Paracetamol
Paracetamol (INN), also known as acetaminophen or acetaminophen or p-Acetylaminophenol, is a drug with analgesic and antipyretic properties used primarily to treat fever and mild to moderate pain, although its efficacy in relieving fever in children is unclear.
It is often marketed in medications where it is combined with other active ingredients, such as cough suppressants, or in opioid pain relief medications, where acetaminophen is used for the relief of very severe pain, such as cancer pain or after an operation. It is usually administered orally although it is also available for use rectally or intravenously, so it can come in the form of capsules, tablets, suppositories or drops. Its effects last between two and four hours.
Acetaminophen is normally safe, as long as recommended doses are respected, it can also continue to be used in patients with liver disease at low doses and is safe during pregnancy and breastfeeding. However, at high doses It can cause liver failure, alter platelet function, cause severe skin reactions or anaphylactic shock (although only rarely), and an overdose of the drug can be life-threatening. Paracetamol is classified as a mild pain reliever. and it does not have significant anti-inflammatory activity, although it is not yet known for sure how it works in this area.
Pacetaminophen was discovered in Germany in 1877 and is the most widely used medicine for pain and fever relief in Europe and the United States. It is on the list of essential medicines drawn up by the World Health Organization, where all the basic drugs needed in any health system are listed. Paracetamol is available as a generic drug and under numerous trade names. The wholesale price in developing countries is less than one cent on the dollar (USD) the dose, while in developed countries its price is significantly higher, for example in the United States its price is around four cents per dose.
Medical uses
Acetaminophen has a number of accepted medical uses, focusing on the treatment of fever and pain, either alone or in combination with other medications.
Fever
Paracetamol is used to reduce fever in people of all ages, however the World Health Organization (WHO) recommends that paracetamol should only be used in children when their body temperature is above 38.5°C The efficacy of paracetamol in relieving fever in children has been questioned when not used in conjunction with other medications, even a meta-analysis seemed to show that it is less effective than ibuprofen.
Pain
Acetaminophen is used to relieve mild and moderate pain. The efficacy of its use intravenously to relieve pain in people in the emergency department has been questioned.
The American College of Rheumatology recommends acetaminophen as one of several options for the treatment of hip, hand, or knee pain from arthritis that does not improve with weight loss or exercise. However, a review of 2015 concluded that it provides only a small benefit in the treatment of osteoarthritis. Paracetamol has relatively little anti-inflammatory activity, unlike other widely used drugs such as aspirin or ibuprofen, which are part of the NSAIDs, although ibuprofen and paracetamol have similar effects in the treatment of headache. Paracetamol also relieves pain from mild arthritis, but has no effect on inflammation and swelling of the joint. Its analgesic properties have been described as similar to those of aspirin, but as mentioned, the anti-inflammatory effects they are much weaker, although they have a higher tolerance index than acetylsalicylic acid. Similarly, paracetamol in combination with an NSAID may be more effective in relieving pain resulting from an operation than if it is administered individually.
The American College of Physicians and the American Pain Society recommend the use of acetaminophen to treat back pain, however there are discrepancies, as these recommendations are based on a 2007 systematic review and subsequent reviews have concluded, on the contrary, that there is no evidence of its effectiveness in treating this condition.
NSAIDs such as ibuprofen, naproxen, or diclofenac are more effective than acetaminophen in controlling dental pain, but combining an NSAID with acetaminophen is more effective, and in fact this combination can be used when NSAIDs are not effective in managing this pain on their own. Acetaminophen is particularly useful when the user cannot take NSAIDs due to allergy, hypersensitivity, or bleeding (among others). An investigation by the Cochrane Collaboration group on the use of analgesics before oral treatment in children and adolescents concluded that there is no evidence that the consumption of paracetamol before a dental operation reduces pain after treatment, however the quality of the study is considered low.
The effectiveness of the medication when combined with weak opioids such as codeine is increased in approximately 50% of patients, but comes with an increased number of possible side effects; similarly, medications that combine acetaminophen and strong opioids, such as morphine, have a better analgesic effect. There is also evidence that the combination of paracetamol and caffeine is more effective than paracetamol alone, although only in relieving mild common pain.
Patent ductus arteriosus
Paracetamol is also used to treat patent ductus arteriosus, a disease that consists of the persistence, after birth, of the communication that normally exists between the pulmonary arterial system and the aorta during fetal life, however there is no insufficient evidence on the efficacy and safety of the drug for the treatment of this problem. Non-steroidal anti-inflammatory drugs (NSAIDs), particularly indomethacin and ibuprofen, have also been used for this, but their efficacy is also disputed.
