<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Ergocalciferol and can you explain it in depth? [/INST] Ergocalciferol, also known as vitamin D2 and nonspecifically calciferol, is a type of vitamin D found in food and used as a dietary supplement. As a supplement it is used to prevent and treat vitamin D deficiency. This includes vitamin D deficiency due to poor absorption by the intestines or liver disease. It may also be used for low blood calcium due to hypoparathyroidism. It is used by mouth or injection into a muscle.Excessive doses can result in increased urine production, high blood pressure, kidney stones, kidney failure, weakness, and constipation. If high doses are taken for a long period of time, tissue calcification may occur. Normal doses are safe in pregnancy. It works by increasing the amount of calcium absorbed by the intestines and kidneys. Food in which it is found include some mushrooms.Ergocalciferol was first described in 1936. Ergocalciferol is available as a generic medication and over the counter. In 2020, it was the 46th most commonly prescribed medication in the United States, with more than 14 million prescriptions. Certain foods such as breakfast cereal and margarine have ergocalciferol added to them in some countries. It is on the World Health Organizations List of Essential Medicines.

Use
Ergocalciferol may be used as a vitamin D supplement, whereas cholecalciferol (vitamin D3) is produced naturally by the skin when exposed to ultraviolet light. Ergocalciferol (D2) and cholecalciferol (D3) are considered to be equivalent for vitamin D production, as both forms appear to have similar efficacy in ameliorating rickets and reducing the incidence of falls in elderly patients.  Conflicting reports exist, however, concerning the relative effectiveness, with some studies suggesting that ergocalciferol has less efficacy based on limitations in absorption, binding, and inactivation. A meta-analysis concluded that evidence usually favors cholecalciferol in raising vitamin D levels in blood, although it stated more research is needed.

Mechanism
Ergocalciferol is a secosteroid formed by a photochemical bond breaking of a steroid, specifically, by the action of ultraviolet light (UV-B or UV-C) on ergosterol, a form of provitamin D2.Like cholecalciferol, ergocalciferol is inactive by itself. It requires two hydroxylations to become active: the first in the liver by CYP2R1 to form 25-hydroxyergocalciferol (ercalcidiol or 25-OH D2), and the second in the kidney by CYP27B1, to form the active 1,25-dihydroxyergocalciferol (ercalcitriol or 1,25-(OH)2D2), which activates the vitamin D receptor. Unlike cholecalciferol, 25-hydroxylation is not performed by CYP27A1 for ergocalciferol.Ergocalciferol and metabolites have lower affinity to the vitamin D-binding protein compared to the D3 counterparts. The binding affinity of ercalcitriol to the vitamin D receptor is similar to that of calcitriol. Ergocalciferol itself and metabolites can be deactivated by 24-hydroxylation.

Sources
Fungus, from USDA nutrient database (per 100g), D2 + D3:
Mushrooms, Agaricus bisporus:
raw portobello: 0.3 μg (10 IU); exposed to ultraviolet light: 11.2 µg (446 IU)
raw crimini: 0.1 μg (3 IU); exposed to ultraviolet light: 31.9 µg (1276 IU)
Mushrooms, shiitake:
raw: Vitamin D (D2 + D3): 0.4 μg (18 IU)
dried: Vitamin D (D2 + D3): 3.9 μg (154 IU)Lichen

Cladina arbuscula specimens grown under different natural conditions contain provitamin D2 and vitamin D2, ranges 89-146 and 0.22-0.55 μg/g dry matter respectively. They also contain vitamin D3 (range 0.67 to 2.04 μg/g) although provitamin D3 could not be detected. Vitamin D levels correlate positively with UV irradiation.Plantae

Alfalfa (Medicago sativa subsp. sativa), shoot: 4.8 μg (192 IU) vitamin D2, 0.1 μg (4 IU) vitamin D3

Biosynthesis
The vitamin D2 content in mushrooms and C. arbuscula increase with exposure to ultraviolet light </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Azilsartan and can you explain it in depth? [/INST] Azilsartan is an angiotensin II receptor antagonist used in the treatment of hypertension, developed by Takeda. It is marketed in tablet form under the brand name Edarbi as the prodrug azilsartan medoxomil.The most common adverse reaction in adults is diarrhea.It is also sold as a combination drug with chlortalidone under the brand name Edarbyclor.

Structure activity relationship
Like other ARBs, the Azilsartan group has an extended diphenyl group within the structure. An interesting aspect of the molecule is that unlike other ARBs which have a tetrazole attached to the molecule, Azilsartan has an oxadiazole, which has an acidic proton at the nitrogen. The tetraziole represents a non-classical bio-isostere. The carboxylate seen in the molecule is the active moiety after the molecule has been metabolized. Azilsartan is a pro-drug.

Medical uses
Azilsartan is used for the treatment of hypertension in adults. One of the benefits of the medication is that Azilsartan does not need dose adjustments for patients with renal or hepatic dysfunction.

Contraindications
Azilsartan must not be used with aliskiren, a renin inhibitor, in patients with diabetes as this increases the risk of serious adverse effects. Like other antihypertensive drugs acting on the renin–angiotensin system, it is contraindicated during the second and third trimesters of pregnancy. It should not be used during pregnancy in the United States.

Interactions
No relevant drug interactions have been found in studies. Based on experiences with other drugs acting on the renin–angiotensin system, it is theorized that azilsartan could increase the toxicity of lithium and of other drugs increasing potassium levels, such as potassium sparing diuretics.

Pharmacology
Mechanism of action
Azilsartan medoxomil lowers blood pressure by blocking the action of angiotensin II at the AT1 receptor, a hormone that contracts blood vessels and reduces water excretion through the kidneys.

Pharmacokinetics
Azilsartan medoxomil is quickly absorbed from the gut, independently of food intake. Maximal blood plasma concentrations are reached after one to three hours. The liver enzyme CYP2C9 is involved in the formation of the two main metabolites, which are pharmacologically inactive; they are the O-deethylation and decarboxylation products of azilsartan. Elimination half life is about 11 hours. 55% are excreted via the feces, and 42% via the urine, of which 15% are present as azilsartan and the rest in form of the metabolites.

Chemistry
The drug formulation contains the potassium salt of azilsartan medoxomil (codenamed TAK-491), an ester of azilsartans carboxyl group with the alcohol (5-methyl-2-oxo-1,3-dioxol-4-yl)methanol </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Pyridostigmine and can you explain it in depth? [/INST] Pyridostigmine is a medication used to treat myasthenia gravis and underactive bladder. It is also used together with atropine to end the effects of neuromuscular blocking medication of the non-depolarizing type. It is typically given by mouth but can also be used by injection. The effects generally begin within 45 minutes and last up to 6 hours.Common side effects include nausea, diarrhea, frequent urination, and abdominal pain. More severe side effects include low blood pressure, weakness, and allergic reactions. It is unclear if use in pregnancy is safe for the fetus. Pyridostigmine is an acetylcholinesterase inhibitor in the cholinergic family of medications. It works by blocking the action of acetylcholinesterase and therefore increases the levels of acetylcholine.Pyridostigmine was patented in 1945 and came into medical use in 1955. It is on the World Health Organizations List of Essential Medicines. Pyridostigmine is available as a generic medication.

Medical uses
Pyridostigmine is used to treat muscle weakness in people with myasthenia gravis or forms of congenital myasthenic syndrome and to combat the effects of curariform drug toxicity </s>


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Apomorphine and can you explain it in depth? [/INST] Apomorphine, sold under the brand name Apokyn among others, is a type of aporphine having activity as a non-selective dopamine agonist which activates both D2-like and, to a much lesser extent, D1-like receptors. It also acts as an antagonist of 5-HT2 and α-adrenergic receptors with high affinity. The compound is historically a morphine decomposition product made by boiling morphine with concentrated acid, hence the -morphine suffix. Contrary to its name, apomorphine does not actually contain morphine or its skeleton, nor does it bind to opioid receptors. The apo- prefix relates to it being a morphine derivative ("[comes] from morphine").
Historically, apomorphine has been tried for a variety of uses, including as a way to relieve anxiety and craving in alcoholics, an emetic (to induce vomiting), for treating stereotypies (repeated behaviour) in farmyard animals, and more recently in treating erectile dysfunction. Currently, apomorphine is used in the treatment of Parkinsons disease. It is a potent emetic and should not be administered without an antiemetic such as domperidone. The emetic properties of apomorphine are exploited in veterinary medicine to induce therapeutic emesis in canines that have recently ingested toxic or foreign substances.
Apomorphine was also used as a private treatment of heroin addiction, a purpose for which it was championed by the author William S. Burroughs. Burroughs and others claimed that it was a "metabolic regulator" with a restorative dimension to a damaged or dysfunctional dopaminergic system. Despite anecdotal evidence that this offers a plausible route to an abstinence-based mode, no clinical trials have ever tested this hypothesis. A recent study indicates that apomorphine might be a suitable marker for assessing central dopamine system alterations associated with chronic heroin consumption. There is, however, no clinical evidence that apomorphine is an effective and safe treatment regimen for opiate addiction.

Medical uses
Apomorphine is used in advanced Parkinsons disease intermittent hypomobility ("off" episodes), where a decreased response to an anti-Parkinson drug such as L-DOPA causes muscle stiffness and loss of muscle control. While apomorphine can be used in combination with L-DOPA, the intention is usually to reduce the L-DOPA dosing, as by this stage the patient often has many of dyskinesias caused by L-DOPA and hypermobility periods. When an episode sets in, the apomorphine is injected subcutaneously or applied sublingually, and signs subside. It is used an average of three times a day. Some people use portable mini-pumps that continuously infuse them with apomorphine, allowing them to stay in the "on" state and using apomorphine as an effective monotherapy.

