<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Zoledronic acid and explain in detail? [/INST] Zoledronic acid, also known as zoledronate and sold under the brand name Zometa by Novartis among others, is a medication used to treat a number of bone diseases. These include osteoporosis, high blood calcium due to cancer, bone breakdown due to cancer,  Pagets disease of bone and Duchenne muscular dystrophy (DMD). It is given by injection into a vein.Common side effects include fever, joint pain, high blood pressure, diarrhea, and feeling tired. Serious side effects may include kidney problems, low blood calcium, and osteonecrosis of the jaw. Use during pregnancy may result in harm to the baby. It is in the bisphosphonate family of medications. It works by blocking the activity of osteoclast cells and thus decreases the breakdown of bone.Zoledronic acid was patented in 1986 and approved for medical use in the United States in 2001. It is on the World Health Organizations List of Essential Medicines.

Medical uses
Bone complications of cancer
Zoledronic acid is used to prevent bone fractures in patients with cancers such as multiple myeloma and prostate cancer, as well as for treating osteoporosis. It can also be used to treat hypercalcaemia of malignancy and can be helpful for treating pain from bone metastases.It can be given at home rather than in hospital. Such use has shown safety and quality-of-life benefits in people with breast cancer and bone metastases.

Osteoporosis
Zoledronic acid, in brand name products Aclasta and Reclast among others, may be given as a 5 mg infusion once per year for treatment of osteoporosis in men and post-menopausal women at increased risk of fracture.In 2007, the U.S. Food and Drug Administration (FDA) also approved it for the treatment of postmenopausal osteoporosis.

Other
Zoledronic acid may be used for treatment of osteogenesis imperfecta.A single 5 mg dose of zoledronic acid is used for the treatment of Pagets disease.

Contraindications
Poor kidney function (e.g. estimated glomerular filtration rate less than 30 mL/min)
Hypocalcaemia
Pregnancy
Paralysis

Side effects
Side effects can include fatigue, anemia, muscle aches, fever, and/or swelling in the feet or legs. Flu-like symptoms are common after the first infusion, although not subsequent infusions, and are thought to occur because of its potential to activate human gamma delta T cell (γδ T cells).

Kidneys
There is a risk of severe renal impairment. Appropriate hydration is important before administration, as is adequate calcium and vitamin D intake before Aclasta therapy in patients with hypocalcaemia, and for ten days following Aclasta in patients with Pagets disease of the bone. Monitoring for other mineral metabolism disorders and the avoidance of invasive dental procedures for those who develop osteonecrosis of the jaw is recommended.Zoledronate is rapidly processed via the kidneys; consequently its administration is not recommended for patients with reduced renal function or kidney disease. Some cases of acute kidney injury either requiring dialysis or having a fatal outcome following Reclast use have been reported to the U.S. Food and Drug Administration (FDA). This assessment was confirmed by the European Medicines Agency (EMA), whose Committee for Medicinal Products for Human Use (CHMP) specified new contraindications for the medication on 15 December 2011, which include hypocalcaemia and severe renal impairment with a creatinine clearance of less than 35 ml/min.

Bone
Osteonecrosis of the jaw
A rare complication that has been recently observed in cancer patients being treated with bisphosphonates is osteonecrosis of the jaw.  This has mainly been seen in patients with multiple myeloma treated with zoledronic acid who have had dental extractions.

Atypical fractures
After approving the drug on 8 July 2009, the European Medicines Agency conducted a class review of all bisphosphonates, including zoledronic acid, after several cases of atypical fractures were reported. In 2008, the EMAs Pharmacovigilance Working Party (PhVWP) noted that alendronic acid was associated with an increased risk of atypical fracture of the femur that developed with low or no trauma </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Insulin (medication) and explain in detail? [/INST] As a medication, insulin is any pharmaceutical preparation of the protein hormone insulin that is used to treat high blood glucose. Such conditions include type 1 diabetes, type 2 diabetes, gestational diabetes, and complications of diabetes such as diabetic ketoacidosis and hyperosmolar hyperglycemic states. Insulin is also used along with glucose to treat hyperkalemia (high blood potassium levels). Typically it is given by injection under the skin, but some forms may also be used by injection into a vein or muscle. There are various types of insulin, suitable for various time spans. The types are often all called insulin in the broad sense, although in a more precise sense, insulin is identical to the naturally occurring molecule whereas insulin analogues have slightly different molecules that allow for modified time of action. It is on the World Health Organizations List of Essential Medicines. In 2019, regular human insulin was the 298th most commonly prescribed medication in the United States, with more than 1 million prescriptions.Insulin can be made from the pancreas of pigs or cows. Human versions can be made either by modifying pig versions or recombinant technology. It comes in three main types: short–acting (such as regular insulin), intermediate-acting (such as neutral protamine Hagedorn (NPH) insulin), and longer-acting (such as insulin glargine).

History
Insulin was first used as a medication in Canada by Charles Best and Frederick Banting in 1922.This is a chronology of key milestones in the history of the medical use of insulin. For more details on the discovery, extraction, purification, clinical use, and synthesis of insulin, see Insulin

1921 Research on the role of pancreas in the nutritive assimilation
1922 Frederick Banting, Charles Best and James Collip use bovine insulin extract in humans at Connaught Laboratories in Toronto, Canada.
1922 Leonard Thompson becomes the first human to be treated with insulin.
1922 James D. Havens, son of former congressman James S. Havens, becomes the first American to be treated with insulin.
1922 Elizabeth Hughes Gossett, daughter of the U.S. Secretary of State, becomes the first American to be (officially) treated in Toronto.
1923 Eli Lilly produces commercial quantities of much purer bovine insulin than Banting et al. had used
1923 Farbwerke Hoechst, one of the forerunners of todays Sanofi Aventis, produces commercial quantities of bovine insulin in Germany
1923 Hans Christian Hagedorn founds the Nordisk Insulinlaboratorium in Denmark – forerunner of todays Novo Nordisk
1923 Constance Collier returns to health after being successfully treated with insulin in Strasbourg
1926 Nordisk receives a Danish charter to produce insulin as a non-profit
1936 Canadians David M. Scott and Albert M. Fisher formulate a zinc insulin mixture at Connaught Laboratories in Toronto and license it to Novo
1936 Hagedorn discovers that adding protamine to insulin prolongs the duration of action of insulin
1946 Nordisk formulates Isophane porcine insulin aka Neutral Protamine Hagedorn or NPH insulin
1946 Nordisk crystallizes a protamine and insulin mixture
1950 Nordisk markets NPH insulin
1953 Novo formulates Lente porcine and bovine insulins by adding zinc for longer lasting insulin
1955 Frederick Sanger determines the amino acid sequence of insulin
1965 Synthesized by total synthesis by Wang Yinglai, Chen-Lu Tsou, et al.
1969 Dorothy Crowfoot Hodgkin solves the crystal structure of insulin by X-ray crystallography
1973 Purified monocomponent (MC) insulin is introduced
1973 The U.S. officially "standardized" insulin sold for human use in the U.S. to U-100 (100 units per milliliter). Prior to that, insulin was sold in different strengths, including U-80 (80 units per milliliter) and U-40 formulations (40 units per milliliter), so the effort to "standardize" the potency aimed to reduce dosage errors and ease doctors job of prescribing insulin for people. Other countries also followed suit.
1978 Genentech produces biosynthetic human insulin in Escherichia coli bacteria using recombinant DNA techniques, licenses to Eli Lilly
1981 Novo Nordisk chemically and enzymatically converts porcine to human insulin
1982 Genentech synthetic human insulin (above) approved
1983 Eli Lilly and Company produces biosynthetic human insulin with recombinant DNA technology, Humulin
1985 Axel Ullrich sequences a human cell membrane insulin receptor.
1988 Novo Nordisk produces recombinant biosynthetic human insulin
1996 Lilly Humalog "lispro" insulin analogue approved.
2000 Sanofi Aventis Lantus insulin "glargine" analogue approved for clinical use in the US and Europe.
2004 Sanofi Aventis Apidra insulin "glulisine" insulin analogue approved for clinical use in the US.
2006 Novo Nordisk Levemir "detemir" insulin analogue approved for clinical use in the US.

Medical uses
Insulin is used to treat a number of diseases including diabetes and its acute complications such as diabetic ketoacidosis and hyperosmolar hyperglycemic states. It is also used along with glucose to treat high blood potassium levels. Use during pregnancy is relatively safe for the baby. Insulin was formerly used in a psychiatric treatment called insulin shock therapy.