Summary
The reaction of p-aminophenol with acetic anhydride produces the acetylation of the former, obtaining paracetamol and acetic acid as products.
Pharmacodynamics
For a long time it has been believed that the mechanism of action of acetaminophen is almost the same as that of acetylsalicylic acid (ASA). In other words, it works by reducing the synthesis of prostaglandins, compounds related to febrile processes and pain, by inhibiting cyclooxygenase (COX).
But, there are important differences between the effects of aspirin and acetaminophen. Prostaglandins are involved in inflammatory processes, but paracetamol does not have appreciable anti-inflammatory activity. In addition, COX also participates in the synthesis of thromboxanes that promote blood coagulation; ASA has antiplatelet effects, but paracetamol does not. Finally, ASA and other NSAIDs are harmful to the gastric mucosa, where prostaglandins play a protective role, but in this case paracetamol is safe.
In this way, while ASA acts as an irreversible inhibitor of COX and blocks the active center of the enzyme directly, paracetamol blocks it indirectly and this block is useless in the presence of peroxides. This could explain why Paracetamol is effective on the central nervous system and endothelial cells, but not on platelets and cells of the immune system, which have high levels of peroxides.
Swierkosz et al. (2002) found evidence indicating that acetaminophen inhibits a variant of the COX enzyme that is different from the COX-1 and COX-2 variants, now called COX-3 Its exact mechanism of action is not yet well understood, but future research may clarify it.
Recent studies indicate that paracetamol could apparently modulate the endogenous cannabinoid system in the brain through its metabolite, AM404 (N-arachidonoylaminophenol), which appears to inhibit the reuptake of endogenous anandamide thereby which is further available to reduce pain, as well as possibly directly activating TRPV1 which also inhibits pain signals in the brain.
Pharmacokinetics
Paracetamol is rapidly and completely absorbed orally, and fairly well rectally, having the advantage of avoiding the first hepatic pass. There are also intravenous preparations. The maximum plasma concentrations are reached depending on the pharmaceutical form, with a time, until the maximum concentration, of 0.5-2 hours. Paracetamol is rapidly distributed throughout all tissues. Concentrations are similar in blood, saliva, and plasma. The binding rate to plasma proteins is low. Bioavailability is very high (close to 100%), with oral bioavailability of 75-85%. Paracetamol is mainly metabolized in the liver. The two main metabolic pathways are glucide and sulfide conjugation. This last pathway is quickly saturated with doses higher than therapeutic. Only a small proportion is metabolized by the cytochrome P-450 enzymatic system in the liver, by action of mixed oxidases, generating a reactive intermediate, N-acetylbenzoquinoneimide, which is inactivated (detoxified) under normal conditions by reaction with sulfhydryl groups. glutathione and excreted in the urine conjugated with cysteine and mercapturic acid. On the contrary, during severe poisoning the amount of this toxic metabolite increases. High doses of acetaminophen saturate your other two metabolic pathways and create an excess of N-acetylbenzoquinoneimide that depletes liver glutathione levels. The metabolite can then covalently react with amino acids in liver enzymes and proteins, inactivating them, eventually leading to acute hepatic necrosis. Children have a lower capacity for glucuronidation, which makes them more susceptible to this disorder. Elimination is mainly urinary. 90% of the ingested dose is eliminated by the kidney in 24 hours, mainly as glucuronides (60 to 80%) and sulfoconjugates (20 to 30%). Less than 5% is removed unchanged. The elimination half-life of paracetamol is 2-4 hours in patients with normal liver function, being practically undetectable in plasma 8 hours after its administration. In patients with hepatic dysfunction the half-life is substantially increased, which may lead to the development of hepatic necrosis.
Toxicity
General considerations
The recommended dose per administration for an adult is 1 g and toxic doses are described as ranging from 7.5 to 10 g.
