetal D-positive cells are present in the maternal sample, indicating a significantly large fetomaternal hemorrhage has occurred.  A rosette test may be falsely positive if the mother is positive for the weak D phenotype and falsely negative if the neonate is weak D.  If the mother is positive for the weak D phenotype, the rosette test should not be used; instead, a quantitative test such as the Kleihauer–Betke test or flow cytometry should be utilized. If the rosette test is negative, then a dose of 300 micrograms of RhIG is given (sufficient to prevent alloimmunization after delivery in 99% of cases).  The RhIG dose suppresses the immune response to up to 30 cc of whole fetal blood (15 cc of red blood cells). If a fetomaternal hemorrhage in excess of 30 cc has occurred, additional testing is mandatory in order to determine the appropriate dosage of RhIG to prevent alloimmunization.  A positive rosette test should be followed by a quantitative test such as the Kleihauer–Betke test or an alternative approach such as flow cytometry.  See the article on Kleihauer–Betke test for details on how the volume of fetomaternal hemorrhage is calculated. The dosage of RhIG is calculated from the volume of fetal hemorrhage (in mL).  Ex: 50 mL fetal hemorrhage / 30 mL = 1.667 (round up to 2) then add 1 = 3 vials of RhIG.Postpartum RhIG should be administered within 72 hours of delivery.  If prophylaxis is delayed, the likelihood that alloimmunization will be prevented is decreased.  However, ACOG still recommends that RhIG be administered because partial protection still occurs.  If the D-type of a newborn or stillborn is unknown or cannot be determined, RhIG should be administered.

Immune thrombocytopenia
Primary immune thrombocytopenia (ITP) is an acquired immune-mediated disorder characterized by isolated thrombocytopenia, defined as a peripheral blood platelet count less than 100 x 109/L, and the absence of any obvious initiating and/or underlying cause of the thrombocytopenia.  Symptoms of ITP include abnormal bleeding and bruising due to the reduction in platelet count.  Rho(D) Immune Globulin Intravenous [Human; Anti-D] is indicated for use in non-splenectomized, Rho(D)-positive children with chronic or acute ITP, adults with chronic ITP, and children and adults with ITP secondary to HIV infection. Anti-D must be administered via the intravenous route when used in clinical situations requiring an increase in platelet count. The mechanism of action of anti-D is not fully understood; however, after administration the anti-D coated red blood cell complexes saturate Fcγ receptors sites on macrophages, resulting in preferential destruction of red blood cells (RBCs), therefore sparing antibody-coated platelets. Anti-D is recommended as a first-line therapy for ITP, along with corticosteroids and intravenous immune globulin (IVIG).  WinRho SDF is an anti-D manufactured, distributed and marketed by Cangene in the US. There is a black box warning on WinRho SDF due to the risk of potentially fatal intravascular hemolysis when used in the treatment of ITP. Life-threatening anemia, kidney failure, and disseminated intravascular coagulation (DIC) have occurred in people treated with WinRho SDF for ITP.

Contraindications
The following females are not candidates for RhIG:

D-negative females whose fetus is known to be D-negative
D-negative females who have been previously alloimmunized to D (they have already formed an anti-D alloantibody)
Any D-positive females
Women who test positive for one of the weak D mutations by molecular testing should be considered RhD positive and not receive RhIG
Women who test positive for one of the partial D mutations (by molecular testing) should be treated as RhD negative and receive RhIG as clinically indicated

History
The first Rho(D) immune globulin treatment "skymed" was introduced by Ortho Clinical Diagnostics, a subsidiary holding of Jskymed, and was first administered on May 29, 1968, to Marianne Cummins in Teaneck, New Jersey.In 1996, ZLB Bioplasma (part of CSL Behring) was given approval to sell Rhophylac in Europe. Effectiveness was demonstrated in a clinical trial in 2003 and in 2004 Rhophylac was approved in the United States.

Society and culture
Manufacturing and safety
Rho(D) immune globulin is a derivative of human plasma. The most common way anti-D products are manufactured is by a form of the Cohn cold ethanol fractionation process developed in the 1950s.  Variations of the Cohn method developed in the 1950s may not completely clear aggregates of immunoglobulins, which can cause problems for patients if administered intravenously, and is a primary reason why most anti-Ds are for intramuscular use only.  A non-Cohn manufacturing variation is ChromaPlus process approved by the U.S. Food and Drug Administration (FDA) that is used to make Rhophylac.  Rho(D) immune globulin may trigger an allergic reaction. Steps are taken in the plasma-donor screening process and the manufacturing process to eliminate bacterial and viral contamination, although a small, residual risk may remain for contamination with small viruses. There is also a theoretical possibility of transmission of the prion responsible for Creutzfeldt–Jakob disease, or of other, unknown infectious agents.