Side effects
Some side effects are hypoglycemia (low blood sugar), hypokalemia (low blood potassium), and allergic reactions. Allergy to insulin affected about 2% of people, of which most reactions are not due to the insulin itself but to preservatives added to insulin such as zinc, protamine, and meta-cresol. Most reactions are Type I hypersensitivity reactions and rarely cause anaphylaxis. A suspected allergy to insulin can be confirmed by skin prick testing, patch testing and occasionally skin biopsy. First line therapy against insulin hypersensitivity reactions include symptomatic therapy with antihistamines. The affected persons are then switched to a preparation that does not contain the specific agent they are reacting to or undergo desensitization.Cutaneous adverse effects
Other side effects may include pain or skin changes at the sites of injection. Repeated subcutaneous injection without site rotation can lead to lipohypertrophy and amyloidomas, which manifest as firm palpable nodules under the skin.

Principles
Insulin is an endogenous hormone, which is produced by the pancreas.
The insulin protein has been highly conserved across evolutionary time, and is present in both mammals and invertebrates. The insulin/insulin-like growth factor signalling pathway (IIS) has been extensively studied in species including nematode worms (e.g.C. elegans), flies (Drosophila melanogaster) and mice (Mus musculus). Its mechanisms of action are highly similar across species.Both type 1 diabetes and type 2 diabetes are marked by a loss of pancreatic function, though to differing degrees. People who are affected with diabetes are referred to as diabetics. Many diabetics require an exogenous source of insulin to keep their blood sugar levels within a safe target range.In 1916, Nicolae C. Paulescu (1869-1931) succeeded in developing an aqueous pancreatic extract that normalized a diabetic dog. In 1921, he published 4 papers in the Society of Biology in Paris centering on the successful effects of the pancreatic extract in diabetic dogs. Research on the Role of the Pancreas in Food Assimilation by Paulescu was published in August 1921 in the Archives Internationales de Physiologie, Liège, Belgium.
Initially, the only way to obtain insulin for clinical use was to extract it from the pancreas of another creature. Animal glands were obtainable as a waste product of the meatpacking industry. Insulin was derived primarily from cows (Eli Lilly and Company) and pigs (Nordisk Insulinlaboratorium). The making of eight ounces of purified insulin could require as much as two tons of pig parts.
Insulin from these sources is effective in humans as it is highly similar to human insulin (three amino acid difference in bovine insulin, one amino acid difference in porcine). Initially, lower preparation purity resulted in allergic reactions to the presence of non-insulin substances. Purity has improved steadily since the 1920s ultimately reaching purity of 99% by the mid-1970s thanks to high-pressure liquid chromatography (HPLC) methods. Minor allergic reactions still occur occasionally, even to synthetic "human" insulin varieties.Beginning in 1982, biosynthetic "human" insulin has been manufactured for clinical use through genetic engineering techniques using recombinant DNA technology. Genentech developed the technique used to produce the first such insulin, Humulin, but did not commercially market the product themselves. Eli Lilly marketed Humulin in 1982. Humulin was the first medication produced using modern genetic engineering techniques in which actual human DNA is inserted into a host cell (E. coli in this case). The host cells are then allowed to grow and reproduce normally, and due to the inserted human DNA, they produce a synthetic version of human insulin. Manufacturers claim this reduces the presence of many impurities. However, the clinical preparations prepared from such insulins differ from endogenous human insulin in several important respects; an example is the absence of C-peptide which has in recent years been shown to have systemic effects itself.
Novo Nordisk has also developed a genetically engineered insulin independently using a yeast process.According to a survey that the International Diabetes Federation conducted in 2002 on the access to and availability of insulin in its member countries, approximately 70% of the insulin that is currently sold in the world is recombinant, biosynthetic human insulin. A majority of insulin used clinically today is produced this way, although clinical experience has provided conflicting evidence on whether these insulins are any less likely to produce an allergic reaction. Adverse reactions have been reported; these include loss of warning signs that patients may slip into a coma through hypoglycemia, convulsions, memory lapse and loss of concentration. However, the International Diabetes Federations position statement from 2005 is very clear in stating that "there is NO overwhelming evidence to prefer one species of insulin over another" and "[modern, highly purified] animal insulins remain a perfectly acceptable alternative."Since January 2006, all insulins distributed in the U.S. and some other countries are synthetic "human" insulins or their analogues. A special FDA importation process is required to obtain bovine or porcine derived insulin for use in the U.S., although there may be some remaining stocks of porcine insulin made by Lilly in 2005 or earlier, and porcine lente insulin is also sold and marketed under the brand name Vetsulin(SM) in the U.S. for veterinary usage in the treatment of companion animals with diabetes.

Basal insulin
In type 1 diabetes, insulin production is extremely low, and as such the body requires exogenous insulin. Some people with type 2 diabetes, particularly those with very high hemoglobin A1c values, may also require a baseline rate of insulin, as their body is desensitized to the level of insulin being produced. Basal insulin regulates the bodys blood glucose between mealtimes, as well as overnight. This basal rate of insulin action is generally achieved via the use of an intermediate-acting insulin (such as NPH) or a long-acting insulin analog. In type 1 diabetics, it may also be achieved via continuous infusion of rapid-acting insulin using an insulin pump. Approximately half of a persons daily insulin requirement is administered as a basal insulin, usually administered once per day at night.

Prandial insulin
When a person eats food containing carbohydrates and glucose, insulin helps regulate the bodys metabolism of the food. Prandial insulin, also called mealtime or bolus insulin, is designed as a bolus dose of insulin prior to a meal to regulate the spike in blood glucose that occurs following a meal. The dose of prandial insulin may be static, or may be calculated by the patient using either their current blood sugar, planned carbohydrate intake, or both. This calculation may also be performed by an insulin pump in patients using a pump. Insulin regiments that consist of doses calculated in this manner are considered intensive insulin regimens. Prandial insulin is usually administered no more than 15–30 minutes prior to a meal using a rapid-acting insulin or a regular insulin. In some patients, a combination insulin may be used that contains both NPH (long acting) insulin and a rapid/regular insulin to provide both a basal insulin and prandial insulin.

Challenges in treatment
There are several challenges involved in the use of insulin as a clinical treatment for diabetes:
Mode of administration.
Selecting the right dose and timing. The amount of carbohydrates one unit of insulin handles varies widely between persons and over the day but values between 7 and 20 grams per 1 IE is typical.
Selecting an appropriate insulin preparation (typically on speed of onset and duration of action grounds).
Adjusting dosage and timing to fit food intake timing, amounts, and types.
Adjusting dosage and timing to fit exercise undertaken.
Adjusting dosage, type, and timing to fit other conditions, for instance the increased stress of illness.
Variability in absorption into the bloodstream via subcutaneous delivery
The dosage is non-physiological in that a subcutaneous bolus dose of insulin alone is administered instead of combination of insulin and C-peptide being released gradually and directly into the portal vein.
It is simply a nuisance for people to inject whenever they eat carbohydrate or have a high blood glucose reading.
It is dangerous in case of mistake (most especially too much insulin).

Types
Medical preparations of insulin are never just insulin in water (with nothing else). Clinical insulins are mixtures of insulin plus other substances including preservatives. These prevent the protein from spoiling or denaturing too rapidly, delay absorption of the insulin, adjust the pH of the solution to reduce reactions at the injection site, and so on.Slight variations of the human insulin molecule are called insulin analogues, (technically "insulin receptor ligands") so named because they are not technically insulin, rather they are analogues which retain the hormones glucose management functionality. They have absorption and activity characteristics not currently possible with subcutaneously injected insulin proper. They are either absorbed rapidly in an attempt to mimic real beta cell insulin (as with insulin lispro, insulin aspart, and insulin glulisine), or steadily absorbed after injection instead of having a peak followed by a more or less rapid decline in insulin action (as with insulin detemir and insulin glargine), all while retaining insulins glucose-lowering action in the human body. However, a number of meta-analyses, including those done by the Cochrane Collaboration in 2005, Germanys Institute for Quality and Cost Effectiveness in the Health Care Sector [IQWiG] released in 2007, and the Canadian Agency for Drugs and Technology in Health (CADTH) also released in 2007 have shown no unequivocal advantages in clinical use of insulin analogues over more conventional insulin types.Choosing insulin type and dosage/timing should be done by an experienced medical professional working closely with people who are diabetic .The commonly used types of insulin are as follows.

Fast-acting
Includes the insulin analogues aspart, lispro, and glulisine. These begin to work within 5 to 15 minutes and are active for 3 to 4 hours. Most insulins form hexamers, which delay entry into the blood in active form; these analog insulins do not but have normal insulin activity. Newer varieties are now pending regulatory approval in the U.S. which are designed to work rapidly, but retain the same genetic structure as regular human insulin.

Short-acting
Includes regular insulin, which begins working within 30 minutes and is active about 5 to 8 hours.

Intermediate-acting
Includes NPH insulin, which begins working in 1 to 3 hours and is active for 16 to 24 hours.

Long-acting
Includes the analogues glargine U100 and detemir, each of which begins working within 1 to 2 hours and continues to be active, without major peaks or dips, for about 24 hours, although this varies in many individuals.

Ultra-long acting
Includes the analogues insulin glargine U300 and degludec, which begin working within 30 to 90 minutes and continues to be active for greater than 24 hours.

