Acetaminophen, aspirin, and caffeine Side Effects
Please note - some side effects for Acetaminophen, aspirin, and caffeine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.
Side Effects by Body System - for Healthcare Professionals
Applies to: oral powder for reconstitution; oral tablet
Alcoholic patients may develop hepatotoxicity after even modest doses of acetaminophen. In healthy patients, approximately 15 grams of acetaminophen is necessary to deplete liver glutathione stores by 70% in a 70 kg person. However, hepatotoxicity has been reported following smaller doses. Glutathione concentrations may be repleted by the antidote N-acetylcysteine. One case report has suggested that hypothermia may also be beneficial in decreasing liver damage during overdose.
In a recent retrospective study of 306 patients admitted for acetaminophen overdose, 6.9% had severe liver injury but all recovered. None of the 306 patients died.
One study has suggested that acetaminophen may precipitate acute biliary pain and cholestasis. The mechanism of this effect may be related to inhibition of prostaglandin and alterations in the regulation of the sphincter of Oddi.
Cases of acute pancreatitis have been reported rarely with the use of acetaminophen.
A 19 year old female developed hepatotoxicity, reactive plasmacytosis and agranulocytosis followed by a leukemoid reaction after acute acetaminophen toxicity.
Hepatic side effects including hepatotoxicity and hepatitis have been reported.
In alcoholic patients, severe and sometimes fatal dose dependent hepatitis has been reported with acetaminophen use. Hepatotoxicity has been increased during fasting.
Cases of aspirin induced hepatotoxicity and cholestatic hepatitis, particularly at high doses, have been reported rarely.
Gastrointestinal side effects have been common and have included epigastric distress (in as many as 83% of patients treated with regular aspirin), abdominal discomfort or pain, endoscopically identifiable gastric mucosal lesions, nausea, and vomiting. More serious gastrointestinal effects include hemorrhage, peptic ulcers, perforation, and esophageal ulcerations.
In clinical trials of caffeine citrate, five cases of necrotizing enterocolitis were reported among the 46 infants exposed to the caffeine citrate injection.
Gastrointestinal side effects have been rare with the use of acetaminophen, except in alcoholics and after overdose.
Endoscopically identifiable gastric mucosal lesions occur in most patients who receive a single dose of aspirin. Clinically evident gastrointestinal bleeding has been reported in as many as 3% of treated elderly patients. Anorectal ulceration and rectal stenosis have been reported in patients who abuse aspirin containing rectal suppositories. One case controlled study has suggested that an association between aspirin (and other NSAID) consumption and appendicitis may exist.
General side effects including caffeinism have been reported. Consumption of higher doses of caffeine (>600 mg/day) has been reported to have lead to caffeinism. Caffeinism is a syndrome characterized by anxiety, restlessness, and sleep disorders (similar to anxiety states). It has also been reported that chronic, heavy caffeine ingestion may be associated with depression. Caffeine may cause anxiety and panic in panic disorder patients and may aggravate PMS.
In general, many side effects noted with aspirin use are dose-related.
The mechanism of an aspirin induced decrease in renal function may be related to inhibition of renal prostaglandin synthesis with consequent decreases in renal blood flow. Vasodilating renal prostaglandins may be particularly important in patients who exhibit arterial underfilling (i.e. heart failure, cirrhosis). The administration of high doses of NSAIDs to such patients has produced acute renal failure in rare instances.
Acetaminophen: Acute tubular necrosis usually occurs in conjunction with liver failure, but has been observed as an isolated finding in rare cases. A possible increase in the risk of renal cell carcinoma has been associated with chronic acetaminophen use as well.
A case control study of patients with end stage renal disease suggested that long term consumption of acetaminophen may significantly increase the risk of end stage renal disease particularly in patients taking more than two pills per day.
Renal side effects of aspirin have included reduction in glomerular filtration rate (particularly in patients who are sodium restricted or who exhibit diminished effective arterial blood volume, such as patients with advanced heart failure or cirrhosis), interstitial nephritis, papillary necrosis, elevations in serum creatinine, elevations in blood urea nitrogen, proteinuria, hematuria, and renal failure.
Renal side effects have been rare with acetaminophen use and have included acute tubular necrosis and interstitial nephritis. Adverse renal effects are most often observed after overdose, after chronic abuse (often with multiple analgesics), or in association with acetaminophen related hepatotoxicity.