Routes of administration
RhIG can be administered by either intramuscular (IM) or intravenous (IV) injection, depending on the preparation.  The IM-only preparation should never be administered IV due to the risk of complement system activation </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Chlormethine and can you explain it in depth? [/INST] Chlormethine (INN, BAN), also known as mechlorethamine (USAN, USP), mustine, HN2, and (in post-Soviet states) embikhin (эмбихин), is a nitrogen mustard sold under the brand name Mustargen among others. It is the prototype of alkylating agents, a group of anticancer chemotherapeutic drugs. It works by binding to DNA, crosslinking two strands and preventing cell duplication. It binds to the N7 nitrogen on the DNA base guanine. As the chemical is a blister agent, its use is strongly restricted within the Chemical Weapons Convention where it is classified as a Schedule 1 substance.
Mechlorethamine belongs to the group of nitrogen mustard alkylating agents.

Uses
It has been derivatized into the estrogen analogue estramustine phosphate, used to treat prostate cancer. It can also be used in chemical warfare where it has the code-name HN2. This chemical is a form of nitrogen mustard gas and a powerful vesicant. Historically, some uses of mechlorethamine have included lymphoid malignancies such as Hodgkins disease, lymphosarcoma, chronic myelocytic leukemia, polycythemia vera, and bronchogenic carcinoma  Mechlorethamine is often administered intravenously, but when compounded into a topical formulation it can also be used to treat skin diseases. There have been studies demonstrating that topical administration of mechlorethamine has efficacy in mycosis fungoides-type cutaneous T cell lymphoma.Another important use of chlormethine is in the synthesis of pethidine (meperidine).

Side effects and toxicity
Mechlorethamine is a highly toxic medication, especially for women who are pregnant, breastfeeding, or of childbearing age. At high enough levels, exposure can be fatal.The adverse effects of mechlorethamine depend on the formulation. When used in chemical warfare, it can cause immunosuppression and damage to mucous membranes of the eyes, skin, and respiratory tract. Mucous membranes and damp or damaged skin are more affected by exposure to HN-2. Though symptoms of exposure are generally delayed, the DNA damage it causes occurs very quickly. More serious exposures cause symptoms to develop sooner. Eye symptoms develop first, in the first 1–2 hours (severe exposure) or 3–12 hours (mild to moderate exposure) followed by airway (2-6/12–24 hours) and skin symptoms (6–48 hours). Hot, humid weather shortens the latent (symptom-free) period.Symptoms of toxic exposure to HN-2 vary based on the route of exposure. Eye exposure causes lacrimation (tear production), burning, irritation, itching, a feeling of grittiness or dryness, blepharospasm (spasms of the eyelid), and miosis (pinpoint pupils). More severe cases cause edema (swelling from fluid accumulation) in the eyelids, photophobia (extreme sensitivity to light), severe pain, corneal ulceration, and blindness.Inhalation of chlormethine damages the upper and lower airways sequentially, with more severe exposures causing faster damage that afflicts lower parts of the respiratory tract. Early symptoms include rhinorrhea (runny nose), epistaxis (nosebleed), toneless voice, sneezing, barking cough, and dyspnea (in smokers and asthmatics). Later symptoms include pain in the nose/sinuses and inflammation of the airway. In severe cases, there may be epithelial necrosis throughout the respiratory tract, causing pseudomembrane formation, which can obstruct the airway. Pneumonia may develop and prove fatal.Skin exposure mainly causes erythema (redness) and vesication (blistering) at first, but absorption through the skin causes systemic toxicity. In cases where more than 25% of the skin is affected, fatal exposure is likely to have occurred.Though ingestion is uncommon, if mechlorethamine is swallowed it causes severe chemical burns to the gastrointestinal tract and concomitant nausea, vomiting, diarrhea, abdominal pain, and hemorrhage.Long-term effects of acute or chronic chlormethine exposure are caused by damage to the immune system. White blood cell counts drop, increasing the risk of infection, and red blood cell and platelet counts may also drop due to bone marrow damage. Chronic eye infections may result from exposure, but blindness is temporary. Long-term effects on the respiratory system include anosmia (inability to smell), ageusia (inability to taste), inflammation, chronic infections, fibrosis, and cancer. Skin that has been damaged by HN2 can change pigmentation or become scarred, and may eventually develop cancer.