Acetaminophen has a very tight therapeutic index. This means that the maximum normal dose (4 g per day in adults) is close to overdose, making it a dangerous compound. A single dose of paracetamol of 10 g grams or continued doses of 5 g per day in a person in good health, and even 4 g per day in a regular consumer of alcohol, can cause significant liver damage. When taken in toxic doses, it becomes a potent hepatoxin, causing fulminant renal and hepatic tubular necrosis, lethal in humans and many species of animals such as rodents. Due to the wide availability without a prescription of paracetamol (acetaminophen)—as a Pharmaceutical Specialty Advertising, EFP=OTC (OTC in the US)—, this has been used in many suicide attempts. The specific antidote for poisoning by paracetamol—or acetaminophen—is intravenous acetyl-cysteine. The FDA —the US Food and Drug Administration— asked all laboratories to stop marketing paracetamol —acetaminophen— in unit doses greater than 650 mg; Total daily doses of 3,000 mg (3 g) can be highly toxic or fatal to some people.
Used responsibly, acetaminophen is one of the safest treatments available for analgesia. The compound has no effect on the cyclooxygenase system, therefore it does not have negative effects on the esophagus, stomach, small intestine or large intestine, unlike NSAIDs. Also, patients with kidney disease can take acetaminophen while NSAIDs can cause acute renal failure in certain patients. Also, acetaminophen has few drug interaction problems.
The potency of the analgesic is equivalent, when there is no inflammation, to that of NSAIDs, as long as the dose of paracetamol is adequate. A daily gram of paracetamol has an analgesic effect equivalent to that of NSAIDs, for example in osteoarthritis (in Spain, osteoarthritis). When given concomitantly with the tricyclic antidepressant amitriptyline 50 mg twice daily, this combination is as effective as acetaminophen and codeine but does not lose effectiveness over time as occurs with chronic narcotic administration. Unlike aspirin, acetaminophen does not contribute to Reye's syndrome in children with viral illnesses. These factors have made acetaminophen the analgesic of choice for inpatients for mild to moderate pain, as well as the most widely used analgesic for outpatients.
This analgesic is also used to control myalgias and arthralgias that occur with classic dengue fever, dengue hemorrhagic fever, chikungunya, and Zika, since NSAIDs are contraindicated in this type of viral infection, as they favor the destruction of platelets. It is also used in patients with hematological diseases such as leukemia, Hodgkin's lymphoma, Hodgkin's disease when they develop fever or pain and in rheumatic diseases such as both seropositive and seronegative rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome.
Acetaminophen is extremely toxic to cats and should not be administered under any circumstances. In dogs and other companion animals, the recommended dose differs from the usual dose for humans and its administration should always be supervised by a veterinarian. Any suspected case of overdose or poisoning should be evaluated by a veterinarian for treatment. Treatment in cats is very similar to that in humans. Acetaminophen is the most widely used pain reliever in the United States (Tylenol), but it can cause liver damage at ordinary or slightly higher doses. That fact will be news to many consumers, but known to liver specialists, and was officially recognized in April 2009 by the Food and Drug Administration (FDA). The FDA's advisory committee stated 32 years ago: "the recommended dosage [acetaminophen-Tylenol] should not be exceeded because it can cause severe liver injury and even death."[citation needed]
Diagnosis
Clear symptoms of liver toxicity may occur within 1 to 4 days, although in some cases these may be evident in as little as 12 hours. There may be discomfort in the upper right quadrant. Analysis can determine the existence of massive hepatic necrosis if elevated levels of AST, ALT, bilirubin, and elevated clotting times (specifically, elevated prothrombin times) are detected. Acetaminophen hepatotoxicity can be diagnosed if after an overdose of acetaminophen the AST and ALT exceed 1000 IU/L. However, AST and ALT levels can exceed 10,000 IU/L. In general, in acetaminophen-induced hepatotoxicity, AST levels are somewhat higher than ALT.
There are paracetamol nomograms that allow estimating the risk of toxicity based on its concentration in blood serum after a certain number of hours. To determine the potential risk of hepatotoxicity, the acetaminophen level should be followed along with the standard nomogram. A paracetamol level traced during the first hours of ingestion could underestimate the actual amount in the body, because at that time the paracetamol could still be absorbed from the gastrointestinal tract. A delay in determining the level of paracetamol in the body is not recommended, since in these cases the estimates may not be adequate and a toxic level at any time is sufficient to administer the antidote.
Mechanism of toxicity
As mentioned above, paracetamol is metabolized into inactive compounds by combination with sulfate and glucuronic acid, with a small part being metabolized by the cytochrome P-450 system. It oxidizes acetaminophen to produce a highly reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Under normal conditions, NAPQI is neutralized by the action of glutathione.
