<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Albendazole and can you explain it in depth? [/INST] Albendazole, also known as albendazolum, is a medication used for the treatment of a variety of parasitic worm infestations. It is useful for giardiasis, trichuriasis, filariasis, neurocysticercosis, hydatid disease, pinworm disease, and ascariasis, among other diseases. It is taken orally.Common side effects include nausea, abdominal pains, and headaches. Potentially serious side effects include bone marrow suppression which usually improves on stopping the medication. Liver inflammation has been reported and those with prior liver problems are at greater risk. It is pregnancy category C in the United States and category D in Australia, meaning it may cause harm if taken by pregnant women. Albendazole is a broad-spectrum antihelminthic agent of the benzimidazole type.Albendazole was developed in 1975. It is on the World Health Organizations List of Essential Medicines.

Medical uses
Albendazole is an effective treatment for:

Flatworms
Fasciolosis
Cestodes (tapeworms), as an alternative to praziquantel or niclosamide for adult beef tapeworms (Taenia saginata) and as an alternative to praziquantel for pork tapeworms (T. solium). It is also given for infections by T. crassiceps. Though praziquantel is often better at treating tapeworm infections, albendazole is used more often in endemic countries due to being cheaper and having a broader spectrum.Cysticercosis (especially neurocysticercosis), which is caused by the larval form of the pork tapeworm (i.e. albendazole is the drug of choice for larval pork tapeworms, but not adult pork tapeworms). Old cysts are not affected.
Hydatid disease (aka echinococcosis) of the liver, lung, and peritoneum (caused by the larval form of the dog tapeworm, Echinococcus granulosus) or of the alveoli (caused by E. multilocularis) when surgical excision is not possible. Some suggest that alveolar and cystic echinococcosis require lifelong treatment with albendazole, which only prevents the parasites from growing and reproducing rather than killing them outright.
Nematodes
Ascariasis, which can be cured with a single dose of albendazole.
Baylisascariasis, caused by the raccoon roundworm.  If treatment with Albendazole is initiated within 72 hours of ingestion of the egg-containing raccoon feces, good results (95%-100% efficacy, with Albendazole being orally administered for a 10-day period) can be expected.  Corticosteroids are sometimes added in cases of eye and CNS infections.
Enterobiasis (pinworm infection)
Filariasis; since albendazoles disintegration of the microfilarie ("pre-larva") can cause an allergic reaction, antihistamines or corticosteroids are sometimes added to treatment. In cases of lymphatic filariasis (elephantiasis) caused by Wuchereria bancrofti or Brugia malayi, albendazole is sometimes given as an adjunct to ivermectin or diethylcarbamazine in order to suppress microfilaremia. It can also be given for loa loa filariasis as an adjunct or replacement to diethylcarbamazine. Albendazole has an embryotoxic effect on Loa loa adults and thus slowly reduces microfilaremia.
Gnathostomiasis when caused by Gnathostoma spinigerum. Albendazole has a similar effectiveness to ivermectin in these cases, though it needs to be given for 21 days rather than the 2 days needed for ivermectin.
Gongylonemiasis
Hookworm infections, including cutaneous larva migrans caused by hookworms in the genus Ancylostoma. A single dose of albendazole is sufficient to treat intestinal infestations by A. duodenale or Necator americanus
Intestinal capillariasis, as an alternative to mebendazole
Mansonelliasis when caused by Mansonella perstans. Albendazole works against the adult worms but not against the younger microfilariae.
Oesophagostomumiasis, when caused by Oesophagostomum bifurcum
Strongyloidiasis, as an alternative to ivermectin or thiabendazole Albendazole can be given with diethylcarbamazine to lower microfilaremia levels.
Toxocariasis, also called "visceral larva migrans", when caused by the dog roundworm Toxocara canis or cat roundworm T. catis. Corticosteroids can be added in severe cases, and surgery might be required to repair secondary damage.
Trichinosis, when caused by Trichinella spiralis or T. pseudospiralis. Albendazole has a similar efficacy to thiabendazole, but fewer side effects. It works best when given early, acting on the adult worms in the intestine before they generate larva that can penetrate the muscle and cause a more widespread infection. Corticosteroids are sometimes added on to prevent inflammation caused by dying larva.
Trichostrongyliasis, as an alternative to pyrantel pamoate. A single dose is sufficient for treatment.
Trichuriasis (whipworm infection), sometimes considered as an alternative to mebendazole and sometimes considered to be the drug of choice. Only a single dose of albendazole is needed. It can also be given with ivermectin.
Giardiasis, as an alternative or adjunct to metronidazole, especially in children
Microsporidiosis, including ocular microsporidiosis caused by Encephalitozoon hellem or E. cuniculi, when combined with topical fumagillin
Granulomatous amoebic encephalitis, when caused by the ameba Balamuthia mandrillaris, in combination with miltefosine and fluconazole
Arthropods
Crusted scabies, when combined with topical crotamiton and salicylic acid
Head lice infestation, though ivermectin is much better
Intestinal myiasisThough albendazole is effective in treating many diseases, it is only FDA-approved for treating hydatid disease caused by dog tapeworm larvae and neurocysticercosis caused by pork tapeworm larvae.

Pregnancy
Albendazole is a pregnancy class D drug in Australia and pregnancy class C in the United States. It is contraindicated in the first trimester of pregnancy, and should be avoided up to one month before conception. While studies in pregnant rats and rabbits have shown albendazole to be teratogenic, albendazole has been found to be safe in humans during the second and third trimesters. It can, however, possibly cause infantile eczema when given during pregnancy.In pregnant dogs, albendazole use has led to puppies with reduced weight and with cleft palates. Birds have lower rates of laying eggs and hatching when given albendazole.Albendazole sulfoxide is secreted into breast milk at around 1.5% of the maternal dose, though oral absorption is poor enough that it is unlikely to affect nursing infants.

Contraindications
Hypersensitivity to the benzimidazole class of compounds contraindicates its use.