Combination insulin products
Includes a combination of either fast-acting or short-acting insulin with a longer acting insulin, typically an NPH insulin. The combination products begin to work with the shorter acting insulin (5–15 minutes for fast-acting, and 30 minutes for short acting), and remain active for 16 to 24 hours. There are several variations with different proportions of the mixed insulins (e.g. Novolog Mix 70/30 contains 70% aspart protamine [akin to NPH], and 30% aspart.)

Methods of administration
Unlike many medicines, insulin cannot be taken orally at the present time. Like nearly all other proteins introduced into the gastrointestinal tract, it is reduced to fragments (single amino acid components), whereupon all activity is lost. There has been some research into ways to protect insulin from the digestive tract, so that it can be administered in a pill. So far this is entirely experimental.

Subcutaneous
Insulin is usually taken as subcutaneous injections by single-use syringes with needles, an insulin pump, or by repeated-use insulin pens with needles. People who wish to reduce repeated skin puncture of insulin injections often use an injection port in conjunction with syringes.The use of subcutaneous injections of insulin is designed to mimic the natural physiological cycle of insulin secretion, while taking into account the various properties of the formulations used such as half-life, onset of action, and duration of action. In many people, both a rapid- or short-acting insulin product as well as an intermediate- or long-acting product are used to decrease the amount of injections per day. In some, insulin injections may be combined with other injection therapy such as GLP-1 agonists. Cleansing of the injection site and injection technique are required to ensure effective insulin therapy.

Insulin pump
Insulin pumps are a reasonable solution for some. Advantages to the person are better control over background or basal insulin dosage, bolus doses calculated to fractions of a unit, and calculators in the pump that may help with determining bolus infusion dosages. The limitations are cost, the potential for hypoglycemic and hyperglycemic episodes, catheter problems, and no "closed loop" means of controlling insulin delivery based on current blood glucose levels.Insulin pumps may be like electrical injectors attached to a temporarily implanted catheter or cannula. Some who cannot achieve adequate glucose control by conventional (or jet) injection are able to do so with the appropriate pump.Indwelling catheters pose the risk of infection and ulceration, and some peoples may also develop lipodystrophy due to the infusion sets. These risks can often be minimized by keeping infusion sites clean. Insulin pumps require care and effort to use correctly.

Dosage and timing
Dosage units
One international unit of insulin (1 IU) is defined as the "biological equivalent" of 34.7 μg pure crystalline insulin.
The first definition of a unit of insulin was the amount required to induce hypoglycemia in a rabbit. This was set by James Collip at the University of Toronto in 1922. Of course, this was dependent on the size and diet of the rabbits. The unit of insulin was set by the insulin committee at the University of Toronto. The unit evolved eventually to the old USP insulin unit, where one unit (U) of insulin was set equal to the amount of insulin required to reduce the concentration of blood glucose in a fasting rabbit to 45 m g/d l (2.5 m mol/L). Once the chemical structure and mass of insulin was known, the unit of insulin was defined by the mass of pure crystalline insulin required to obtain the USP unit.
The unit of measurement used in insulin therapy is not part of the International System of Units (abbreviated SI) which is the modern form of the metric system. Instead the pharmacological international unit (IU) is defined by the WHO Expert Committee on Biological Standardization.

Potential complications
The central problem for those requiring external insulin is picking the right dose of insulin and the right timing.
Physiological regulation of blood glucose, as in the non-diabetic, would be best. Increased blood glucose levels after a meal is a stimulus for prompt release of insulin from the pancreas. The increased insulin level causes glucose absorption and storage in cells, reduces glycogen to glucose conversion, reducing blood glucose levels, and so reducing insulin release. The result is that the blood glucose level rises somewhat after eating, and within an hour or so, returns to the normal fasting level. Even the best diabetic treatment with synthetic human insulin or even insulin analogs, however administered, falls far short of normal glucose control in the non-diabetic.Complicating matters is that the composition of the food eaten (see glycemic index) affects intestinal absorption rates. Glucose from some foods is absorbed more (or less) rapidly than the same amount of glucose in other foods. In addition, fats and proteins cause delays in absorption of glucose from carbohydrates eaten at the same time. As well, exercise reduces the need for insulin even when all other factors remain the same, since working muscle has some ability to take up glucose without the help of insulin.Because of the complex and interacting factors, it is, in principle, impossible to know for certain how much insulin (and which type) is needed to cover a particular meal to achieve a reasonable blood glucose level within an hour or two after eating. Non-diabetics beta cells routinely and automatically manage this by continual glucose level monitoring and insulin release. All such decisions by a diabetic must be based on experience and training (i.e., at the direction of a physician, PA, or in some places a specialist diabetic educator) and, further, specifically based on the individual experience of the person. But it is not straightforward and should never be done by habit or routine. With some care however, it can be done reasonably well in clinical practice. For example, some people with diabetes require more insulin after drinking skim milk than they do after taking an equivalent amount of fat, protein, carbohydrate, and fluid in some other form. Their particular reaction to skimmed milk is different from other people with diabetes, but the same amount of whole milk is likely to cause a still different reaction even in that person. Whole milk contains considerable fat while skimmed milk has much less. It is a continual balancing act for all people with diabetes, especially for those taking insulin.
People with insulin-dependent diabetes typically require some base level of insulin (basal insulin), as well as short-acting insulin to cover meals (bolus also known as mealtime or prandial insulin). Maintaining the basal rate and the bolus rate is a continuous balancing act that people with insulin-dependent diabetes must manage each day. This is normally achieved through regular blood tests, although continuous blood sugar testing equipment (Continuous Glucose Monitors or CGMs) are now becoming available which could help to refine this balancing act once widespread usage becomes common.

Strategies
A long-acting insulin is used to approximate the basal secretion of insulin by the pancreas, which varies in the course of the day. NPH/isophane, lente, ultralente, glargine, and detemir may be used for this purpose. The advantage of NPH is its low cost, the fact that you can mix it with short-acting forms of insulin, thereby minimizing the number of injections that must be administered, and that the activity of NPH will peak 4–6 hours after administration, allowing a bedtime dose to balance the tendency of glucose to rise with the dawn, along with a smaller morning dose to balance the lower afternoon basal need and possibly an afternoon dose to cover evening need. A disadvantage of bedtime NPH is that if not taken late enough (near midnight) to place its peak shortly before dawn, it has the potential of causing hypoglycemia. One theoretical advantage of glargine and detemir is that they only need to be administered once a day, although in practice many people find that neither lasts a full 24 hours. They can be administered at any time during the day as well, provided that they are given at the same time every day. Another advantage of long-acting insulins is that the basal component of an insulin regimen (providing a minimum level of insulin throughout the day) can be decoupled from the prandial or bolus component (providing mealtime coverage via ultra-short-acting insulins), while regimens using NPH and regular insulin have the disadvantage that any dose adjustment affects both basal and prandial coverage. Glargine and detemir are significantly more expensive than NPH, lente and ultralente, and they cannot be mixed with other forms of insulin.A short-acting insulin is used to simulate the endogenous insulin surge produced in anticipation of eating. Regular insulin, lispro, aspart and glulisine can be used for this purpose. Regular insulin should be given with about a 30-minute lead-time prior to the meal to be maximally effective and to minimize the possibility of hypoglycemia. Lispro, aspart and glulisine are approved for dosage with the first bite of the meal, and may even be effective if given after completing the meal. The short-acting insulin is also used to correct hyperglycemia.The usual schedule for checking fingerstick blood glucose and administering insulin is before all meals and sometimes also at bedtime. More recent guidelines also call for a check 2 hours after a meal to ensure the meal has been covered effectively.

Sliding scales
First described in 1934, what physicians typically refer to as sliding-scale insulin (SSI) is fast- or rapid-acting insulin only, given subcutaneously, typically at meal times and sometimes bedtime, but only when blood glucose is above a threshold (e.g. 10 mmol/L, 180 mg/dL). The so-called "sliding-scale" method is widely taught, although it has been heavily criticized. Sliding scale insulin (SSI) is not an effective way of managing long-term diabetes in individuals residing in nursing homes. Sliding scale insulin leads to greater discomfort and increased nursing time.
Sample regimen using insulin glargine and insulin lispro:

Insulin glargine: 20 units at bedtime

Carb counting and DAFNE
A more complicated method that allows greater freedom with meal times and snacks is "carb counting." This approach is taught to people who are diabetic in the UK and elsewhere as "Dose Adjustment For Normal Eating" or DAFNE.
In Europe, people who are not familiar with the DAFNE regime can take an educational course where the basic starting insulin dose guideline is "for every 10g of carbohydrates you eat, take 1 unit of insulin". DAFNE courses also cover topics that naturally work alongside this regime, such as blood glucose monitoring, exercise and carbohydrate estimation to help the person work out their personal control requirements.
People can also use their total daily dose (TDD) of insulin to estimate how many grams of carbohydrates will be "covered" by 1 unit of insulin, and using this result, estimate how many units of insulin should be administered depending on the carbohydrate content of their meal. For example, if the person determines that 1 unit of insulin will cover 15 grams of carbohydrates, then they must administer 5 units of insulin before consuming a meal that contains 75 grams of carbohydrates.
Some alternative methods also consider the protein content of the meal (since excess dietary protein can be converted to glucose via gluconeogenesis).
With DAFNE, most dosages involve a fair degree of guesswork, especially with non-labeled foods, and will only work fairly consistently from one dosage to the next if the person is aware of their bodys requirements. For example, a person finds they can take 1 unit of insulin to 10g of carbohydrates in the morning and the evening, but find that their body requires more insulin for a meal in the middle of the day so they have to adjust to 1 unit per 8.5g of carbohydrates.
Other less obvious factors that affect the bodys use of insulin must also be taken into account. For example, some people may find that their bodies process insulin better on hot days so require less insulin. With this, the person again has to adjust their dose to the best of their understanding from their past experiences.
The DAFNE regime requires the person to learn about their bodys needs through experience, which takes time and patience, but it can then become effective.

