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Treatment of Pain or Fever with Paracetamol (Acetaminophen) in the Alcoholic Patient

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An unexpected clinical question has emerged in the treatment of pain or fever in the alcoholic patient: Is paracetamol a safe medication for the alcoholic patient? After decades of use in a variety of patients, sporadic reports suggest a relationship between liver injury and the use of paracetamol by alcoholic patients. We performed a systematic review of the medical literature to answer the question: Can administration of therapeutic doses of paracetamol cause hepatic injury in the alcoholic patient? After extensive data retrieval, each article in any language that involved the use of paracetamol by an alcoholic patient was abstracted and categorized for strength of evidence. Class I data (randomized, controlled trials) show that repeated ingestion of a therapeutic dose of paracetamol over 48 hours by patients with severe alcoholism did not produce an increase in hepatic aminotransferase enzyme levels nor any clinical manifestations compared with a placebo group. Class II data (prospective, nonrandomized trials) reveal that therapeutic doses of paracetamol have been administered to patients and an array of liver diseases (alcoholic, primary biliary, postnecrotic, or unspecified cirrhosis or alcoholic, acute viral, chronic active, or other infectious hepatitis) for periods up to 14 days without adverse effect. Finally, in several studies, a 1- to 2-g single dose of paracetamol was administered to alcoholic patients to study metabolism, again without adverse effect. In contrast, Class III data (retrospective case reviews and case reports) describe hepatic injury after repeated paracetamol ingestion with therapeutic intent, although usually not at therapeutic doses. Unfortunately, the information contained in Class III reports is often incomplete and contradictory. The history of ingestion is often unknown or contradicts other clinical information provided. For example, the history may indicate a therapeutic dose, but the serum paracetamol is elevated to levels only produced by ingestion much larger than the history indicates. In summary, all methodologically sound studies available indicate that therapeutic dosing of paracetamol to the alcoholic patient is not associated with hepatic injury. In fact, there is no change at all in hepatic aminotransferase enzymes, prothrombin time, or other biochemical parameters when compared with a placebo group in well-designed trials. Unless stronger evidence of a potentially dangerous interaction emerges, the use of paracetamol in the alcoholic patient is reasonable. During chronic treatment of pain, paracetamol may be preferred in the compliant alcoholic patients owing to the adverse effects associated with long-term use of nonsteroidal anti-inflammatory agents.
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... AAP is highly consumed pharmaceutical, and it is a constituent in commonly available over-the-counter non-prescribed as well as prescribed drugs [2][3][4]. AAP is useful in treating patients with high fever and pain [5]. It is estimated about 1.4 × 10 5 tons/year of AAP is consumed throughout the world [4]. ...
... AAP is useful in treating patients with high fever and pain [5]. It is estimated about 1.4 × 10 5 tons/year of AAP is consumed throughout the world [4]. AAP absorption in the body is estimated to be in the range of 5-15% [6]. ...
... The photocatalytic degradation of AAP at different initial pH (3)(4)(5)(6)(7)(8)(9)(10) values is shown in Fig. 12a. The isoelectronic point of HT-g-C 3 N 4 was determined to be 4.6 (Fig. S6). ...
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Photocatalytic degradation of organic pollutants in water using graphitic carbon nitride and persulfate under visible light (g-C3N4/PS system) has been studied. Here, we demonstrate augmentation of photocatalytic degradation of Acetaminophen (AAP) using hydrothermally treated g-C3N4 and PS under 400 nm LED irradiation (HT-g-C3N4/PS system). A pseudo-first-order rate constant (kobs, 0.328 min−1) for degradation of AAP using HT-g-C3N4/PS system was determined to be 15 times higher compared to g-C3N4/PS system (kobs, 0.022 min−1). HT-g-C3N4 showed a higher surface area (81 m2/g) than g-C3N4 (21 m2/g). Photocurrent response for HT-g-C3N4 was higher (1.5 times) than g-C3N4. Moreover, Nyquist plot semicircle for HT-g-C3N4 was smaller compared to g-C3N4. These results confirm effective photoelectron-hole separation and charge-transfer in HT-g-C3N4 compared to g-C3N4. AAP degradation using HT-g-C3N4/PS system was significantly inhibited with O2.− and h+ scavengers compared to 1O2, SO4.− and HO. scavengers. ESR results revealed O2.− formation in HT-g-C3N4/PS system. Moreover, photocurrent measurements reveal AAP oxidation by h+ of HT-g-C3N4 was effective than g-C3N4. HT-g-C3N4 was reused for five cycles in HT-g-C3N4/PS system. Augmented photocatalytic degradation of AAP by HT-g-C3N4/PS system compared to g-C3N4/PS is attributed to effective photoelectron hole separation of HT-g-C3N4 that generates O2.− and h+ for oxidation of pollutant. Importantly, electrical energy per order (EEO) was 7.2 kWh m−3 order−1. kobs for degradation of AAP in simulated groundwater and tap water were determined as 0.029 and 0.035 min−1, respectively. Degradation intermediates of AAP were proposed. AAP ecotoxicity against marine bacteria Aliivibrio fischeri was completely removed after treatment by HT-g-C3N4/PS system.