In episodes of acetaminophen toxicity, the sulfate and glucuronide metabolic pathways become saturated and more acetaminophen is diverted to the cytochrome P-450 system where NAPQI is produced. Consequently, hepatocellular supplies of glutathione are depleted and in NAPQI it can freely react with cell membranes, causing extensive damage and death of many hepatocytes, resulting in acute hepatic necrosis. In animal studies, 70% of hepatic glutathione must be consumed before hepatotoxicity occurs.
Risk factors
The toxic dose of paracetamol is highly variable:
- In adults, unique doses above 7.5 g or 150 mg/kg have a reasonable probability of causing hepatotoxicity; dose of more than 25 grams are potentially lethal.[chuckles]required]
- Children are considered toxic to 150 mg/kg.
- Hepatotoxicity may also occur when small doses, but multiple doses exceed such amounts in 24 hours, or by chronic intake of small doses.
- Excessive alcohol consumption can affect kidney function and increase the toxicity of paracetamol. For this reason, after large intakes of alcohol, other painkillers such as ibuprofen or acetylsalicylic acid are recommended.[chuckles]required] While there is a risk of injury to the gastric mucosa, it is therefore appropriate to take them together with an H2 antagonist such as the ranitidine or a proton pump inhibitor such as omeprazole.
Some people are more prone to hepatotoxicity, even at low doses like 4 g/day, and lethal doses can be as low as 6 g/day. Fasting is a risk factor, possibly due to reduced liver glutathione stores. Use in combination with CYP2E1 inducers such as isoniazid is well documented to potentiate hepatotoxicity, although this relationship is not entirely clear. Alcoholism, which also results in CYP2E1 production, also increases the risk of hepatotoxicity of paracetamol.
The use in combination with other drugs that induce the synthesis of CYP enzymes, such as antiepileptics (carbamazepine, phenytoin, barbiturates, etc.) have also been presented as risk factors.
Evolution
People who have overdosed on acetaminophen usually have no symptoms for the first 24 hours. Although nausea, vomiting, and diaphoresis are common symptoms initially, they subside after several hours. After alleviating these symptoms, patients experience an improvement, and may even think that the worst is over. However, after ingesting a toxic dose, liver failure would occur after these symptoms.
The damage generally occurs in the hepatocytes as they metabolize the acetaminophen. However, acute renal failure can also occur. This is also usually caused by hepatorenal failure or multiple organ failure. The main clinical manifestation of poisoning could also be acute renal failure. In these cases, it is possible that the toxic metabolite is produced in greater quantities in the kidneys than in the liver.
The prognosis of paracetamol overdose varies depending on the dose and the treatment used. In some cases, massive hepatic necrosis results in fulminant liver failure, with complications such as hemorrhage, hypoglycemia, renal failure, hepatic encephalopathy, cerebral edema, sepsis, multiple organ failure, and death within a few days. In many cases, hepatic necrosis can continue, normal liver function returns, and the patient can survive with normal liver function within a few weeks.
Overdose
Rescue measures
- Gastric washing
The treatment for paracetamol overdose, without complications, is similar to that used in other medications, a gastrointestinal lavage. Additionally, administering N-acetylcysteine, either intravenously or orally, helps a lot in these cases. There is sufficient leeway for the physician to judge in this case whether a complete gastrointestinal lavage is necessary or simply administering activated charcoal. Total absorption of paracetamol from the gastrointestinal tract is complete in approximately two hours. In these cases, syrup of ipecac (an emetic) is not effective, since it induces vomiting and this only delays the effectiveness of activated charcoal and N-acetylcysteine, as they have to be administered after the vomiting has stopped.. Gastric lavage is effective for the first two hours after ingestion. After that, it is of no clinical utility.
- Carboon activated
Typically, administration of activated charcoal is more effective than gastric lavage. This absorbs paracetamol well, and therefore the amount absorbed from the gastrointestinal tract is reduced. In addition, it also poses less risk of aspiration than gastric lavage. Some time ago there was some reluctance to administer activated charcoal, due to the fear that it would also absorb N-acetylcysteine. Recent studies have shown that the amount absorbed by this route does not exceed 39% when both are administered together. Other studies have shown that activated charcoal appears to be beneficial for the patient. There is a general consensus on administering activated charcoal during the first 4 hours after the overdose; After this time, it depends on the doctor's criteria, but in any case it is considered a benign treatment. If there are concerns about the ingestion of paracetamol along with other medications, then activated charcoal should be administered. There is disagreement as to whether to change the dose of N-acetylcysteine administered, or even whether it should be changed.