Closed-loop predictive modeling
People with fluctuating insulin requirements may benefit from a closed-loop predictive modeling approach. As an extension on "carb counting", in this closed-loop predictive modeling approach, the four daily insulin dosages needed to reach the target blood sugar levels for the "normal" daily carbohydrate consumption and amount of physical activity, are continuously adjusted based on the pre-meal and pre-night blood sugar level readings. Each new blood sugar reading provides the feedback to fine-tune and track the bodys insulin requirements. Within this strategy, the key specific factors, which have to be determined experimentally, are the blood sugar correction factor and the carbohydrate ratio. The blood sugar correction factor sets both the "proportional gain" and "integral gain" factors for the four feedback loops. When taken too low, deviations from the target blood sugar level are not corrected for effectively, when taken too high, the blood sugar regulation will become unstable. Since in this approach, the carbohydrate ratio is only used to account for non-standard carbohydrate intakes, it is usually not required to work with meal specific ratios.

Dose calculation
Insulin dosage is given by the formula

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    {\displaystyle \mathrm {insulin} ={\frac {\mathrm {glucose} -{\mathit {TR}}}{\mathit {CF}}}+{\frac {\mathrm {carbohydrates} }{\mathit {KF}}}={\frac {{({\mathit {KF}}}\times (\mathrm {glucose} -{\mathit {TR}}))+({\mathit {CF}}\times \mathrm {carbohydrates} )}{{\mathit {CF}}\times {\mathit {KF}}}}}
  based on the persons blood glucose and carbohydrate intake and these constants:

TR = target rate
CF = corrective factor
KF = carbohydrate factorBlood glucose and target rate are expressed in mg/dL or mmol/L. Constants should be set by a physician or clinical pharmacist.

Abuse
The abuse of exogenous insulin carries with it an attendant risk of hypoglycemic coma and death when the amount used is in excess of that required to handle ingested carbohydrate. Acute risks include brain damage, paralysis, and death. Symptoms may include dizziness, weakness, trembling, palpitations, seizures, confusion, headache, drowsiness, coma, diaphoresis and nausea. All persons with overdoses should be referred for medical assessment and treatment, which may last for hours or days.Data from the US National Poison Data System (2013) indicates that 89.3% of insulin cases reported to poison centers are unintentional, as a result of therapeutic error. Another 10% of cases are intentional, and may reflect attempted suicide, abuse, criminal intent, secondary gain or other unknown reasons. Hypoglycemia that has been induced by exogenous insulin can be chemically detected by examining the ratio of insulin to C-peptide in peripheral circulation. It has been suggested that this type of approach could be used to detect exogenous insulin abuse by athletes.The possibility of using insulin in an attempt to improve athletic performance was suggested as early as the 1998 Winter Olympics in Nagano, Japan, as reported by Peter Sönksen in the July 2001 issue of Journal of Endocrinology. The question of whether non-diabetic athletes could legally use insulin was raised by a Russian medical officer. Whether insulin would actually improve athletic performance is unclear, but concerns about its use led the International Olympic Committee to ban use of the hormone by non-diabetic athletes in 1998.The book Game of Shadows (2001), by reporters Mark Fainaru-Wada and Lance Williams, included allegations that baseball player Barry Bonds used insulin (as well as other drugs) in the apparent belief that it would increase the effectiveness of the growth hormone he was alleged to be taking.
Bonds eventually testified in front of a federal grand jury as part of a government investigation of BALCO.Bodybuilders in particular are claimed to be using exogenous insulin and other drugs in the belief that they will increase muscle mass. Bodybuilders have been described as injecting up to 10 IU of regular synthetic insulin before eating sugary meals.
A 2008 report suggested that insulin is sometimes used in combination with anabolic steroids and growth hormone (GH), and that "Athletes are exposing themselves to potential harm by self‐administering large doses of GH, IGF‐I and insulin".
Insulin abuse has been mentioned as a possible factor in the deaths of bodybuilders Ghent Wakefield and Rich Piana.Insulin, human growth hormone (HGH) and insulin-like growth factor 1 (IGF-1) are self-administered by those looking to increase muscle mass beyond the scope offered by anabolic steroids alone. Their rationale is that since insulin and HGH act synergistically to promote growth, and since IGF-1 is a primary mediator of musculoskeletal growth, the stacking of insulin, HGH and IGF-1 should offer a synergistic growth effect on skeletal muscle. This theory has been supported in recent years by top-level bodybuilders whose competition weight is in excess of 50 lb (23 kg) of muscle, larger than that of competitors in the past, and with even lower levels of body fat.

Detection in biological fluids
Insulin is often measured in serum, plasma or blood in order to monitor therapy in people who are diabetic, confirm a diagnosis of poisoning in hospitalized persons or assist in a medicolegal investigation of suspicious death. Interpretation of the resulting insulin concentrations is complex, given the numerous types of insulin available, various routes of administration, the presence of anti-insulin antibodies in insulin-dependent diabetics and the ex vivo instability of the drug. Other potential confounding factors include the wide-ranging cross-reactivity of commercial insulin immunoassays for the biosynthetic insulin analogs, the use of high-dose intravenous insulin as an antidote to antihypertensive drug overdosage and postmortem redistribution of insulin within the body. The use of a chromatographic technique for insulin assay may be preferable to immunoassay in some circumstances, to avoid the issue of cross-reactivity affecting the quantitative result and also to assist identifying the specific type of insulin in the specimen.

Combination with other antidiabetic drugs
A combination therapy of insulin and other antidiabetic drugs appears to be most beneficial in people who are diabetic, who still have residual insulin secretory capacity. A combination of insulin therapy and sulfonylurea is more effective than insulin alone in treating people with type 2 diabetes after secondary failure to oral drugs, leading to better glucose profiles and/or decreased insulin needs.

Society and culture
Economics
In the United States the unit price of insulin has increased steadily from 1991 to 2019. It rose threefold from 2002 to 2013. Costs can be as high as US$900 per month. Concerns were raised in 2016 of pharmaceutical companies working together to increase prices. In January 2019, lawmakers from the United States House of Representatives sent letters to insulin manufacturers Eli Lilly and Co., Sanofi and Novo Nordisk asking for explanations for their rapidly raising insulin prices. The annual cost of insulin for people with type 1 diabetes in the U.S. almost doubled from $2,900 to $5,700 over the period from 2012 to 2016.People in the U.S. pay two to six times more than the rest of the world, including Canada, for brand name prescription medicine, according to the International Federation of Health Plans. Canada, like many other industrialized countries, has price controls on the cost of pharmaceuticals.California, in July 2022, approved a budget that allocates $100 million for the state to create its own insulin at a close-to-cost price.

Regulatory status
In March 2020, the FDA changed the regulatory pathway for approval of new insulin products. Insulin is regulated as a biologic rather than as a drug. The changed status gives the FDA more flexibility for approval and labeling. In July 2021, the FDA approved insulin glargine-yfgn (Semglee), a biosimilar product that contains the long acting analog insulin glargine. Insulin glargine-yfgn is interchangeable and less expensive than the reference product, insulin glargine (Lantus), which had been approved in 2000. The FDA requires that new insulin products are non-inferior to existing insulin products with respect to reduction in hemoglobin A1c. See Misbin, RI (February 2022). Insulin - History from an FDA Insider. Politics and Prose Publishing, Washington DC. Text ISBN 978-I-62429-391-7

Research
Inhalation
In 2006 the U.S. Food and Drug Administration (FDA) approved the use of Exubera, the first inhalable insulin. It was withdrawn from the market by its maker as of third quarter 2007, due to lack of acceptance.
Inhaled insulin claimed to have similar efficacy to injected insulin, both in terms of controlling glucose levels and blood half-life. Currently, inhaled insulin is short acting and is typically taken before meals; an injection of long-acting insulin at night is often still required. When people were switched from injected to inhaled insulin, no significant difference was observed in HbA1c levels over three months. Accurate dosing was a particular problem, although people showed no significant weight gain or pulmonary function decline over the length of the trial, when compared to the baseline.Following its commercial launch in 2005 in the United Kingdom, it was not (as of July 2006) recommended by National Institute for Health and Clinical Excellence for routine use, except in cases where there is "proven injection phobia diagnosed by a psychiatrist or psychologist".In January 2008, the worlds largest insulin manufacturer, Novo Nordisk, also announced that the company was discontinuing all further development of the companys own version of inhalable insulin, known as the AERx iDMS inhaled insulin system. Similarly, Eli Lilly and Company ended its efforts to develop its inhaled Air Insulin in March 2008. However, MannKind Corp. (majority owner, Alfred E. Mann) remains optimistic about the concept.