... A systematic review concluded that alcoholic patients can safely receive acetaminophen in therapeutic doses (23). A randomized double-blinded placebo-controlled study aimed to assess if a maximal therapeutic dose of acetaminophen was associated with hepatic injury in patients with chronic alcohol abuse immediately following the cessation of alcohol intake. ...
... However, class 3 studies reported hepatotoxicity of acetaminophen in alcohol drinkers. Additionally, there is no effect on hepatic aminotransferase enzymes, prothrombin time, or other biochemical parameters in well-designed trials (23). A multicenter randomized study in which alcoholic patients took 4 g/d for 3 consecutive days and glutathione, aspartate aminotransferase (AST), ALT, and INR levels were compared with placeboreceiving group until 2 days following acetaminophen ingestion. ...
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Context: Pain management is essential for all patients, including those with liver diseases. Opiates should be used with caution in patients with liver diseases as they are well-known for constipation, sedation, and precipitate encephalopathy. Meanwhile, the principal fear of the use of non-steroidal anti-inflammatory drugs (NSAIDs) in liver disease is the danger of hastening renal impairment. Thus, acetaminophen is considered first-line therapy because of the side effects of other analgesics. However, there is an assumption that patients with chronic liver disease may be in danger when consuming the drug at therapeutic doses. Methods: Data were extracted from 33 papers. All articles were published until July 2020. The search was done using the following keywords: acetaminophen, Paracetamol, Cirrhosis, liver disease, chronic hepatitis, safety in reliable databases. A total of 414 articles were selected some of which were excluded owing to irrelevance, studies on animals and, the lack of access to the full text. Results: Cirrhotic patients could safely take acetaminophen in adjusted doses. Although acetaminophen was safely administered in therapeutic doses in alcoholic patients, there were reports of hepatotoxicity even in therapeutic doses. Acetaminophen was not recommended in patients with acute hepatitis but could be safely used in patients with chronic hepatitis. Patients with non-alcoholic fatty liver disease (NAFLD) were susceptible to acetaminophen toxicity. Conclusions: In spite of the conception that acetaminophen has dire consequences in liver disease, it can be safely administered in adjusted doses in most liver diseases.
... This is because of the reported cases on liver injury which have been associated with ofirmev injection involving acetaminophen (US National Institute Health, 2013). As reported in the same study, it is necessary to apply caution while using acetaminophen in treating patients with liver disease, severe malnutrition, severe hypovolemia, severe renal impairment with creatinine clearance of 30mL/min and alcoholism (Dart, et al., 2000). ...
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The use of aspirin and paracetamol have been beneficial to the general population. They aid to relief certain clinical symptoms. The beneficial effects have led to the wide study on how these drugs work in the human body. Following the numerous publications on PubMed and PubChem, some studies are still on clinical trials. Aspirin is a nonsteroid anti-inflammatory drugs which helps in pain management, fever, and inflammation as in osteoarthritis while paracetamol is an analgesic and antipyretic drug for pain and fever control. The function of these medications seems similar, but the formulation and dosage are different. Though both can inhibit the synthesis of prostaglandin responsible for pain sensation and reduce brain thermoregulatory process by inhibiting prostaglandin E1, they have different adverse effect when overdosed. These drugs have different half-life. The volume of distribution and elimination process as well varies. This is because of the mechanism of action in which they can inhibit the cyclooxygenase pathways preventing the synthesis of prostaglandins. The World Health Organization (WHO) recommendations in the administration of these medications which have been in effect over the years can help prevent the adverse reaction which can cause morbidity and mortality. It was advised that the withdrawal of these medication is required if there is any reaction to either of them. The synergic use of these medication is based on the classical case the patient is having. Though any of the drugs can be used in combination with other medications like aspirin can be administered with methotrexate drugs for arthritis patients while non-aspirin drugs can be used in combination with paracetamol for decreasing the risk of amyotrophic lateral sclerosis. The clinical implication of paracetamol is that it can cause chronic obstructive pulmonary disease and asthma while aspirin can induce respiratory and systemic allergen. More clinical studies on the use of these medications are required for more in-depth understanding on the adverse effect.
