<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Butorphanol and explain in detail? [/INST] Butorphanol is a morphinan-type synthetic agonist–antagonist opioid analgesic developed by Bristol-Myers. Butorphanol is most closely structurally related to levorphanol. Butorphanol is available as the tartrate salt in injectable, tablet, and intranasal spray formulations. The tablet form is only used in dogs, cats and horses due to low bioavailability in humans.
It was patented in 1971 and approved for medical use in 1979.

Medical uses
The most common indication for butorphanol is management of migraine using the intranasal spray formulation. It may also be used parenterally for management of moderate-to-severe pain, as a supplement for balanced general anesthesia, and management of pain during labor.  Butorphanol is also quite effective at reducing post-operative shivering (owing to its Kappa agonist activity). Butorphanol is more effective in reducing pain in women than in men.

Pharmacology
Butorphanol exhibits partial agonist and antagonist activity at the μ-opioid receptor, as well as partial agonist activity at the κ-opioid receptor (Ki = 2.5 nM; EC50 = 57 nM; Emax = 57%). Stimulation of these receptors on central nervous system neurons causes an intracellular inhibition of adenylate cyclase, closing of influx membrane calcium channels, and opening of membrane potassium channels. This leads to hyperpolarization of the cell membrane potential and suppression of action potential transmission of ascending pain pathways.
Because of its κ-agonist activity, at analgesic doses butorphanol increases pulmonary arterial pressure and cardiac work. Additionally, κ-agonism can cause dysphoria at therapeutic or supertherapeutic doses; this gives butorphanol a lower potential for abuse than other opioid drugs.

Side effects
As with other opioid analgesics, central nervous system effects (such as sedation, confusion, and dizziness) are considerations with butorphanol. Nausea and vomiting are common. Less common are the gastrointestinal effects of other opioids (mostly constipation).  Another side effect experienced by people taking the medication is increased perspiration.

Name
Within the INN, USAN, BAN, and AAN naming systems this drug is known as butorphanol, while within JAN it is named torbugesic. As the tartrate salt, butorphanol is known as butorphanol tartrate (USAN, BAN).Its tradename Stadol was recently discontinued by the manufacturer. It is now only available in its generic formulations manufactured by Apotex, Mylan, Novex and Ben Venue Laboratories.

Availability
Butorphanol is available in the U.S. as a generic drug; it is available in various nations under one of any number of trade names, including Moradol and Beforal (Brand name Stadol no longer available in the US); veterinary trade names include Butorphic, Dolorex, Morphasol, Torbugesic, and Torbutrol.

Legality
Butorphanol is listed under the Single Convention on Narcotic Drugs 1961 and in the United States is a Schedule IV Narcotic controlled substance with a DEA ACSCN of 9720; being in Schedule IV it is not subject to annual aggregate manufacturing quotas </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Digoxin immune fab and explain in detail? [/INST] Digoxin immune fab or digoxin-specific antibody is an antidote for overdose of digoxin. It is made from immunoglobulin fragments from sheep that have already been immunized with a digoxin derivative, digoxindicarboxymethoxylamine (DDMA). Its brand names include Digibind (GlaxoSmithKline) and DigiFab (BTG plc).

Medical uses
It is used for digoxin toxicity. Digoxin toxicity can emerge during long-term therapy as well as after an overdose. It can occur even when the serum digoxin concentration is within the therapeutic range when one of the following is present:
Hemodynamically unstable arrhythmia
End organ damage
digoxin level > 4 ng/ml if chronic ingestion
digoxin level > 10 ng/ml if acute ingestion
potassium > 5 mEq/L and symptomaticSide effects of digoxin immune fab may occur:

hives
difficult breathing
swelling of the lips, tongue, face, or throat
itching
skin redness
wheezing
cough
lightheadedness

Contraindications
Avoid use in hypokalemia as this drug, while reversing the effects of digitalis, will further reduce serum potassium levels and could precipitate dangerous and even fatal cardiac arrhythmias.
The patient must be closely monitored for anaphylactic shock, and anyone allergic to sheep protein, papain, bromelain, or papaya extracts (papain is used to cleave the antibody into Fab and Fc fragments) should not use ovine digoxin immune fab. Because it is relatively new, no drug interaction studies have been performed yet.

Pharmacology
It works by binding to the digoxin, rendering it unable to bind to its action sites on target cells. The complexes accumulate in the blood and are expelled by the kidney.