Contraindications
The main and absolute contraindication to using apomorphine is the concurrent use of adrenergic receptor antagonists; combined, they cause a severe drop in blood pressure and fainting. Alcohol causes an increased frequency of orthostatic hypotension (a sudden drop in blood pressure when getting up), and can also increase the chances of pneumonia and heart attacks. Dopamine antagonists, by their nature of competing for sites at dopamine receptors, reduce the effectiveness of the agonistic apomorphine.IV administration of apomorphine is highly discouraged, as it can crystallize in the veins and create a blood clot (thrombus) and block a pulmonary artery (pulmonary embolism).

Side effects
Nausea and vomiting are common side effects when first beginning therapy with apomorphine; antiemetics such as trimethobenzamide or domperidone, dopamine antagonists, are often used while first starting apomorphine. Around 50% of people grow tolerant enough to apomorphines emetic effects that they can discontinue the antiemetic.Other side effects include orthostatic hypotension and resultant fainting, sleepiness, dizziness, runny nose, sweating, paleness, and flushing. More serious side effects include dyskinesias (especially when taking L-DOPA), fluid accumulation in the limbs (edema), suddenly falling asleep, confusion and hallucinations, increased heart rate and heart palpitations, and persistent erections (priapism). The priapism is caused by apomorphine increasing arterial blood supply to the penis. This side effect has been exploited in studies attempting to treat erectile dysfunction.

Pharmacology
Mechanism of action
Apomorphines R-enantiomer is an agonist of both D1 and D2 dopamine receptors, with higher activity at D2. The members of the D2 subfamily, consisting of D2, D3, and D4 receptors, are inhibitory G protein–coupled receptors. The D4 receptor in particular is an important target in the signaling pathway, and is connected to several neurological disorders. Shortage or excess of dopamine can prevent proper function and signaling of these receptors leading to disease states.Apomorphine improves motor function by activating dopamine receptors in the nigrostriatal pathway, the limbic system, the hypothalamus, and the pituitary gland. It also increases blood flow to the supplementary motor area and to the dorsolateral prefrontal cortex (stimulation of which has been found to reduce the tardive dyskinesia effects of L-DOPA). Parkinsons has also been found to have excess iron at the sites of neurodegeneration; both the (R)- and (S)-enantiomers of apomorphine are potent iron chelators and radical scavengers.Apomorphine also decreases the breakdown of dopamine in the brain (though it inhibits its synthesis as well). It is an upregulator of certain neural growth factors, in particular NGF but not BDNF, epigenetic downregulation of which has been associated with addictive behaviour in rats.Apomorphine causes vomiting by acting on dopamine receptors in the chemoreceptor trigger zone of the medulla; this activates the nearby vomiting center.

Pharmacokinetics
While apomorphine has lower bioavailability when taken orally, due to not being absorbed well in the GI tract and undergoing heavy first-pass metabolism, it has a bioavailability of 100% when given subcutaneously. It reaches peak plasma concentration in 10–60 minutes. Ten to twenty minutes after that, it reaches its peak concentration in the cerebrospinal fluid. Its lipophilic structure allows it to cross the blood–brain barrier.Apomorphine possesses affinity for the following receptors (note that a higher Ki indicates a lower affinity):

It has a Ki of over 10,000 nM (and thus negligible affinity) for β-adrenergic, H1, and mACh.Apomorphine has a high clearance rate (3–5 L/kg/hr) and is mainly metabolized and excreted by the liver. It is likely that while the cytochrome P450 system plays a minor role, most of apomorphines metabolism happens via auto-oxidation, O-glucuronidation, O-methylation, N-demethylation, and sulfation. Only 3–4% of the apomorphine is excreted unchanged and into the urine. The half-life is 30–60 minutes, and the effects of the injection last for up to 90 minutes.Toxicity depends on the route of administration; the LD50s in mice were 300 mg/kg for the oral route, 160 mg/kg for intraperitoneal, and 56 mg/kg intravenous.

Chemistry
Properties
Apomorphine has a catechol structure similar to that of dopamine.

Synthesis
Several techniques exist for the creation of apomorphine from morphine. In the past, morphine had been combined with hydrochloric acid at high temperatures (around 150 °C) to achieve a low yield of apomorphine, ranging anywhere from 0.6% to 46%.
More recent techniques create the apomorphine in a similar fashion, by heating it in the presence of any acid that will promote the essential dehydration rearrangement of morphine-type alkaloids, such as phosphoric acid. The method then deviates by including a water scavenger, which is essential to remove the water produced by the reaction that can react with the product and lead to decreased yield. The scavenger can be any reagent that will irreversibly react with water such as phthalic anhydride or titanium chloride. The temperature required for the reaction varies based upon choice of acid and water scavenger. The yield of this reaction is much higher: at least 55%.

History
The pharmacological effects of the naturally-occurring analog aporphine in the blue lotus (Nymphaea caerulea) were known to the ancient Egyptians and Mayans, with the plant featuring in tomb frescoes and associated with entheogenic rites. It is also observed in Egyptian erotic cartoons, suggesting that they were aware of its erectogenic properties.
The modern medical history of apomorphine begins with its synthesis by Arppe in 1845 from morphine and sulfuric acid, although it was named sulphomorphide at first. Matthiesen and Wright (1869) used hydrochloric acid instead of sulfuric acid in the process, naming the resulting compound apomorphine. Initial interest in the compound was as an emetic, tested and confirmed safe by London doctor Samuel Gee, and for the treatment of stereotypies in farmyard animals. Key to the use of apomorphine as a behavioural modifier was the research of Erich Harnack, whose experiments in rabbits (which do not vomit) demonstrated that apomorphine had powerful effects on the activity of rabbits, inducing licking, gnawing and in very high doses convulsions and death.

Treatment of alcoholism
Apomorphine was one of the earliest used pharmacotherapies for alcoholism. The Keeley Cure (1870s to 1900) contained apomorphine, among other ingredients, but the first medical reports of its use for more than pure emesis come from James Tompkins and Charles Douglas. Tompkins reported, after injection of 6.5 mg ("one tenth of a grain"):In four minutes free emesis followed, rigidity gave way to relaxation, excitement to somnolence, and without further medication the patient, who before had been wild and delirious, went off into a quiet sleep.Douglas saw two purposes for apomorphine:[it can be used to treat] a paroxysm of dipsomania [an episode of intense alcoholic craving]... in minute doses it is much more rapidly efficient in stilling the dipsomaniac craving than strychnine or atropine… Four or even 3m [minim – roughly 60 microlitres] of the solution usually checks for some hours the incessant demands of the patient… when he awakes from the apomorphine sleep he may still be demanding alcohol, though he is never then so insistent as before. Accordingly it may be necessary to repeat the dose, and even to continue to give it twice or three times a day. Such repeated doses, however, do not require to be so large: 4 or even 3m is usually sufficient.This use of small, continuous doses (1/30th of a grain, or 2.16 mg by Douglas) of apomorphine to reduce alcoholic craving comes some time before Pavlovs discovery and publication of the idea of the "conditioned reflex" in 1903. This method was not limited to Douglas; the Irish doctor Francis Hare, who worked in a sanatorium outside London from 1905 onward, also used low-dose apomorphine as a treatment, describing it as "the most useful single drug in the therapeutics of inebriety". He wrote:In (the) sanatorium it is used in three different sets of circumstances: (1) in maniacal or hysterical drunkenness: (2) during the paroxysm of dipsomania, in order to still the craving for alcohol; and (3) in essential insomnia of a special variety... [after giving apomorphine] the patients mental condition is entirely altered. He may be sober: he is free from the time being from any craving from alcohol. The craving may return, however, and then it is necessary to repeat the injection, it may be several times at intervals of a few hours. These succeeding injections should be quite small, 3 to 6 min. being sufficient. Doses of this size are rarely emetic. There is little facial pallor, a sensation as of the commencement of sea-sickness, perhaps a slight malaise with a sudden subsidence of the craving for alcohol, followed by a light and short doze.He also noted there appeared to be a significant prejudice against the use of apomorphine, both from the associations of its name and doctors being reluctant to give hypodermic injections to alcoholics. In the US, the Harrison Narcotics Tax Act made working with any morphine derivatives extremely hard, despite apomorphine itself not being an opiate.
In the 1950s the neurotransmitter dopamine was discovered in the brain by Katharine Montagu, and characterised as a neurotransmitter a year later by Arvid Carlsson, for which he would be awarded the Nobel Prize. A. N. Ernst then discovered in 1965 that apomorphine was a powerful stimulant of dopamine receptors. This, along with the use of sublingual apomorphine tablets, led to a renewed interest in the use of apomorphine as a treatment for alcoholism. A series of studies of non-emetic apomorphine in the treatment of alcoholism were published, with mostly positive results. However, there was little clinical consequence.

Parkinsons disease
The use of apomorphine to treat "the shakes" was first suggested by Weil in France in 1884, although seemingly not pursued until 1951. Its clinical use was first reported in 1970 by Cotzias et al., although its emetic properties and short half-life made oral use impractical. A later study found that combining the drug with the antiemetic domperidone improved results significantly. The commercialization of apomorphine for Parkinsons disease followed its successful use in patients with refractory motor fluctuations using intermittent rescue injections and continuous infusions.

Aversion therapy
Aversion therapy in alcoholism had its roots in Russia in the early 1930s, with early papers by Pavlov, Galant and Sluchevsky and Friken, and would remain a strain in the Soviet treatment of alcoholism well into the 1980s. In the US a particularly notable devotee was Dr Voegtlin, who attempted aversion therapy using apomorphine in the mid to late 1930s. However, he found apomorphine less able to induce negative feelings in his subjects than the stronger and more unpleasant emetic emetine.