Side effects
The most common side effects by albendazole are experienced by over 10% of people and include headache and abnormal liver function. Elevation of liver enzymes occur in 16% of patients receiving treatment specifically for hydatid disease and goes away when treatment ends. Liver enzymes usually increase to two to four times the normal levels (a mild to moderate increase). An estimated 1–10% of people experience abdominal pain, nausea or vomiting, dizziness or vertigo, increased intracranial pressure, meningeal signs, temporary hair loss, and fever. The headache, nausea, and vomiting are thought to be caused by the sudden destruction of cysticerci (tapeworm larvae), which causes acute inflammation. Fewer than 1% of people get hypersensitivity reactions such as rashes and hives, leukopenias (drop in white blood cell levels) such as agranulocytosis and granulocytopenia, thrombocytopenia (reduced platelet count), pancytopenia (drop in white blood cells, red blood cells, and platelets), hepatitis, acute liver failure, acute kidney injury, irreversible bone marrow suppression, and aplastic anemia.Side effects can be different when treating for hydatid disease versus neurocysticercosis: for example, those being treated for the former are more likely to experience elevated liver enzymes and abdominal pain, while those being treated for the latter are more likely to experience headache. Treating hydatid disease can also unmask undiagnosed neurocysticercosis. People receiving albendazole for the treatment of neurocysticercosis can have neurological side effects such as seizures, increased intracranial pressure, and focal signs caused by the inflammatory reaction that occurs when parasites in the brain are killed. Steroids and anticonvulsants are often given with albendazole when treating neurocysticercosis to avoid these effects. Those being treated for retinal neurocysticercosis can face retinal damage if they are not first checked for ocular cysticeri, since changes to existing lesions in the eye by albendazole can cause permanent blindness.

Overdose
Because of its low solubility, albendazole often cannot be absorbed in high enough quantities to be toxic. The oral LD50 of albendazole in rats was found to be 2,500 mg/kg. It takes 20 times the normal dose to kill a sheep, and 30 times the normal dose to kill cattle. Overdose affects the liver, testicles, and GI tract the most. It can manifest with lethargy, loss of appetite, vomiting, diarrhea, intestinal cramps, dizziness, convulsions, and sleepiness. There is no specified antidote.

Interactions
The antiepileptics carbamazepine, phenytoin, and phenobarbital lower the plasma concentration and the half life of albendazole sulfoxides R(+) enantiomer.
The antacid cimetidine heightens serum albendazole concentrations, increases the half life of albendazole, and doubles albendazole sulfoxide levels in bile. It was originally thought to work by increasing albendazole bioavailability directly; however, it is now known that cimetidine inhibits the breakdown of albendazole sulfoxide by interfering with CYP3A4. The half-life of albendazole sulfoxide thus increases from 7.4 hours to 19 hours. This might be a helpful interaction on more severe cases, because it boosts the potency of albendazole. Paradoxically, cimetidine also inhibits the absorption of albendazole by reducing gastric acidity.Several other interactions exist. Corticosteroids increase the steady-state plasma concentration of albendazole sulfoxide; dexamethasone, for example, can increase the concentration by 56% by inhibiting the elimination of albendazole sulfoxide. The anti-parasitic praziquantel increases the maximum plasma concentration of albendazole sulfoxide by 50%, and the anti-parasitic levamisole increases the AUC (total drug exposure) by 75%. Grapefruit inhibits the metabolism of albendazole within the intestinal mucosa. Finally, long-term administration of the antiretroviral ritonavir, which works as a CYP3A4 inhibitor, decreases the maximum concentration of albendazole in the plasma as well as the AUC.

Pharmacology
Mechanism of action
As a vermicide, albendazole causes degenerative alterations in the intestinal cells of the worm by binding to the colchicine-sensitive site of β-tubulin, thus inhibiting its polymerization or assembly into microtubules (it binds much better to the β-tubulin of parasites than that of mammals). Albendazole leads to impaired uptake of glucose by the larval and adult stages of the susceptible parasites, and depletes their glycogen stores. Albendazole also prevents the formation of spindle fibers needed for cell division, which in turn blocks egg production and development; existing eggs are prevented from hatching. Cell motility, maintenance of cell shape, and intracellular transport are also disrupted. At higher concentrations, it disrupts the helminths metabolic pathways by inhibiting metabolic enzymes such as malate dehydrogenase and fumarate reductase, with inhibition of the latter leading to less energy produced by the Krebs cycle. Due to diminished ATP production, the parasite is immobilized and eventually dies.
Some parasites have evolved some resistance to albendazole by having a different set of acids constituting β-tubulin, decreasing the binding affinity of albendazole. Some are not vulnerable to albendazole itself but instead live in symbiosis with Wolbachia. Wolbachia are necessary to the parasitic worms moulting and population reduction by albendazole prevents this and kills the adults.

Pharmacokinetics
Oral absorption of albendazole varies among species, with 1–5% of the drug being successfully absorbed in humans, 20–30% in rats, and 50% in cattle.The absorption also largely depends on gastric pH. People have varying gastric pHs on empty stomachs, and thus absorption from one person to another can vary wildly when taken without food. Generally, the absorption in the GI tract is poor due to albendazoles low solubility in water. It is, however, better absorbed than other benzimidazole carbamates. Food stimulates gastric acid secretion, lowering the pH and making albendazole more soluble and thus more easily absorbed. Oral absorption is especially increased with a fatty meal, as albendazole dissolves better in lipids, allowing it to cross the lipid barrier created by the mucus surface of the GI tract. To target intestinal parasites, albendazole is taken on an empty stomach to stay within the gut.Absorption is also affected by how much of the albendazole is degraded within the small intestine by metabolic enzymes in the villi.