Transdermal
There are several methods for transdermal delivery of insulin. Pulsatile insulin uses microjets to pulse insulin into the person, mimicking the physiological secretions of insulin by the pancreas. Jet injection had different insulin delivery peaks and durations as compared to needle injection. Some diabetics may prefer jet injectors to hypodermic injection.Both electricity using iontophoresis and ultrasound have been found to make the skin temporarily porous. The insulin administration aspect remains experimental, but the blood glucose test aspect of "wrist appliances" is commercially available.
Researchers have produced a watch-like device that tests for blood glucose levels through the skin and administers corrective doses of insulin through pores in the skin. A similar device, but relying on skin-penetrating "microneedles", was in the animal testing stage in 2015.

Intranasal
Intranasal insulin is being investigated. A randomized controlled trial that will determine whether intranasal insulin can delay or prevent the onset of type 1 diabetes in at-risk children and young adults is expected to yield results in 2016.

By mouth
The basic appeal of hypoglycemic agents by mouth is that most people would prefer a pill or an oral liquid to an injection. However, insulin is a peptide hormone, which is digested in the stomach and gut and in order to be effective at controlling blood sugar, cannot be taken orally in its current form.
The potential market for an oral form of insulin is assumed to be enormous, thus many laboratories have attempted to devise ways of moving enough intact insulin from the gut to the portal vein to have a measurable effect on blood sugar.A number of derivatization and formulation strategies are currently being pursued to in an attempt to develop an orally available insulin. Many of these approaches employ nanoparticle delivery systems and several are being tested in clinical trials.

Pancreatic transplantation
Another improvement would be a transplantation of the pancreas or beta cell to avoid periodic insulin administration. This would result in a self-regulating insulin source. Transplantation of an entire pancreas (as an individual organ) is difficult and relatively uncommon. It is often performed in conjunction with liver or kidney transplant, although it can be done by itself. It is also possible to do a transplantation of only the pancreatic beta cells. However, islet transplants had been highly experimental for many years, but some researchers in Alberta, Canada, have developed techniques with a high initial success rate (about 90% in one group). Nearly half of those who got an islet cell transplant were insulin-free one year after the operation; by the end of the second year that number drops to about one in seven. However, researchers at the University of Illinois at Chicago (UIC) have slightly modified the Edmonton Protocol procedure for islet cell transplantation and achieved insulin independence in diabetic people, with fewer but better-functioning pancreatic islet cells. Longer-term studies are needed to validate whether it improves the rate of insulin-independence.
Beta cell transplant may become practical in the near future. Additionally, some researchers have explored the possibility of transplanting genetically engineered non-beta cells to secrete insulin. Clinically testable results are far from realization at this time </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Tafasitamab and explain in detail? [/INST] Tafasitamab, sold under the brand name Monjuvi, is a medication used in combination with lenalidomide for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).Tafasitamab may cause serious side effects including infusion related reactions, bone marrow suppression, infections, and harm to an unborn baby. The most common side effects of tafasitamab are low blood cell counts, fatigue, diarrhea, cough, fever, limb swelling, upper respiratory infection, and decreased appetite.Tafasitamab is a humanized Fc-modified cytolytic CD19 antibody.Tafasitamab was approved for medical use in the United States in July 2020. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Calcipotriol and explain in detail? [/INST] Calcipotriol, also known as calcipotriene, is a synthetic derivative of calcitriol, a form of vitamin D.  It is used in the treatment of psoriasis. It is safe for long-term application in psoriatic skin conditions.It was patented in 1985 and approved for medical use in 1991. It is marketed under the trade name "Dovonex" in the United States, "Daivonex" outside North America, and "Psorcutan" in Germany.It is on the World Health Organizations List of Essential Medicines.Calcipotriol is also available as Calcipotriol/betamethasone dipropionate, a fixed-dose combination medication with the synthetic corticosteroid betamethasone dipropionate for the treatment of plaque psoriasis.

Medical uses
Chronic plaque psoriasis is the chief medical use of calcipotriol. It has also been used successfully in the treatment of alopecia areata.

Contraindications
Hypersensitivity, use on face, hypercalcaemia, or evidence of vitamin D toxicity are the only contraindications for calcipotriol use.Cautions include exposure to excessive natural or artificial light, due to the potential for calcipotriol to cause photosensitivity.

Adverse effects
Adverse effects by frequency:
Very common (> 10% frequency)
Burning
Itchiness
Skin irritationCommon (1–10% frequency)

Uncommon (0.1–1% frequency)
Exacerbation of psoriasisRare (< 0.1% frequency)

Interactions
No drug interactions are known.

Pharmacology
Mechanism of action
The efficacy of calcipotriol in the treatment of psoriasis was first noticed by the observation of patients receiving various forms of vitamin D in an osteoporosis study.  Unexpectedly, some patients who also had psoriasis experienced dramatic reductions in lesion counts.The precise mechanism of calcipotriol in remitting psoriasis is not well understood.  However, it has been shown to have comparable affinity with calcitriol for the vitamin D receptor (VDR), while being less than 1% as active as the calcitriol in regulating calcium metabolism </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Nicotine replacement therapy and explain in detail? [/INST] Nicotine replacement therapy (NRT) is a medically approved way to treat people with tobacco use disorder by taking nicotine by means other than tobacco. It is used to help with quitting smoking or stopping chewing tobacco. It increases the chance of quitting tobacco smoking by about 55%. Often it is used along with other behavioral techniques. NRT has also been used to treat ulcerative colitis. Types of NRT include the adhesive patch, chewing gum, lozenges, nose spray, and inhaler. The use of multiple types of NRT at a time may increase effectiveness.Common side effects depend on the formulation of nicotine. Common side effects with the gum include nausea, hiccups, and irritation of the mouth. Common side effects with the patch include skin irritation and a dry mouth while the inhaler commonly results in a cough, runny nose, or headaches. Serious risks include nicotine poisoning and continued addiction. They do not appear to increase the risk of heart attacks. There are possible harms to the baby if used during pregnancy. Nicotine replacement therapy works by reducing cravings caused by nicotine addiction.They were first approved for use in 1984, in the United States. Nicotine replacement products are on the World Health Organizations List of Essential Medicines. They are available as generic medications.

Medical uses
Nicotine replacement therapy, in the form of gum, patches, nasal spray, inhaler and lozenges all improve the ability of people trying to quit tobacco products. Nicotine replacement therapy is as effective as medications, such as bupropion, in helping people quit smoking for at least six months. All forms of nicotine replacement therapy, including nicotine gum, patches, nasal spray, inhalers, and lozenges, have similar success rates in terms of helping people stop smoking. However, the likelihood that someone will stick to a certain treatment varies, with compliance being the highest with nicotine patches, followed by nicotine gum, inhalers, and nasal sprays. Using a few different nicotine replacement methods in combination may improve success rates in stopping tobacco use. Additionally, using nicotine replacement with counseling has been proven to improve tobacco abstinence rates. These other strategies include: creating a plan to quit and utilizing quit programs, a quit phone line, or app that provides tips and inspiration to help quit.Using nicotine replacement therapy to quit smoking should be considered for people who are severely dependent on nicotine. People who are severely dependent include those who smoke: more than one pack per day, within five minutes of awakening, while ill, when they wake up in the middle of the night, to ease withdrawal signs and symptoms.Nicotine replacement products are most beneficial for heavy smokers who smoke more than 15 cigarettes per day. There are not enough studies to show whether NRT helps those who smoke fewer than 10 cigarettes per day.