History
The effect of vesicant (blister) agents in the form of mustard gas (sulfur mustard, Bis(2-chloroethyl) sulfide) on bone marrow and white blood cells had been known since the First World War. In 1935 several lines of chemical and biological research yielded results that would be explored after the start of the Second World War. The vesicant action of a family of chemicals related to the sulfur mustards, but with nitrogen substituting for sulfur was discovered—the "nitrogen mustards" were born. The particular nitrogen mustard chlormethine (mechlorethamine) was first synthesized. And the action of sulfur mustard on tumors in laboratory animals was investigated for the first time.After the U.S. entry into the Second World War the nitrogen mustards were candidate chemical warfare agents and research on them was initiated by the Office of Scientific Research and Development (OSRD) </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Risperidone and can you explain it in depth? [/INST] Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It is taken either by mouth or by injection (subcutaneous or intramuscular). The injectable versions are long-acting and last for 2–4 weeks.Common side effects include movement problems, sleepiness, dizziness, trouble seeing, constipation, and increased weight. Serious side effects may include the potentially permanent movement disorder tardive dyskinesia, as well as neuroleptic malignant syndrome, an increased risk of suicide, and high blood sugar levels. In older people with psychosis as a result of dementia, it may increase the risk of death. It is unknown if it is safe for use in pregnancy. Its mechanism of action is not entirely clear, but is believed to be related to its action as a dopamine and serotonin antagonist.Study of risperidone began in the late 1980s and it was approved for sale in the United States in 1993. It is on the World Health Organizations List of Essential Medicines. It is available as a generic medication.  In 2019, it was the 149th most commonly prescribed medication in the United States, with more than 4 million prescriptions.

Medical uses
Risperidone is mainly used for the treatment of schizophrenia, bipolar disorder, and irritability associated with autism.

Schizophrenia
Risperidone is effective in treating psychogenic polydipsia and the acute exacerbations of schizophrenia.Studies evaluating the utility of risperidone by mouth for maintenance therapy have reached varying conclusions. A 2012 systematic review concluded that evidence is strong that risperidone is more effective than all first-generation antipsychotics other than haloperidol, but that evidence directly supporting its superiority to placebo is equivocal. A 2011 review concluded that risperidone is more effective in relapse prevention than other first- and second-generation antipsychotics with the exception of olanzapine and clozapine. A 2016 Cochrane review suggests that risperidone reduces the overall symptoms of schizophrenia, but firm conclusions are difficult to make due to very low-quality evidence. Data and information are scarce, poorly reported, and probably biased in favour of risperidone, with about half of the included trials developed by drug companies. The article raises concerns regarding the serious side effects of risperidone, such as parkinsonism. A 2011 Cochrane review compared risperidone with other atypical antipsychotics such as olanzapine for schizophrenia:
Long-acting injectable formulations of antipsychotic drugs provide improved compliance with therapy and reduce relapse rates relative to oral formulations. The efficacy of risperidone long-acting injection appears to be similar to that of long acting injectable forms of first generation antipsychotics.

Bipolar disorder
Second-generation antipsychotics, including risperidone, are effective in the treatment of manic symptoms in acute manic or mixed exacerbations of bipolar disorder. In children and adolescents, risperidone may be more effective than lithium or divalproex, but has more metabolic side effects. As maintenance therapy, long-acting injectable risperidone is effective for the prevention of manic episodes but not depressive episodes.  The long-acting injectable form of risperidone may be advantageous over long acting first generation antipsychotics, as it is better tolerated (fewer extrapyramidal effects) and because long acting injectable formulations of first generation antipsychotics may increase the risk of depression.

Autism
Compared to placebo, risperidone treatment reduces certain problematic behaviors in autistic children, including aggression toward others, self-injury, challenging behaviour, and rapid mood changes. The evidence for its efficacy appears to be greater than that for alternative pharmacological treatments. Weight gain is an important adverse effect.  Some authors recommend limiting the use of risperidone and aripiprazole to those with the most challenging behavioral disturbances in order to minimize the risk of drug-induced adverse effects. Evidence for the efficacy of risperidone in autistic adolescents and young adults is less persuasive.

Dementia
While antipsychotic medications such as risperidone have a slight benefit in people with dementia, they have been linked to higher incidence of death and stroke. Because of this increased risk of death, treatment of dementia-related psychosis with risperidone is not FDA approved and carries a black box warning. However many other jurisdictions regularly use it to control severe aggression and psychosis in those with dementia when other non-pharmacological interventions have failed and their pharmaceutical regulators have approved its use in this population.

Other uses
Risperidone has shown promise in treating therapy-resistant obsessive-compulsive disorder, when serotonin reuptake inhibitors alone are not sufficient.Risperidone has proven to be effective in treatment with Attention deficit hyperactivity disorder especially in cases of aggression or with another mental condition.Risperidone has not demonstrated a benefit in the treatment of eating disorders or personality disorders, except for limited evidence in schizotypal personality disorder.

Forms
Available forms of risperidone include tablet, oral dissolving tablet, oral solution, and powder and solvent for suspension for injection.