The pharmacokinetics of albendazole differ slightly between men and women: women have a lower oral clearance and volume of distribution, while men have a lower serum peak concentration.Albendazole undergoes very fast 1st-pass metabolism in all species, such that the unchanged drug is undetectable in plasma. Most of it is oxidized into albendazole sulfoxide (also known as ricobendazole and albendazole oxide) in the liver by cytochrome P450 oxidases (CYPs) and a flavin-containing monooxygenase (FMO), which was discovered later. In humans, the cytochrome P450 oxidases are thought to include CYP3A4 and CYP1A1, while those in the rats are thought to be CYP2C6 and CYP2A1.Oxidation to albendazole sulfoxide by FMO produces R(+) enantiomers, while oxidation the cytochromes and by some enzymes in the gut epithelium produce S(-). Different species produce the R(+) and S(-) enantiomers in different quantities; humans, dogs, and most other species produce the R(+) enantiomer more (with the human AUC ratio being 80:20). Compared to the S(-) enantiomer, the R(+) has greater pharmacological activity, lasts longer in the bloodstream, is found in higher concentrations in the infected host tissues, and is found in higher concentrations within the parasites themselves. Some albendazole is also converted to hydroxyalbendazole, mainly by CYP2J2.For systemic parasites, albendazole acts as a prodrug, while albendazole sulfoxide reaches systemic circulation and acts as the real antihelminthic. Albendazole sulfoxide is able to cross the blood-brain barrier and enter the cerebrospinal fluid at 43% of plasma concentrations; its ability to enter the central nervous system allows it to treat neurocystocercosis.Albendazole sulfoxide is converted to the inactive albendazole sulfone by cytochrome P450 oxidases, thought to include CYP3A4 or CYP2C. Other inactive metabolites include: 2-aminosulfone, ω-hydroxysulfone, and β-hydroxysulfone. The major final metabolites that are excreted by humans are:
methyl [5-(propylsulfonyl-1H-benzimidazol-2-yl)] carbamate,
methyl [6-hydroxy 5-(n-propylsulfonyl)-1H-benzimidazole-2-yl)] carbamate,
methyl [5-(n-propylsulfinyl)-1H-benzimidazole-2-yl)] carbamate,
5-(n-propylsulfonyl)-1H-benzimidazole-2-yl amine, and
5-(n-propysulfinyl)-1H-benzimidazole-2-yl amine.There are also some minor hydroxylated sulfated or glucuronidated derivatives. No unchanged albendazole is excreted, as it is metabolized too quickly.In humans, the metabolites are excreted mostly in bile, with only a small amount being excreted in the urine (less than 1%) and feces. In ruminants, 60–70% of the metabolites are excreted in the urine.Like all benzimidazoles, albendazole has no residual effect, and thus protects poorly against reinfestations.

History
Albendazole, patented in 1975, was invented by Robert J. Gyurik and Vassilios J. Theodorides and assigned to SmithKline Corporation. It was introduced in 1977 as an antihelminthic for sheep in Australia, and was registered for human use in 1982.

Society and culture
Brand names
Brand names include: Albenza, Alworm, Andazol, Eskazole, Noworm, Zentel, Alben-G, ABZ, Cidazole, Wormnil etc.

Cost
In Raleigh, North Carolina, the brand-name prescription cost was around US$800, and US$540 for the generic. The pharmaceutical company Amedra increased the price after purchasing the rights to the drug, instead of lowering it as generics are predicted to do, drawing criticism from patients rights advocates.In 2013, GlaxoSmithKline donated 763 million albendazole tablets for the treatment and prevention of parasitic infections in developing countries, bringing the total to over 4 billion tablets donated since 1998.

Veterinary use
Albendazole is mainly used in cattle and sheep, but has found some use in cats and dogs as well; it is also used in ratite birds for flagellate parasites and tapeworms. It is also used off-label to treat endoparasites in goats and pigs.
Albendazole has been used as an anthelminthic and for control of flukes in a variety of animal species, including cattle, sheep, goats, swine, camels, dogs, cats, elephants, poultry, and others. Side effects include anorexia in dogs and lethargy, depression, and anorexia in cats, with more than 10% of dogs and cats having anorexia. Of dogs and cats, 1–10% experience elevated liver enzymes, nausea, vomiting, and diarrhea. Less than 1% experience neutropenia or aplastic anemia, though these require a use of at least 5 days. While it is also associated with bone marrow suppression and toxicity in cats and dogs at high doses, albendazole has a higher margin of safety in other species. Thus, it is usually only prescribed in cats and dogs when an infection is present that is resistant to the commonly prescribed metronidazole and fenbendazole.It is extensively used for ruminant livestock in Latin America. It is marketed for this purpose by Zoetis (formerly Pfizer Animal Health) in numerous countries (including the United States and Canada) as Valbazen in oral suspension and paste formulations; by Interchemie in the Netherlands and elsewhere as Albenol-100; by Channelle Animal Health Ltd. in the United Kingdom as Albex; and by Ravensdown in New Zealand (as Albendazole). Although most formulations are administered orally, Ricomax (ricobendazole, or albendazole sulfoxide) is administered by subcutaneous injection.Albendazole has greater bioavailability in ruminants: some albendazole sulfoxide, when released back into the rumen, is reduced to albendazole by the resident microbiota, with a preference of the (+) enantiomer being the substrate. Cats and dogs, having no rumen reservoir, sometimes need higher or more frequent doses as compared to ruminants </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Protriptyline and can you explain it in depth? [/INST] Protriptyline, sold under the brand name Vivactil among others, is a tricyclic antidepressant (TCA), specifically a secondary amine, indicated for the treatment of depression and attention-deficit hyperactivity disorder (ADHD). Uniquely among most of the TCAs, protriptyline tends to be energizing instead of sedating, and is sometimes used for narcolepsy to achieve a wakefulness-promoting effect.
TCAs including protriptyline are also used to reduce the incidence of recurring headaches such as migraine, and for other types of chronic pain.

Medical uses
Protriptyline is used primarily to treat depression and to treat the combination of symptoms of anxiety and depression. Like most antidepressants of this chemical and pharmacological class, protriptyline has also been used in limited numbers of patients to treat panic disorder, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, enuresis, eating disorders such as bulimia nervosa, cocaine dependency, and the depressive phase of bipolar disorder (manic-depressive) disorder. It has also been used to support smoking cessation programs.Protriptyline is available as 5 mg and 10 mg tablets. Doses range from 15 to 40 mg per day and can be taken in one daily dose or divided into up to four doses daily. Some people with severe depression may require up to 60 mg per day.In adolescents and people over age 60, therapy should be initiated at a dose of 5 mg three times a day and increased under supervision of a physician as needed. Patients over age 60 who are taking daily doses of 20 mg or more should be closely monitored for side effects such as rapid heart rate and urinary retention.Like all TCAs, protriptyline should be used cautiously and with close physician supervision. This is especially so for persons with glaucoma, especially angle-closure glaucoma (the most severe form) or urinary retention, for men with benign prostatic hypertrophy (enlarged prostate gland), and for the elderly. Before starting treatment, people should discuss the relative risks and benefits of treatment with their doctors to help determine if protriptyline is the right antidepressant for them.