Regulatory information and clinical studies
Case series have reported benefits from anti‐digoxin Fab, but data regarding the response in acute or chronic poisoning are conflicting. Recent observational data support an effect in acute poisoning, but efficacy in chronic poisoning be minimally effective in alleviating cardiac toxicities in chronic digoxin poisoning.
Data also support outcomes of acute digoxin poisoning without use of anti‐digoxin Fab. A case series of 147 patients showed that not all cases of acute digoxin overdose require anti‐digoxin Fab, nor should anti‐digoxin Fab dose be calculated based on ingested dose. In contrast, a higher mortality (7.6%) was noted in a case series of acute and chronic digoxin and digitoxin poisoning despite Fab being used first line. Further, a retrospective case‐controlled study of chronic digoxin poisoning did not observe a beneficial effect of anti‐digoxin Fab on mortality.
An RCT (n = 66) in yellow oleander poisoning showed an early improvement in cardiac rhythm and hyperkalaemia from anti‐digoxin Fab, prompting early termination of the trial. It was not powered to detect a change in mortality and no deaths were noted.
As with all foreign proteins, anaphylaxis, serum sickness or febrile reactions are a source of concern, especially with repeated administration. These reactions appear uncommon for example, in a study of 717 adults where only six patients (0.8%) exhibited any evidence of allergic response.
Nevertheless, theoretically, patients previously dependent upon the inotropic effects of digoxin could develop heart failure and hypokalaemia could result within 1–5 hours, owing to intracellular shifts of potassium, as the effects of digoxin are reversed. Patients who require redigitalization must wait for the complexes to be eliminated from the body by the kidneys, this taking 2–3 days with normal renal function. Unfortunately, fab fragments interfere with both fluorescence excitation transfer immunoassays and radioimmunoassays for digoxin. This means that serum drug levels cannot be monitored until the drug-antibody complexes are cleared from the circulation.

Intellectual property
DigiFab is used as an antidote to treat a life-threatening overdose of digoxin or digitoxin. DigiFab is manufactured and distributed by BTG international Inc. under U.S. License No. 186. DigiFab is a sterile, lyophilized preparation of digoxin-immune ovine Fab (monovalent) immunoglobulin fragments. It is prepared by isolating the immunoglobulin fraction of the ovine serum, digesting it with papain and isolating the digoxin-specific Fab fragments by affinity chromatography </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Zinc sulfate and explain in detail? [/INST] Zinc sulfate is an inorganic compound. It is used as a dietary supplement to treat zinc deficiency and to prevent the condition in those at high risk. Side effects of excess supplementation may include abdominal pain, vomiting, headache, and tiredness.The most common form includes water of crystallization as the heptahydrate, with the formula ZnSO4·7H2O. It was historically known as "white vitriol". Zinc sulfate and its hydrates are colourless solids.

Uses
Medicine
In medicine it is used together with oral rehydration therapy (ORT) and an astringent.

Manufacturing
The hydrates, especially the heptahydrate, are the primary forms used commercially.  The main application is as a coagulant in the production of rayon.  It is also a precursor to the pigment lithopone.
It is also used as an electrolyte for zinc electroplating, as a mordant in dyeing, and as a preservative for skins and leather.

Other
Zinc sulfate is used to supply zinc in animal feeds, fertilizers, toothpaste, and agricultural sprays.  Zinc sulfate, like many zinc compounds, can be used to control moss growth on roofs.Zinc sulfate can be used to supplement zinc in the brewing process. Zinc is a necessary nutrient for optimal yeast health and performance, although it is not a necessary supplement for low-gravity beers, as the grains commonly used in brewing already provide adequate zinc. It is a more common practice when pushing yeast to their limit by increasing alcohol content beyond their comfort zone </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Tramadol and explain in detail? [/INST] Tramadol, sold under the brand name Ultram among others, is an opioid pain medication used to treat moderate to moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief usually begins within an hour. It is also available by injection. It is available in combination with paracetamol (acetaminophen).
As is typical of opioids, common side effects include constipation, itchiness, and nausea. Serious side effects may include hallucinations, seizures, increased risk of serotonin syndrome, decreased alertness, and drug addiction. A change in dosage may be recommended in those with kidney or liver problems. It is not recommended in those who are at risk of suicide or in those who are pregnant. While not recommended in women who are breastfeeding, those who take a single dose should not generally stop breastfeeding. Tramadol is converted in the liver to O-desmethyltramadol (desmetramadol), an opioid with a stronger affinity to the μ-opioid receptor. Tramadol is also a serotonin–norepinephrine reuptake inhibitor (SNRI).Tramadol was patented in 1963 and launched under the name "Tramal" in 1977 by the West German pharmaceutical company Grünenthal GmbH. In the mid-1990s, it was approved in the United Kingdom and the United States. It is available as a generic medication and marketed under many brand names worldwide. In 2020, it was the 35th most commonly prescribed medication in the United States, with more than 17 million prescriptions.