In the UK, however, the publication of J Y Dents (who later went on to treat Burroughs) 1934 paper "Apomorphine in the treatment of Anxiety States" laid out the main method by which apomorphine would be used to treat alcoholism in Britain. His method in that paper is clearly influenced by the then-novel idea of aversion:He is given his favourite drink, and his favourite brand of that drink... He takes it stronger than is usual to him... The small dose of apomorphine, one-twentieth of a grain [3.24mg], is now given subcutaneously into his thigh, and he is told that he will be sick in a quarter of an hour. A glass of whisky and water and a bottle of whisky are left by his bedside. At six oclock (four hours later) he is again visited and the same treatment is again administered... The nurse is told in confidence that if he does not drink, one-fortieth [1.62 mg] of a grain of apomorphine should be injected during the night at nine oclock, one oclock, and five oclock, but that if he drinks the injection should be given soon after the drink and may be increased to two hourly intervals. In the morning at about ten he is again given one or two glasses of whisky and water... and again one-twentieth of a grain [3.24 mg] of apomorphine is injected... The next day he is allowed to eat what he likes, he may drink as much tea as he likes... He will be strong enough to get up and two days later he leaves the home.However, even in 1934 he was suspicious of the idea that the treatment was pure conditioned reflex – "though vomiting is one of the ways that apomorphine relives the patient, I do not believe it to be its main therapeutic effect." – and by 1948 he wrote:It is now twenty-five years since I began treating cases of anxiety and alcoholism with apomorphine, and I read my first paper before this Society fourteen years ago. Up till then I had thought, and, unfortunately, I said in my paper, that the virtue of the treatment lay in the conditioned reflex of aversion produced in the patient. This statement is not even a half truth… I have been forced to the conclusion that apomorphine has some further action than the production of a vomit.This led to his development of lower-dose and non-aversive methods, which would inspire a positive trial of his method in Switzerland by Dr Harry Feldmann and later scientific testing in the 1970s, some time after his death. However, the use of apomorphine in aversion therapy had escaped alcoholism, with its use to treat homosexuality leading to the death of a British Army Captain Billy Clegg Hill in 1962,  helping to cement its reputation as a dangerous drug used primarily in archaic behavioural therapies.

Opioid addiction
In his Deposition: Testimony Concerning a Sickness in the introduction to later editions of Naked Lunch (first published in 1959), William S. Burroughs wrote that apomorphine treatment was the only effective cure to opioid addiction he has encountered:

The apomorphine cure is qualitatively different from other methods of cure.  I have tried them all.  Short reduction, slow reduction, cortisone, antihistamines, tranquilizers, sleeping cures, tolserol, reserpine.  None of these cures lasted beyond the first opportunity to relapse.  I can say that I was never metabolically cured until I took the apomorphine cure... The doctor, John Yerbury Dent, explained to me that apomorphine acts on the back brain to regulate the metabolism and normalize the blood stream in such a way that the enzyme stream of addiction is destroyed over a period of four to five days.  Once the back brain is regulated apomorphine can be discontinued and only used in case of relapse.
He goes on to lament the fact that as of his writing, little to no research has been done on apomorphine or variations of the drug to study its effects on curing addiction, and perhaps the possibility of retaining the positive effects while removing the side effect of vomiting.
Despite his claims throughout his life, Burroughs never really cured his addiction and was back to using opiates within years of his apomorphine "cure". However, he insisted on apomorphines effectiveness in several works and interviews.

Society and culture
Apomorphine has a vital part in Agatha Christies detective story Sad Cypress.
The 1965 Tuli Kupferberg song "Hallucination Horrors" recommends apomorphine at the end of each verse as a cure for hallucinations brought on by a humorous variety of intoxicants; the song was recorded by The Fugs and appears on the album Virgin Fugs.

Research
There is renewed interest in the use of apomorphine to treat addiction, in both smoking cessation and alcoholism. As the drug is known to be reasonably safe for use in humans, it is a viable target for repurposing.

Apomorphine has been researched as a possible treatment for erectile dysfunction and female hypoactive sexual desire disorder, though its efficacy has been limited. Nonetheless, it  was under development as a treatment for erectile dysfunction by TAP Pharmaceuticals under the brand name Uprima. In 2000, TAP withdrew its new drug application after an FDA review panel raised questions about the drugs safety, due to many clinical trial subjects fainting after taking the drug.

Alzheimers disease
Apomorphine is reported to be an inhibitor of amyloid beta protein fiber formation, whose presence is a hallmark of Alzheimers disease, and a potential therapeutic under the amyloid hypothesis.

Alternative administration routes
Two routes of administration are currently clinically utilized: subcutaneous (either as intermittent injections or continuous infusion) and sublingual </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Somapacitan and can you explain it in depth? [/INST] Somapacitan, sold under the brand name Sogroya, is a growth hormone medication. Somapacitan is a human growth hormone analog. Somapacitan-beco is produced in Escherichia coli by recombinant DNA technology.The most common side effects include: back pain, joint paint, indigestion, a sleep disorder, dizziness, tonsillitis, swelling in the arms or lower legs, vomiting, adrenal insufficiency, hypertension, increase in blood creatine phosphokinase (a type of enzyme), weight increase, and anemia.It was approved for medical use in the United States in August 2020, and in the European Union in March 2021.Somapacitan is the first human growth hormone (hGH) therapy that adults only take once a week by injection under the skin; other FDA-approved hGH formulations for adults with growth hormone deficiency must be administered daily. It contains a small non-covalent moiety that reversibly binds to serum albumin which slows down elimination.

Medical uses
Somapacitan is indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency (GHD).GHD is a condition when the body doesnt produce enough growth hormone on its own. Growth hormone regulates many functions in the body including accumulation of fat in the trunk or central area of the body that can be associated with serious medical issues.

Contraindications
Somapacitan should not be used in people with active malignancy, any stage of diabetic eye disease in which high blood sugar levels cause damage to blood vessels in the retina, acute critical illness, or those with acute respiratory failure, because of the increased risk of mortality with use of pharmacologic doses of somapacitan in critically ill individuals without growth hormone deficiency.

History
Somapacitan was evaluated in a randomized, double-blind, placebo-controlled trial (NCT02229851) in 300 participants with growth hormone deficiency who had never received growth hormone treatment or had stopped treatment with other growth hormone formulations at least three months before the study. Participants were randomly assigned to receive injections of weekly somapacitan, weekly placebo (inactive treatment), or daily somatropin, an FDA-approved growth hormone. The effectiveness of somapacitan was determined by the percentage change of truncal fat, the fat that is accumulated in the trunk or central area of the body that is regulated by growth hormone and can be associated with serious medical issues. The trial was conducted at 92 sites in 16 countries: the United States, Australia, Germany, India, Japan, Latvia, Lithuania, Malaysia, Poland, Romania, Russian Fed, South Africa, Sweden, Turkey, Ukraine and the United Kingdom.Adult participants were assigned at random to weekly Sogroya or placebo injections for 34 weeks. Neither the participants nor the investigators knew which treatment was given until the end of the trial. One additional group of participants with GHD received daily injections of somatotropin (an approved treatment for GHD). At the end of the 34-week treatment period, truncal fat decreased by 1.06%, on average, among participants taking weekly somapacitan while it increased among participants taking the placebo by 0.47% </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Meropenem/vaborbactam and can you explain it in depth? [/INST] Meropenem/vaborbactam, sold under the brand name Vabomere among others, is a combination medication used to treat complicated urinary tract infections, complicated abdominal infections, and hospital-acquired pneumonia. It contains meropenem, a β-lactam antibiotic, and vaborbactam, a β-lactamase inhibitor. It is given by injection into a vein.Common side effects include headache, inflammation at the site of injection, nausea, diarrhea, liver inflammation, and low blood potassium. Severe side effects may include anaphylaxis, seizures, and Clostridium difficile-associated diarrhea. It is unclear if use during pregnancy is safe </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Flurazepam and can you explain it in depth? [/INST] Flurazepam (marketed under the brand names Dalmane and Dalmadorm) is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. It produces a metabolite with a long half-life, which may stay in the bloodstream for days.
Flurazepam was patented in 1968 and came into medical use the same year. Flurazepam, developed by Roche Pharmaceuticals was one of the first benzo hypnotics (sleeping pills) to be marketed.

Medical uses
Flurazepam is officially indicated for mild to moderate insomnia and as such it is used for short-term treatment of patients with mild to moderate insomnia such as difficulty falling asleep, frequent awakening, early awakenings or a combination of each. Flurazepam is a long-acting benzodiazepine and is sometimes used in patients who have difficulty in maintaining sleep, though benzodiazepines with intermediate half-lives  such as loprazolam, lormetazepam, and temazepam are also indicated for patients with difficulty maintaining sleep.
Flurazepam was temporarily unavailable in the United States when its sole producer, Mylan Pharmaceuticals, discontinued making it in January 2019. In October 2019, the FDA informed pharmacies that they could expect to be resupplied by manufacturers in early to mid December 2019.  As of this date, Flurazepam is now again available in the United States.