Effectiveness
Evaluation of NRT in real-world studies produces more modest outcomes than efficacy studies conducted by industry-funded trials. The National Health Service (NHS) in England has a smoking cessation service based on pharmacotherapy in combination with counseling support. An Action on Smoking and Health (UK) (ASH) report claims that the average cost per life-year gained for every smoker successfully treated by these services is less than £1,000 (below the NICE guidelines of £20,000 per QALY (quality-adjusted life year). However, the investment in NHS stop smoking services is relatively low. A comparison with treatment costs for illicit drug users shows that £585 million is committed for 350,000 problem drug users compared to £56 million for 9 million users of tobacco. This is £6.20 for each smoker, compared to £1,670 per illegal drug user.The claims for high efficacy and cost-effectiveness of NRT have not been substantiated in real-world effectiveness studies. Pierce and Gilpin (2002) stated their conclusion as follows: “Since becoming available over the counter, NRT appears no longer effective in increasing long-term successful cessation” (p. 1260). Efficacy studies, which are conducted using randomized controlled trials, do not transfer very well to real-world effectiveness. Bauld, Bell, McCullough, Richardson and Greaves (2009) reviewed 20 studies on the effectiveness of intensive NHS treatments for smoking cessation published between 1990 and 2007. Quit rates showed a dramatic decrease between 4-weeks and one year. A quit rate of 53% at four weeks fell to only 15% at one year. Younger smokers, females, pregnant smokers and more deprived smokers had lower quit rates than other groups.
The efficacy for each of the formulations alone (lozenges, nasal spray, gum, and transdermal patch) to aid in smoking cessation is equal. Efficacy increases 15% to 36% with combining treatments such as gum and lozenges. Higher doses increase the chance of stopping smoking for a period of six months and more. For patches, the most efficient doses were 25 mg worn over 16 hours or 21 mg worn over 24 hours. The evidence suggests that 4 mg nicotine gum leads to higher quit rates compared with 2 mg in heavy smokers.E-cigarettes are twice as effective as NRT in helping people quit smoking.

Toxicity
N-Nitrosonornicotine, a strong carcinogen present in unburned tobacco and cigarette smoke, has been found in the urine of some users of oral NRT products. Nicotine patches is an alternative.

Side effects
Some side effects are caused by the nicotine, and are common to NRT products. Other common side effects depend on the formulation of nicotine. Common side effects with the gum include nausea, hiccups, and irritation of the mouth. Common side effects with the patch include skin irritation and a dry mouth while the inhaler commonly results in a cough, runny nose, or headaches. To minimize local skin reactions from the patch, the application site should be moved daily. The nicotine patch can also cause strange dreams if worn while asleep. Nasal sprays commonly cause nasal irritation, watering eyes, and coughing.Serious risks include nicotine poisoning, which includes symptoms like visual disturbances, hyper-salivation, nausea, and vomiting; and continued addiction to nicotine products. Avoiding smoking and other products with nicotine are recommended since it may lead to nicotine overdose. Although overdose is rare, it can be problematic, especially in children and pets. The symptoms of nicotine overdose include headache, pale skin and mouth, belly pain, weakness, diarrhea, tremors or seizures, agitation, confusion, restlessness, high or low blood pressure, fast or irregular heartbeat, fast breathing, and cold sweats.Limited evidence exists regarding long-term NRT use.

Safety
Pregnancy
Nicotine is not safe to use in any amount during pregnancy. Nicotine crosses the placenta and is found in the breast milk of mothers who smoke as well as mothers who inhale passive smoke. There are possible harms to the baby if NRT is used during pregnancy. Thus, pregnant women and those who are breastfeeding should also consult a physician before initiating NRT. The gum, lozenge, and nasal spray are pregnancy category C. The transdermal patch is pregnancy category D. The transdermal patch is considered less safe for the fetus because it delivers continuous nicotine exposure, as opposed to the gum or lozenge, which delivers intermittent and thus lower nicotine exposure.Strong evidence suggests that nicotine cannot be regarded as a safe substance of cigarette use. Nicotine itself could be at least partly responsible for many of the adverse after birth health results related to cigarette use while the mother was pregnant. There is evidence that nicotine negatively affects fetal brain development and pregnancy outcomes. There is also risk of stillbirth and pre-term birth. Nicotine use will probably harm fetal neurological development. Risks to the child later in life from nicotine exposure during pregnancy include type 2 diabetes, obesity, hypertension, neurobehavioral defects, respiratory dysfunction, and infertility. Nicotine exposure during pregnancy can result in attention deficit hyperactivity disorder (ADHD) and learning disabilities in the child. It also puts the child at increased risk for nicotine addiction in the future.Pregnant women should consider behavioral therapy before NRT is considered.

Youth
In people under the age of eighteen, a physician is often consulted before starting NRT. The evidence suggests that exposure to nicotine between the ages of 10 and 25 years causes lasting harm to the brain and cognitive ability. Evidence is unclear whether adolescents gain benefit from cognitive-behavioral therapy or smoking cessation over the long-term as of 2017. Most tobacco users are under-eighteens when they start, and almost no-one over the age of 25 starts using.

Cardiovascular conditions
While there is no evidence that NRT can increase the risk of heart attacks, individuals with pre-existing cardiovascular conditions or recent heart attacks should consult a physician before initiating NRT.Smoking is known to cause cardiovascular diseases such as coronary heart disease, hypertension, heart attack, stroke, and peripheral artery disease. Cigarette smoking is the cause of 20% of all cardiovascular deaths in the United States, which is the leading cause of mortality.

Other conditions
Nicotine replacement therapies should be used cautiously in individuals with the following conditions: severe reactive airway diseases (for nasal spray), chronic nasal disorders such as sinusitis, polyps, rhinitis, or allergy (for nasal spray), diabetes (insulin-dependent), gastrointestinal diseases such as esophagitis, active gastric or peptic ulcer disease, liver problems, hyperthyroidism,pheochromocytoma, phenylketonuria (for lozenges), renal problems, and skin conditions such as psoriasis or dermatitis (for the transdermal patch).

Mechanism of action
Nicotine replacement therapy works by reducing cravings due to nicotine addiction. Smoking cigarettes releases high doses of nicotine to the brain in a matter of seconds as opposed to low doses released over a period of minutes to hours by the various forms of nicotine replacement therapy. Nicotine from NRT does not reach as high a concentration in the blood as does nicotine from smoke inhalation due to different absorption methods. NRT relies on systemic venous absorption, whereas nicotine from cigarettes reaches the arterial system. Nicotine replacement products vary in the time it takes for the nicotine to enter the body and the total time nicotine stays in the body. The more quickly a dose of nicotine is delivered and absorbed, the higher the addiction risk. It is possible to become dependent on some NRTs.Nicotine patches are applied to the skin and continuously administer a stable dose of nicotine slowly over 16–24 hours. Nicotine gum, nicotine sprays, nicotine toothpicks, nicotine sublingual tablets, and nicotine lozenges administer nicotine orally with quicker nicotine uptake into the body but lasting a shorter amount of time. Nicotine inhalers are metered-dose inhalers that administer nicotine through the lungs and mucous membranes of the throat quickly, lasting for a short amount of time. For example, blood nicotine levels are the highest 5–10 minutes after using the nicotine nasal spray, 20 minutes after using a nicotine inhaler or chewing nicotine gum, and 2–4 hours after using a nicotine patch.

Society and culture
NRT products were first approved for use in the United States in 1984. Nicotine replacement products are on the World Health Organizations List of Essential Medicines.. They are available as generic medication.

Formulations
The nicotine patch is a once-daily, longer-acting form of NRT. An advantage of the nicotine patch is its simple compliance; it does not require active use throughout the day. The gum, lozenge, sublingual tablet, oral inhaler, oral spray, and nasal spray are acutely dosed products, providing the user with the benefit and ability of self-titrating based on cravings.Brand names include Commit Lozenge, Nicoderm, Nicogum, Nicorette, Nicotex, Nicotinell, and Thrive. NRT products contain similar pharmaceutical grade nicotine as is used in e-cigarettes.

Medicines
In 2015, the United States Public Health Service listed seven agents for the stopping of tobacco, which included five nicotine replacement treatments (nicotine patches, gum, lozenges, inhalers, and nasal sprays) and two oral medications (bupropion and varenicline). Other NRT options are available, including nicotine mouth sprays and sublingual tablets.

Dosing
The dose of nicotine replacement therapy products is generally based on if the user is considered a heavy, average, or light smoker.
A cigarette delivers an average of 1 mg to 3 mg of the nicotine contained in it. NRT products typically aim to parallel this, but the amount of nicotine absorbed by the user is less than the original dose.
Nicotine nasal sprays are formulated in doses of lowest strength, available in 0.5 mg and 1 mg strengths.
Nicotine lozenges deliver doses as low as 1 mg up to 4 mg. It is not chewed as the gum would be, and dissolves in approximately 30 minutes. This formulation may be preferred by those individuals who do not find gum chewing to be acceptable.
Nicotine gum is available in doses of 2 mg and 4 mg. Using 4 mg nicotine gum versus 2 mg gum increases the likelihood of successful smoking cessation. When using the gum, acidic beverages like soda, coffee, or beer should be avoided fifteen minutes prior and during use because they can impede proper absorption of nicotine.Nicotine inhalers come in 10 mg and 15 mg cartridge strengths and typically deliver around 4 mg in one dose. The inhaler may be preferred in individuals who want to satisfy the hand-to-mouth ritual that smoking provides.Transdermal patches deliver between 5 mg and 52.5 mg of nicotine, which results in plasma levels similar to that of heavy smokers. Combining nicotine patch treatment with a faster nicotine-delivery means, like nicotine gum or spray, improves the likelihood of successful treatment.