Medical uses
Tramadol (a schedule IV drug in the US) is used primarily to treat mild to severe pain, both acute and chronic. There is moderate evidence for use as a second-line treatment for fibromyalgia but it is not FDA approved for this use; however, its use is approved for treatment of fibromyalgia as a secondary painkiller by the NHS.Its analgesic effects take about one hour to come into effect and 2 to 4 h to peak after oral administration with an immediate-release formulation. On a dose-by-dose basis, tramadol has about one-tenth the potency of morphine (thus 100 mg is commensurate with 10 mg morphine but may vary) and is practically equally potent when compared with pethidine and codeine. For pain moderate in severity, its effectiveness is equivalent to that of codeine at low doses, and hydrocodone at very high doses; for severe pain it is less effective than morphine.These painkilling effects last about 6 h. The potency of analgesia varies considerably as it depends on an individuals genetics. People with specific variants of CYP2D6 enzymes may not produce adequate amounts of the active metabolite (desmetramadol) for effective pain control.Sleep medicine physicians sometimes prescribe tramadol (or other opiate medications) for refractory restless legs syndrome (RLS); that is, RLS that does not respond adequately to treatment with first-line medications such as dopamine agonists (like pramipexole) or alpha-2-delta (α2δ) ligands (gabapentinoids), often due to augmentation.

Contraindications
Tramadol may not provide adequate pain control for individuals with certain genetic variants of CYP2D6 enzymes as they metabolize tramadol to the inactive molecule. These genetic polymorphisms are not currently routinely tested for in clinical practice.

Pregnancy and lactation
Tramadols use in pregnancy is generally avoided, as it may cause some reversible withdrawal effects in the newborn. A small prospective study in France found, while an increased risk of miscarriages existed, no major malformations were reported in the newborn. Its use during lactation is also generally advised against, but a small trial found that infants breastfed by mothers taking tramadol were exposed to about 2.88% of the dose the mothers were taking. No evidence of this dose harming the newborn was seen.

Labor and delivery
Its use as an analgesic during labor is not advised due to its long onset of action (1 hour). The ratio of the mean concentration of the drug in the fetus compared to that of the mother when it is given intramuscularly for labor pains has been estimated to be 1:94.

Children
Its use in children is generally advised against, although it may be done under the supervision of a specialist. On 21 September 2015, the FDA started investigating the safety of tramadol in use in persons under the age of 17. The investigation was initiated because some of these people have experienced slowed or difficult breathing. The FDA lists age under 12 years old as a contraindication.

Elderly
The risk of opioid-related adverse effects such as respiratory depression, falls, cognitive impairment and sedation is increased. Tramadol may interact with other medications and increase the risk for adverse events.

Liver and kidney failure
The drug should be used with caution in those with liver or kidney failure, due to metabolism in the liver (to the active molecule desmetramadol) and elimination by the kidneys.

Side effects
The most common adverse effects of tramadol include nausea, dizziness, dry mouth, indigestion, abdominal pain, vertigo, vomiting, constipation, drowsiness, and headache. Other side effects may result from interactions with other medications. Tramadol has the same dose-dependent adverse effects as morphine including respiratory depression.

Dependence and withdrawal
Long-term use of high doses of tramadol causes physical dependence and withdrawal syndrome. These include both symptoms typical of opioid withdrawal and those associated with serotonin–norepinephrine reuptake inhibitor (SNRI) withdrawal; symptoms include numbness, tingling, paresthesia, and tinnitus.  Psychiatric symptoms may include hallucinations, paranoia, extreme anxiety, panic attacks, and confusion. In most cases, tramadol withdrawal will set in 12–20 hours after the last dose, but this can vary. Tramadol withdrawal typically lasts longer than that of other opioids. Seven days or more of acute withdrawal symptoms can occur as opposed to typically 3 or 4 days for other codeine analogues.

Overdose
Recognised risk factors for tramadol overdose include respiratory depression, addiction, and seizures. Naloxone only partially reverses the toxic effects of tramadol overdose and may increase the risk of seizures.Deaths with tramadol overdose have been reported and are increasing in frequency in Northern Ireland; the majority of these overdoses involve other drugs including alcohol. There were 254 tramadol-related deaths in England and Wales in 2013, and 379 in Florida in 2011. In 2011, 21,649 emergency room visits in the United States were related to tramadol.

Interactions
Tramadol can interact with other medications with similar mechanisms of action.
Tramadol acts as a serotonin-norephinephrine reuptake inhibitor and thus can interact with other serotonergic medications (selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, tricyclic antidepressants, triptans, cough and cold medications containing dextromethorphan, herbal products containing St. John’s wort, and medications that inhibit the metabolism of serotonin, such as monoamine oxidase inhibitors) and, in combination, may lead to serotonin syndrome. It may also make some  serotonergic antagonist anti-emetic medications (ondansetron) less effective.Tramadol also acts as an opioid agonist and thus can increase the risk for side effects when used with other opioid analgesics (such as morphine, pethidine, tapentadol, oxycodone, and fentanyl).Tramadol is metabolized by CYP2D6 enzymes which contribute to the metabolism of approximately 25% of all medications. Any medications with the ability to inhibit or induce these enzymes may interact with tramadol.Tramadol increases the risk for seizures by lowering the seizure threshold. Using other medications that lower seizure threshold (such as antipsychotic medications or amphetamines), further increases this risk.