Side effects
The most common adverse effects are dizziness, drowsiness, light-headedness, and ataxia. Flurazepam has abuse potential and should never be used with alcoholic beverages or any other substance that can cause drowsiness.  Addictive and possibly fatal results may occur. Flurazepam users should only take this drug strictly as prescribed, and should only be taken directly before the user plans on sleeping a full night. Next day drowsiness is common and may increase during the initial phase of treatment as accumulation occurs until steady-state plasma levels are attained.
A 2009 meta-analysis found a 44% higher rate of mild infections, such as pharyngitis or sinusitis, in people taking hypnotic drugs compared to those taking a placebo.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, dependence and withdrawal
A review paper found that long-term use of flurazepam is associated with drug tolerance, drug dependence, rebound insomnia and central nervous system (CNS) related adverse effects. Flurazepam is best used for a short time period and at the lowest possible dose to avoid complications associated with long-term use. Non-pharmacological treatment options however, were found to have sustained improvements in sleep quality. Flurazepam and other benzodiazepines such as fosazepam, and nitrazepam lost some of their effect after seven days administration in psychogeriatric patients. Flurazepam shares cross tolerance with barbiturates and barbiturates can easily be substituted by flurazepam in those who are habituated to barbiturate sedative hypnotics.After discontinuation of flurazepam a rebound effect or benzodiazepine withdrawal syndrome may occur about four days after discontinuation of medication.

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
Flurazepam, similar to other benzodiazepines and nonbenzodiazepine hypnotic drugs causes impairments in body balance and standing steadiness in individuals who wake up at night or the next morning. Falls and hip fractures are frequently reported. The combination with alcohol increases these impairments. Partial, but incomplete tolerance develops to these impairments. 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 flurazepam, the nonbenzodiazepine sedative-hypnotics appeared to offer few, if any, significant clinical advantages in efficacy in elderly persons </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Polystyrene sulfonate and can you explain it in depth? [/INST] Polystyrene sulfonates are a group of medications used to treat high blood potassium. Effects generally take hours to days. They are also used to remove potassium, calcium, and sodium from solutions in technical applications.
Common side effects include loss of appetite, gastrointestinal upset, constipation, and low blood calcium. These polymers are derived from polystyrene by the addition of sulfonate functional groups.
Sodium polystyrene sulfonate was approved for medical use in the United States in 1958.A polystyrene sulfonate was developed in the 2000s to treat Clostridium difficile associated diarrhea under the name Tolevamer, but it was never marketed.

Medical uses
Polystyrene sulfonate is usually supplied in either the sodium or calcium form.  It is used as a potassium binder in acute and chronic kidney disease for people with hyperkalemia (abnormal high blood serum potassium levels).  However, it is unclear if it is beneficial and there is concern about possible side effects when it is combined with sorbitol.Polystyrene sulfonates are given by mouth with a meal or rectally by retention enema.

Side effects
Intestinal disturbances are common, including loss of appetite, nausea, vomiting, and constipation. In rare cases, it has been associated with colonic necrosis. Changes in electrolyte blood levels such as hypomagnesemia, hypocalcemia, and hypokalemia may occur. Polystyrene sulfonates should not be used in people with obstructive bowel disease and in newborns with reduced gut motility.

Intestinal injury
A total of 58 cases of intestinal injury including necrosis of the colon have been reported with polystyrene sulfonate as of 2013. Well more cases have been reported when used in combination  with sorbitol and other cases have occurred when used alone.

Interactions
Polystyrene sulfonates can bind to various drugs within the digestive tract and thus lower their absorption and effectiveness. Common examples include lithium, thyroxine, and digitalis. In September 2017, the FDA recommended separating the dosing of polystyrene sulfonate from any other oral medications by at least three hours to avoid any potential interactions.

Mechanism of action
Hyperkalemia
Polystyrene sulfonates release sodium or calcium ions in the stomach in exchange for hydrogen ions. When the resin reaches the large intestine the hydrogen ions are exchanged for free potassium ions; the resin is then eliminated in the feces. The net effect is lowering the amount of potassium available for absorption into the blood and increasing the amount that is excreted via the feces. The effect is a reduction of potassium levels in the body, at a capacity of 1 mEq of potassium exchanged per 1 g of resin.

Production and chemical structure
Polystyrene sulfonic acid, the acid whose salts are the polystyrene sulfonates, has the idealized formula (CH2CHC6H4SO3H)n.  The material is prepared by sulfonation of polystyrene:

(CH2CHC6H5)n  +  n SO3   →   (CH2CHC6H4SO3H)nSeveral methods exist for this conversion, which can lead to varying degree of sulfonation.  Usually the polystyrene is crosslinked, which keeps the polymer from dissolving </s>


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Diflunisal and can you explain it in depth? [/INST] Diflunisal is a salicylic acid derivative with analgesic and anti-inflammatory activity. It was developed by Merck Sharp & Dohme in 1971, as MK647, after showing promise in a research project studying more potent chemical analogs of aspirin. It was first sold under the brand name Dolobid, marketed by Merck & Co., but generic versions are now widely available. It is classed as a nonsteroidal anti-inflammatory drug (NSAID) and is available in 250 mg and 500 mg tablets.

Mechanism of action
Like all NSAIDs, diflunisal acts by inhibiting the production of prostaglandins, hormones which are involved in inflammation and pain. Diflunisal also has an antipyretic effect, but this is not a recommended use of the drug.It has been found to inhibit p300 and CREB-binding protein (CBP), which are epigenetic regulators that control the levels of proteins that cause inflammation or are involved in cell growth.It has been reported that diflunisal has some antibacterial activity  in vitro  against  Francisella tularensis  live vaccine strain (LVS).

Duration of effect
Though diflunisal has an onset time of 1 hour, and maximum analgesia at 2 to 3 hours, the plasma levels of diflunisal will not be steady until repeated doses are taken. The long plasma half-life is a distinctive feature of diflunisal in comparison to similar drugs. To increase the rate at which the diflunisal plasma levels become steady, a loading dose is usually used. It is primarily used to treat symptoms of arthritis, and for acute pain following oral surgery, especially removal of wisdom teeth.Effectiveness of diflunisal is similar to other NSAIDs, but the duration of action is twelve hours or more. This means fewer doses per day are required for chronic administration. In acute use, it is popular in dentistry when a single dose after oral surgery can maintain analgesia until the patient is asleep that night.

Medical uses
Pain, mild to moderate
Osteoarthritis
Rheumatoid arthritis
Injury to tendons
Inflammation
ATTR  amyloidosis

Amyloidosis
Both diflunisal and several of its analogues have been shown to be inhibitors of transthyretin-related hereditary amyloidosis, a disease which currently has few treatment options.
Phase I trials have shown the drug to be well tolerated, with a small Phase II trial (double-blind, placebo-controlled, 130 patients for 2 years) in 2013 showing a reduced rate of disease progression and preserved quality of life </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hyoscyamine and can you explain it in depth? [/INST] Hyoscyamine (also known as daturine or duboisine) is a naturally occurring tropane alkaloid and plant toxin. It is a secondary metabolite found in certain plants of the family Solanaceae, including henbane, mandrake, angels trumpets, jimsonweed, tomato, the sorcerers tree, and deadly nightshade. It is the levorotary isomer of atropine (third of the three major nightshade alkaloids) and thus sometimes known as levo-atropine.Brand names for hyoscyamine include Symax, HyoMax, Anaspaz, Egazil, Buwecon, Cystospaz, Levsin, Levbid, Levsinex, Donnamar, NuLev, Spacol T/S, and Neoquess.

Uses
Hyoscyamine is used to provide symptomatic relief of spasms caused by various lower abdominal and bladder disorders including peptic ulcers, irritable bowel syndrome, diverticulitis, pancreatitis, colic, and interstitial cystitis. It has also been used to relieve some heart problems, control some of the symptoms of Parkinsons disease, as well as for control of abnormal respiratory symptoms and "hyper-mucus secretions" in patients with lung disease.It is also useful in pain control for neuropathic pain, chronic pain and palliative care – "comfort care" – for those with intractable pain from treatment resistant, untreatable, and incurable diseases. When combined with opioids it increases the level of analgesia (pain relief) obtained. Several mechanisms are thought to contribute to this effect. The closely related drugs atropine and hyoscine and other members of the anticholinergic drug group like cyclobenzaprine, trihexyphenidyl, and orphenadrine are also used for this purpose. When hyoscyamine is used along with opioids or other anti-peristaltic agents, measures to prevent constipation are especially important given the risk of paralytic ileus.

Adverse effects
Side effects include dry mouth and throat, increased appetite leading to weight gain, eye pain, blurred vision, restlessness, dizziness, arrhythmia, flushing, and faintness. An overdose will cause headache, nausea, vomiting, and central nervous system symptoms including disorientation, hallucinations, euphoria, sexual arousal, short-term memory loss, and possible coma in extreme cases. The euphoric and sexual effects are stronger than those of atropine but weaker than those of Hyoscine, as well as dicycloverine, orphenadrine, cyclobenzaprine, trihexyphenidyl, and ethanolamine antihistamines like phenyltoloxamine.

Pharmacology
Hyoscyamine is an antimuscarinic; i.e., an antagonist of muscarinic acetylcholine receptors.  It blocks the action of acetylcholine at parasympathetic sites in sweat glands, salivary glands, stomach secretions, heart muscle, sinoatrial node, smooth muscle in the gastrointestinal tract, and the central nervous system. It increases cardiac output and heart rate, lowers blood pressure and dries secretions </s>


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Amoxapine and can you explain it in depth? [/INST] Amoxapine, sold under the brand name Asendin among others, is a tricyclic antidepressant (TCAs). It is the N-demethylated metabolite of loxapine. Amoxapine first received marketing approval in the United States in 1992 (approximately 30 to 40 years after most of the other TCAs were introduced in the United States).

Medical uses
Amoxapine is used in the treatment of major depressive disorder. Compared to other antidepressants it is believed to have a faster onset of action, with therapeutic effects seen within four to seven days. In excess of 80% of patients that do respond to amoxapine are reported to respond within two weeks of the beginning of treatment. It also has properties similar to those of the atypical antipsychotics, and may behave as one and may be used in the treatment of schizophrenia off-label. Despite its apparent lack of extrapyramidal side effects in patients with schizophrenia it has been found to exacerbate motor symptoms in patients with Parkinsons disease and psychosis.