Not approved as NRTs
Some smokeless consumer products available can function as alternative nicotine delivery systems (ANDS) but they have not received FDA approval as smoking-cessation therapy aids that are safe and effective.
Snus and nasal snuff also allow for nicotine administration outside of tobacco smoking. Nicotine pouches are described as similar to or a tobacco-free variant of snus. They are pre-portioned and are held in the users lip or cheek allowing for sublingual or buccal delivery of flavors and high doses of nicotine. The small pouches are not like chewing tobacco, as the user does not need to spit since the contents of the pouches stay inside during use. Swedish pouches have been available on the American consumer market since at least 2016 but their popularity and controversy surged in 2019 & 2020. In the US and UK concerns have been raised that nicotine pouches are seemingly too similar to banned snus products, is aimed at teenagers, further complicating the youth vaping trend, falling into the hands of adolescents easily, and are discrete enough to easily pass for regular gums or lozenges.Nicotine infused toothpicks are another product that has been available in the United States since at least 2013. They can have a total nicotine delivery that is comparable to that of nicotine gum. Nicotine toothpicks generally are infused with food-grade flavorings and 1–3 mg of nicotine, which is similar to that of other oral-delivery nicotine products and some cigarettes. In spite of these similarities, as of 2018 they have been a subject of controversy. Online retailers have been under scrutiny for allowing their products to be too easily purchased by youth. Various news outlets and school districts have expressed the concern that these products have a high appeal to minors wanting to experiment with nicotine due to; the multitude of sweet flavors offered, ease & speed of use, seeming innocuous, and having a discrete nature. In 2015, NRT sales fell for the first time since 2008 while sales for e-cigarettes or electronic nicotine delivery systems (ENDS) continued to increase at a substantial rate. The evidence is that UK smokers are trying to quit with e-cigarettes rather than NRT methods.E-cigarettes are often, although not always, designed to look and feel like cigarettes. They have been marketed as less harmful alternatives to cigarettes, but very few are as yet approved as NRTs in any jurisdiction. Some electronic cigarettes have coarsely adjustable nicotine levels. Some healthcare groups have hesitated to recommend e-cigarettes for quitting smoking, because of limited evidence of effectiveness and safety. E-cigarettes are more effective than NRT in terms of abstinence from smoking at twelve months.The U.S. Food and Drug Administration (FDA) has a list of additional tobacco products they are seeking to regulate, including electronic cigarettes. Most approved NRT products have been approved for over 20 years, however the FDA has also approved nicotine inhalers as a form of NRT.Future approaches of NRT could include nicotine preloading, a true pulmonary inhaler, and nicotine vaccines. Nicotine preloading, otherwise known as pre-cessation or pre-quitting NRT, has found that using the patch for a few weeks before the quit date produces significantly higher quit rates than if it was started on the quit day. The true pulmonary inhaler would deliver nicotine to the lungs in a manner that more resembles cigarette smoking, which would provide better relief of background cravings as well as acute cravings. Nicotine vaccines are under investigation as a method to treat tobacco dependence through priming the body to mount an immune response against nicotine.

References
External links

"Nicotine". Drug Information Portal </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Fexinidazole and explain in detail? [/INST] Fexinidazole is a medication used to treat African trypanosomiasis (sleeping sickness) caused by Trypanosoma brucei gambiense. It is effective against both first and second stage disease. Some evidence also supports its use in Chagas disease. It is taken by mouth.Common side effects include nausea, vomiting, headache, and trouble sleeping. Other side effects may include QT prolongation, psychosis, and low white blood cells. It is unclear if use during pregnancy or breast feeding is safe. Fexinidazole is in the antiparasitic and the nitroimidazole family of medications. It is believed to work by turning on certain enzymes within the parasites that result in their death.Fexinidazole was first described in 1978. It was given a positive opinion by the European Medicines Agency in 2018. It is on the World Health Organizations List of Essential Medicines. Development for sleeping sickness was funded by the Drugs for Neglected Diseases initiative in collaboration with Sanofi. Fexinidazole was approved for medical use in the United States in July 2021.

Medical use
Sleeping sickness
A trial in Africa found fexinidazole to be 91% effective at treating sleeping sickness. Though less effective than nifurtimox with eflornithine in severe disease, fexinidazole has the benefit that it can be taken by mouth.Fexinidazole is the first drug candidate for the treatment of advanced-stage sleeping sickness in thirty years.

Other
It has activity against Trypanosoma cruzi, Tritrichomonas foetus, Trichomonas vaginalis, Entamoeba histolytica, and Trypanosoma brucei. It has not been found to be useful for visceral leishmaniasis.

Mechanism of action
The biologically relevant active metabolites in vivo are the sulfoxide and sulfone.

History
Fexinidazole was discovered by the German pharmaceutical company Hoechst AG, but its development as a pharmaceutical was halted in the 1980s.

Society and culture
Fexinidazole Winthrop, a Sanofi-Aventis product developed with the Drugs for Neglected Diseases Initiative (DNDi), received a positive endorsement from the European Medicines Agency in 2018, for use in non-European markets </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Estazolam and explain in detail? [/INST] Estazolam, sold under the brand name Prosom among others, is a tranquilizer medication of the triazolobenzodiazepine (TBZD) class, which are benzodiazepines (BZDs) fused with a triazole ring . It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. Estazolam is an intermediate-acting oral benzodiazepine. It is used for short-term treatment of insomnia.
It was patented in 1968 and came into medical use in 1975.

Medical uses
Estazolam is prescribed for the short-term treatment of certain sleep disorders. It is an effective hypnotic drug showing efficacy in increasing the time spent asleep as well as reducing awakenings during the night. Combination with non-pharmacological options for sleep management results in long-term improvements in sleep quality after discontinuation of short-term estazolam therapy. Estazolam is also sometimes used as a preoperative sleep aid. It was found to be superior to triazolam in side effect profile in preoperative patients in a trial. Estazolam also has anxiolytic properties and due to its long half life can be an effective short-term treatment for insomnia associated with anxiety.

Side effects
A hang-over effect commonly occurs with next day impairments of mental and physical performance. Other side effects of estazolam include somnolence, dizziness, hypokinesia, and abnormal coordination.In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.

Tolerance and dependence
The main safety concern of benzodiazepines such as estazolam is a benzodiazepine dependence and the subsequent benzodiazepine withdrawal syndrome which can occur upon discontinuation of the estazolam. A review of the literature found that long-term use of benzodiazepines such as estazolam is associated with drug tolerance, drug dependence, rebound insomnia and CNS related adverse effects. Estazolam should only be used short term and at the lowest effective dose to avoid complications related to long-term use. Non-pharmacological treatment options however, were found to have sustained improvements in sleep quality. The short-term benefits of benzodiazepines on sleep begin to reduce after a few days due to tolerance to the hypnotic effects of benzodiazepines in the elderly.

Contraindications and special caution
Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, alcohol or drug-dependent individuals and individuals with comorbid psychiatric disorders.

Elderly
An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and durability of non-drug treatments for insomnia in adults of all ages and that these interventions are underutilized. Compared with the benzodiazepines including estazolam, the nonbenzodiazepine sedative-hypnotics appeared to offer few, if any, significant clinical advantages in efficacy or tolerability in elderly persons. It was found that newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, hold promise for the management of chronic insomnia in elderly people. Long-term use of sedative-hypnotics for insomnia lacks an evidence base and has traditionally been discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment (anterograde amnesia), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls. In addition, the effectiveness and safety of long-term use of these agents remain to be determined. It was concluded that more research is needed to evaluate the long-term effects of treatment and the most appropriate management strategy for elderly persons with chronic insomnia.

Pharmacology
Estazolam is classed as a "triazolo" benzodiazepine drug. Estazolam exerts its therapeutic effects via its benzodiazepines receptor agonist properties. Estazolam at high doses decreases histamine turnover via its action at the benzodiazepine-GABA receptor complex in mouse brains.

Pharmacokinetics
Peak plasma levels are achieved within 1–6 hours. Estazolam is an intermediate acting benzodiazepine. The elimination half life of estazolam is an average of 19 hours, with a range of 8–31 hours. The major metabolite of estazolam is 4-hydroxyestazolam. Other identified metabolites include 1-oxo-estazolam, 4-hydroxy-estazolam, and benzophenone.

Interactions
Alcohol enhances the sedative hypnotic properties of estazolam. In package inserts, the manufacturer clearly warns about an interaction with Ritonavir, and although clinical interactions of Ritonavir with estazolam have not yet been described, the lack of clinical descriptions of the interactions does not negate the seriousness of the interaction.

