PARACETAMOL

Paracetamol has a role as a cyclooxygenase 2 inhibitor, a cyclooxygenase 1 inhibitor, a non-narcotic analgesic, an antipyretic, a non-steroidal anti-inflammatory drug, a cyclooxygenase 3 inhibitor, a xenobiotic, an environmental contaminant, a human blood serum metabolite, a hepatotoxic agent, a ferroptosis inducer and a geroprotector.
Paracetamol is a member of phenols and a member of acetamides. 
Paracetamol is functionally related to a 4-aminophenol.

CAS Number: 103-90-2
Molecular Formula: C8H9NO2
Molecular Weight: 151.16
EINECS Number: 203-157-5

Synonyms: Acetaminophen, Acetamidophenol, Acetominophen, Hydroxyacetanilide, N-Acetyl-p-aminophenol, p-Acetamidophenol, p-Hydroxyacetanilide, Paracetamol, N-(4-Hydroxyphenyl)acetanilide, APAP, PARACETAMOL BP2001, PARACETAMOL POWDER, PARACETAMOL POWDER BP, PARACETAMOL BP, ACETAMINOPHENOL POWDER PB/USP, PARACETAMOL DC GRADE, PARACETAMOL BP98, PARACETAMOL USP23,BP98

Paracetamol differs from the nonsteroidal anti-inflammatory agents described in that it is devoid of anti-inflammatory and antirheumatic properties. 
Paracetamol was recently shown that acetaminophen, like aspirin, inhibits cyclooxygenase action in the brain and is even stronger than aspirin. 
On the other hand, the mechanism of analgesic action of Paracetamol is not fully clear, since it acts poorly on peripheral cyclooxygenase.

Obtain prism crystallization from ethanol. 
Melting point 169-171℃, relative density 1.293(21/4℃). 
Soluble in ethanol, acetone and hot water, difficult to dissolve in water, insoluble in petroleum ether and benzene. 

The pH value of saturated aqueous solution is 5.5-6.5.
Paracetamol, also known as acetaminophen, is a widely used analgesic and antipyretic agent that functions primarily by inhibiting the synthesis of prostaglandins in the central nervous system, thereby reducing the sensation of pain and lowering elevated body temperature, while exhibiting minimal anti-inflammatory activity compared with nonsteroidal anti-inflammatory drugs (NSAIDs), which makes it a preferred option for individuals who cannot tolerate NSAIDs due to gastrointestinal, renal, or cardiovascular concerns.

Paracetamol is used as antipyretic analgesics. 
Paracetamol has the antipyretic activity by means of mediated peripheral vasodilation and perspiration caused by inhibiting the cyclooxygenase which selectively inhibiting the synthesis of hypothalamic thermoregulation prostaglandins, and its strength of antipyretic effect is similar to aspirin. 
As a peripheral analgesic, it can produce analgesic effect by inhibiting the synthesis and release of prostaglandins and increasing pain threshold. 

However, its action is weaker than aspirin and it is only effective for mild to moderate pain. 
There is no obvious anti-inflammation effect.
Paracetamol is a member of the class of phenols that is 4-aminophenol in which one of the hydrogens attached to the amino group has been replaced by an acetyl group. 

Paracetamol or acetaminophen,[b] is a non-opioid analgesic and antipyretic agent used to treat fever and mild to moderate pain.
Paracetamol is a widely available over-the-counter drug sold under various brand names, including Tylenol and Panadol.
Paracetamol relieves pain in both acute mild migraine and episodic tension headache.

Paracetamol a standard dose, paracetamol slightly reduces fever, though it is inferior to ibuprofen in that respect and the benefits of its use for fever are unclear, particularly in the context of fever of viral origins.
The aspirin/paracetamol/caffeine combination also helps with both conditions when the pain is mild and is recommended as a first-line treatment for them.
Paracetamol is effective for pain after wisdom tooth extraction, but it is less effective than ibuprofen.

The combination of paracetamol and ibuprofen provides greater analgesic efficacy than either drug alone.
The pain relief paracetamol provides in osteoarthritis is small and clinically insignificant.
Evidence supporting its use in low back pain, cancer pain, and neuropathic pain is insufficient.

In the short term, paracetamol is safe and effective when used as directed.
Short term adverse effects are uncommon and similar to ibuprofen, but paracetamol is typically safer than nonsteroidal anti-inflammatory drugs (NSAIDs) for long-term use.
Paracetamol is also often used in patients who cannot tolerate NSAIDs like ibuprofen.