Contraindications
As with all FDA-approved antidepressants it carries a black-box warning about the potential of an increase in suicidal thoughts or behaviour in children, adolescents and young adults under the age of 25. Its use is also advised against in individuals with known hypersensitivities to either amoxapine or other ingredients in its oral formulations. Its use is also recommended against in the following disease states:
Severe cardiovascular disorders (potential of cardiotoxic adverse effects such as QT interval prolongation)
Uncorrected narrow angle glaucoma
Acute recovery post-myocardial infarctionIts use is also advised against in individuals concurrently on monoamine oxidase inhibitors or if they have been on one in the past 14 days and in individuals on drugs that are known to prolong the QT interval (e.g. ondansetron, citalopram, pimozide, sertindole, ziprasidone, haloperidol, chlorpromazine, thioridazine, etc.).

Lactation
Its use in breastfeeding mothers not recommended as it is excreted in breast milk and the concentration found in breast milk is approximately a quarter that of the maternal serum level.

Side effects
Adverse effects by incidence:Note: Serious (that is, those that can either result in permanent injury or are irreversible or are potentially life-threatening) are written in bold text.
Very common (>10% incidence) adverse effects include:

Constipation
Dry mouth
SedationCommon (1–10% incidence) adverse effects include:

Oedema. An abnormal accumulation of fluids in the tissues of the body leading to swelling.
Prolactin levels increased. Prolactin is a hormone that regulates the generation of breast milk. Prolactin elevation is not as significant as with risperidone or haloperidol.Uncommon/Rare (<1% incidence) adverse effects include:

Vasculitis a disorder where blood vessels are destroyed by inflammation. Can be life-threatening if it affects the right blood vessels.
Galactorrhoea (lactation that is not associated with pregnancy or breast feeding)
Delayed micturition (that is, delays in urination from when a conscious effort to urinate is made)
Hyperthermia (elevation of body temperature; its seriousness depends on the extent of the hyperthermia)
Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) this is basically when the bodys level of the hormone, antidiuretic hormone, which regulates the conservation of water and the restriction of blood vessels, is elevated. This is potentially fatal as it can cause electrolyte abnormalities including hyponatraemia (low blood sodium), hypokalaemia (low blood potassium) and hypocalcaemia (low blood calcium) which can be life-threatening.
Agranulocytosis a drop in white blood cell counts. The white blood cells are the cells of the immune system that fight off foreign invaders. Hence agranulocytosis leaves an individual open to life-threatening infections.
Leukopaenia the same as agranulocytosis but less severe.
Neuroleptic malignant syndrome (a potentially fatal reaction to antidopaminergic agents, most often antipsychotics. It is characterised by hyperthermia, diarrhoea, tachycardia, mental status changes [e.g </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Nortriptyline and can you explain it in depth? [/INST] Nortriptyline, sold under the brand name Pamelor, among others, is a medication used to treat depression. This medicine is used for: neuropathic pain, attention deficit hyperactivity disorder (ADHD), smoking cessation and anxiety. As with many antidepressants, its use for young people with depression and other psychiatric disorders may be limited due to increased suicidality in the 18-24 population initiating treatment. Nortriptyline is a less preferred treatment for ADHD and stopping smoking. It is taken by mouth.Common side effects include dry mouth, constipation, blurry vision, sleepiness, low blood pressure with standing, and weakness. Serious side effects may include seizures, an increased risk of suicide in those less than 25 years of age, urinary retention, glaucoma, mania, and a number of heart issues. Nortriptyline may cause problems if taken during pregnancy. Use during breastfeeding appears to be relatively safe. It is a tricyclic antidepressant (TCA) and is believed to work by altering levels of serotonin and norepinephrine.Nortriptyline was approved for medical use in the United States in 1964. It is available as a generic medication. In 2019, it was the 153rd most commonly prescribed medication in the United States, with more than 4 million prescriptions.

Medical uses
Nortriptyline is used to treat depression. This medication is in capsule or liquid and is taken by the mouth one to four times a day, with or without food. Usually people are started on a low dose and it is gradually increased. A level between 50 and 150 ng/mL of nortriptyline in the blood generally corresponds with an antidepressant effect.In the United Kingdom, it may also be used for treating nocturnal enuresis, with courses of treatment lasting no more than three months. It is also used off-label for the treatment of panic disorder, irritable bowel syndrome, migraine prophylaxis and chronic pain or neuralgia modification, particularly temporomandibular joint disorder.

Neuropathic pain
Although not approved by the FDA for neuropathic pain, many randomized controlled trials have demonstrated the effectiveness of TCAs for the treatment of this condition in both depressed and non-depressed individuals. In 2010, an evidence-based guideline sponsored by the International Association for the Study of Pain recommended nortriptyline as a first-line medication for neuropathic pain. However, in a 2015 Cochrane systematic review the authors did not recommend nortriptyline as a first-line agent for neuropathic pain.

Irritable Bowel Syndrome
Nortriptyline has also been used as an off-label treatment for Irritable Bowel Syndrome, or IBS.

Contraindications
Nortriptyline should not be used in the acute recovery phase after myocardial infarction (viz, heart attack). Use of tricyclic antidepressants along with a monoamine oxidase (MAO) inhibitor, linezolid, and IV methylene blue are contraindicated as it can cause an increased risk of developing serotonin syndrome.Closer monitoring is required for those with a history of cardiovascular disease, stroke,  glaucoma, or seizures, as well as in persons with hyperthyroidism or receiving thyroid hormones.

Side effects
The most common side effects include dry mouth, sedation, constipation, increased appetite, blurred vision and tinnitus. An occasional side effect is a rapid or irregular heartbeat. Alcohol may exacerbate some of its side effects.

Overdose
The symptoms and the treatment of an overdose are generally the same as for the other TCAs, including anticholinergic effects,  serotonin syndrome and adverse cardiac effects. TCAs, particularly nortriptyline, have a relatively narrow therapeutic index, which increase the chance of an overdose (both accidental and intentional). Symptoms of overdose include: irregular heartbeat, seizures, coma, confusion, hallucination, widened pupils, drowsiness, agitation, fever, low body temperature, stiff muscles and vomiting.

Interactions
Excessive consumption of alcohol in combination with nortriptyline therapy may have a potentiating effect, which may lead to the danger of increased suicidal attempts or overdosage, especially in patients with histories of emotional disturbances or suicidal ideation.
It may interact with the following drugs:
heart rhythm medications such as flecainide (Tambocor), propafenone (Rhythmol), or quinidine (Cardioquin, Quinidex, Quinaglute)
cimetidine
guanethidine
reserpine

Pharmacology
Nortriptyline is a strong norepinephrine reuptake inhibitor and a moderate  serotonin reuptake inhibitor. Its pharmacologic profile is as the table shows with (inhibition or antagonism of all sites).

Pharmacodynamics
Nortriptyline is an active metabolite of amitriptyline by demethylation in the liver. Chemically, it is a secondary amine dibenzocycloheptene and pharmacologically it is classed as a first-generation antidepressant.Nortriptyline may also have a sleep-improving effect due to antagonism of the H1 and 5-HT2A receptors. In the short term, however, nortriptyline may disturb sleep due to its activating effect.
In one study, nortriptyline had the highest affinity for the dopamine transporter among the TCAs (KD = 1,140 nM) besides amineptine (a norepinephrine–dopamine reuptake inhibitor), although its affinity for this transporter was still 261- and 63-fold lower than for the norepinephrine and serotonin transporters (KD = 4.37 and 18 nM, respectively).

Pharmacokinetics
Pharmacogenetics
Nortriptyline is metabolized in the liver by the hepatic enzyme CYP2D6, and genetic variations within the gene coding for this enzyme can affect its metabolism, leading to changes in the concentrations of the drug in the body. Increased concentrations of nortriptyline may increase the risk for side effects, including anticholinergic and nervous system adverse effects, while decreased concentrations may reduce the drugs efficacy.Individuals can be categorized into different types of CYP2D6 metabolizers depending on which genetic variations they carry. These metabolizer types include poor, intermediate, extensive, and ultrarapid metabolizers. Most individuals (about 77–92%) are extensive metabolizers, and have "normal" metabolism of nortriptyline. Poor and intermediate metabolizers have reduced metabolism of the drug as compared to extensive metabolizers; patients with these metabolizer types may have an increased probability of experiencing side effects. Ultrarapid metabolizers use nortriptyline much faster than extensive metabolizers; patients with this metabolizer type may have a greater chance of experiencing pharmacological failure.The Clinical Pharmacogenetics Implementation Consortium recommends avoiding nortriptyline in persons who are CYP2D6 ultrarapid or poor metabolizers, due to the risk of a lack of efficacy and side effects, respectively. A reduction in starting dose is recommended for patients who are CYP2D6 intermediate metabolizers. If use of nortriptyline is warranted, therapeutic drug monitoring is recommended to guide dose adjustments. The Dutch Pharmacogenetics Working Group recommends reducing the dose of nortriptyline in CYP2D6 poor or intermediate metabolizers, and selecting an alternative drug or increasing the dose in ultrarapid metabolizers.