The mechanism of aspirin induced hypersensitivity may be related to an up-regulation of the 5-lipoxygenase pathway of arachidonic acid metabolism with a resulting increase in the products of 5-lipoxygenase (such as leukotrienes).
Hypersensitivity side effects of aspirin have included bronchospasm, rhinitis, conjunctivitis, urticaria, angioedema, and anaphylaxis. Approximately 10% to 30% of asthmatics are aspirin sensitive (with the clinical triad of aspirin sensitivity, bronchial asthma, and nasal polyps).
Hypersensitivity reactions such as anaphylaxis and fixed drug eruptions have rarely been reported in association with acetaminophen use.
Hematologic side effects of aspirin (in addition to predictable antiplatelet effects which may result in hemorrhage) have included increased blood fibrinolytic activity. In addition, hypoprothrombinemia, thrombocytopenia, thrombocyturia, megaloblastic anemia, and pancytopenia have been reported rarely. Aplastic anemia has also been reported.
Rare cases of thrombocytopenia associated with acetaminophen have been reported. Methemoglobinemia with resulting cyanosis has also been observed in the setting of acute overdose.
Dermatologic side effects from the use of aspirin including Stevens-Johnson syndrome and a lichenoid eruption have been reported rarely.
Erythematous skin rashes associated with acetaminophen have been reported, but are rare. Acetaminophen associated bullous erythema and purpura fulminans have been reported.
Respiratory side effects including hyperpnea, pulmonary edema, and tachypnea have occurred in patients receiving aspirin.
A case of acetaminophen induced eosinophilic pneumonia has been reported.
Cardiovascular side effects of aspirin have been reported rarely and have included salicylate induced variant angina, ventricular ectopy, conduction abnormalities, and hypotension, particularly during salicylate toxicity.
Several cases of hypotension have been reported following the administration of acetaminophen.
Two cases hypotension have been reported following the administration of acetaminophen. Both patients experienced significant decreases in blood pressure. One of the two patients required pressor agents to maintain adequate mean arterial pressures. Neither episode was associated with symptoms of anaphylaxis. Neither patient was rechallenged after resolution of the initial episode.
Metabolic side effects of aspirin have included dehydration and hyperkalemia. Respiratory alkalosis and metabolic acidosis, particularly during salicylate toxicity, have been reported. A case of hypoglycemia has also been reported in a patient on hemodialysis.
Nervous system side effects in patients receiving aspirin have included agitation, cerebral edema, coma, confusion, dizziness, headache, cranial hemorrhage, lethargy, and seizures. Some investigators have reported that modest doses may result in decreased frequency selectivity and may therefore impair hearing performance, particularly in the setting of background noise.
Regarding the use of aspirin, some investigators have suggested that tinnitus may be a less reliable indicator of salicylate toxicity than previously believed. Patients with high frequency hearing loss may have difficulty perceiving tinnitus. In a study of rheumatoid arthritis patients, those with tinnitus had no greater salicylate levels than those without tinnitus. Elderly patients may be less likely to perceive tinnitus than younger patients.
Other side effect have also been reported. In one study of the effects of caffeine, 634 women with fibrocystic breast disease (compared to 1066 women without the disease), the occurrence of fibrocystic breast disease was positively associated with average daily consumption of caffeine. Women who consumed 31 to 250 mg/day of caffeine were reported to have a 1.5 times increase in odds to have the disease. Women who consumed over 500 mg/day of caffeine were reported to have a 2.3 times increase in odds.
Reye's syndrome, although rare, has been associated with aspirin use in children with an acute viral illness. Reye's syndrome has also been reported even more rarely in adults.
Prolonged labor and pregnancy, decreased infant birth weight and stillborn births, antepartum and postpartum bleeding have occurred due to aspirin use by women during the third trimester of pregnancy.
Reye's syndrome typically involves vomiting, neurologic dysfunction, and hepatic dysfunction during or shortly after an acute viral infection.
Musculoskeletal side effects including rhabdomyolysis have occurred in patients receiving aspirin.
Endocrine side effects of aspirin use have included hypoglycemia and hyperglycemia.
Ocular side effects including cases of localized periorbital edema have been reported rarely in patients receiving aspirin.
Oncologic side effects have been reported. Several epidemiologic studies have suggested that chronic aspirin use may decrease the risk of large bowel neoplasms. However, other studies have not found this beneficial effect.Top
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