EEG effects in rabbits
An animal study in rabbits demonstrated that estazolam induces a drowsy pattern of spontaneous EEG including high voltage slow waves and spindle bursts increase in the cortex and amygdala, while the hippocampal theta rhythm is desynchronized </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Methyl cellulose and explain in detail? [/INST] Methyl cellulose (or methylcellulose) is a chemical compound derived from cellulose. It is sold under a variety of trade names and is used as a thickener and emulsifier in various food and cosmetic products, and also as a bulk-forming laxative. Like cellulose, it is not digestible, not toxic, and not an allergen.
In 2017, it was the 272nd most commonly prescribed medication in the United States, with more than one million prescriptions.

Uses
Methyl cellulose has a wide range of uses.

Medical
Constipation
Methyl cellulose is used to treat constipation. Effects generally occur within three days. It is taken by mouth and is recommended with sufficient water. Side effects may include abdominal pain. It is classified as a bulk forming laxative. It works by increasing the amount of stool present which improves intestinal contractions.It is available over the counter. It is sold under the brand name Citrucel among others.

Artificial tears and saliva
The lubricating property of methylcellulose is of particular benefit in the treatment of dry eyes. Solutions containing methyl cellulose or similar cellulose derivatives are used as substitute for tears or saliva if the natural production of these fluids is disturbed.

Medication manufacturing
Methyl cellulose is used in the manufacture of drug capsules; its edible and nontoxic properties provide a vegetarian alternative to the use of gelatin.

Consumer products
Thickener and emulsifier
Methyl cellulose is occasionally added to hair shampoos, tooth pastes and liquid soaps, to generate their characteristic thick consistency. This is also done for foods, for example ice cream or croquette. Methyl cellulose is also an important emulsifier, preventing the separation of two mixed liquids because it is an emulsion stabilizer.

Food
The E number of methyl cellulose as food additive is E461. E464 is hydroxypropylcellulose and more soluble in water.Methyl cellulose, as a gel, has the unique property of setting when hot and melting when cold.Methyl cellulose is used as an ingredient in some meat analogues that are intended to replicate the texture of meat.

Lubricant
Methyl cellulose may be used in personal lubricant.

Construction materials
Methyl cellulose finds a major application as a performance additive in construction materials. It is added to mortar dry mixes to improve the mortars properties such as workability, open and adjustment time, water retention, viscosity, adhesion to surfaces etc. Construction grade methyl cellulose is not to be identified with food and pharmaceutical grade methyl cellulose and hydroxypropyl methyl cellulose, as it may be cross-linked with glyoxal for easy dispersion in water.
The construction materials can be cement-based or gypsum-based. Notable examples of dry mixture mortars which utilize methyl cellulose include tile adhesives, EIFS, insulating plasters, hand-trowelled and machine-sprayed plaster, stucco, self-leveling flooring, extruded cement panels, skim coats, joint & crack fillers, and tile grouts. Typical usage is about 0.2% – 0.5% of total dry powder weight for dry mixtures.
Derivatives of methyl cellulose which improve performance characteristics include hydroxypropyl methyl cellulose (HPMC) and hydroxyethyl methyl cellulose (HEMC). These derivatives typically improve the characteristics such as water retention, vertical surface slip resistance, open time, etc.

Glue and binder
Methyl cellulose can be employed as a mild glue which can be washed away with water. This may be used in the fixing of delicate pieces of art as well as in book conservation to loosen and clean off old glue from spines and bookboards.
Methyl cellulose is the main ingredient in many wallpaper pastes. It is also used as a binder in pastel crayons and also as a binder in medications. Hydroxypropyl methylcellulose (HPMC) is an FDA-approved water-soluble adhesive, has been used in various wet-adhesion applications in construction products, paints, and drug delivery for 70 years.HPMC adheres strongly to all wet surfaces, regardless of hydrophobicity.

Paint
Methyl cellulose is used as a rheological modifier in paint to prevent sagging.

Paper and textile sizing
Methyl cellulose is used as sizing in the production of papers and textiles as it protects the fibers from absorbing water or oil. When applied to several pieces of paper, methyl cellulose will bind the layers together, often to create a more durable or multicolored sheet. In addition, origami artists use it to coat their origami models, as the compound will stiffen and protect the paper against time.

Dust control
Hydroxypropyl methyl cellulose (HPMC) and hydroxyethyl methyl cellulose (HEMC) is used as a binder in dust control technologies. They mitigate fugitive dust released from arid/semi-arid area as well as improve commercial face mask when used as a filtering material.

Cell culture
Methyl cellulose is also used in cell culture to study viral replication. It is dissolved in the same nutrient-containing medium in which cells are normally grown. A single layer of cells is grown on a flat surface, then infected with a virus for a short time. The strength of the viral sample used will determine how many cells get infected during this time. The thick methyl cellulose medium is then added on top of the cells in place of normal liquid medium. As the viruses replicate in the infected cells, they are able to spread between cells whose membranes touch each other, but are trapped when they enter the methyl cellulose. Only cells closely neighboring an infected cell will become infected and die. This leaves small regions of dead cells called plaques in a larger background of living uninfected cells. The number of plaques formed is determined by the strength of the original sample.

Bacterial and protozoal motility inhibitor
Aqueous methyl cellulose solutions have been used to slow bacterial and protozoal cell motility for closer inspection. Changing the amount of methyl cellulose in solution permits the adjustment of the solutions viscosity.

Stem cell differentiation
Methyl cellulose is used in the most common approaches to quantify multiple or single lineage-committed hematopoietic progenitors, called colony-forming cells (CFCs) or colony-forming units (CFUs), in combination with culture supplements that promote their proliferation and differentiation, and allow the clonal progeny of a single progenitor cell to stay together and thus form a colony of more mature cells.

Chemistry
It is a hydrophilic white powder in pure form and dissolves in cold (but not in hot) water, forming a clear viscous solution or gel.
Methyl cellulose is used as a buffer additive in capillary electrophoresis to control electroosmotic flow for improved separations.

Special effects
The slimy, gooey appearance of an appropriate preparation of methyl cellulose with water, in addition to its nontoxic, nonallergenic, and edible properties, makes it popular for use in special effects for motion pictures and television wherever vile slimes must be simulated. In the film Ghostbusters, the gooey substance the supernatural entities used to "slime" the Ghostbusters was mostly a thick water solution of methyl cellulose. The Aliens ooze and drip a great deal of methyl cellulose—especially the queen.Methyl cellulose has been used to safely simulate molten materials, as well. In several of the Terminator films, it was back-lit with colored gels and films to reproduce the heated glow of iron in the large pouring ladles used to transport the metal from the smelting ovens to the various molds and forms. Methyl cellulose was also a stand-in for the lava flows in Los Angeles in Volcano and on the volcanic surface of Mustafar, in Star Wars: Episode III – Revenge of the Sith.

Chemistry
Methyl cellulose does not occur naturally and is synthetically produced by heating cellulose with caustic solution (e.g. a solution of sodium hydroxide) and treating it with methyl chloride. In the substitution reaction that follows, the hydroxyl residues (-OH functional groups) are replaced by methoxide (-OCH3 groups).
Different kinds of methyl cellulose can be prepared depending on the number of hydroxyl groups substituted. Cellulose is a polymer consisting of numerous linked glucose molecules, each of which exposes three hydroxyl groups. The Degree of Substitution (DS) of a given form of methyl cellulose is defined as the average number of substituted hydroxyl groups per glucose. The theoretical maximum is thus a DS of 3.0, however more typical values are 1.3–2.6.
Different methyl cellulose preparations can also differ in the average length of their polymer backbones.

Solubility and temperature
Methyl cellulose has a lower critical solution temperature (LCST) between 40 °C and 50 °C. At temperatures below the LCST, it is readily soluble in water; above the LCST, it is not soluble, which has a paradoxical effect that heating a saturated solution of methyl cellulose will turn it solid, because methyl cellulose will precipitate out. The temperature at which this occurs depends on DS-value, with higher DS-values giving lower solubility and lower precipitation temperatures because the polar hydroxyl groups are masked.
Preparing a solution of methyl cellulose with cold water is difficult however: as the powder comes into contact with water, a gel layer forms around it, dramatically slowing the diffusion of water into the powder; hence, the inside remains dry. A better way is to first mix the powder with hot water, so that the methyl cellulose particles are well dispersed (and so have a much higher effective surface area) in the water, and cool down this dispersion while stirring, leading to the much more rapid dissolution of those particles.

See also
Carboxymethyl cellulose
Ethyl cellulose
Ethyl methyl cellulose
Hydroxypropyl cellulose
Hydroxyethyl cellulose

References
Further reading
Cathleen Baker (1984). Methylcellulose & Sodium Carboxymethylcellulose: An Evaluation for Use in Paper Conservation through Accelerated Aging. Preprints of the Contributions to the Paris Congress, 2–8 September 1984: Adhesives and Consolidants, pp. 55–59. International Institute of Conservation.
Robert L. Feller and Myron H </s>


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