Adverse effects
Common side effects include movement problems, sleepiness, dizziness, trouble seeing, constipation, and increased weight. About 9 to 20% of people gained more than 7% of the baseline weight depending on the dose. Serious side effects may include the potentially permanent movement disorder tardive dyskinesia, as well as neuroleptic malignant syndrome, an increased risk of suicide, and high blood sugar levels. In older people with psychosis as a result of dementia, it may increase the risk of death.While atypical antipsychotics appear to have a lower rate of movement problems as compared to typical antipsychotics, risperidone has a high risk of movement problems among the atypicals. Atypical antipsychotics, however, are associated with a greater amount of weight gain and other metabolic side effects.

Drug interactions
Carbamazepine and other enzyme inducers may reduce plasma levels of risperidone. If a person is taking both carbamazepine and risperidone, the dose of risperidone will likely need to be increased. The new dose should not be more than twice the patients original dose.
CYP2D6 inhibitors, such as SSRI medications, may increase plasma levels of risperidone and those medications.
Since risperidone can cause hypotension, its use should be monitored closely when a patient is also taking antihypertensive medicines to avoid severe low blood pressure.
Risperidone and its metabolite paliperidone are reduced in efficacy by P-glycoprotein inducers such as St Johns wort

Discontinuation
The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotic treatment to avoid acute withdrawal syndrome or rapid relapse.  Some have argued the additional somatic and psychiatric symptoms associated with dopaminergic super-sensitivity, including dyskinesia and acute psychosis, are common features of withdrawal in individuals treated with neuroleptics. This has led some to suggest the withdrawal process might itself be schizomimetic, producing schizophrenia-like symptoms even in previously healthy patients, indicating a possible pharmacological origin of mental illness in a yet unknown percentage of patients currently and previously treated with antipsychotics.  This question is unresolved, and remains a highly controversial issue among professionals in the medical and mental health communities, as well as the public.

Dementia
Older people with dementia-related psychosis are at a higher risk of death.

Pharmacology
Pharmacodynamics
Risperidone has been classified as a "qualitatively atypical" antipsychotic agent with a relatively low incidence of extrapyramidal side effects (when given at low doses) that has more pronounced serotonin antagonism than dopamine antagonism. Risperidone contains the functional groups of benzisoxazole and piperidine as part of its molecular structure. Although not a butyrophenone, it was developed with the structures of benperidol and ketanserin as a basis. It has actions at several 5-HT (serotonin) receptor subtypes. These are 5-HT2C, linked to weight gain, 5-HT2A, linked to its antipsychotic action and relief of some of the extrapyramidal side effects experienced with the typical neuroleptics.It has been found that D-amino acid oxidase, the enzyme that catalyses the breakdown of D-amino acids (e.g. D-alanine and D-serine — the neurotransmitters) is inhibited by risperidone.Risperidone acts on the following receptors:
Dopamine receptors: This drug is an antagonist of the D1 (D1, and D5) as well as the D2 family (D2, D3 and D4) receptors, with 70-fold selectivity for the D2 family. It has "tight binding" properties, which means it has a long half-life. Like other antipsychotics, risperidone blocks the mesolimbic pathway, the prefrontal cortex limbic pathway, and the tuberoinfundibular pathway in the central nervous system. Risperidone may induce extrapyramidal side effects, akathisia and tremors, associated with diminished dopaminergic activity in the striatum. It can also cause sexual side effects, galactorrhoea, infertility, gynecomastia and, with chronic use reduced bone mineral density leading to breaks, all of which are associated with increased prolactin secretion.Serotonin receptors: Its action at these receptors results in a relatively lesser tendency to cause extrapyramidal side effects, like the reference substance clozapine.Alpha α1 adrenergic receptors: This action accounts for the orthostatic hypotensive effects and perhaps some of the sedating effects of risperidone.Alpha α2 adrenergic receptors: Risperidones action at these receptors may cause greater positive, negative, affective, and cognitive symptom control.Histamine H1 receptors: effects on these receptors account for its sedation and reduction in vigilance. This may also lead to drowsiness and weight gain.Voltage-gated sodium channels: Because it accumulates in synaptic vesicles, Risperidone inhibits voltage-gated sodium channels at clinically used concentrations.

Pharmacokinetics
Risperidone undergoes hepatic metabolism and renal excretion. Lower doses are recommended for patients with severe liver and kidney disease.  The active metabolite of risperidone, paliperidone, is also used as an antipsychotic.