Pharmacology
Mechanism of action
Tramadol induces analgesic effects through a variety of different targets on the noradrenergic system, serotoninergic system and opioid receptors system. Tramadol exists as a racemic mixture, the positive enantiomer inhibits serotonin reuptake while the negative enantiomer inhibits noradrenaline re-uptake, by binding to and blocking the transporters. Tramadol has also been shown to act as a serotonin releasing agent. Both enantiomers of tramadol are agonists of the μ-opioid receptor and its M1 metabolite, O-desmetramadol, is also a μ-opioid receptor agonist but is 6 times more potent than tramadol itself. All these effects work synergistically to induce analgesia.

Tramadol has been found to possess these actions:
Agonist of the μ-opioid receptor (MOR) and to a far lesser extent of the δ-opioid receptor (DOR) and κ-opioid receptor (KOR)
Serotonin reuptake inhibitor (SRI) and norepinephrine reuptake inhibitor; hence, an SNRI
Serotonin 5-HT2C receptor antagonist
M1 and M3 muscarinic acetylcholine receptor antagonist
α7 nicotinic acetylcholine receptor antagonist
NMDA receptor antagonist (very weak)
TRPA1 inhibitorTramadol acts on the opioid receptors through its major active metabolite desmetramadol, which has as much as 700-fold higher affinity for the MOR relative to tramadol. Moreover, tramadol itself has been found to possess no efficacy in activating the MOR in functional activity assays, whereas desmetramadol activates the receptor with high intrinsic activity (Emax equal to that of morphine). As such, desmetramadol is exclusively responsible for the opioid effects of tramadol. Both tramadol and desmetramadol have pronounced selectivity for the MOR over the DOR and KOR in terms of binding affinity.Tramadol is well-established as an SRI. In addition, a few studies have found that it also acts as a serotonin releasing agent (1–10 μM), similar in effect to fenfluramine. The serotonin releasing effects of tramadol could be blocked by sufficiently high concentrations of the serotonin reuptake inhibitor 6-nitroquipazine, which is in accordance with other serotonin releasing agents such as fenfluramine and MDMA. However, two more recent studies failed to find a releasing effect of tramadol at respective concentrations up to 10 and 30 μM. In addition to serotonergic activity, tramadol is also a norepinephrine reuptake inhibitor. It is not a norepinephrine releasing agent. Tramadol does not inhibit the reuptake or induce the release of dopamine.A positron emission tomography imaging study found that single oral 50-mg and 100-mg doses of tramadol to human volunteers resulted in 34.7% and 50.2% respective mean occupation of the serotonin transporter (SERT) in the thalamus. The estimated median effective dose (ED50) for SERT occupancy hence was 98.1 mg, which was associated with a plasma tramadol level of about 330 ng/ml (1,300 nM). The estimated maximum daily dosage of tramadol of 400 mg (100 mg q.i.d.) would result in as much as 78.7% occupancy of the SERT (in association with a plasma concentration of 1,220 ng/ml or 4,632 nM). This is close to that of SSRIs, which occupy the SERT by 80% or more.Peak plasma concentrations during treatment with clinical dosages of tramadol have generally been found to be in the range of 70 to 592 ng/ml (266–2,250 nM) for tramadol and 55 to 143 ng/ml (221–573 nM) for desmetramadol. The highest levels of tramadol were observed with the maximum oral daily dosage of 400 mg per day divided into one 100-mg dose every 6 hours (i.e., four 100-mg doses evenly spaced out per day). Some accumulation of tramadol occurs with chronic administration; peak plasma levels with the maximum oral daily dosage (100 mg q.i.d.) are about 16% higher and the area-under-the-curve levels 36% higher than following a single oral 100-mg dose. Positron emission tomography imaging studies have reportedly found that tramadol levels are at least four-fold higher in the brain than in plasma. Conversely, brain levels of desmetramadol "only slowly approach those in plasma". The plasma protein binding of tramadol is only 4 to 20%; hence, almost all tramadol in circulation is free, thus bioactive.