Contraindications
Protriptyline may increase heart rate and stress on the heart. It may be dangerous for people with cardiovascular disease, especially those who have recently had a heart attack, to take this drug or other antidepressants in the same pharmacological class. In rare cases in which patients with cardiovascular disease must take protriptyline, they should be monitored closely for cardiac rhythm disturbances and signs of cardiac stress or damage.When protriptyline is used to treat the depressive component of schizophrenia, psychotic symptoms may be aggravated. Likewise, in manic-depressive psychosis, depressed patients may experience a shift toward the manic phase if they are treated with an antidepressant drug. Paranoid delusions, with or without associated hostility, may be exaggerated. In any of these circumstances, it may be advisable to reduce the dose of protriptyline or to use an antipsychotic drug concurrently.

Side effects
Protriptyline shares side effects common to all TCAs. The most frequent of these are dry mouth, constipation, urinary retention, increased heart rate, sedation, irritability, decreased coordination, anxiety, blood disorders, confusion, decreased libido, dizziness, flushing, headache, impotence, insomnia, low blood pressure, nightmares, rapid or irregular heartbeat, rash, seizures, sensitivity to sunlight, stomach and intestinal problems. Other more complicated side effects include; chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling; sudden numbness or weakness, especially on one side of the body; sudden headache, confusion, problems with vision, speech, or balance; hallucinations, or seizure (convulsions); easy bruising or bleeding, unusual weakness; restless muscle movements in your eyes, tongue, jaw, or neck; urinating less than usual or not at all; extreme thirst with headache, nausea, vomiting, and weakness; or feeling light-headed or fainting.Dry mouth, if severe to the point of causing difficulty speaking or swallowing, may be managed by dosage reduction or temporary discontinuation of the drug. Patients may also chew sugarless gum or suck on sugarless candy in order to increase the flow of saliva. Some artificial saliva products may give temporary relief.
Men with prostate enlargement who take protriptyline may be especially likely to have problems with urinary retention. Symptoms include having difficulty starting a urine flow and more difficulty than usual passing urine. In most cases, urinary retention is managed with dose reduction or by switching to another type of antidepressant. In extreme cases, patients may require treatment with bethanechol, a drug that reverses this particular side effect.A common problem with TCAs is sedation (drowsiness, lack of physical and mental alertness), but protriptyline is considered the least sedating agent among this class of agents. Its side effects are especially noticeable early in therapy. In most people, early TCA side effects decrease or disappear entirely with time, but, until then, patients taking protriptyline should take care to assess which side effects occur in them and should not perform hazardous activities requiring mental acuity or coordination. Protriptyline may increase the possibility of having seizures.

Withdrawal
Though not indicative of addiction, abrupt cessation of treatment after prolonged therapy may produce nausea, headache, and malaise.

List of side effects
Cardiovascular: Myocardial infarction; stroke; heart block; arrhythmias; hypotension, particularly orthostatic hypotension; hypertension; tachycardia; palpitation.Psychiatric: Confusional states (especially in the elderly) with hallucinations, disorientation, delusions, anxiety, restlessness, agitation; hypomania; exacerbation of psychosis; insomnia, panic, and nightmares.Neurological: Seizures; incoordination; ataxia; tremors; peripheral neuropathy; numbness, tingling, and paresthesias of extremities; extrapyramidal symptoms; drowsiness; dizziness; weakness and fatigue; headache; syndrome of inappropriate ADH (antidiuretic hormone) secretion; tinnitus; alteration in EEG patterns.Anticholinergic: Paralytic ileus; hyperpyrexia; urinary retention, delayed micturition, dilatation of the urinary tract; constipation; blurred vision, disturbance of accommodation, increased intraocular pressure, mydriasis; dry mouth and rarely associated sublingual adentitis.Allergic: Drug fever; petechiae, skin rash, urticaria, itching, photosensitization (avoid excessive exposure to sunlight); edema (general, or of face and tongue).Hematologic: Agranulocytosis; bone marrow depression; leukopenia;thrombocytopenia; purpura; eosinophilia.Gastrointestinal: Nausea and vomiting; anorexia; epigastric distress; diarrhea; peculiar taste; stomatitis; abdominal cramps; black tongue.Endocrine: Impotence, increased or decreased libido: gynecomastia in the male; breast enlargement and galactorrhea in the female; testicular swelling; elevation or depression of blood sugar levels.Other: Jaundice (simulating obstructive); altered liver function; parotid swelling; alopecia; flushing; weight gain or loss; urinary frequency, nocturia; perspiration.

Overdose
Deaths may occur from overdose with this class of drugs. Multiple drug ingestion (including alcohol) is common in deliberate TCA overdose. As management of overdose is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. Signs and symptoms of toxicity develop rapidly after TCA overdose, therefore, hospital monitoring is required as soon as possible.Critical manifestations of overdose include: cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of TCA toxicity.
Other signs of overdose may include: confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia.

Interactions
The side effects of protriptyline are increased when it is taken with central nervous system depressants, such as alcoholic beverages, sleeping medications, other sedatives, or antihistamines, as well as with other antidepressants including SSRIs, SNRIs or monoamine oxidase inhibitors. It may be dangerous to take protriptyline in combination with these substances.