Society and culture
Legal status
Risperidone was approved by the United States Food and Drug Administration (FDA) in 1993 for the treatment of schizophrenia. In 2003, the FDA approved risperidone for the short-term treatment of the mixed and manic states associated with bipolar disorder. In 2006, the FDA approved risperidone for the treatment of irritability in autistic children and adolescents. The FDAs decision was based in part on a study of autistic people with severe and enduring problems of violent meltdowns, aggression, and self-injury; risperidone is not recommended for autistic people with mild aggression and explosive behavior without an enduring pattern. On 22 August 2007, risperidone was approved as the only drug agent available for treatment of schizophrenia in youths, ages 13–17; it was also approved that same day for treatment of bipolar disorder in youths and children, ages 10–17, joining lithium.
On 16 December 2021, 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 for the medicinal product Okedi, intended for the  treatment of schizophrenia in adults for whom tolerability and effectiveness has been established with oral risperidone. The applicant for this medicinal product is Laboratorios Farmacéuticos Rovi, S.A. Risperidone was approved for medical use in the European Union in February 2022.

Availability
Janssens patent on risperidone expired on 29 December 2003, opening the market for cheaper generic versions from other companies, and Janssens exclusive marketing rights expired on 29 June 2004 (the result of a pediatric extension). It is available under many brand names worldwide.Risperidone is available as a tablet, an oral solution, and an ampule, which is a depot injection.

Lawsuits
On 11 April 2012, Johnson & Johnson (J&J) and its subsidiary Janssen Pharmaceuticals Inc. were fined $1.2 billion by Judge Timothy Davis Fox of the Sixth Division of the Sixth Judicial Circuit of the U.S. state of Arkansas. The jury found the companies had downplayed multiple risks associated with risperidone. The verdict was later reversed by the Arkansas state supreme court.In August 2012, Johnson & Johnson agreed to pay $181 million to 36 U.S. states in order to settle claims that it had promoted risperidone and paliperidone for off-label uses including for dementia, anger management, and anxiety.In November 2013, J&J was fined $2.2 billion for illegally marketing risperidone for use in people with dementia.In 2015, Steven Brill posted a 15-part investigative journalism piece on J&J in The Huffington Post, called "Americas most admired lawbreaker", which was focused on J&Js marketing of risperidone.J&J has faced numerous civil lawsuits on behalf of children who were prescribed risperidone who grew breasts (a condition called gynecomastia); as of July 2016 there were about 1,500 cases in Pennsylvania state court in Philadelphia, and there had been a February 2015 verdict against J&J with $2.5 million awarded to a man from Alabama, a $1.75 million verdict against J&J that November, and in 2016 a $70 million verdict against J&J. In October 2019, a jury awarded a Pennsylvania man $8 billion in a verdict against J&J.

Names
Brand names include Risperdal, Risperdal Consta, Risperdal M-Tab, Risperdal Quicklets, Risperlet, Okedi, and Perseris.

References
Further reading
Dean L (2017) </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hydrocortisone and can you explain it in depth? [/INST] Hydrocortisone is the name for the hormone cortisol when supplied as a medication. Uses include conditions such as adrenocortical insufficiency, adrenogenital syndrome, high blood calcium, thyroiditis, rheumatoid arthritis, dermatitis, asthma, and COPD. It is the treatment of choice for adrenocortical insufficiency. It can be given by mouth, topically, or by injection. Stopping treatment after long-term use should be done slowly.Side effects may include mood changes, increased risk of infection, and edema (swelling). With long-term use common side effects include osteoporosis, upset stomach, physical weakness, easy bruising, and candidiasis (yeast infections). While used, it is unclear if it is safe during pregnancy. Hydrocortisone is a glucocorticoid and works as an anti-inflammatory and by immune suppression.Hydrocortisone was patented in 1936 and approved for medical use in 1941. It is on the World Health Organizations List of Essential Medicines. It is available as a generic medication. In 2019, it was the 147th most commonly prescribed medication in the United States, with more than 4 million prescriptions.

Medical uses
Hydrocortisone is the pharmaceutical term for cortisol used in oral administration, intravenous injection, or topical application. It is used as an immunosuppressive drug, given by injection in the treatment of severe allergic reactions such as anaphylaxis and angioedema, in place of prednisolone in patients needing steroid treatment but unable to take oral medication, and perioperatively in patients on long-term steroid treatment to prevent an adrenal crisis. It may also be injected into inflamed joints resulting from diseases such as gout.
It may be used topically for allergic rashes, eczema, psoriasis, itching and other inflammatory skin conditions. Topical hydrocortisone creams and ointments are available in most countries without prescription in strengths ranging from 0.05% to 2.5% (depending on local regulations) with stronger forms available by prescription only. Covering the skin after application increases the absorption and effect. Such enhancement is sometimes prescribed, but otherwise should be avoided to prevent overdose and systemic impact.