Correspondence to effects
Co-administration of quinidine, a potent CYP2D6 enzyme inhibitor, with tramadol, a combination which results in markedly reduced levels of desmetramadol, was found not to significantly affect the analgesic effects of tramadol in human volunteers. However, other studies have found that the analgesic effects of tramadol are significantly decreased or even absent in CYP2D6 poor metabolizers. The analgesic effects of tramadol are only partially reversed by naloxone in human volunteers, hence indicating that its opioid action is unlikely the sole factor; tramadols analgesic effects are also partially reversed by α2-adrenergic receptor antagonists such as yohimbine, the 5-HT3 receptor antagonist ondansetron, and the 5-HT7 receptor antagonists SB-269970 and SB-258719. Pharmacologically, tramadol is similar to tapentadol and methadone in that it not only binds to the MOR, but also inhibits the reuptake of serotonin and norepinephrine due to its action on the noradrenergic and serotonergic systems, such as its "atypical" opioid activity.Tramadol has inhibitory actions on the 5-HT2C receptor. Antagonism of 5-HT2C could be partially responsible for tramadols reducing effect on depressive and obsessive–compulsive symptoms in patients with pain and co-morbid neurological illnesses. 5-HT2C blockade may also account for its lowering of the seizure threshold, as 5-HT2C knockout mice display significantly increased vulnerability to epileptic seizures, sometimes resulting in spontaneous death. However, the reduction of seizure threshold could be attributed to tramadols putative inhibition of GABAA receptors at high doses (significant inhibition at 100 μM). In addition, desmetramadol is a high-affinity ligand of the DOR, and activation of this receptor could be involved in tramadols ability to provoke seizures in some individuals, as DOR agonists are well known for inducing seizures.Nausea and vomiting caused by tramadol are thought to be due to activation of the 5-HT3 receptor via increased serotonin levels. In accordance, the 5-HT3 receptor antagonist ondansetron can be used to treat tramadol-associated nausea and vomiting. Tramadol and desmetramadol themselves do not bind to the 5-HT3 receptor.

Pharmacokinetics
Tramadol undergoes hepatic metabolism via the cytochrome P450 isozyme CYP2B6, CYP2D6, and CYP3A4, being O- and N-demethylated to five different metabolites. Of these, desmetramadol (O-desmethyltramadol) is the most significant, since it has 200 times the μ-affinity of (+)-tramadol, and furthermore has an elimination half-life of 9 hours, compared with 6 hours for tramadol itself. As with codeine, in the 6% of the population who have reduced CYP2D6 activity (hence reducing metabolism), a reduced analgesic effect is seen. Those with decreased CYP2D6 activity require a dose increase of 30% to achieve the same degree of pain relief as those with a normal level of CYP2D6 activity.Phase II hepatic metabolism renders the metabolites water-soluble, which are excreted by the kidneys. Thus, reduced doses may be used in renal and hepatic impairment.Its volume of distribution is around 306 L after oral administration and 203 L after parenteral administration.

Chemistry
Tramadol is marketed as a racemic mixture of both R- and S-stereoisomers, because the two isomers complement each others analgesic activities.  The (+)-isomer is predominantly active as an opiate with a higher affinity for the µ-opiate receptor (20 times higher affinity than the (-)-isomer).

Synthesis and stereoisomerism
The chemical synthesis of tramadol is described in the literature. Tramadol [2-(dimethylaminomethyl)-1-(3-methoxyphenyl)cyclohexanol] has two stereogenic centers at the cyclohexane ring. Thus, 2-(dimethylaminomethyl)-1-(3-methoxyphenyl)cyclohexanol may exist in four different configurational forms:

(1R,2R)-isomer
(1S,2S)-isomer
(1R,2S)-isomer
(1S,2R)-isomerThe synthetic pathway leads to the racemate (1:1 mixture) of (1R,2R)-isomer and the (1S,2S)-isomer as the main products. Minor amounts of the racemic mixture of the (1R,2S)-isomer and the (1S,2R)-isomer are formed as well. The isolation of the (1R,2R)-isomer and the (1S,2S)-isomer from the diastereomeric minor racemate [(1R,2S)-isomer and (1S,2R)-isomer] is realized by the recrystallization of the hydrochlorides.
The drug tramadol is a racemate of the hydrochlorides of the (1R,2R)-(+)- and the (1S,2S)-(−)-enantiomers.
The resolution of the racemate [(1R,2R)-(+)-isomer / (1S,2S)-(−)-isomer] was described employing (R)-(−)- or (S)-(+)-mandelic acid. This process does not find industrial application, since tramadol is used as a racemate, despite known different physiological effects of the (1R,2R)- and (1S,2S)-isomers, because the racemate showed higher analgesic activity than either enantiomer in animals and in humans.

Detection in biological fluids
Tramadol and desmetramadol may be quantified in blood, plasma, serum, or saliva to monitor for abuse, confirm a diagnosis of poisoning or assist in the forensic investigation of a sudden death. Most commercial opiate immunoassay screening tests do not cross-react significantly with tramadol or its major metabolites, so chromatographic techniques must be used to detect and quantitate these substances. The concentration of desmetramadol in the blood or plasma of a person who has taken tramadol is generally 10–20% those of the parent drug.

Society and culture
Formulations
Available dosage forms include liquids, syrups, drops, elixirs, effervescent tablets and powders for mixing with water, capsules, tablets including extended-release formulations, suppositories, compounding powder, and injections.

