What is Paracetamol?

Chinese aliases: acetaminophen, acetaminophen, paracetamol, antipyretic net, acetaminophen, acetaminophen, somir, acetaminophen, diacetalol.

paracetamol

Paracetamol, trade names include Baifu Ning, Britton, Tylenol, Acetaminophen, etc. The international non-proprietary drug is called Paracetamol. It is the most commonly used non-anti-inflammatory antipyretic and analgesic, with antipyretic effect similar to aspirin, weak analgesic effect, no anti-inflammatory and anti-rheumatic effect, and is the best variety among acetanilides. Especially suitable for patients who cannot use carboxylic acid drugs. For colds, toothaches, etc. Paracetamol is also an intermediate in organic synthesis, a stabilizer for hydrogen peroxide, and a photographic chemical.

Paracetamol Basic Information

Chinese aliases: acetaminophen, acetaminophen, paracetamol, antipyretic net, acetaminophen, acetaminophen, somir, acetaminophen, diacetalol.

English name: 4-Acetamido phenol, paracetamol or acetaminophen.

English aliases: Acetamino phen, 4-Hydroxyacetanilide, APAP, p-Hydroxyacetanilide, Paracetamol (Acetaminophen).

Quality standard: BP \ USP.

Paracetamol structural formula

Content: 99% -101%.

CAS number: 103-90-2.

Molecular formula: C8H9NO2.

Molecular weight: 151.16.

Physical and chemical properties: White crystalline powder, tasteless, soluble in hot water, ether, chloroform, etc.

Product use: Antipyretic and analgesic.

Packaging: 25 kg per barrel (carton) (woven bag).

Physical properties of paracetamol

Prism crystals were obtained from ethanol. Melting point is 169-171 ° C, relative density is 1.293 (21/4 ° C). Soluble in ethanol, acetone and hot water, hardly soluble in water, insoluble in petroleum ether and benzene. No smell, bitter taste. The pH of the saturated aqueous solution is 5.5-6.5.

Preparation method of paracetamol

This product is obtained by acetylating p-aminophenol.

Method 1: Add p-aminophenol to dilute acetic acid, then add glacial acetic acid, heat to 150 ° C for 7h, add acetic anhydride, and react for 2h, check the end point, cool to 25 ° C or lower after passing, filter, and wash with water Tart, dried to get a crude product.

Method 2: Distill p-aminophenol, glacial acetic acid, and acid mother liquor containing more than 50% of acid together, and dilute the dilute acid at a rate of one-tenth of the total amount of distillate per hour, until the internal temperature rises to more than 130 ° C. Sampling check the residual amount of p-aminophenol is less than 2.5%, add dilute acid (content above 50%), and cool to crystallize. Shake the filter, wash with a small amount of dilute acid, and then wash with a large amount of water until the filtrate is nearly colorless to obtain a crude product.

The yield of Method 1 was 90%, and the yield of Method 2 was 90-95%.

Refining method: When the water is heated to near boiling, put the crude product. Warm to complete dissolution, add activated carbon soaked with water, adjust to pH = 4.2-4.6 with dilute acetic acid, and boil for 10min. Filter press and add a small amount of sodium bisulfite to the filtrate. After cooling to 20 ° C or less, crystals were precipitated. Filter, wash, and dry to obtain the finished product of paracetamol.

Other production methods include: (1) reduction of p-nitrophenol with zinc in glacial acetic acid, and acetylation to obtain acetaminophen; (2) plutonium produced by p-hydroxyacetophenone, placed in sulfuric acid solution Add sodium nitrite and translocate to produce acetaminophen. ^[1] .

Paracetamol drug pharmacology

Pharmacodynamics This product is an acetanilide antipyretic and analgesic. By inhibiting cyclooxygenase, it selectively inhibits the synthesis of central prostaglandins in hypothalamic body temperature regulation, which leads to peripheral vasodilation and sweating to achieve antipyretic effects. Its antipyretic effect is similar to aspirin. And release, raise the pain threshold and play an analgesic effect, belongs to peripheral analgesics, the effect is weaker than aspirin, only effective for mild to moderate pain. This product has no obvious anti-inflammatory effect.

Pharmacokinetics Absorption from the gastrointestinal tract is rapid and complete after oral administration (taking medication after a high carbohydrate diet may reduce absorption), and it is evenly distributed in body fluids after absorption, with about 25% binding to plasma proteins. At a small amount (blood concentration <60 g / ml), the binding to protein is not obvious, and the binding rate is high at a large amount or poisoning amount, which can reach 43%. 90 to 95% of this product is metabolized in the liver, mainly combined with glucuronic acid, sulfuric acid and cysteine. Intermediate metabolites have toxic effects on the liver. The half-life is generally 1 to 4 hours (average 2 hours), and it remains unchanged during renal insufficiency, but it may be prolonged in some patients with liver disease, it may be prolonged in the elderly and newborns, and shortened in children. The blood concentration can reach the peak value within 0.5 to 2 hours after oral administration. The blood concentration is 5 to 20 g / ml when the dosage is below 650 mg, and the duration of action is 3 to 4 hours. During breastfeeding, women take 650mg of this product, and the concentration in milk is 10-15g / ml for 1 to 2 hours. The half-life is 1.35 to 3.5 hours. This product is mainly excreted from the kidney in the form of glucuronic acid, and about 3% is excreted in the original form within 24 hours.