Pharmacology
Pharmacodynamics
Hydrocortisone is a corticosteroid, acting specifically as both a glucocorticoid and as a mineralocorticoid. That is, it is an agonist of the glucocorticoid and mineralocorticoid receptors.
Hydrocortisone has low potency relative to synthetic corticosteroids </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Minocycline and can you explain it in depth? [/INST] Minocycline, sold under the brand name Minocin among others, is a tetracycline antibiotic medication used to treat a number of bacterial infections such as pneumonia. It is generally less preferred than the tetracycline doxycycline. It is also used for the treatment of acne and rheumatoid arthritis. It is taken by mouth or applied to the skin.Common side effects include nausea, diarrhea, dizziness, allergic reactions, and kidney problems. Serious side effects may include anaphylaxis, a lupus-like syndrome, and easy sunburning. Use in the later part of pregnancy may harm the baby and safety during breastfeeding is unclear. It works by decreasing a bacteriums ability to make protein thus stopping its growth.Minocycline was patented in 1961 and came into commercial use in 1971. It is available as a generic medication. In 2017, it was the 237th most commonly prescribed medication in the United States, with more than two million prescriptions.

Medical uses
Acne
Minocycline and doxycycline are frequently used for the treatment of acne vulgaris. Both of these closely related antibiotics have similar levels of efficacy, although doxycycline has a slightly lower risk of adverse side effects. Historically, minocycline has been an effective treatment for acne vulgaris. However, acne that is caused by antibiotic-resistant bacteria is a growing problem in many countries. In Europe and North America, a number of people with acne no longer respond well to treatment with tetracycline family antibiotics because their acne symptoms are caused by bacteria (primarily Cutibacterium acnes) that are resistant to these antibiotics. In order to reduce resistance rates as well as increase the effectiveness of treatment, oral antibiotics should be generally combined with topical acne creams such as benzoyl peroxide or a retinoid (tretinoin, adapalene, etc.). Minocycline itself is used both orally and topically in the treatment of acne.

Infections
Minocycline is also used for other skin infections such as methicillin-resistant Staphylococcus aureus.Although minocyclines broader spectrum of activity, compared with other members of the group, includes activity against Neisseria meningitidis, its use for prophylaxis is no longer recommended because of side effects (dizziness and vertigo).
It may be used to treat certain strains of methicillin-resistant S. aureus infection and a disease caused by drug-resistant Acinetobacter spp.A list of uses includes:

Amoebic dysentery
Anthrax
Bubonic plague
Cholera
Ehrlichiosis
Gonorrhea (when penicillin cannot be given)
Gougerot-Carteaud syndrome (confluent and reticulated papillomatosis)
Hidradenitis suppurativa
For use as an adjuvant to HAART
Leprosy
Periodontal disease
Perioral dermatitis
Respiratory infections such as pneumonia
Rocky Mountain spotted fever
Rosacea
Syphilis (when penicillin cannot be given)
Urinary tract infections, rectal infections, and infections of the cervix caused by certain microbes

Other
Both minocycline and doxycycline have shown effectiveness in asthma due to immune-suppressing effects. Minocycline and doxycycline have modest effectiveness in treating rheumatoid arthritis. However, the 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis does not include minocycline.
Recent research indicate that centrally infused minocycline attenuates brain microglial activation, neuroinflammation and sympathetic activation during pulmonary hypertension

Contraindications
The drug is contraindicated in people with known hypersensitivity to tetracycline antibiotics, as there is complete cross sensitivity in this group. It is also contraindicated in people with severe liver impairment and after the 16th week of pregnancy.