Pharmacology
Pharmacodynamics
Protriptyline acts by decreasing the reuptake of norepinephrine and to a lesser extent serotonin (5-HT) in the brain. Its affinity for the human norepinephrine transporter (NET) is 1.41 nM, 19.6 nM for the serotonin transporter and 2,100 nM for the dopamine transporter. TCAs act to change the balance of naturally occurring chemicals in the brain that regulate the transmission of nerve impulses between cells. Protriptyline increases the concentration of norepinephrine and serotonin (both chemicals that stimulate nerve cells) and, to a lesser extent, blocks the action of another brain chemical, acetylcholine. The therapeutic effects of protriptyline, like other antidepressants, appear slowly. Maximum benefit is often not evident for at least two weeks after starting the drug.Protriptyline is a TCA. It was thought that TCAs work by inhibiting the reuptake of the neurotransmitters norepinephrine and serotonin by neurons. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. TCAs are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain. A precise mechanism for their analgesic action is unknown, but it is thought that they modulate anti-pain opioid systems in the central nervous system via an indirect serotonergic route. TCAs are also effective in migraine prophylaxis, but not in abortion of acute migraine attack. The mechanism of their anti-migraine action is also thought to be serotonergic, similar to psilocybin.

Pharmacokinetics
Metabolic studies indicate that protriptyline is well absorbed from the gastrointestinal tract and is rapidly sequestered in tissues. Relatively low plasma levels are found after administration, and only a small amount of unchanged drug is excreted in the urine of dogs and rabbits. Preliminary studies indicate that demethylation of the secondary amine moiety occurs to a significant extent, and that metabolic transformation takes place in the liver. It penetrates the brain rapidly in mice and rats, and moreover that which is present in the brain is almost all unchanged drug.
Studies on the disposition of radioactive protriptyline in human test subjects showed significant plasma levels within 2 hours, peaking at 8 to 12 hours, then declining gradually.Urinary excretion studies in the same subjects showed significant amounts of radioactivity in 2 hours. The rate of excretion was slow. Cumulative urinary excretion during 16 days accounted for approximately 50% of the drug. The fecal route of excretion did not seem to be important.Protriptyline has uniquely low dosing among TCAs, likely due to its exceptionally long terminal half-life. It is used in dosages of 15 to 40 mg/day, whereas most other TCAs are used at dosages of 75 to 300 mg/day. The maximum dose is 60 mg/day </s>


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Macrogol and can you explain it in depth? [/INST] Macrogol, also known as polyethylene glycol (PEG), is used as a medication to treat constipation in children and adults. It is also used to empty the bowels before a colonoscopy. It is taken by mouth. Benefits usually occur within three days. Generally it is only recommended for up to two weeks. It is also used as an excipient.Side effects may include increased bowel gas, abdominal pain, and nausea. Rare but serious side effects may include an abnormal heartbeat, seizures, and kidney problems. Use appears to be safe during pregnancy. It is classified as an osmotic laxative. It works by increasing the amount of water in the stool.Macrogol came into use as a bowel prep in 1980 and was approved for medical use in the United States in 1999. It is available as a generic medication and over the counter. In 2018, it was the 163rd most commonly prescribed medication in the United States, with more than 3 million prescriptions. Typically it is formulated together with electrolytes.

Medical uses
Constipation
Macrogol 3350, often in combination with electrolytes, is used for short-term relief of constipation as well as for long-term use in constipation of various causes, including in multiple sclerosis and Parkinsons disease patients (an often-overlooked non-motor symptom) as well as constipation caused by pharmaceutical drugs such as opioids and anticholinergics. Whole bowel irrigation with macrogol is part of the bowel preparation before surgery or colonoscopy. Limited data also support its use for the treatment of fecal impaction.In those with chronic constipation it works better than lactulose.A 2007 comparison showed that people with constipation had a better response to macrogol than to tegaserod. Popular types include: macrogol 3350, macrogol 4000, and macrogol 6000. The number represents the average molecular mass. Combining different molecular masses provides some control over the consistency.

Excipient
Macrogol is used as an excipient in pharmaceutical products. Lower-molecular-weight variants are used as solvents in oral liquids and soft capsules, whereas solid variants are used as ointment bases, tablet binders, film coatings, and lubricants.For example, PEG-2000 is one of the excipients in the Moderna COVID-19 vaccine.

PEGylation
Macrogols are also attached to biopharmaceutical drugs to slow down their degradation in the human body and increase their duration of action, as well as to reduce immunogenicity. This process is called PEGylation.

Contraindications
Contraindications for macrogol taken orally as a laxative are intestinal perforation, bowel obstruction, ileus, inflammatory bowel diseases, and toxic megacolon.The doses of macrogol as an excipient are too low to have relevant contraindications.Allergy to macrogol is rare, and usually appears as an allergy to an increasing number of seemingly unrelated products, including cosmetics, drugs that use it as an excipient, and peri-procedural substances such as ultrasound gel.

Adverse effects
Oral macrogol is generally well tolerated. Possible side effects include headache, bloating, nausea, allergies, and electrolyte imbalance, mainly hypokalaemia (low blood potassium levels) and hyperkalaemia (high blood potassium levels). Hyperkalaemia is not an effect of macrogol itself but of potassium salts which are usually part of macrogol formulations. With excessive use, it can cause diarrhea.

Interactions
The interaction potential is low. Resorption of other pharmaceutical drugs can be reduced because oral macrogol accelerates intestinal passage, but this is seldom clinically relevant. For antiepileptic drugs, such a mechanism has been described in rare cases.

Pharmacology
Mechanism of action as a laxative
Macrogol is an osmotically acting laxative; that is, an inert substance that passes through the gut without being absorbed into the body. It relieves constipation because it causes water to be retained in the bowel instead of being absorbed into the body. This increases the water content and volume of the stools in the bowel, making them softer and easier to pass, as well as improving gut motility.