The dose of activated charcoal is 2 g/kg of the patient's weight up to a maximum of 100 total grams. In children, the dose is 1 g/kg. It is administered orally and can be mixed with water or juice to partly mask its bad taste.
Acetylcysteine
N-acetylcysteine (NAC) acts by providing sulfhydryl groups so that they react with the toxic metabolite and thus do not attack hepatocytes. If NAC is administered within the first eight hours, toxicity is markedly reduced. If administered after eight hours, its effectiveness is reduced because the cascade of toxic reactions in the liver has already begun, and the risk of hepatic necrosis is greatly increased. Oral NAC is a safe medication, it is reliable in cases of paracetamol overdose during pregnancy, and there are no adverse reactions with a fatal prognosis. The manufacturer recommends not administering NAC if there is encephalopathy, because there are theoretical reasons that the encephalopathy could worsen. In early 2004, the US Food and Drug Administration (FDA) authorized the use, for patients with an overdose of more than 10 hours, of a NAC preparation for intravenous infusion (total dose 300 mg/ kg) for a period of 20 hours, which lacks pyrogenic effects. This preparation has been used successfully for years in other countries, such as Australia, Canada and Great Britain.
- Administration
This treatment consists of an initial administration of 150 mg/kg over 15 minutes, followed by 50 mg/kg over the next four hours and finally 100 mg/kg over the remaining 16 hours. The oral formulation can also be dissolved, filtered, and sterilized by a hospital pharmacist for intravenous administration. This is a good option in cases where the enteral route is not feasible or is contraindicated. Intravenous administration of NAC is related to cases of allergic reactions such as anaphylactic shock and bronchospasms.
In practice, if more than eight hours have elapsed after ingestion, activated charcoal is ineffective and NAC should be administered immediately. If less than 8 hours have elapsed, give activated charcoal, start NAC, and wait to see paracetamol levels. In patients with an overdose of less than 8 hours, the risk of hepatotoxicity is reduced. If more than two doses of activated charcoal are administered because the patient has ingested two or more medications, subsequent administrations of activated charcoal and NAC should be delayed by two hours. NAC is effective if administered promptly, but can be effective even 48 hours after the overdose.
Oral NAC is generally administered enterally with a first dose of 140 mg/kg followed by 17 additional doses, every four hours, of 40 mg/kg or until nontoxic acetaminophen plasma concentrations are obtained. NAC can be difficult to administer due to its taste and often causes vomiting and nausea. To maximize your tolerance, it can be diluted 20% to 5% from commercial doses. Initial laboratory studies should include bilirubin, AST, ALT, and prothrombin time. Analyzes should be repeated at least daily. Once it has been determined that a potentially toxic dose has been ingested, all 17 doses of NAC should be administered, even though acetaminophen becomes undetectable in the blood. If liver failure develops, the 17 doses should be continued until normal liver function is restored or a liver transplant is performed.
Forecast
The risk of mortality from overdose begins to increase after two days, peaks at four days, and then gradually decreases. Patients with a poor outcome should be immediately transferred to a center capable of performing liver transplants. Acidosis is the most ominous factor that betrays the risk of mortality and the need for a transplant.
In non-transplant patients, a 95% mortality factor has been established when the blood pH falls below 7.3. Other indicators of a poor medical prognosis include renal failure, grade 3 or greater hepatic encephalopathy, a markedly elevated prothrombin time or an increase in prothrombin time from day 3 to 4. One study has shown that a lower than factor V test 10% of normal indicates a poor prognosis (91% mortality), while a ratio of less than 30 between factor VIII and V are indicators of a good prognosis (100% survival).
History
In ancient times and during the Middle Ages, the only known antipyretic agents were compounds present in willow bark (a family of compounds known as salicillins, which eventually gave rise to acetylsalicylic acid), and others contained in the bark of the quina The cinchona bark was used to obtain quinine, a compound with antimalarial activity. Quinine itself also has antipyretic activity. Efforts to isolate and purify salicin and salicylic acid took place during the mid to late 19th century century.
When quina became scarce in the 1880s, people began looking for alternatives. Two alternative antipyretic agents were developed in the 1880s: acetanilide in 1886 and phenacetin in 1887. At that time, paracetamol had already been synthesized by Harmon Northrop Morse using the reduction of p-nitrophenol to glacial acetic acid. This fact occurred in 1873, but paracetamol was not used for medical purposes for two decades. In 1893, paracetamol was found in the urine of people who had ingested phenacetin and was isolated as a white, crystalline compound with a bitter taste. In 1899, paracetamol was identified as a metabolite of acetanilide. This discovery was widely ignored at the time.
