In another study, CNS depression was reported in 10% of subjects. In a prospective population-based ibuprofen overdose study, CNS depression was the second most clinical finding after gastrointestinal disturbances at 30%, but symptoms were mild. Īcute ibuprofen overdose causing central nervous system (CNS) toxicity is not uncommon, particularly when the ingestion is massive at more than 400 mg/kg. There has been a report of a patient requiring hemodialysis for months after developing renal failure following ingestion of massive amounts of ibuprofen, with the eventual recovery of renal function. In most cases, renal impairment is reversible after supportive care and intravenous fluids. A prospective study of ibuprofen poisoning at Rocky Mountain Poison Control Center showed that 2 out of 63 cases had an elevation of creatinine after ingesting 4 and 4.5 g of ibuprofen, respectively, suggesting that it is not a common occurrence. Normalization of creatinine occurred after 72 hours. In children, there has been a report of a 2-year-old who had consumed 640 mg/kg of ibuprofen and developed acute renal failure with significant elevation of creatinine and microscopic hematuria with no proteins or casts in urine. Renal impairment has been described in individuals who had consumed therapeutic as well as supratherapeutic doses of ibuprofen. Perforation of the duodenum has been described in a patient after a single ingestion. GI hemorrhage has been described in multiple case reports, particularly after large ingestions. The severity of GI adverse effects can range from dyspepsia to life-threatening upper GI hemorrhage or viscus organ rupture. Symptoms include nausea, vomiting, dyspeptic symptoms, and abdominal pain. In susceptible individuals, they may progress to peptic ulcer. These may progress to erosions with continued use but are typically reversible. Intramucosal hemorrhages occur within a few hours of ingestion in all NSAIDs , especially with acidic ones like ibuprofen. Ibuprofen, being a nonselective inhibitor of COX, can disrupt the mucosal integrity of the gastric mucosa. The COX-1 enzyme is found in the gastric mucosa and is instrumental in producing prostaglandins that regulate blood flow and bicarbonate production in the stomach. Ibuprofen toxicity can be discussed based on the organ system involved: When symptoms do occur, onset typically occurs within 4 hours. Most patients report no or mild symptoms following ibuprofen overdose. In children, caregivers should be asked explicitly about acetaminophen ingestion, as it is commonly mistaken for ibuprofen. Important points to be noted in history include the amount of ibuprofen ingested, the time of ingestion, and any co-ingestants. There have been reports of metabolic acidosis after an acute overdose of ibuprofen and other NSAIDs, which may be explained by the accumulation of acidic metabolites in the blood. Thromboxane A2, another substance produced by the COX enzyme, is vital for platelet aggregation and hence, coagulation. The depletion of thromboxane A2 could, therefore, in theory, inhibit platelet aggregation and cause bleeding, especially in patients on anticoagulants or antiplatelets. In the kidneys, this can lead to decreased renal perfusion in the afferent renal vessels, especially in individuals with preexisting dehydration or renal impairment, thereby leading to reduced glomerular filtration rate (GFR). Ibuprofen can, therefore, cause dyspeptic symptoms and gastrointestinal (GI) ulcers even at therapeutic doses.
Ibuprofen also works on the thermoregulatory center of the hypothalamus to control fever.Īdverse effects associated with chronic ibuprofen use stem from prostaglandins' important roles, and thromboxanes play in various organ systems, including maintaining gastric mucosal integrity and renal blood flow. Prostaglandins also play a role in sensitizing pain-sensing nerve fibers, which explains the analgesic effect of ibuprofen and other NSAIDs. This prevents the conversion of arachidonic acid to the various prostaglandins that are instrumental in causing the 4 defining features of inflammation, namely redness ( rubor), heat ( calor), swelling ( tumor), and pain ( dolor). The therapeutic effects of ibuprofen are mediated by reversible binding to COX receptors (both COX-1 and COX-2) on prostaglandin synthase (also called cyclooxygenase, COX), thereby preventing arachidonic acid from binding to these sites.
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