Chemistry
Nortriptyline is a tricyclic compound, specifically a dibenzocycloheptadiene, and possesses three rings fused together with a side chain attached in its chemical structure. Other dibenzocycloheptadiene TCAs include amitriptyline (N-methylnortriptyline), protriptyline, and butriptyline. Nortriptyline is a secondary amine TCA, with its N-methylated parent amitriptyline being a tertiary amine </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Triheptanoin and can you explain it in depth? [/INST] Triheptanoin, sold under the brand name Dojolvi, is a medication for the treatment of children and adults with molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAOD).The most common adverse reactions include abdominal pain, diarrhea, vomiting, and nausea.Triheptanoin was approved for medical use in the United States in June 2020.Triheptanoin is a triglyceride that is composed of three seven-carbon (C7:0) fatty acids. These odd-carbon fatty acids are able to provide anaplerotic substrates for the TCA cycle. Triheptanoin is used clinically in humans to treat inherited metabolic diseases, such as pyruvate carboxylase deficiency and carnitine palmitoyltransferase II deficiency. It also appears to increase the efficacy of the ketogenic diet as a treatment for epilepsy.
Since triheptanoin is composed of odd-carbon fatty acids, it can produce ketone bodies with five carbon atoms, as opposed to even-carbon fatty acids which are metabolized to ketone bodies with four carbon atoms. The five-carbon ketones produced from triheptanoin are beta-ketopentanoate and beta-hydroxypentanoate. Each of these ketone bodies easily crosses the blood–brain barrier and enters the brain.

Medical uses
Dojolvi is indicated as a source of calories and fatty acids for the treatment of children and adults with molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAOD).

History
Triheptanoin was designated an orphan drug by the U.S. Food and Drug Administration (FDA) in 2006, 2008, 2014, and 2015. Triheptanoin was also designated an orphan drug by the European Medicines Agency (EMA).Triheptanoin was approved for medical use in the United States in June 2020.The FDA approved triheptanoin based on evidence from three clinical trials (Trial 1/NCT018863, Trial 2/NCT022141 and Trial 3/NCT01379625). The trials enrolled children and adults with LC-FAOD. Trials 1 and 2 were conducted at 11 sites in the United States and the United Kingdom, and Trial 3 was conducted at two sites in the United States.Trial 1 and Trial 2 were used to evaluate the side effects of triheptanoin. Both trials enrolled children and adults diagnosed with LC-FAOD. In Trial 1, participants received triheptanoin for 78 weeks. Trial 2 enrolled participants from other trials who were already treated with triheptanoin (including those from Trial 1) as well as participants who were never treated with triheptanoin before. Trial 2 is still ongoing and is planned to last up to five years.The benefit of triheptanoin was evaluated in Trial 3 which enrolled children and adults with LC-FAOD. Half of the participants received triheptanoin and half received trioctanoin for four months. Neither the participants nor the investigators knew which treatment was given until the end of the trial. The benefit of triheptanoin in comparison to trioctanoin was assessed by measuring the changes in heart and muscle function.

Names
Triheptanoin is the international nonproprietary name.

References
Further reading
de Almeida Rabello Oliveira M, da Rocha Ataíde T, de Oliveira SL, de Melo Lucena AL, de Lira CE, Soares AA,  et al. (March 2008). "Effects of short-term and long-term treatment with medium- and long-chain triglycerides ketogenic diet on cortical spreading depression in young rats". Neurosci. Lett. 434 (1): 66–70. doi:10.1016/j.neulet.2008.01.032. PMID 18281154. S2CID 7754768.
Mochel F, DeLonlay P, Touati G, Brunengraber H, Kinman RP, Rabier D,  et al. (April 2005). "Pyruvate carboxylase deficiency: clinical and biochemical response to anaplerotic diet therapy". Mol. Genet. Metab. 84 (4): 305–12. doi:10.1016/j.ymgme.2004.09.007 </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Nifurtimox and can you explain it in depth? [/INST] Nifurtimox, sold under the brand name Lampit, is a medication used to treat Chagas disease and sleeping sickness. For sleeping sickness it is used together with eflornithine in nifurtimox-eflornithine combination treatment. In Chagas disease it is a second-line option to benznidazole. It is given by mouth.Common side effects include abdominal pain, headache, nausea, and weight loss. There are concerns from animal studies that it may increase the risk of cancer but these concerns have not been found in human trials. Nifurtimox is not recommended in pregnancy or in those with significant kidney or liver problems. It is a type of nitrofuran.Nifurtimox came into medication use in 1965. It is on the World Health Organizations List of Essential Medicines. It is not available commercially in Canada. It was approved for medical use in the United States in August 2020. In regions of the world where the disease is common nifurtimox is provided for free by the World Health Organization (WHO).

Medical uses
Nifurtimox has been used to treat Chagas disease, when it is given for 30 to 60 days. However, long-term use of nifurtimox does increase chances of adverse events like gastrointestinal and neurological side effects. Due to the low tolerance and completion rate of nifurtimox, benznidazole is now being more considered for those who have Chagas disease and require long-term treatment.In the United States nifurtimox is indicated in children and adolescents (birth to less than 18 years of age and weighing at least 2.5 kilograms (5.5 lb) for the treatment of Chagas disease (American Trypanosomiasis), caused by Trypanosoma cruzi.Nifurtimox has also been used to treat African trypanosomiasis (sleeping sickness), and is active in the second stage of the disease (central nervous system involvement). When nifurtimox is given on its own, about half of all patients will relapse, but the combination of melarsoprol with nifurtimox appears to be efficacious. Trials are awaited comparing melarsoprol/nifurtimox against melarsoprol alone for African sleeping sickness.Combination therapy with eflornithine and nifurtimox is safer and easier than treatment with eflornithine alone, and appears to be equally or more effective. It has been recommended as first-line treatment for second-stage African trypanosomiasis.

Pregnancy and breastfeeding
Use of nifurtimox should be avoided in pregnant women due to limited use. There is limited data shown that nifurtimox doses up to 15 mg/kg daily can cause adverse effects in breastfed infants. Other authors do not consider breastfeeding a contraindication during nifurtimox use.

Side effects
Side effects occur following chronic administration, particularly in elderly people.
Major toxicities include immediate hypersensitivity such as anaphylaxis and delayed hypersensitivity reaction involving icterus and dermatitis. Central nervous system disturbances and peripheral neuropathy may also occur.Most common side effects
anorexia
weight loss
nausea
vomiting
headache
dizziness
amnesiaLess common effects
rash
depression
anxiety
confusion
fever
sore throat
chills
seizures
impotence
tremors
muscle weakness
numbness of hands or feet

Contraindications
Nifurtimox is contraindicated in people with severe liver or kidney disease, as well as people with a background of neurological or psychiatric disorders.

Mechanism of action
Nifurtimox forms a nitro-anion radical metabolite that reacts with nucleic acids of the parasite causing significant breakdown of DNA </s>


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Procaine benzylpenicillin and can you explain it in depth? [/INST] Procaine benzylpenicillin also known as penicillin G procaine, is an antibiotic useful for the treatment of a number of bacterial infections. Specifically it is used for syphilis, anthrax, mouth infections, pneumonia, diphtheria, cellulitis, and animal bites. It is given by injection into a muscle.Side effects include pain at the site of injection, blood clotting problems, seizures, and allergic reactions including anaphylaxis. When used to treat syphilis a reaction known as Jarisch-Herxheimer may occur. It is not recommended in those with a history of penicillin allergy or procaine allergy. Use during pregnancy and breastfeeding is relatively safe </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hydrochlorothiazide and can you explain it in depth? [/INST] Hydrochlorothiazide is a diuretic medication often used to treat high blood pressure and swelling due to fluid build up. Other uses include treating diabetes insipidus and renal tubular acidosis and to decrease the risk of kidney stones in those with a high calcium level in the urine. Hydrochlorothiazide is less effective than chlortalidone for prevention of heart attack or stroke. Hydrochlorothiazide is taken by mouth and may be combined with other blood pressure medications as a single pill to increase effectiveness.Potential side effects include poor kidney function; electrolyte imbalances, including low blood potassium, and, less commonly, low blood sodium, gout, high blood sugar, and feeling lightheaded with standing. While allergies to hydrochlorothiazide are reported to occur more often in those with allergies to sulfa drugs, this association is not well supported. It may be used during pregnancy, but it is not a first-line medication in this group.It is in the thiazide medication class and acts by decreasing the kidneys ability to retain water. This initially reduces blood volume, decreasing blood return to the heart and thus cardiac output. It is believed to lower peripheral vascular resistance in the long run.Two companies, Merck and Ciba, state they discovered the medication which became commercially available in 1959. It is on the World Health Organizations List of Essential Medicines. It is available as a generic drug and is relatively affordable. In 2020, it was the eleventh most commonly prescribed medication in the United States, with more than 41 million prescriptions.

Medical uses
Hydrochlorothiazide is used for the treatment of hypertension, congestive heart failure, symptomatic edema, diabetes insipidus, renal tubular acidosis. It is also used for the prevention of kidney stones in those who have high levels of calcium in their urine.Multiple studies suggest hydrochlorothiazide could be used as initial monotherapy in people with primary hypertension; however, the decision should be weighed against the consequence of long-term adverse metabolic abnormalities. A review of randomised trials showed varying efficacy in cardiovascular outcomes on age, ethnicity and existing cardiovascular risks. A systematic, multinational, large-scale analysis by Suchard et al. supported equivalence between drug classes for initiating monotherapy in hypertension, however thiazide or thiazide-like diuretics showed better primary effectiveness and safety profiles than angiotensin-converting enzyme inhibitors and non-dihydropyridine calcium channel blockers.Hydrochlorothiazide is less potent but not necessarily less effective than chlorthalidone in reducing blood pressure.  More robust studies are required to confirm which drug is superior in reducing cardiovascular events. Side effect profile for both drugs appear similar and are dose dependant.Hydrochlorothiazide is also sometimes used to prevent osteopenia and for treatment of hypoparathyroidism, hypercalciuria, Dents disease, and Ménières disease. For diabetes insipidus, the effect of thiazide diuretics is presumably mediated by a hypovolemia-induced increase in proximal sodium and water reabsorption, thereby diminishing water delivery to the ADH-sensitive sites in the collecting tubules and increasing the urine osmolality.A low level of evidence, predominantly from observational studies, suggests that thiazide diuretics have a modest beneficial effect on bone mineral density and are associated with a decreased fracture risk when compared with people not taking thiazides. Thiazides decrease mineral bone loss by promoting calcium retention in the kidney, and by directly stimulating osteoblast differentiation and bone mineral formation.The combination of fixed-dose preparation such as losartan/hydrochlorothiazide has added advantages of a more potent antihypertensive effect with additional antihypertensive efficacy at the dose of 100 mg/25 mg when compared to monotherapy.