Chemistry
Available forms
Macrogol is sold as a non-prescription preparation in the form of powder. When sold for gut cleansing (and as a laxative), it is usually in combination with salts such as sodium bicarbonate, sodium chloride and potassium chloride to help mitigate the possibility of electrolyte imbalance and dehydration. Brand names include SoftLax, Purelax, MiraLax, Laxido, Glycoprep, CosmoCol, Movicol, Cololyt, Osmolax, and others.It is dissolved in water to create a clear and odorless solution which is then drunk </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Gelesis100 and can you explain it in depth? [/INST] Gelesis100, sold under the brand name Plenity, is an oral hydrogel used to treat overweight and obesity. It absorbs water and expands in the stomach and small bowel thereby increasing feelings of fullness. Possible side effects include primarily gastrointestinal symptoms, such as diarrhea, abdominal distention, infrequent bowel movements, constipation, abdominal pain, and flatulence </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Edaravone and can you explain it in depth? [/INST] Edaravone, sold under the brand name Radicava among others, is a medication used to treat stroke and amyotrophic lateral sclerosis (ALS). It is given by intravenous infusion and by mouth.The most common side effects include bruising (contusions), problems walking (gait disturbances), and headaches.The mechanism by which edaravone might be effective is unknown. The medication is known to be an antioxidant, and oxidative stress has been hypothesized to be part of the process that kills neurons in people with ALS.The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.

Medical uses
Edaravone is used to help people recover from stroke in Japan, and is used to treat ALS in the US and Japan.

Adverse effects
The label carries a warning about the potential for hypersensitivity reactions to edaravone, and adverse effects include bruising, gait disturbances, headache, skin inflammation, eczema, problems breathing, excess sugar in urine, and fungal skin infections.The following adverse effects in at least 2% more people given the medication than were given placebo: bruising, gait disturbances, headache, skin inflammation, eczema, problems breathing, excess sugar in urine, and fungal skin infections.There is no data on whether it is safe for pregnant women to take, and it is unknown if edaravone is secreted in breast milk.

Pharmacology
The mechanism by which edaravone might be effective in ALS is unknown. The medication is known to be an antioxidant, and oxidative stress has been hypothesized to be part of the process that kills neurons in people with ALS.The half-life of edaravone is 4.5 to 6 hours and the half-lives of its metabolites are 2 to 3 hours. It is metabolized to a sulfate conjugate and a glucuronide conjugate, neither of which are active. It is primarily excreted in urine as the glucuronide conjugate form.

History
Researchers first developed the free radical scavenger edaravone in late 1980s as a treatment for stroke. The approach, introduced by Koji Abe, now at Okayama University Hospital in Japan, aimed to prevent the swelling of the brain which may occur after a stroke.It has been marketed in Japan by Mitsubishi Pharma for stroke since 2001 and is now generic.Mitsubishi Tanabe started a phase III clinical trial in ALS in 2011, in Japan, and by June 2015, it had been approved for that use in Japan. The company had received Orphan Drug Designation for edaravone from the FDA and EU by 2016.It was approved for ALS in the US in 2017, based on a small randomized controlled clinical trial with people who had early-stage ALS in Japan, who were administered the medication for 6 months; it had failed two earlier trials in people with all stages of ALS.In May 2017, I.V. edaravone was approved by the FDA to treat people with amyotrophic lateral sclerosis (ALS) in the United States. The FDA approval was conditioned on Mitsubishi Tanabe completing several additional studies to clarify the risks of cancer and liver disease, among other effects of the medication.Formulation of edaravone by mouth called TW001 (mixture of the edaravone and SBE-HP-βCD ) has been under development by Treeway for ALS; as of 2015, it had successfully completed Phase I trial and had received orphan status in the US and in the European Union.An oral formulation of edaravone was approved for medical use in the United States in May 2022. The effectiveness of oral edaravone is based on a study that showed comparable levels of oral edaravone in the bloodstream to the levels from the IV formulation of edaravone. The efficacy of edaravone for the treatment of ALS was previously demonstrated in a six-month clinical trial that served as the basis for approval in 2017. In that trial, 137 participants were randomized to receive edaravone or placebo. At week 24, individuals receiving edaravone declined less on a clinical assessment of daily functioning compared to those receiving placebo.

Society and culture
Economics
The price for the medication when it launched in Japan for stroke in 2001, was set by the Japanese government at 9,931 yen/ampule.When the medication launched in Japan for ALS in 2001, the price was $35,000; the price in Japan in 2017 was $5,000, the US price at launch was around $145,000. In the US the medication was approved for all people with ALS but it was unclear at approval whether insurers would agree to pay for the medication for all people with ALS, or only people in the early stages of the disease. There are three filed trials for edaravone, demonstrating it may work in less than 5% of all ALS population.

Brand names
Brand names include Radicut, ラジカット, Radicava, Xavron.

References
Further reading
Yoshino H (March 2019). "Edaravone for the treatment of amyotrophic lateral sclerosis". Expert Rev Neurother. 19 (3): 185–193 </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Crotalidae polyvalent immune fab and can you explain it in depth? [/INST] Crotalidae polyvalent immune fab, sold under the brandname CroFab, is a snake antivenin, indicated for minimal or moderate North American Crotalid (Rattlesnake, Copperhead and Cottonmouth/Water moccasin) snake envenomation.
CroFab is composed of several monovalent Fragment antigen-binding proteins (Fab) derived from the blood of sheep immunized with one of four snake venom: Crotalus atrox (western diamondback rattlesnake), Crotalus adamanteus (Eastern diamondback rattlesnake), Crotalus scutulatus (Mojave rattlesnake), or Agkistrodon piscivorus (Cottonmouth or Water Moccasin).  Each monospecific antivenin is purified from sheep serum, digested with the enzyme papain, and purified further resulting in specific Fab fragments.  The resulting four different Fab preparations are mixed to formulate the final product.

Background
It was developed by the Venom Immunochemistry, Pharmacology and Emergency Response (VIPER) Institute, University of Arizona, and commercialized by BTG plc (formerly Protherics PLC).  As reported in the Washington Post in July 2015, this was the only commercially available antivenin in the United States for the treatment of venomous snakebites until the release of a competing product, ANAVIP.

Treatment
Crotalid snakebites can range from mild to life-threatening, depending on the size and type of snake, the amount of venom injected and the location of the bite. This in turn determines the number of vials of CroFab that are required by the patient. Untreated, the snake venom can cause severe pain and tissue damage that can result in the loss of a limb or even death. Prompt (within six hours of snake bite) treatment with CroFab is recommended. Fab refers to Fragment Antigen-Binding, the active mechanism for this antivenom.

