Acetaminophen / brompheniramine / dextromethorphan / pseudoephedrine Side Effects
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.
Pseudoephedrine causes vasoconstriction which generally does not produce hypertension, but may be problematic for patients with preexisting hypertension. Arrhythmias may be produced in predisposed patients. Rarely, pseudoephedrine has been reported to cause coronary artery spasm and chest pain.
One report evaluated the effect with 60 mg of pseudoephedrine on individuals in a hyperbaric chamber at 1 atmosphere (simulated scuba dive to 66 feet of sea water). Pseudoephedrine and depth (stimulated) were found to have significant but opposite effects on heart rate, although these effects were unlikely to be clinically significant during diving.[Ref]
Cardiovascular side effects of acetaminophen have included two cases of hypotension.
Cardiovascular effects of brompheniramine have included hypotension, tachycardia, and palpitations.
Cardiovascular side effects of pseudoephedrine have included tachycardia. Some patients have developed hypertension and/or arrhythmias.[Ref]
Dermatologic side effects have included erythematous skin rashes. Acetaminophen associated bullous erythema and purpura fulminans have been reported. One case of toxic epidermal necrolysis associated with acetaminophen administered to a pediatric patient has been reported.[Ref]
Gastrointestinal side effects of acetaminophen have been rare except in alcoholics and after overdose.
Gastrointestinal side effects of brompheniramine have include nausea, dry mouth and constipation.
Gastrointestinal side effects of dextromethorphan have included stomach upset.
Gastrointestinal side effects of pseudoephedrine have included anorexia and gastric irritation in approximately 5% of patients. Dry mouth, nose, or throat have occurred in up to 15% of patients.[Ref]
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, although hepatotoxicity has been reported with 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. Another study has suggested that acetaminophen may precipitate acute biliary pain and cholestasis. The mechanism for this side effect may be related to inhibition of prostaglandins and alterations in the regulation of the sphincter of Oddi.[Ref]
Hematologic side effects of acetaminophen have included rare cases of thrombocytopenia. Methemoglobinemia with resulting cyanosis has also been observed in the setting of acute overdose.
Hematologic side effects of brompheniramine have included rare cases of hemolytic anemia, thrombocytopenia, and agranulocytosis.[Ref]
Hypersensitivity side effects of acetaminophen have included anaphylaxis and fixed drug eruptions.
Hypersensitivity side effects of dextromethorphan have included rare reports of fixed-drug eruptions.
Hypersensitivity side effects of pseudoephedrine have included fixed drug eruptions.[Ref]
Nervous system side effects of brompheniramine have included central nervous system (CNS) depression, resulting in drowsiness and sedation in nearly 50% of patients treated. This effect has often been transient and ceased with continued use. Motor skills have be impaired and patients should be advised to avoid tasks which require attention. Patients should also avoid concomitant use with alcohol and other sedative-hypnotic drugs. Dyskinesias have rarely been reported following chronic use of brompheniramine.
Nervous system side effects of dextromethorphan have included drowsiness and dizziness. Other side effects such as excitation, mental confusion, and opiate-like respiratory depression have been rare and occurred at higher dosages. In some cases of abuse, patients experienced euphoria, hyperactivity, mania, and auditory and visual hallucinations.
Nervous system side effects of pseudoephedrine have included insomnia in up to 30% of patients. Tremor, anxiety, nervousness, and headache have also been reported.[Ref]
A few cases of dyskinesias and tremors, often of the face, have been reported in patients whose chronic use of brompheniramine extended over a period of up to 10 years. Some of these cases were only partially relieved by discontinuation of the drug. Haloperidol was successful in relieving symptoms in these patients. Spasmodic torticollis has been reported in a child given brompheniramine over an eight month period.[Ref]
Ocular side effects of brompheniramine have included blurred vision, diplopia, and dry eyes due to anticholinergic effects.[Ref]
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.
A 19-year-old female developed hepatotoxicity, reactive plasmacytosis and agranulocytosis followed by a leukemoid reaction after acute acetaminophen toxicity.[Ref]
Hepatic side effects of acetaminophen have included severe and sometimes fatal dose dependent hepatitis in alcoholic patients. Hepatotoxicity has been increased during fasting.[Ref]
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.
One 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.
However, a recent cohort study of analgesia use of initially healthy men concluded that moderate use of analgesics including acetaminophen was not associated with increased risk of renal disease.[Ref]
Renal side effects of acetaminophen have included acute renal failure, 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.[Ref]
In the case of metabolic acidosis, causality is uncertain as more than one drug was ingested. The case of metabolic acidosis followed the ingestion of 75 grams of acetaminophen, 1.95 grams of aspirin, and a small amount of a liquid household cleaner The patient also had a history of seizures which the authors reported may have contributed to an increased lactate level indicative of metabolic acidosis.[Ref]
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