Chronic consumption of paracetamol may result in a drop in hemoglobin level, indicating possible gastrointestinal bleeding, and abnormal liver function tests. 
The recommended maximum daily dose for an adult is three to four grams.
Higher doses may lead to toxicity, including liver failure.

Paracetamol poisoning is the foremost cause of acute liver failure in the Western world, and accounts for most drug overdoses in the United States, the United Kingdom, Australia, and New Zealand.
Paracetamol was first made in 1878 by Harmon Northrop Morse or possibly in 1852 by Charles Frédéric Gerhardt.
Paracetamol is the most commonly used medication for pain and fever in both the United States and Europe.

Paracetamol is on the World Health Organization's List of Essential Medicines.
Paracetamol is available as a generic medication, with brand names including Tylenol and Panadol among others.
In 2023, it was the 112th most commonly prescribed medication in the United States, with more than 5 million prescriptions.

The chemiacal name of Acetaminophen is N-(4-hydroxy phenyl) acetamide and the trade name is paracetamol belonging to acetanilide antipyretic analgesics. 
Paracetamol was first synthesized by Morse in 1878 and first used in clinic by VonMering in 1893. 
Paracetamol has become an over the counter drug in the USA since 1955 and our country started production at the end of the 1950’s. 

Paracetamol is a white crystalline or a crystalline powder in appearance with melting point from 168℃ to 172℃, odorless, slightly bitter taste, freely soluble in hot water or ethanol, dissolved in acetone, practically insoluble in cold water and petroleum ether. 
Paracetamol is stable below 45℃ but will be hydrolyzed into p-aminophenol when exposed to humid air, then oxidized further. 
The color grades gradually from pink to brown then to black, so it should be sealed and stored in a cool and dry 

Paracetamol has the antipyretic activity by inhibiting the synthesis of hypothalamic thermoregulation prostaglandins and its strength of antipyretic effect is similar to aspirin. 
On the other hand, Paracetamol can produce analgesic effect by inhibiting the synthesis of prostaglandins in the central nervous system and blocking impulses of nociceptive nerve endings, but weaker than aspirin. 
Compared with aspirin, Acetaminophen has minor irritation, few allergic reactions and other advantages. 

Its antipyretic and analgesic effect is similar to phenacetin, and the use of Acetaminophen increases due to limiting or banning using phenacetin in many countries.
In clinical, it is mainly used for fever and headache caused by cold and relieving mild to moderate pain such as joint pain, muscle pain, neuralgia, migraine, dysmenorrhea, cancer pain, postoperative analgesia and so on. 
Paracetamol can be used for patients who are allergic to aspirin, intolerant of aspirin, or unsuited for aspirin, such as patients with varicella, hemophilia and other hemorrhagic disease (patients having anticoagulant therapy included), as well as patients with slight peptic ulcer and gastritis. 

In addition, it also can be used for the synthesis of benorylate and used as asymmetric synthetic intermediates, photographic chemicals and stabilizer of hydrogen peroxide.
Paracetamol is an effective antipyretic and analgesic that is well tolerated at therapeutic doses. 
Paracetamol has only weak antiinflammatory activity; thus, it is not useful in the treatment of rheumatoid arthritis and other inflammatory conditions.

Paracetamol is exactly the same drug as acetaminophen (Tylenol). 
Paracetamol is the drug's name assigned using the International Nonproprietary Name (INN) generic name system. 
Paracetamol is the name used for the drug in places such as Europe, Australia, New Zealand and India. 

Paracetamol is the generic name assigned using the United States Adopted Names (USAN) system. 
Paracetamol is the name used in countries such as the US, Canada and Japan. 
Usually the INN and USAN generic names for a drug are the same and don't differ between countries.

Paracetamol, also commonly known as Tylenol, is the most commonly taken analgesic worldwide and is recommended as first-line therapy in pain conditions by the World Health Organization (WHO).
Paracetamol is also used for its antipyretic effects, helping to reduce fever.
This drug was initially approved by the U.S. FDA in 1951 and is available in a variety of forms including syrup form, regular tablets, effervescent tablets, injection, suppository, and other forms.

Paracetamol is often found combined with other drugs in more than 600 over the counter (OTC) allergy medications, cold medications, sleep medications, pain relievers, and other products.
Confusion about dosing of this drug may be caused by the availability of different formulas, strengths, and dosage instructions for children of different ages.
Due to the possibility of fatal overdose and liver failure associated with the incorrect use of Paracetamol, it is important to follow current and available national and manufacturer dosing guidelines while this drug is taken or prescribed.