Patent history
The U.S. Food and Drug Administration (FDA) approved tramadol in March 1995, and an extended-release (ER) formulation in September 2005. ER Tramadol was protected by US patents nos. 6,254,887 and 7,074,430. The FDA listed the patents expiration as 10 May 2014. However, in August 2009, US District Court for the District of Delaware ruled the patents invalid, a decision upheld the following year by the Court of Appeals for the Federal Circuit. Manufacture and distribution of generic equivalents of Ultram ER in the United States was therefore permitted prior to the expiration of the patents.

Legal status
Effective 18 August 2014, tramadol has been placed into Schedule IV of the federal Controlled Substances Act in the United States. Before that, some US states had already classified tramadol as a Schedule IV controlled substance under their respective state laws.Tramadol is classified in Schedule 4 (prescription only) in Australia, rather than as a Schedule 8 Controlled Drug (Possession without authority illegal) like most other opioids.Effective May 2008, Sweden classified tramadol as a controlled substance in the same category as codeine and dextropropoxyphene, but allows a normal prescription to be used.The UK classified tramadol as a Class C, Schedule 3 controlled drug on 10 June 2014, but exempted it from the safe custody requirement.

Misuse
Illicit use of the drug is thought to be a major factor in the success of the Boko Haram terrorist organization. When used at higher doses, the drug "can produce similar effects to heroin." Said one former member, "whenever we took tramadol, nothing mattered to us anymore except what we were sent to do because it made us very high and very bold, it was impossible to go on a mission without taking it." Tramadol is also used as a coping mechanism in the Gaza Strip. It is also abused in the United Kingdom, inspiring the title of the TV show Frankie Boyles Tramadol Nights (2010).From March 2019, the Union Cycliste Internationale (UCI) banned the drug, after riders were using the painkiller to improve their performance.

Research
Investigational uses
Diabetic neuropathy
Antidepressant
Postherpetic neuralgia
Premature ejaculation
Adjunct to local anaesthesia

False findings about sources in nature
In 2013, researchers reported that tramadol was found in relatively high concentrations (1%+) in the roots of the African pin cushion tree (Nauclea latifolia). In 2014, however, it was reported that the presence of tramadol in the tree roots was the result of tramadol having been administered to cattle by farmers in the region: tramadol and its metabolites were present in the animals excreta, which contaminated the soil around the trees. Therefore, tramadol and its mammalian metabolites were found in tree roots in the far north of Cameroon, but not in the south where it is not administered to farm animals.A 2014 editorial in Lab Times online contested the notion that tramadol in tree roots was the result of anthropogenic contamination, stating that samples were taken from trees that grew in national parks, where livestock were forbidden; it also quoted researcher Michel de Waard, who stated that "thousands and thousands of tramadol-treated cattle sitting around a single tree and urinating there" would be required to produce the concentrations discovered.In 2015, radiocarbon analysis confirmed that the tramadol found in N.latifolia roots could not be plant-derived and was of synthetic origin.

Veterinary medicine
Tramadol may be used to treat post-operative, injury-related, and chronic (e.g., cancer-related) pain in dogs and cats as well as rabbits, coatis, many small mammals including rats and flying squirrels, guinea pigs, ferrets, and raccoons.

See also
Tramadol/paracetamol

References
Further reading
Dean L (2015). "Tramadol Therapy and CYP2D6 Genotype".  In Pratt VM, McLeod HL, Rubinstein WS,  et al. (eds.) </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Lidocaine/prilocaine and explain in detail? [/INST] Lidocaine/prilocaine is a eutectic mixture of equal quantities (by weight) of lidocaine and prilocaine. A 5% emulsion preparation, containing 2.5% each of lidocaine/prilocaine, is marketed by APP Pharmaceuticals under the trade name EMLA (an abbreviation for Eutectic Mixture of Local Anesthetics). As a spray, it is marketed under the name Tempe (topical eutectic-like mixture for premature ejaculation) (PSD502) that can be used by men to help with premature ejaculation. The spray is manufactured by Plethora Solutions and branded as Fortacin in the UK and Recordati in the EU.

Eutectic mixture
Separately, lidocaine and prilocaine are solid bases. When mixed in equal quantities by weight, however, they form a eutectic mixture – that is the melting point of the mixture is lower than the melting points of the individual components. The lidocaine/prilocaine eutectic mixture is an oil with a melting point of 18 °C, and can be formulated into preparations without the use of a non-aqueous solvent. This allows higher concentrations of anaesthetic to be formulated into the preparation and maintained during application.

Clinical use
Indications
The lidocaine/prilocaine combination is indicated for dermal anaesthesia. Specifically it is applied to prevent pain associated with intravenous catheter insertion, blood sampling, superficial surgical procedures, and topical anaesthesia of leg ulcers for cleansing or debridement. Also, it can be used to numb the skin before tattooing as well as electrolysis and laser hair removal. It is also sometimes used in advance of injected local anaesthetics for minor surgery and biopsies.
A topical spray consisting of an aerosol formulation of lidocaine and prilocaine was evaluated under the name PSD502 for use in treating premature ejaculation. The spray is applied on the penile skin prior to intercourse. While this formulation was not approved by the FDA, a similar product, Promescent, is available over-the-counter in the U.S.