... The free radicals generated bind to microsomal protein, especially the CYP2E1 itself, resulting in lipid peroxidation which may cause ethanol-induced hepatotoxicity [125]. However, prospective studies in controlled clinical trials have found no relationship with chronic intake of alcohol and increased susceptibility to paracetamol poisoning at therapeutic doses [59,117,123,[126][127][128][129]. ...
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Paracetamol, also known as acetaminophen (N-acetyl-para-aminophenol, APAP) is the world’s most used over-the-counter analgesic-antipyretic drug. Despite its good safety profile, acetaminophen can cause severe hepatotoxicity in overdose, and poisoning from paracetamol has become a major public health concern. Paracetamol is now the major cause of acute liver failure in the United States and Europe. This systematic review aims at examining the likelihood of paracetamol use in Nigeria causing more liver toxicity vis-à-vis the reduced maximum recommended daily adult dose of 3 g for the 500 mg tablet. Online searches were conducted in the databases of PubMed, Google Scholar and MEDLINE for publications using terms like “paracetamol toxicity,” “acetaminophen and liver toxicity,” “paracetamol and liver diseases in Nigeria,” and other variants. Further search of related references in PubMed was carried out, and synthesis of all studies included in this review finalized. There were 94 studies that met the inclusion criteria. Evaluation of hepatic disorder was predicated mostly on a constellation of clinical features and limited clinical laboratory investigations. Determination of blood paracetamol concentration was rarely reported, thus excluding paracetamol poisoning as one of the likely causes of liver disorders in Nigeria. In Nigeria and elsewhere, several factors are known to increase paracetamol’s predisposition to liver injury. They include: the over-the-counter status of paracetamol, use of fixed-dose combinations of paracetamol with other drugs, malnutrition, dose miscalculations, and chronic alcohol consumption. The tendency to exceed the new paracetamol maximum daily dose of 3 g in Nigeria may increase its risk for hepatotoxicity than observed in the United States of America known for emphasizing lower dose of the drug. In addition to recommending the new maximal daily paracetamol dose allowance, the historical maximum daily adult dose of 4 g should be de-emphasized in Nigeria.
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Acetaminophen (Paracetamol, APAP) has been widely used for many decades as an analgesic and antipyretic agent but APAP overdose often causes acute adverse reactions, particularly liver damage. The metabolically oxidized form of APAP, N-acetyl-p-benzoquinone imine (NAPQI), is chemically reactive and binds covalently to proteins. Therefore, NAPQI is believed to be the key metabolite that causes hepatotoxicity, especially under conditions of glutathione depletion. Other APAP-induced adverse reactions, such as skin damage, are rare and remain poorly studied. Here, we report a case study of a male patient who presented with an acute swelling skin rash (without hepatotoxicity) caused by therapeutic doses of APAP. Plasma samples were collected at 17 hr after dosing (during the manifestation of symptoms) and at one month (after recovery) and were subjected to LC-MS analysis of NAPQI-adducts. A significant concentration of NAPQI-cysteine adduct (33 pmol/mL) was found together with low concentrations of NAPQI-N-acetylcysteine adduct (2.0 pmol/mL) and NAPQI-glutathione adduct (0.13 pmol/mL). However, the NAPQI-albumin adduct was below the detection limit (below 0.001% modification on albumin) despite a previous report of high concentrations of NAPQI-albumin adduct following acute liver injury. Therefore, the observed APAP-induced skin damage may have had a different cause from APAP-induced liver injury.
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Background: Paracetamol, either alone or in combination with codeine or dihydrocodeine, is commonly used to treat chronic neuropathic pain. This review sought evidence for efficacy and harm from randomised double-blind studies. Objectives: To assess the analgesic efficacy and adverse events of paracetamol with or without codeine or dihydrocodeine for chronic neuropathic pain in adults. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to July 2016, together with reference lists of retrieved papers and reviews, and two online study registries. Selection criteria: We included randomised, double-blind studies of two weeks' duration or longer, comparing paracetamol, alone or in combination with codeine or dihydrocodeine, with placebo or another active treatment in chronic neuropathic pain. Data collection and analysis: Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE. Main results: No study satisfied the inclusion criteria. Effects of interventions were not assessed as there were no included studies. We have only very low quality evidence and have no reliable indication of the likely effect. Authors' conclusions: There is insufficient evidence to support or refute the suggestion that paracetamol alone, or in combination with codeine or dihydrocodeine, works in any neuropathic pain condition.
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