Melting point: 168–172 °C (lit.)
Boiling point: 273.17 °C (rough estimate)
Density: 1.293 g/cm³
Vapor pressure: 0.008 Pa at 25 °C
Refractive index: 1.5810 (rough estimate)
Flash point: 11 °C
Storage temperature: Inert atmosphere, room temperature
Solubility in ethanol: Soluble, 0.5 M, clear, colorless
Form: Crystals or crystalline powder
pKa: 9.86 ± 0.13 (Predicted)
Color: White
pH range (saturated solution): 5.5–6.5 (H₂O, 20 °C)
Odor: Odorless
Explosive limit: 15% (V)
Water solubility: 14 g/L (20 °C)
Merck: 14,47
BRN: 2208089
BCS Class: 3,4
InChIKey: RZVAJINKPMORJF-UHFFFAOYSA-N
LogP: 1.098 at 25 °C

Paracetamol is an analgesic and antipyretic compound. Unlike many NSAIDs, which inhibit both COX-1 and COX-2, early studies suggested that acetaminophen is a poor inhibitor of both isoforms. 
However, it does inhibit COX-2 by 83% and COX-1 by 56% in human blood ex vivo, albeit at a high 1,000 mg dose, with IC50 values of 25.8 and 113.7 μM, respectively. 
Paracetamol is enzymatically and non-enzymatically converted to several reactive metabolites that contribute to adverse or indirect effects, including liver injury. 

At toxic doses, the acetaminophen metabolite N-acetyl-4-benzoquinone imine (NAPQI; ) depletes glutathione reserves in the liver, leading to an accumulation of NAPQI and subsequent hepatocyte necrosis. 
Paracetamol decreases glutathione levels and reduces glutathione peroxidase activity in mice when administered at a dose of 250 mg/kg and induces ferroptotic cell death in primary mouse hepatocytes, an effect that can be blocked by the ferroptosis inhibitor ferrostatin-1. 
Paracetamol has analgesic and antipyretic properties in animal models.

Paracetamol is absorbed rapidly from the small intestine after oral administration; peak plasma concentrations are reached after 30–60min. 
It may also be given rectally and intravenously (either as paracetamol or the prodrug propacetamol). 
Paracetamol has good oral bioavailability (70%–90%); rectal absorption is more variable (bioavailability ~50%–80%) with a longer time to reach peak plasma concentration. 

The plasma half-life is approximately 2–3 h.
Paracetamol is metabolised by hepatic microsomal enzymes mainly to the glucuronide, sulphate and cysteine conjugates. 
None of these metabolites is pharmacologically active. 

Aminimal amount of the metabolite N-acetyl-pamino- benzoquinone imine is normally produced by cytochrome P450– mediated hydroxylation. 
This reactive toxic metabolite is rendered harmless by conjugation with liver glutathione, then excreted renally as mercapturic derivatives. 
With larger doses of paracetamol, the rate of formation of the reactive metabolite exceeds that of glutathione conjugation, and the reactive metabolite combines with hepatocellular macromolecules, resulting in cell death and potentially fatal hepatic failure. 

The formation of this metabolite is increased by drugs inducing cytochrome P450 enzymes, such as barbiturates or carbamazepine.
Side effects are rare and may include hematological reactions, leucopenia, agranulocytosis and other hypersensitivity reactions. 
Paracetamol has a narrowtherapeutic dose range and overdosage induces severe liver and renal damage via accumulation of a toxic metabolite, N-acetylbenzoquinoneimine (NABQI). 

Paracetamol or methionine, which increase glutathione conjugation of the metabolite, are used as antidote.
Paracetamol is metabolized by mice, and nine metabolites are identified in the urine. 
The main metabolites are APAP-glucuronide and 3-cysteinyl- APAP. 

Hydroquinone metabolites of S-(2,5- dihydroxyphenyl)cysteine and S-(2,5-dihydroxyphenyl)- N-acetylcysteine result from the benzoquinone metabolite of APAP.
Paracetamol is antipyretic and analgesic whose international nonproprietary name is Paracetamol. 
Paracetamol is the most common non anti-inflammatory analgesia-antipyretic drugs without anti inflammatory and anti rheumatism action. 

Its antipyretic effect is similar to aspirin, but analgesic effect is weak. 
Paracetamol is the best of breed of acetanilid drugs. 
Paracetamol is especially suitable for patients who cannot use carboxylic acids drugs. 

Paracetamol is used for cold and toothache. 
Paracetamol is also used as organic synthesis intermediates, stabilizer of hydrogen peroxide, photographic chemicals.
Paracetamol is recommended by the ACR as first-line drug therapy for pain management of OA. 