Dosage forms
Lidocaine/prilocaine eutectic mixture is marketed as a 5% oil-in-water emulsion incorporated in a cream base (EMLA cream) or  a cellulose disk (EMLA patch). The cream is applied under an occlusive dressing, while the patch incorporates an occlusive dressing to facilitate absorption of lidocaine and prilocaine into the area where anaesthesia is required. Local dermal anaesthesia is achieved after approximately 60 minutes, whereupon the occlusive dressing (or patch) is removed. The duration of anaesthesia is approximately two hours following removal of the occlusive dressing.
E. Fougera & Co., makers of the generic cream widely used in the United States as Lidocaine and Prilocaine Cream, 2.5%/2.5%, recommends different timing for application of the cream as well as length of anesthesia </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Dimenhydrinate and explain in detail? [/INST] Dimenhydrinate, sold under the brand name Dramamine, among others, is an over-the-counter drug used to treat motion sickness and nausea. Dimenhydrinate is a theoclate salt composed of diphenhydramine, an ethanolamine derivative, and 8-chlorotheophylline, a chlorinated theophylline derivative, in a 1∶1 ratio.

Medical uses
Nausea
Dimenhydrinate is an over-the-counter (OTC) antihistamine indicated for the prevention and relief of nausea and vomiting from a number of causes. It is an H1 receptor antagonist that demonstrates anticholinergic activity.

Medicinal chemistry
Diphenhydramine is the primary constituent of dimenhydrinate and dictates the primary effect. The main difference relative to pure diphenhydramine is a lower potency due to being combined with 8-chlorotheophylline. By weight, dimenhydrinate is between 53% to 55.5% diphenhydramine.

Side effects
Common side effects may include:
Drowsiness
Dry mouth, nose, or throat
Constipation
Blurred vision
Feeling restless or excited (especially in children)

Recreational use
Dimenhydrinate is recreationally used as a deliriant. Slang terms for Dramamine used this way include "drama", "dime", "dime tabs", "D-Q", "substance D", "d-house", and "drams". Abusing Dramamine is sometimes referred to as Dramatizing or "going a dime a dozen", a reference to the amount of Dramamine tablets generally necessary for a trip.Many users report a side-effect profile consistent with tropane alkaloid (e.g. atropine) poisoning as both show antagonism of muscarinic acetylcholine receptors in both the central and autonomic nervous system, which inhibits various signal transduction pathways.Other CNS effects occur within the limbic system and hippocampus, causing confusion and temporary amnesia due to decreased acetylcholine signaling. Toxicology also manifests in the autonomic nervous system, primarily at the neuromuscular junction, resulting in ataxia and extrapyramidal side effects and the feeling of heaviness in the legs, and at sympathetic post-ganglionic junctions, causing urinary retention, pupil dilation, tachycardia, irregular urination, and dry red skin caused by decreased exocrine gland secretions, and mucous membranes </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Cenegermin and explain in detail? [/INST] Cenegermin, sold under the brand name Oxervate, also known as recombinant human nerve growth factor (rhNGF), is a recombinant form of human nerve growth factor (NGF). In July 2017, it was approved in the European Union as an eye drop formulation for the treatment of moderate or severe neurotrophic keratitis in adults.As a recombinant form of NGF, cenegermin is a peripherally selective agonist of the TrkA and LNGFR (p75NTR) which must be administered parenterally.The U.S </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Rho(D) immune globulin and explain in detail? [/INST] Rho(D) immune globulin (RhIG) is a medication used to prevent RhD isoimmunization in mothers who are RhD negative and to treat idiopathic thrombocytopenic purpura (ITP) in people who are Rh positive. It is often given both during and following pregnancy. It may also be used when RhD-negative people are given RhD-positive blood. It is given by injection into muscle or a vein. A single dose lasts 12 weeks.Common side effects include fever, headache, pain at the site of injection, and red blood cell breakdown. Other side effects include allergic reactions, kidney problems, and a very small risk of viral infections. In those with ITP, the amount of red blood cell breakdown may be significant. Use is safe with breastfeeding. Rho(D) immune globulin is made up of antibodies to the antigen Rho(D) present on some red blood cells. It is believed to work by blocking a persons immune system from recognizing this antigen.Rho(D) immune globulin came into medical use in the 1960s. It is on the World Health Organizations List of Essential Medicines. It is made from human blood plasma.