Adverse events
The most common adverse events reported in clinical studies were mild or moderate reactions involving the skin and appendages (primarily urticaria, rash, or pruritus), which occurred in 14 out of 42 patients. Three patients experienced a serious adverse event. Two patients had a severe allergic reaction (severe hives and a severe rash and pruritus) following treatment </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Vasopressin and can you explain it in depth? [/INST] Human vasopressin, also called antidiuretic hormone (ADH),   arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travels down the axon terminating in the posterior pituitary, and is released from vesicles into the circulation in response to extracellular fluid hypertonicity (hyperosmolality). AVP has two primary functions. First, it increases the amount of solute-free water reabsorbed back into the circulation from the filtrate in the kidney tubules of the nephrons. Second, AVP constricts arterioles, which increases peripheral vascular resistance and raises arterial blood pressure.A third function is possible. Some AVP may be released directly into the brain from the hypothalamus, and may play an important role in social behavior, sexual motivation and pair bonding, and maternal responses to stress.Vasopressin induces differentiation of stem cells into cardiomyocytes and promotes heart muscle homeostasis.It has a very short half-life, between 16 and 24 minutes.

Physiology
Function
Vasopressin regulates the  tonicity of body fluids. It is released from the posterior pituitary in response to hypertonicity and causes the kidneys to reabsorb solute-free water and return it to the circulation from the tubules of the nephron, thus returning the tonicity of the body fluids toward normal. An incidental consequence of this renal reabsorption of water is concentrated urine and reduced urine volume. AVP released in high concentrations may also raise blood pressure by inducing moderate vasoconstriction.
AVP also may have a variety of neurological effects on the brain. It may influence pair-bonding in voles. The high-density distributions of vasopressin receptor AVPr1a in prairie vole ventral forebrain regions have been shown to facilitate and coordinate reward circuits during partner preference formation, critical for pair bond formation.A very similar substance, lysine vasopressin (LVP) or lypressin, has the same function in pigs and its synthetic version was used in human AVP deficiency, although it has been largely replaced by desmopressin.

Kidney
Vasopressin has three main effects which are:

Increasing the water permeability of distal and cortical collecting tubules (DCT & CCT), as well as outer and inner medullary collecting duct (OMCD & IMCD) in the kidney, thus allowing water reabsorption and excretion of more concentrated urine, i.e., antidiuresis. This occurs through increased transcription and insertion of water channels (Aquaporin-2) into the apical membrane of collecting tubule and collecting duct epithelial cells. Aquaporins allow water to move down their osmotic gradient and out of the nephron, increasing the amount of water re-absorbed from the filtrate (forming urine) back into the bloodstream. This effect is mediated by V2 receptors. Vasopressin also increases the concentration of calcium in the collecting duct cells, by episodic release from intracellular stores.  Vasopressin, acting through cAMP, also increases transcription of the aquaporin-2 gene, thus increasing the total number of aquaporin-2 molecules in collecting duct cells.
Increasing permeability of the inner medullary portion of the collecting duct to urea by regulating the cell surface expression of urea transporters, which facilitates its reabsorption into the medullary interstitium as it travels down the concentration gradient created by removing water from the connecting tubule, cortical collecting duct, and outer medullary collecting duct.
Acute increase of sodium absorption across the ascending loop of Henle. This adds to the countercurrent multiplication which aids in proper water reabsorption later in the distal tubule and collecting duct.

Central nervous system
Vasopressin released within the brain may have several actions:

Vasopressin is released into the brain in a circadian rhythm by neurons of the suprachiasmatic nucleus.
Vasopressin released from posterior pituitary is associated with nausea.
Recent evidence suggests that vasopressin may have analgesic effects.  The analgesia effects of vasopressin were found to be dependent on both stress and sex.

Regulation
Gene regulation
Vasopressin is regulated by AVP gene expression which is managed by major clock controlled genes. In this circadian circuit known as the transcription-translation feedback loop (TTFL), Per2 protein accumulates and is phosphorylated by CK1E. Per2 subsequently inhibits the transcription factors Clock and BMAL1 in order to reduce Per2 protein levels in the cell. At the same time, Per2 also inhibits the transcription factors for the AVP gene in order to regulate its expression, the expression of vasopressin, and other AVP gene products.Many factors influence the secretion of vasopressin:

Ethanol (alcohol) reduces the calcium-dependent secretion of AVP by blocking voltage-gated calcium channels in neurohypophyseal nerve terminals in rats.
Angiotensin II stimulates AVP secretion, in keeping with its general pressor and pro-volumic effects on the body.
Atrial natriuretic peptide inhibits AVP secretion, in part by inhibiting Angiotensin II-induced stimulation of AVP secretion.
Cortisol inhibits secretion of antidiuretic hormone.

Production and secretion
The physiologic stimulus for secretion of vasopressin is increased osmolality of the plasma, monitored by the hypothalamus. A decreased arterial blood volume, (such as can occur in cirrhosis, nephrosis and heart failure), stimulates secretion, even in the face of decreased osmolality of the plasma: it supersedes osmolality, but
with a milder effect. In other words, vasopressin is secreted in spite of the presence of hypoosmolality (hyponatremia) when the arterial blood volume is low.
The AVP that is measured in peripheral blood is almost all derived from secretion from the posterior pituitary gland (except in cases of AVP-secreting tumours). Vasopressin is produced by magnocellular neurosecretory neurons in the paraventricular nucleus of hypothalamus (PVN) and supraoptic nucleus (SON). It then travels down the axon through the infundibulum within neurosecretory granules that are found within Herring bodies, localized swellings of the axons and nerve terminals. These carry the peptide directly to the posterior pituitary gland, where it is stored until released into the blood.
There are other sources of AVP, beyond the hypothalamic magnocellular neurons.  For example, AVP is also synthesized by parvocellular neurosecretory neurons of the PVN, transported and released at the median eminence, from which it travels through the hypophyseal portal system to the anterior pituitary, where it stimulates corticotropic cells synergistically with CRH to produce ACTH (by itself it is a weak secretagogue).