In 1946, the Institute for the Study of Analgesic and Sedative Drugs awarded a grant to the New York Department of Sanitation[citation needed] to study the problems associated with the use of painkillers. Bernard Brodie and Julius Axelrod were assigned to investigate why compounds unrelated to aspirin give rise to methemoglobinemia, a non-fatal syndrome consisting of the deformation of the hemoglobin molecule and therefore causing its inability to transport oxygen effectively. In 1948 both researchers related the use of acetanilide with methemoglobinemia and deduced that its analgesic effect was due to its metabolite paracetamol. They proposed the use of paracetamol (acetaminophen) since it did not have the toxic effects of acetanilide.
Acetaminophen was released in the United States in 1955 under the trade name Tylenol.[citation needed] In 1956, 500 mg tablets of acetaminophen were released in the UK under the name Panadol, produced by Frederick Stearns & Co, a subsidiary of Sterling Drug Inc. Panadol was initially available only by prescription for pain and fever relief and was advertised as "stomach friendly" because other pain relievers contained acetylsalicylic acid, a known stomach irritant, but as early as April 2009 the US Food and Drug Administration requires manufacturers to report that acetaminophen, when administered in very high doses or with alcoholic beverages, can be highly toxic and potentially fatal, by virtue of the damage it can cause to the liver. In June 1958 a formulation for children, Panadol Elixir, was marketed. In 1963, paracetamol was added to the British formulary, and has since become popular as a pain reliever with few side effects and few drug interactions.
The patent on acetaminophen has expired in the United States, and several generics are widely available under the Price Competitiveness Act and the Patent Restoration Act of 1984, although certain Tylenol preparations were protected until 2007. In US Patent No. 6,126,967 dated September 3, 1998 was issued for "extended release acetaminophen preparations."
Commercial availability
It is usually marketed as a liquid suspension, in tablets or as a suppository.
Sold in Europe, Latin America, Asia and Australia, Panadol is the most widespread brand, sold in more than 80 countries. In North America, acetaminophen is sold as a generic or under various brand names: for example, Tylenol (McNeil-PPC, Inc), Anacin 3, and Datril.
In some formulations, paracetamol is combined with the opioid codeine, sometimes called co-codamol, such as Algidol (Almirall) in Spain, which makes it more toxic[citation required]. In the United States and Canada it is sold as Tylenol 1/2/3/4. In the UK and many other countries this combination is sold as Tylex CD and Panadeine. Other brands available are: Aeknil, Captin, Disprol, Dymadon, Fensum, Hedex, Mexalen, Nofedol, Tachipirin, Pediapirin, and Perfalgan. In Spain it can be purchased without a prescription either as a generic or as a "brand" drug, such as Efferalgan from (Upsa Laboratoires), Termalgin (Novartis), Gelocatil or Frenadol (composed with Dextromethorphan, ascorbic acid and chlorphenamine marketed by Johnson & Johnson).
It can also be combined with oxycodone, for example Percocet in the US.
Pfizer, for its part, markets it under the Atamel brand, Mead Johnson does the same under the Tempra brand, and Elmor as Tachipirin.
Environmental impact and degradation
One of the most widely found drugs and in the highest concentrations is paracetamol, a product that can be found in hospital effluents, effluents from treatment plants, rivers and sludge.
Unfortunately, drugs are designed to have certain characteristics, for example, about 30% of drugs are lipophilic, which means they dissolve in fat, but not in water. This characteristic allows these compounds to pass through cell membranes and act within them. On the other hand, drugs are designed to be persistent, so they maintain their chemical structure long enough to exert their therapeutic action, so once they enter the environment they persist in it.
Pacetaminophen in aqueous solution is susceptible to undergo hydrolysis to form p-aminophenol, it is susceptible to degrade into quinoneimine. The rate of degradation of paracetamol increases with increasing temperature and light. This rate is minimal at a pH close to 6.
To stabilize paracetamol in solution, a buffer and an antioxidant or radical scavenger agent are usually added. In the elimination of acetaminophen it has been observed to react with chlorine to form a large number of by-products, two of which have been identified as toxic.
Contenido relacionado
Síndrome de Alicia en el país de las maravillas
Acidosis respiratoria
Enfermedad de Tay-Sachs