Adverse effects
Hypokalemia, or low blood levels of potassium are an occasional side effect. It can be usually prevented by potassium supplements or by combining hydrochlorothiazide with a potassium-sparing diuretic
Other disturbances in the levels of serum electrolytes, including hypomagnesemia (low magnesium), hyponatremia (low sodium), and hypercalcemia (high calcium)
Hyperuricemia (high levels of uric acid in the blood). All thiazide diuretics including hydrochlorothiazide can inhibit excretion of uric acid by the kidneys, thereby increasing serum concentrations of uric acid.This may increase the incidence of gout in doses of ≥ 25 mg per day and in more susceptible patients such as male gender of <60 years old.
Hyperglycemia, high blood sugar
Hyperlipidemia, high cholesterol and triglycerides
Headache
Nausea/vomiting
Photosensitivity
Weight gain
PancreatitisPackage inserts contain vague and inconsistent data surrounding the use of thiazide diuretics in patients with allergies to sulfa drugs, with little evidence to support these statements. A retrospective cohort study conducted by Strom et al. concluded that there is an increased risk of an allergic reaction occurring in patients with a predisposition to allergic reactions in general rather than cross reactivity from structural components of the sulfonamide-based drug. Prescribers should examine the evidence carefully and assess each patient individually, paying particular attention to their prior history of sulfonamide hypersensitivity rather than relying on drug monograph information.There is an increased risk of non-melanoma skin cancer. In August 2020, the Australian Therapeutic Goods Administration required the Product Information (PI) and Consumer Medicine Information (CMI) for medicines containing hydrochlorothiazide to be updated to include details about an increased risk of non-melanoma skin cancer. In August 2020, the U.S. Food and Drug Administration (FDA) updated the drug label about an increased risk of non-melanoma skin cancer (basal cell skin cancer or squamous cell skin cancer).

Mechanism of action
Hydrochlorothiazide belongs to the thiazide class of diuretics. It reduces blood volume by acting on the kidneys to reduce sodium (Na+) reabsorption in the distal convoluted tubule. The major site of action in the nephron appears on an electroneutral NaCl co-transporter by competing for the chloride site on the transporter. By impairing Na+ transport in the distal convoluted tubule, hydrochlorothiazide induces a natriuresis and concomitant water loss. Thiazides increase the reabsorption of calcium in this segment in a manner unrelated to sodium transport </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Ellipsis and can you explain it in depth? [/INST] The ellipsis ... (, also known informally as dot dot dot) is a series of dots that indicates an intentional omission of a word, sentence, or whole section from a text without altering its original meaning. The plural is ellipses. The term originates from the Ancient Greek: ἔλλειψις, élleipsis meaning leave out.Opinions differ as to how to render ellipses in printed material. According to The Chicago Manual of Style, it should consist of three periods, each separated from its neighbor by a non-breaking space: . . .. According to the AP Stylebook, the periods should be rendered with no space between them: .... A third option is to use the Unicode character U+2026 … HORIZONTAL ELLIPSIS.

Background
The ellipsis is also called a suspension point, points of ellipsis, periods of ellipsis, or (colloquially) "dot-dot-dot". Depending on their context and placement in a sentence, ellipses can indicate an unfinished thought, a leading statement, a slight pause, an echoing voice, or a nervous or awkward silence. Aposiopesis is the use of an ellipsis to trail off into silence—for example: "But I thought he was..." When placed at the end of a sentence, an ellipsis may be used to suggest melancholy or longing.The most common forms of an ellipsis include a row of three periods or full points ... or a precomposed triple-dot glyph, the horizontal ellipsis …. Style guides often have their own rules governing the use of ellipses. For example, The Chicago Manual of Style (Chicago style) recommends that an ellipsis be formed by typing three periods, each with a space on both sides  . . . , while the Associated Press Stylebook (AP style) puts the dots together, but retains a space before and after the group, thus:  ... . Whether an ellipsis at the end of a sentence needs a fourth dot to finish the sentence is a matter of debate; Chicago advises it, as does the Publication Manual of the American Psychological Association (APA style), while some other style guides do not; the Merriam-Webster Dictionary and related works treat this style as optional, saying that it "may" be used.When text is omitted following a sentence, a normal full stop (period) terminates the sentence, and then a separate three-dot ellipsis is commonly used to indicate one or more subsequent omitted sentences before continuing a longer quotation. Business Insider magazine suggests this style and it is also used in many academic journals. The Associated Press Stylebook favors this approach.

In writing
In her book on the ellipsis, Ellipsis in English Literature: Signs of Omission (Cambridge University Press, 2015), Anne Toner suggests that the first use of the punctuation in the English language dates to a 1588 translation of Terences Andria, by Maurice Kyffin. In this case, however, the ellipsis consists not of dots but of short dashes. "Subpuncting" of medieval manuscripts also denotes omitted meaning and may be related.Occasionally, it would be used in pulp fiction and other works of early 20th-century fiction to denote expletives that would otherwise have been censored.An ellipsis may also imply an unstated alternative indicated by context. For example, "I never drink wine ..." implies that the speaker does drink something else—such as vodka.
In reported speech, the ellipsis can be used to represent an intentional silence.
In poetry, an ellipsis is used as a thought-pause or line break at the caesura or this is used to highlight sarcasm or make the reader think about the last points in the poem.
In news reporting, often put inside square brackets, it is used to indicate that a quotation has been condensed for space, brevity or relevance, as in "The President said that [...] he would not be satisfied", where the exact quotation was "The President said that, for as long as this situation continued, he would not be satisfied".
Herb Caen, Pulitzer-prize-winning columnist for the San Francisco Chronicle, became famous for his "three-dot journalism".

In different languages
In English
American English
The Chicago Manual of Style suggests the use of an ellipsis for any omitted word, phrase, line, or paragraph from within but not at the end of a quoted passage. There are two commonly used methods of using ellipses: one uses three dots for any omission, while the second one makes a distinction between omissions within a sentence (using three dots: . . .) and omissions between sentences (using a period and a space followed by three dots: . ...). The Chicago Style Q&A recommends that writers avoid using the precomposed … (U+2026) character in manuscripts and to place three periods plus two nonbreaking spaces (. . .) instead, leaving the editor, publisher, or typographer to replace them later.The Modern Language Association (MLA) used to indicate that an ellipsis must include spaces before and after each dot in all uses. If an ellipsis is meant to represent an omission, square brackets must surround the ellipsis to make it clear that there was no pause in the original quote: [ . . . ]. Currently, the MLA has removed the requirement of brackets in its style handbooks. However, some maintain that the use of brackets is still correct because it clears confusion.The MLA now indicates that a three-dot, spaced ellipsis  . . .  should be used for removing material from within one sentence within a quote. When crossing sentences (when the omitted text contains a period, so that omitting the end of a sentence counts), a four-dot, spaced (except for before the first dot) ellipsis . . . .  should be used. When ellipsis points are used in the original text, ellipsis points that are not in the original text should be distinguished by enclosing them in square brackets (e.g. text [...] text).According to the Associated Press, the ellipsis should be used to condense quotations. It is less commonly used to indicate a pause in speech or an unfinished thought or to separate items in material such as show business gossip. The stylebook indicates that if the shortened sentence before the mark can stand as a sentence, it should do so, with an ellipsis placed after the period or other ending punctuation. When material is omitted at the end of a paragraph and also immediately following it, an ellipsis goes both at the end of that paragraph and at the beginning of the next, according to this style.According to Robert Bringhursts Elements of Typographic Style, the details of typesetting ellipses depend on the character and size of the font being set and the typographers preference. Bringhurst writes that a full space between each dot is "another Victorian eccentricity. In most contexts, the Chicago ellipsis is much too wide"—he recommends using flush dots (with a normal word space before and after), or thin-spaced dots (up to one-fifth of an em), or the prefabricated ellipsis character U+2026 … HORIZONTAL ELLIPSIS (…, …). Bringhurst suggests that normally an ellipsis should be spaced fore-and-aft to separate it from the text, but when it combines with other punctuation, the leading space disappears and the other punctuation follows. This is the usual practice in typesetting. He provides the following examples:

In legal writing in the United States, Rule 5.3 in the Bluebook citation guide governs the use of ellipses and requires a space before the first dot and between the two subsequent dots. If an ellipsis ends the sentence, then there are three dots, each separated by a space, followed by the final punctuation (e.g. Hah . . . ?). In some legal writing, an ellipsis is written as three asterisks, *** or * * *, to make it obvious that text has been omitted or to signal that the omitted text extends beyond the end of the paragraph.

British English
The Oxford Style Guide recommends setting the ellipsis as a single character … or as a series of three (narrow) spaced dots surrounded by spaces, thus:  . . . . If there is an ellipsis at the end of an incomplete sentence, the final full stop is omitted. However, it is retained if the following ellipsis represents an omission between two complete sentences.