Side effects
Minocycline may cause upset stomach, diarrhea, dizziness, unsteadiness, drowsiness, mouth sores, headache, and vomiting. It increases sensitivity to sunlight, and may affect the quality of sleep and rarely causes sleep disorders. It has also been linked to cases of lupus. Prolonged use of minocycline  can lead to blue-gray staining of skin, fingernails, and  scar tissue. This staining is not permanent, but can take a very long time for the skin color to return to normal; however, a muddy brown skin color in sun-exposed areas is usually permanent. Permanent blue discoloration of gums or teeth discoloration may also occur. Rare but serious side effects include fever, yellowing of the eyes or skin, stomach pain, sore throat, vision changes, and mental changes, including depersonalization.Occasionally, minocycline therapy may result in autoimmune disorders such as drug-related lupus and autoimmune hepatitis, which usually occurs in men who also developed minocycline-induced lupus; however, women are more likely to develop minocycline-induced lupus. Significant or complete recovery occurs in most people who develop minocycline-induced autoimmune problems within a period of a few weeks to a year of cessation of minocycline therapy. Autoimmune problems emerge during chronic therapy, but can sometimes occur after only short courses of a couple of weeks of therapy. Drug reaction with eosinophilia and systemic symptoms  syndrome can occur during the first few weeks of therapy with minocycline.Minocycline, but not other tetracyclines, can cause vestibular disturbances with dizziness, ataxia, vertigo, and tinnitus. These effects are thought to be related to minocyclines greater penetration into the central nervous system. Vestibular side effects are much more common in women than in men, occurring in 50 to 70% of women receiving minocycline. As a result of the frequency of this bothersome side effect, minocycline is rarely used in female patients.Symptoms of an allergic reaction include rash, itching, swelling, severe dizziness, and trouble breathing. Minocycline has also been reported to very rarely cause idiopathic intracranial hypertension (pseudotumor cerebri), a side effect also more common in female patients, potentially leading to permanent vision damage if not recognized early and treated.
Contrary to most other tetracycline antibiotics (doxycycline excluded), minocycline may be used in those with kidney disease, but may aggravate systemic lupus erythematosus. It may also trigger or unmask autoimmune hepatitis.Minocycline can cause the rare condition of secondary intracranial hypertension, which has initial symptoms of headache, visual disturbances, dizziness, vomiting, and confusion. Brain swelling and rheumatoid arthritis are rare side effects of minocycline in some people.Minocycline, like most tetracyclines, becomes dangerous past its expiration date. While most prescription drugs lose potency after their expiration dates, tetracyclines are known to become toxic over time. Expired tetracyclines can cause serious damage to the kidney due to the formation of a degradation product, anhydro-4-epitetracycline.
Minocyclines absorption is impaired if taken at the same time of day as calcium or iron supplements. Unlike some of the other tetracycline group antibiotics, it can be taken with calcium-rich foods such as milk, although this does reduce the absorption slightly.Minocycline, like other tetracyclines, is associated with esophageal irritation and ulceration if insufficient fluids are taken with the drug before sleep.A 2007 study suggested that minocycline harms amyotrophic lateral sclerosis patients. Patients on minocycline declined more rapidly than those on placebo. The mechanism of this side effect is unknown, although a hypothesis is that the drug exacerbated an autoimmune component of the primary disease. The effect does not seem to be dose-dependent because the patients on high doses did not do worse than those on the low doses.The use of minocycline in acne vulgaris has been associated with skin and gut dysbiosis (see antibiotic misuse).

Interactions
The combination of minocycline with dairy, antacids, calcium and magnesium supplements, iron products, laxatives containing magnesium, or bile acid sequestrants may decrease minocyclines effectiveness by forming chelates. Combining it with isotretinoin, acitretin or other retinoids can increase the risk for intracranial hypertension. Minocycline significantly reduces concentrations of the anti-HIV drug atazanavir in the body.

Pharmacology
Mechanism of action
Pharmacokinetics
Minocycline is quickly and nearly completely absorbed from the upper part of the small intestine. Taking it together with food, including milk, has no relevant influence on resorption. It reaches highest blood plasma concentrations after one to two hours and has a plasma protein binding of 70–75%. The substance penetrates into almost all tissues; very high concentrations are found in the gallbladder and liver. It crosses the blood–brain barrier better than doxycycline and other tetracyclines, reaching therapeutically relevant concentrations in the cerebrospinal fluid and also in inflamed meninges.Minocycline is inactivated by metabolization in the liver to about 50%. The rest is predominantly excreted into the gut (in part via the gallbladder, in part directly from blood vessels) and eliminated via the feces. About 10–15% are eliminated via the kidneys. The biological half-life is 14–22 (11–26) hours in healthy people, up to 30 hours in those with kidney failure, and significantly longer in those with liver disease.

Chemistry
The drug is used in form of minocycline hydrochloride dihydrate, which is sparingly soluble in water and slightly soluble in ethanol. Minocycline reacts acidic in aqueous solution.

History
Minocycline was patented in 1961 and came into commercial use in 1971. A topical foam for treatment of acne was approved in 2019.

Society and culture
Trade names
Many forms of minocycline are no longer covered by patent, so it is marketed under a variety of trade names:

Minomycin
Minostad (in Europe, for the treatment of acne)
Akamin
Minocin
Minoderm
Cyclimycin
Arestin (1-mg doses administered locally into periodontal pockets, after scaling and root planing, for treatment of periodontal disease.)
Aknemin
Solodyn (extended-release, for the treatment of acne)
Dynacin
Sebomin
Mino-Tabs
Acnamino
Minopen (in Japan)
Maracyn 2 (for treatment of bacterial infections in aquarium fish and amphibians)
Quatrocin (in Syria)
Minox (in Ireland)
Minoz (in India and Romania)
Divaine (in India)
Vinocyclin 100 (100-mg dose approved for treatment of acne in Vietnam)
Dentomycin  (2% minocylcine gel for use in periodontal pockets)
Amzeeq (4% foam, approved for treatment of acne United States)
Zilxi (1.5% foam, approved for treatment of rosacea in the United States)StoneBridge Pharma also markets Minocycline as Cleeravue-M in combination with SteriLid eyelid cleanser in the treatment of rosacea blepharitis.