Paracetamol adapts to symptoms

It is suitable for relieving mild to moderate pain, such as fever, headache, joint pain, neuralgia, migraine and dysmenorrhea caused by colds. This product can only relieve symptoms, has no or minimal anti-inflammatory effect, and cannot eliminate redness, swelling, and movement disorders caused by arthritis, so it cannot be used instead of aspirin or other non-steroidal anti-inflammatory drugs to treat various types of arthritis. However, the product can be used in patients with allergies, intolerances, or unsuitability for aspirin, such as patients with chickenpox, hemophilia, and other bleeding disorders (including those using anticoagulant therapy), as well as peptic ulcers and gastritis. When using this product, other therapies must be applied at the same time to relieve the cause of pain or fever.

Paracetamol Usage and Dosage

1. Adults usually take it orally. 0.3-0.6g at a time, once every 4 hours, or 4 times a day; the daily amount should not exceed 2g, the course of treatment is generally no more than 3 days for antipyretic, and it should not exceed 10 days for analgesia.

2. Commonly used in children. 10-15 mg / kg per weight or 1.5 g / m2 per day based on body surface area, divided into doses, once every 4-6 hours; children under the age of 12 should not exceed 5 doses every 24 hours, and the course of treatment should not exceed 5 days .

Paracetamol poison side effects

White plus black, Parker, Tylenol cold tablets, cold spirits, Qutong tablets, etc. all contain paracetamol, the dosage is about 120-500 mg. However, the widespread clinical application has caused some toxic and side effects, which must arouse everyone's vigilance.

1. Toxic side effects of the liver: Long-term use or overdose can cause liver cell necrosis. Hepatic cell necrosis caused by paracetamol is a direct effect on liver cells. It may be caused by excessive consumption of paracetamol, which results in the generation of a toxic metabolite in the body. When the accumulation reaches a certain amount, the liver glutathione is depleted and the liver's detoxification ability is greatly reduced. Toxic metabolites destroy liver cells, producing cell degeneration and necrosis. Due to acute hepatic lobular central necrosis caused by excessive paracetamol, those who progress rapidly may develop fulminant liver failure and cause death.

2. Toxic side effects of the kidney: Toxic metabolites produced by excessive paracetamol can also damage the kidney and cause necrosis of the kidney cells, especially when combined with sodium salicylate or caffeine, it is easier to damage the kidney.

3. Toxic side effects of the blood system: long-term excessive paracetamol, the toxic metabolites generated can directly affect the bone marrow hematopoietic system, constitute damage, and may induce thrombocytopenic purpura or leukemia.

4. Toxic side effects of the nervous system: If children take too much paracetamol, they can also cause symptoms of poisoning in the central nervous system, mainly brain damage, neurological decline, and coma.

Rarely, stop taking it immediately if an allergic reaction occurs.

Paracetamol precautions

· If overdose, please consult a doctor immediately.

· Do not take at the same time as other acetaminophen-containing drugs.

· If you have severe sore throat, accompanied by fever, headache, skin, nausea or vomiting, you should consult a doctor.

· Avoid drinking alcoholic beverages while taking the medicine. Patients who drink alcohol should take this product and other painkillers under the guidance of a doctor.

Liver damage can be caused by taking paracetamol in the following situations

(1) Overdose.

(2) Take large doses for a long time.

(3) Drink or drink alcoholic beverages.

(4) Small doses of liver disease patients can also damage the liver.

(5) Mix it with other headache, cold medicine and other medicines containing paracetamol. A survey of 300 patients with severe liver failure by US researchers showed that 38% of these cases were related to taking paracetamol. In another group of 307 adult patients with severe liver damage, 35% of cases were found to be related to paracetamol. Most of these cases are accidents and are caused by inattention. ^[2]

Paracetamol cold medicine containing paracetamol

White plus black, Xin Kang Tai Ke, day and night Bai Fu Ning, Gan Kang, Qu Ke, Tylenol, cold Ling, Parker commonly used cold medicines, etc. contain paracetamol, it is best not to take these drugs at the same time. In addition, aspirin, painkillers, paracetamol, gentamicin, kanamycin, etc. also have kidney toxicity. ^[3]

Paracetamol pregnant women need to use paracetamol with caution

US scientists conducted a follow-up survey of 9,000 mothers and found that mothers who took large amounts of paracetamol during the later stages of pregnancy had a much higher chance of having asthma.

Scientists have found that if a mother takes paracetamol daily or almost daily during late pregnancy, when the child reaches three years of age, he will find that his child is more likely to develop asthma than other children.

However, scientists also pointed out that, compared with aspirin, paracetamol is still a better choice for pregnant women. When pregnant women find that they must take paracetamol, they can only take it twice a week, and the dosage cannot exceed the doctor's prescription. Dose so that the adverse effects of the drug on the baby are minimized. ^[4]