Contrary to The Oxford Style Guide, the University of Oxford Style Guide demands an ellipsis not to be surrounded by spaces, except when it stands for a pause; then, a space has to be set after the ellipsis (but not before). An ellipsis is never preceded or followed by a full stop.

In Polish
When applied in Polish syntax, the ellipsis is called wielokropek, literally multidot. The word wielokropek distinguishes the ellipsis of Polish syntax from that of mathematical notation, in which it is known as an elipsa. When an ellipsis replaces a fragment omitted from a quotation, the ellipsis is enclosed in parentheses or square brackets. An unbracketed ellipsis indicates an interruption or pause in speech. The syntactic rules for ellipses are standardized by the 1983 Polska Norma document PN-83/P-55366, Zasady składania tekstów w języku polskim (Rules for Setting Texts in Polish).

In Russian
The combination "ellipsis+period" is replaced by the ellipsis. The combinations "ellipsis+exclamation mark" and "ellipsis+question mark" are written in this way: !.. ?..

In Japanese
The most common character corresponding to an ellipsis is called 3-ten rīdā ("3-dot leaders", …). 2-ten rīdā exists as a character, but it is used less commonly. In writing, the ellipsis consists usually of six dots (two 3-ten rīdā characters, ……). Three dots (one 3-ten rīdā character) may be used where space is limited, such as in a header. However, variations in the number of dots exist. In horizontally written text the dots are commonly vertically centered within the text height (between the baseline and the ascent line), as in the standard Japanese Windows fonts; in vertically written text the dots are always centered horizontally. As the Japanese word for dot is pronounced "ten", the dots are colloquially called "ten-ten-ten" (てんてんてん, akin to the English "dot dot dot").In text in Japanese media, such as in manga or video games, ellipses are much more frequent than in English, and are often changed to another punctuation sign in translation. The ellipsis by itself represents speechlessness, or a "pregnant pause". Depending on the context, this could be anything from an admission of guilt to an expression of being dumbfounded at another persons words or actions. As a device, the ten-ten-ten is intended to focus the reader on a character while allowing the character to not speak any dialogue. This conveys to the reader a focus of the narrative "camera" on the silent subject, implying an expectation of some motion or action. It is not unheard of to see inanimate objects "speaking" the ellipsis.

In Chinese
In Chinese, the ellipsis is six dots (in two groups of three dots, occupying the same horizontal or vertical space as two characters) (i.e. ……).

In Spanish
In Spanish, the ellipsis is commonly used as a substitute of et cetera at the end of unfinished lists. So it means "and so forth" or "and other things".
Other use is the suspension of a part of a text, or a paragraph, or a phrase or a part of a word because it is obvious, or unnecessary, or implied. For instance, sometimes the ellipsis is used to avoid the complete use of expletives.
When the ellipsis is placed alone into a parenthesis (...) or—less often—between brackets [...], which is what happens usually within a text transcription, it means the original text had more contents on the same position but are not useful to our target in the transcription. When the suppressed text is at the beginning or at the end of a text, the ellipsis does not need to be placed in a parenthesis.
The number of dots is three and only three.

In French
In French, the ellipsis is commonly used at the end of lists to represent et cetera. In French typography, the ellipsis is written immediately after the preceding word, but has a space after it, for example: comme ça... pas comme ceci. If, exceptionally, it begins a sentence, there is a space before and after, for example: Lui ? ... vaut rien, je crois... . However, any omitted word, phrase or line at the end of a quoted passage would be indicated as follows: [...] (space before and after the square brackets but not inside), for example: ... à Paris, Nice, Nantes, Toulouse [...].

In German
In German, the ellipsis in general is surrounded by spaces, if it stands for one or more omitted words. On the other side there is no space between a letter or (part of) a word and an ellipsis, if it stands for one or more omitted letters, that should stick to the written letter or letters.
Example for both cases, using German style: The first el...is stands for omitted letters, the second ... for an omitted word.
If the ellipsis is at the end of a sentence, the final full stop is omitted.Example: I think that ...

In Italian
The Accademia della Crusca suggests the use of an ellipsis ("puntini di sospensione") to indicate a pause longer than a period and, when placed between brackets, the omission of letters, words or phrases. "Tra le cose più preziose possedute da Andrea Sperelli era una coperta di seta fina, d’un colore azzurro disfatto, intorno a cui giravano i dodici segni dello Zodiaco in ricamo, con le denominazioni […] a caratteri gotici." (Gabriele D’Annunzio, Il piacere)

Usage in computer system menus
In computer menu functions or buttons, an ellipsis means that upon selection more options (sometimes in the form of a dialog box) will be displayed, where the user can or must make a choice. If the ellipsis is absent, the function is immediately executed upon selection.
For example, the menu item "Save" indicates that the file will be overwritten without further input, whereas "Save as..." indicates that a dialog follows where the user can, for example, select another location, file name, or format.
Ellipses are also used as a separate button (particularly considering the limited screen area of mobile apps) to represent partially or completely hidden options. This usage may alternatively be described as a "More button" (see also hamburger button signifying completely hidden options).
In mobile, web, and general application design, the vertical ellipsis, ⋮, is sometimes used as an interface element, where it is sometimes called a kebab icon. The element typically indicates that a navigation menu can be accessed when the element is activated, and is a smaller version of the hamburger icon (≡) which is a stylized rendering of a menu.

In mathematical notation
An ellipsis is also often used in mathematics to mean "and so forth". In a list, between commas, or following a comma, a normal ellipsis is used, as in:

        1
        ,
        2
        ,
        3
        ,
        …
        ,
        100

    {\displaystyle 1,2,3,\ldots ,100}
  or to mean an infinite list, as:

        1
        ,
        2
        ,
        3
        ,
        …

    {\displaystyle 1,2,3,\ldots }
  To indicate the omission of values in a repeated operation, an ellipsis raised to the center of the line is used between two operation symbols or following the last operation symbol, as in:

        1
        +
        2
        +
        3
        +
        ⋯
        +
        100

    {\displaystyle 1+2+3+\cdots +100}
  Sometimes, e.g. in Russian mathematical texts, normal, non-raised, ellipses are used even in repeated summations.The latter formula means the sum of all natural numbers from 1 to 100. However, it is not a formally defined mathematical symbol. Repeated summations or products may similarly be denoted using capital sigma and capital pi notation, respectively:

        1
        +
        2
        +
        3
        +
        ⋯
        +
        100

        =

          ∑

            n
            =
            1

            100

        n
        =
        100
        ?

    {\displaystyle 1+2+3+\cdots +100\ =\sum _{n=1}^{100}n=100?}
   (see termial)

        1
        ×
        2
        ×
        3
        ×
        ⋯
        ×
        100

        =

          ∏

            n
            =
            1

            100

        n
        =
        100
        !

    {\displaystyle 1\times 2\times 3\times \cdots \times 100\ =\prod _{n=1}^{100}n=100!}
   (see factorial)Normally dots should be used only where the pattern to be followed is clear, the exception being to show the indefinite continuation of an irrational number such as:

        π
        =
        3.14159265
        …

    {\displaystyle \pi =3.14159265\ldots }
  Sometimes, it is useful to display a formula compactly, for example:

        1
        +
        4
        +
        9
        +
        ⋯
        +

          n

            2

        +
        ⋯
        +
        400

    {\displaystyle 1+4+9+\cdots +n^{2}+\cdots +400}
  Another example is the set of positive zeros of the cosine function:

          {

                π
                2

            ,

                  3
                  π

                2

            ,

                  5
                  π

                2

            ,
            …

          }

    {\displaystyle \left\{{\frac {\pi }{2}},{\frac {3\pi }{2}},{\frac {5\pi }{2}},\ldots \right\}}
  There are many related uses of the ellipsis in set notation.
The diagonal and vertical forms of the ellipsis are particularly useful for showing missing terms in matrices, such as the size-n identity matrix:

          I

            n

        =

            [

                  1

                  0

                  ⋯

                  0

                  0

                  1

                  ⋯

                  0

                  ⋮

                  ⋮

                  ⋱

                  ⋮

                  0

                  0

                  ⋯

                  1

            ]

    {\displaystyle I_{n}={\begin{bmatrix}1&0&\cdots &0\\0&1&\cdots &0\\\vdots &\vdots &\ddots &\vdots \\0&0&\cdots &1\end{bmatrix}}}

Computer science
Programming languages
A two- or three-dot ellipsis is used as an operator in some programming languages. One of its most common uses is in defining ranges or sequences, for instance 1..10 means all the numbers from 1 through 10. This is used in many languages, including Pascal, Modula, Oberon, Ada, Haskell, Perl, Ruby, Rust, Swift, Kotlin, Bash shell and F#. It is also used to indicate variadic functions in the C, C++ and Java languages. See Ellipsis (programming operator).

HTML and CSS
The CSS text-overflow property can be set to ellipsis, which cuts off text with an ellipsis when it overflows the content area.

On Internet chat rooms and in text messaging
The ellipsis is a non-verbal cue that is often used in computer-mediated interactions, in particular in synchronous genres, such as chat. The reason behind its popularity is the fact that it allows people to indicate in writing several functions:

The sign of ellipsis can function as a floor holding device, and signal that more is to come, for instance when people break up longer turns in chat.
Dot-dot-dot can be used systematically to enact linguistic politeness, for instance indicating topic change or hesitation.
Suspension dots can be turn construction units to signal silence, for example when indicating disagreement, disapproval or confusion.Although an ellipsis is technically complete with three periods (...), its rise in popularity as a "trailing-off" or "silence" indicator, particularly in mid-20th-century comic strip and comic book prose writing, has led to expanded uses online. Today, extended ellipses anywhere from two to dozens of periods have become common constructions in Internet chat rooms and text messages </s>