Vasopressin during surgery and anaesthesia
Vasopressin concentration is used to measure surgical stress for evaluation of surgical techniques. Plasma vasopressin concentration is elevated by noxious stimuli, predominantly during abdominal surgery, especially at gut manipulation and traction of viscera.

Receptors
Types of AVP receptors and their actions:

Structure and relation to oxytocin
The vasopressins are peptides consisting of nine amino acids (nonapeptides). The amino acid sequence of arginine vasopressin (argipressin) is Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2, with the cysteine residues forming a disulfide bond and the C-terminus of the sequence converted to a primary amide.  Lysine vasopressin (lypressin) has a lysine in place of the arginine as the eighth amino acid, and is found in pigs and some related animals, whereas arginine vasopressin is found in humans.The structure of oxytocin is very similar to that of the vasopressins: It is also a nonapeptide with a disulfide bridge and its amino acid sequence differs at only two positions. The two genes are located on the same chromosome separated by a relatively small distance of less than 15,000 bases in most species. The magnocellular neurons that secrete vasopressin are adjacent to magnocellular neurons that secrete oxytocin, and are similar in many respects. The similarity of the two peptides can cause some cross-reactions: oxytocin has a slight antidiuretic function, and high levels of AVP can cause uterine contractions.Comparison of vasopressin and oxytocin neuropeptide families:

Medical use
Vasopressin is used to manage anti-diuretic hormone deficiency. Vasopressin is used to treat diabetes insipidus related to low levels of antidiuretic hormone. It is available as Pressyn.Vasopressin has off-label uses and is used in the treatment of vasodilatory shock, gastrointestinal bleeding, ventricular tachycardia and ventricular fibrillation.
Vasopressin agonists are used therapeutically in various conditions, and its long-acting synthetic analogue desmopressin is used in conditions featuring low vasopressin secretion, as well as for control of bleeding (in some forms of von Willebrand disease and in mild haemophilia A) and in extreme cases of bedwetting by children. Terlipressin and related analogues are used as vasoconstrictors in certain conditions. Use of vasopressin analogues for esophageal varices commenced in 1970.Vasopressin infusions are also used as second line therapy for septic shock patients not responding to fluid resuscitation or infusions of catecholamines (e.g., dopamine or norepinephrine) to increase the blood pressure while sparing the use of catecholamines. These argipressins have much shorter elimination half-life (around 20 minutes) comparing to synthetic non-arginine vasopresines with much longer elimination half-life of many hours. Further, argipressins act on V1a, V1b, and V2 receptors which consequently lead to higher eGFR and lower vascular resistance in the lungs.  A number of injectable arginine vasopressins are currently in clinical use in the United States and in Europe.

Pharmacokinetics
Vasopressin is administered through an intravenous device, intramuscular injection or a subcutaneous injection. The duration of action depends on the mode of administration and ranges from thirty minutes to two hours. It has a half life of ten to twenty minutes. It is widely distributed throughout the body and remains in the extracellular fluid. It is degraded by the liver and excreted through the kidneys. Arginin vasopressins for use in septic shock are intended for intravenous use only.

Side effects
The most common side effects during treatment with vasopressin are dizziness, angina, chest pain, abdominal cramps, heartburn, nausea, vomiting, trembling, fever, water intoxication, pounding sensation in the head, diarrhoea, sweating, paleness, and flatulence. The most severe adverse reactions are myocardial infarction and hypersensitivity.

Contraindications
The use of lysine vasopressin is contraindicated in the presence of hypersensitivity to beef or pork proteins, increased BUN and chronic kidney failure. It is recommended that it be cautiously used in instances of perioperative polyuria, sensitivity to the drug, asthma, seizures, heart failure, a comatose state, migraine headaches, and cardiovascular disease.

Interactions
alcohol - may lower the antidiuretic effect
carbamazepine, chloropropamide, clofibrate, tricyclic antidepressants and fludrocortisone may raise the diuretic effect
lithium, demeclocycline, heparin or norepinephrine may lower the antidiuretic effect
vasopressor effect may be higher with the concurrent use of ganglionic blocking medications

Deficiency
Decreased AVP release (neurogenic — i.e </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Tralokinumab and can you explain it in depth? [/INST] Tralokinumab sold under the brand names Adtralza (EU/UK) and Adbry (US) among others, is a human monoclonal antibody used for the treatment of atopic dermatitis. Tralokinumab targets the cytokine interleukin 13.The most common side effects include upper respiratory tract infections (colds and other infections of the nose and throat), reactions at the injection site, and redness and discomfort in the eye.Tralokinumab was approved for medical use in the European Union and in the United Kingdom in June 2021 </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Pralidoxime and can you explain it in depth? [/INST] Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM, usually as the chloride or iodide salts, belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase.  It is used to treat organophosphate poisoning in conjunction with atropine and either diazepam or midazolam. It is a white solid.

Chemical synthesis
Pralidoxime, 2-pyridinaldoxime methylchloride, is prepared by treating pyridine-2-carboxaldehyde with hydroxylamine.  The resulting pyridine-2-aldoxime is alkylated with methyl iodide giving pralidoxime as the iodide salt.

Mechanism of action
Pralidoxime is typically used in cases of organophosphate poisoning. Organophosphates such as sarin bind to the hydroxy component (the esteric site) of the active site of the acetylcholinesterase enzyme, thereby  blocking its activity. Pralidoxime binds to the other half (the unblocked, anionic site) of the active site and then displaces the phosphate from the serine residue. The conjoined poison / antidote then unbinds from the site, and thus regenerates the fully functional enzyme.
Some phosphate-acetylcholinesterase conjugates continue to react after the phosphate docks to the esteric site, evolving into a more recalcitrant state </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Progesterone vaginal ring and can you explain it in depth? [/INST] Progesterone vaginal ring, also known as progesterone-only vaginal ring, is a form of vaginal ring used for birth control when breastfeeding. Use can begin at four weeks and continue for at least up to a year following childbirth. Failure rates with usual use is about 1.5 per 100 women. It is used within the vagina with one ring lasting three months </s>