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

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

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

Contraindications
The following females are not candidates for RhIG:

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

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

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

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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Chlormethine and explain in detail? [/INST] Chlormethine (INN, BAN), also known as mechlorethamine (USAN, USP), mustine, HN2, and (in post-Soviet states) embikhin (эмбихин), is a nitrogen mustard sold under the brand name Mustargen among others. It is the prototype of alkylating agents, a group of anticancer chemotherapeutic drugs. It works by binding to DNA, crosslinking two strands and preventing cell duplication. It binds to the N7 nitrogen on the DNA base guanine. As the chemical is a blister agent, its use is strongly restricted within the Chemical Weapons Convention where it is classified as a Schedule 1 substance.
Mechlorethamine belongs to the group of nitrogen mustard alkylating agents.

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

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

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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Risperidone and explain in detail? [/INST] Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It is taken either by mouth or by injection (subcutaneous or intramuscular). The injectable versions are long-acting and last for 2–4 weeks.Common side effects include movement problems, sleepiness, dizziness, trouble seeing, constipation, and increased weight. Serious side effects may include the potentially permanent movement disorder tardive dyskinesia, as well as neuroleptic malignant syndrome, an increased risk of suicide, and high blood sugar levels. In older people with psychosis as a result of dementia, it may increase the risk of death. It is unknown if it is safe for use in pregnancy. Its mechanism of action is not entirely clear, but is believed to be related to its action as a dopamine and serotonin antagonist.Study of risperidone began in the late 1980s and it was approved for sale in the United States in 1993. It is on the World Health Organizations List of Essential Medicines. It is available as a generic medication.  In 2019, it was the 149th most commonly prescribed medication in the United States, with more than 4 million prescriptions.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Hydrocortisone and explain in detail? [/INST] Hydrocortisone is the name for the hormone cortisol when supplied as a medication. Uses include conditions such as adrenocortical insufficiency, adrenogenital syndrome, high blood calcium, thyroiditis, rheumatoid arthritis, dermatitis, asthma, and COPD. It is the treatment of choice for adrenocortical insufficiency. It can be given by mouth, topically, or by injection. Stopping treatment after long-term use should be done slowly.Side effects may include mood changes, increased risk of infection, and edema (swelling). With long-term use common side effects include osteoporosis, upset stomach, physical weakness, easy bruising, and candidiasis (yeast infections). While used, it is unclear if it is safe during pregnancy. Hydrocortisone is a glucocorticoid and works as an anti-inflammatory and by immune suppression.Hydrocortisone was patented in 1936 and approved for medical use in 1941. It is on the World Health Organizations List of Essential Medicines. It is available as a generic medication. In 2019, it was the 147th most commonly prescribed medication in the United States, with more than 4 million prescriptions.

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

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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Minocycline and explain in detail? [/INST] Minocycline, sold under the brand name Minocin among others, is a tetracycline antibiotic medication used to treat a number of bacterial infections such as pneumonia. It is generally less preferred than the tetracycline doxycycline. It is also used for the treatment of acne and rheumatoid arthritis. It is taken by mouth or applied to the skin.Common side effects include nausea, diarrhea, dizziness, allergic reactions, and kidney problems. Serious side effects may include anaphylaxis, a lupus-like syndrome, and easy sunburning. Use in the later part of pregnancy may harm the baby and safety during breastfeeding is unclear. It works by decreasing a bacteriums ability to make protein thus stopping its growth.Minocycline was patented in 1961 and came into commercial use in 1971. It is available as a generic medication. In 2017, it was the 237th most commonly prescribed medication in the United States, with more than two million prescriptions.

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

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

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

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

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

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

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

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

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

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

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

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

Society and culture
It is available as a generic medication.

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


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Rasburicase and explain in detail? [/INST] Rasburicase (trade names Elitek in the US and Fasturtec in the EU) is a medication that helps to clear uric acid from the blood. It is a recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin. Urate oxidase is known to be present in many mammals but does not naturally occur in humans. Rasburicase is produced by a genetically modified Saccharomyces cerevisiae strain. The complementary DNA (cDNA) coding for rasburicase was cloned from a strain of Aspergillus flavus.Rasburicase (Q00511) is a tetrameric protein with identical subunits. Each subunit is made up of a single 301 amino acid polypeptide chain with a molecular mass of about 34 kDa. The drug product is a sterile, white to off-white, lyophilized powder intended for intravenous administration following reconstitution with a diluent. Elitek (rasburicase) is supplied in 3 mL and 10 mL colorless, glass vials containing rasburicase at a concentration of 1.5 mg/mL after reconstitution.It is on the World Health Organizations List of Essential Medicines.

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

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

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

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

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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Benzphetamine and explain in detail? [/INST] Benzphetamine (brand name Didrex) is a substituted amphetamine used short-term along with a doctor-approved, reduced-calorie diet, exercise, and behavioral program for weight loss. It is prescribed for obesity to people who have been unable to lose weight through exercise and dieting alone. It is a prodrug to dextroamphetamine and dextromethamphetamine.Benzphetamine is an anorectic, primarily promoting weight loss through reduced appetite. It also slightly increases metabolism.

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