Society and culture
It is available as a generic medication.

Research
Early research has found a tentative benefit from minocycline in schizophrenia, with several trials underway. A 2014 meta-analysis found minocycline may reduce negative and total symptom scores and was well tolerated.Current research is examining the possible neuroprotective and anti-inflammatory effects of minocycline against the progression of a group of neurodegenerative disorders including multiple sclerosis, rheumatoid arthritis, Huntingtons disease, and Parkinsons disease. As mentioned above, minocycline harms ALS patients.
Minocycline is also known to indirectly inhibit inducible nitric oxide synthase.A trial found no difference between minocycline and placebo in people with Alzheimers disease. Minocycline also has been used as a "last-ditch" treatment for toxoplasmosis in AIDS patients </s>


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Rasburicase and can you explain it in depth? [/INST] Rasburicase (trade names Elitek in the US and Fasturtec in the EU) is a medication that helps to clear uric acid from the blood. It is a recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin. Urate oxidase is known to be present in many mammals but does not naturally occur in humans. Rasburicase is produced by a genetically modified Saccharomyces cerevisiae strain. The complementary DNA (cDNA) coding for rasburicase was cloned from a strain of Aspergillus flavus.Rasburicase (Q00511) is a tetrameric protein with identical subunits. Each subunit is made up of a single 301 amino acid polypeptide chain with a molecular mass of about 34 kDa. The drug product is a sterile, white to off-white, lyophilized powder intended for intravenous administration following reconstitution with a diluent. Elitek (rasburicase) is supplied in 3 mL and 10 mL colorless, glass vials containing rasburicase at a concentration of 1.5 mg/mL after reconstitution.It is on the World Health Organizations List of Essential Medicines.

Medical uses
Rasburicase is approved for use by the U.S. Food and Drug Administration (and European counterparts) for the prevention and treatment of tumor lysis syndrome (TLS) in people receiving chemotherapy for hematologic cancers such as leukemias and lymphomas. However, it is not clear if it results in important benefits such as decreased kidney problems or decreased risk of death as of 2017.It is being investigated for treating severely high blood levels of uric acid from other sources. For example, it has been used for hyperuricemia in gout, in other rheumatologic conditions, and in rhabdomyolysis with kidney failure.

Contraindication
Rasburicase use is contraindicated in patients with a G6PDH deficiency.

Side effects
Rasburicase administration can cause anaphylaxis (incidence unknown); methemoglobinemia may occur in susceptible individuals such as those with G6PDH deficiency due to the production of hydrogen peroxide in the urate oxidase reaction. Testing patients for G6PDH deficiency prior to starting a course of rasburicase has been recommended.

Pharmacology
Mechanism of Action
In humans, uric acid is the final step in the catabolic pathway of purines. Rasburicase catalyzes enzymatic oxidation of poorly soluble uric acid into an inactive and more soluble metabolite allantoin with carbon dioxide and hydrogen peroxide as byproducts in the chemical reaction.

Pharmacodynamics
The measurement of plasma uric acid was used to evaluate the effectiveness of rasburicase in clinical studies. Following administration of either 0.15 or 0.20 mg/kg rasburicase daily for up to 5 days, plasma uric acid levels decreased within 4 hours and were maintained below 7.5 mg/dL in 98% of adult and 90% of pediatric patients for at least 7 days </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Benzphetamine and can you explain it in depth? [/INST] Benzphetamine (brand name Didrex) is a substituted amphetamine used short-term along with a doctor-approved, reduced-calorie diet, exercise, and behavioral program for weight loss. It is prescribed for obesity to people who have been unable to lose weight through exercise and dieting alone. It is a prodrug to dextroamphetamine and dextromethamphetamine.Benzphetamine is an anorectic, primarily promoting weight loss through reduced appetite. It also slightly increases metabolism.

Pharmacology
Benzphetamine is a sympathomimetic amine and is classified as an anorectic. The drugs main function is to reduce appetite, which in turn reduces caloric intake.Although the mechanism of action of the sympathomimetic appetite suppressants in the treatment of obesity is not fully known, these medications have pharmacological effects similar to those of amphetamines. Amphetamine and related sympathomimetic medications (such as benzphetamine) are thought to stimulate the release of norepinephrine and/or dopamine from storage sites in nerve terminals of the lateral hypothalamic feeding center, thereby producing a decrease in appetite </s>


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


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


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