Paracetamol has less and slight side effects a dose treatment except for occasional rashes, hives and other allergic reactions. 
Paracetamol may occur in a few cases.
A large number of long-term use,  hepatorenal damages and thrombocytopenia may occur, even jaundice, oliguria, acute severe hepatitis, which could lead to coma, and death. 

Using at high dosage may cause nausea, vomiting, stomach pain, stomach cramps, diarrhea, anorexia, sweating, etc.
For children under the age of 3, the development of liver and kidney function is not mature with poor detoxification and excretory function, so they should try to avoid using this product. 
In addition, patients with liver and kidney insufficiency and pregnant women should use cautiously. 

The long-term drug users should regularly check renal function and hemogram.
Pain after a dental surgery provides a reliable model for the action of analgesics on other kinds of acute pain.
For the relief of such pain, paracetamol is inferior to ibuprofen.

Full therapeutic doses of nonsteroidal anti-inflammatory drugs (NSAIDs) ibuprofen, naproxen, or diclofenac are clearly more efficacious than the paracetamol/codeine combination which is frequently prescribed for dental pain.
The combinations of paracetamol and NSAIDs ibuprofen or diclofenac are promising, possibly offering better pain control than either paracetamol or the NSAID alone.

Additionally, the paracetamol/ibuprofen combination may be superior to paracetamol/codeine and ibuprofen/codeine combinations.
Paracetamol safety in pregnancy has been under increased scrutiny. 
There appears to be no link between paracetamol use in the first trimester and adverse pregnancy outcomes or birth defects. 

However, indications exist of a possible increase in the risk of asthma and developmental and reproductive disorders in the offspring of women with prolonged use of paracetamol during pregnancy.
Paracetamol use by the mother during pregnancy is associated with an increased risk of childhood asthma, but so are the maternal infections for which paracetamol may be used, and separating these influences is difficult.

Paracetamol, in a small-scale meta-analysis was also associated with a 20–30% increase in autism spectrum disorder, attention deficit hyperactivity disorder, and conduct disorder, with the association being lower in a meta-analysis where a larger demographic was used, but it is unclear whether this is a causal relationship and whether there was potential bias in the findings.
There is also an argument that the large number, consistency, and robust designs of the studies provide strong evidence in favor of paracetamol causing the increased risk of these neurodevelopmental disorders.

In animal experiments, paracetamol disrupts fetal testosterone production, and several epidemiological studies linked cryptorchidism with mother's paracetamol use for more than two weeks in the second trimester. 
On the other hand, several studies did not find any association.

Paracetamol (Panadol, Calpol, Alvedon) is an analgesic and antipyretic drug that is used to temporarily relieve mild-to-moderate pain and fever. 
Paracetamol is commonly included as an ingredient in cold and flu medications and is also used on its own.

Uses:
Paracetamol is widely used as an analgesic and fever-reducing agent. 
Paracetamol is designed for moderate analgesia. 
It is also effective like aspirin and is used in analgesia for headaches (from weak to moderate pain), myalgia, arthralgia, chronic pain, for oncological and post-operational pain, etc.

Paracetamol is used for reducing fever.
However, there has been a lack of research on its antipyretic properties, particularly in adults, and thus its benefits are unclear.
As a result, it has been described as over-prescribed for this application.

In addition, low-quality clinical data indicates that when used for the common cold, paracetamol may relieve a stuffed or runny nose, but not other cold symptoms such as sore throat, malaise, sneezing, or cough.
For people in critical care, paracetamol decreases body temperature by only 0.2–0.3 °C more than control interventions and has no effect on their mortality.
Paracetamol did not change the outcome in febrile patients with stroke.

The results are contradictory for paracetamol use in sepsis: higher mortality, lower mortality, and no change in mortality were all reported.
Paracetamol offered no benefit in the treatment of dengue fever and was accompanied by a higher rate of liver enzyme elevation: a sign of potential liver damage.
Overall, there is no support for a routine administration of antipyretic drugs, including paracetamol, to hospitalized patients with fever and infection.

The efficacy of paracetamol in children with fever is unclear.[54] Paracetamol should not be used solely to reduce body temperature; however, it may be considered for children with fever who appear distressed.
Paracetamol does not prevent febrile seizures.
Paracetamol appears that 0.2 °C decrease of the body temperature in children after a standard dose of paracetamol is of questionable value, particularly in emergencies.

Based on this, some physicians advocate using higher doses that may decrease the temperature by as much as 0.7 °C.
Meta-analyses showed that paracetamol is less effective than ibuprofen in children (marginally less effective, according to another analysis), including children younger than 2 years old, with equivalent safety.

Exacerbation of asthma occurs with similar frequency for both medications.
Giving paracetamol and ibuprofen together at the same time to children under 5 is not recommended; however, doses may be alternated if required.
Paracetamol is widely used as a first-line analgesic for the temporary relief of mild to moderate pain, including headaches, migraines, musculoskeletal pain, osteoarthritis, toothaches, menstrual cramps, post-operative pain, and minor injuries, where its central action on prostaglandin synthesis allows it to reduce pain perception without causing significant gastrointestinal irritation, bleeding, or cardiovascular side effects that are commonly associated with NSAIDs.

Paracetamol is also extensively employed as an antipyretic agent to lower fever associated with infections such as colds, influenza, or other viral illnesses, providing symptomatic relief and comfort in both adults and children, and is often formulated in combination with other medications, such as cough suppressants, decongestants, or opioid analgesics, to enhance therapeutic effects in multi-symptom treatment regimens.
In clinical and hospital settings, Paracetamol is used intravenously or orally to manage post-operative pain, pain associated with cancer or chronic illnesses, and fever in patients who cannot tolerate NSAIDs, such as those with peptic ulcers, renal impairment, or cardiovascular risk factors, due to its generally favorable safety profile at recommended doses.

Paracetamol is used for the relief of mild to moderate pain such as headache, muscle aches, minor arthritis pain, and toothache, as well as pain caused by cold, flu, sprains, and dysmenorrhea.
Paracetamol is recommended, in particular, for acute mild to moderate pain, since the evidence for the treatment of chronic pain is insufficient.
The benefits of paracetamol in musculoskeletal conditions, such as osteoarthritis and backache, are uncertain.

Paracetamol appears to provide only small and not clinically important benefits in osteoarthritis.
American College of Rheumatology and Arthritis Foundation guideline for the management of osteoarthritis notes that the effect size in clinical trials of paracetamol has been very small, which suggests that for most individuals it is ineffective.

The guideline conditionally recommends paracetamol for short-term and episodic use to those who do not tolerate nonsteroidal anti-inflammatory drugs. 
For people taking it regularly, monitoring for liver toxicity is required.[27] Essentially the same recommendation was issued by EULAR for hand osteoarthritis.
Similarly, the ESCEO algorithm for the treatment of knee osteoarthritis recommends limiting the use of paracetamol to short-term rescue analgesia only.

Paracetamol is ineffective for acute low back pain.
No randomized clinical trials evaluated its use for chronic or radicular back pain, and the evidence in favor of paracetamol is lacking.
Paracetamol is effective for acute migraine: 39% of people experience pain relief at one hour compared with 20% in the control group.

The aspirin/paracetamol/caffeine combination also "has strong evidence of effectiveness and can be used as a first-line treatment for migraine".
Paracetamol on its own only slightly alleviates episodic tension headache in those who have them frequently.
However, the aspirin/paracetamol/caffeine combination is superior to both paracetamol alone and placebo and offers meaningful relief of tension headache: two hours after administering the medication, 29% of those who took the combination were pain-free as compared with 21% on paracetamol and 18% on placebo.

The German, Austrian, and Swiss headache societies and the German Society of Neurology recommend this combination as a "highlighted" one for self-medication of tension headache, with paracetamol/caffeine combination being a "remedy of first choice", and paracetamol a "remedy of second choice".
Paracetamol span over-the-counter self-medication for everyday pain and fever, pediatric and adult clinical management of acute and chronic pain conditions, and incorporation into combination therapies to optimize analgesic and antipyretic efficacy while maintaining a safer side-effect profile than many alternative medications, making it one of the most widely consumed and versatile drugs globally.

Safety Profile:
Paracetamol is generally considered safe when used at recommended therapeutic doses, but excessive ingestion can lead to severe hepatotoxicity due to the accumulation of a toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), which depletes glutathione and causes oxidative damage to liver cells, potentially resulting in acute liver failure, jaundice, coagulopathy, and in severe cases, death, making it one of the most common causes of drug-induced liver injury worldwide.

Even at standard doses, individuals with pre-existing liver disease, chronic alcohol consumption, malnutrition, or concurrent use of other hepatotoxic drugs may be at higher risk of liver damage, while overdose may occur accidentally in adults taking multiple combination medications containing Paracetamol, such as cold and flu remedies, or intentionally, which underscores the importance of careful dosing and monitoring of cumulative intake.
Other potential hazards include allergic reactions, skin rashes, or hypersensitivity in sensitive individuals, although these are rare, and long-term excessive use may contribute to renal impairment, gastrointestinal disturbances, or hematologic effects, particularly in vulnerable populations or with chronic high-dose use.