Species of the genus Ephedra are the botanical source for the sympathomimetic alkaloid ephedrine. Also known as ma huang.
Several reports of adverse effects in adults of ephedrine and pseudoephedrine appeared in the medical literature in and outside of the United States prior to 1982. These included hypertension, hypotension, drug interactions, cardiovascular disturbances, and psychosis. (12-17) The first report of fatal intracerebral hemorrhage due to ephedrine abuse appeared in a case report in the Annals of Neurology in 1983 which described the case of a 20 year old male with intracerebral hemorrhage and vasculitis.
By 1984, the misuse and abuse of ephedrine-containing products was widely acknowledged. In a 1984 article in the Journal of the American Medical Association, Paul Pentel wrote "A particularly alarming development of the past few years is the mail-order advertising of OTC stimulants." A year later, in 1985, another case report appeared of non fatal intracerebral hemorrhage following ingestion of a combination drug with ephedrine, phenylpropanolamine, and caffeine.
Notwithstanding these reports, ephedrine preparations were included as generally recognized safe and effective for use as bronchodilators in the final monograph for OTC bronchodilator drug products on October 2, 1986. Between 1986 and 1993, several additional case reports appeared in the literature, including another case of ephedrine-induced cerebral hemorrhage in 1990, and three case reports of ephedrine consumption associated with stroke which appeared in the journal Neurology in 1993.
The 1993 case reports were the result of an investigation initiated in 1991 after a 37 year old male presented with cerebral infarction at the Albuquerque Veterans Affairs Medical Center. The patient had ingested 10 "white-cross" ephedrine tablets daily for weight loss, a dose equivalent to approximately 150 mg/day. A review of records of the New Mexico office of the Medical Investigator 1981 to 1991 revealed a single case of fatal stroke in a 42 year old male who had hypertensive cerebral vasculopathy and a history of taking 10 - 20 white-cross tablets daily (150 - 300 mg/day) for 23 years. On autopsy, evidence of cerebral atherosclerosis, arteriolosclerosis and arteriolonephrosclerosis was found, with blood concentration of 2.7 µg/ml ephedrine.
The New Mexico case review also revealed two other cases of fatal stroke involving ingestion of a combination of caffeine, phenylpropanolamine, and ephedrine. The third report in that case series was identified from an investigation of 17 fatal intracranial hemorrhages in Connecticut during the period April 1989 to April 1990; this case was an 84 year old female whose blood on autopsy was positive for the presence of ephedrine.
The authors hypothesized that ephedrine-induced hypertension caused these three cases, but the disparity between them illustrates the uncertainty in identifying a causal chain, and sets the stage for the unbridled marketing of botanical ephedrine products that occurred after the Dietary Supplement Health and Education Act was passed in 1994. The first case had not significantly exceeded the normal daily therapeutic dose, although the duration is not mentioned. The second case appears to be one of significant long-term abuse; the high consumption of ephedrine over 23 years was a likely cause of the case's predisposition to stroke and the eventual fatality. The conditions surrounding the third case are much less clear; like the younger man in the second case, this patient had signs of cerebral atherosclerosis, atherosclerosis, and arteriolonephrosclerosis. But this was an 84 year old woman, and her history of medication was not evident. While it was possible that her stroke was precipitated by the vasoconstricting and hypertensive effect of ephedrine, it is difficult to determine with any confidence. Nonetheless, it was during the time this case series was being prepared that New Mexico became one of the first states to enact a regulation banning the sale of any OTC product containing ephedrine.
Several reports of adverse effects in adults of ephedrine and pseudoephedrine appeared in the medical literature in and outside of the United States prior to 1982. These included hypertension, hypotension, drug interactions, cardiovascular disturbances, and psychosis. (12-17) The first report of fatal intracerebral hemorrhage due to ephedrine abuse appeared in a case report in the Annals of Neurology in 1983 which described the case of a 20 year old male with intracerebral hemorrhage and vasculitis.
By 1984, the misuse and abuse of ephedrine-containing products was widely acknowledged. In a 1984 article in the Journal of the American Medical Association, Paul Pentel wrote "A particularly alarming development of the past few years is the mail-order advertising of OTC stimulants." A year later, in 1985, another case report appeared of non fatal intracerebral hemorrhage following ingestion of a combination drug with ephedrine, phenylpropanolamine, and caffeine.
Notwithstanding these reports, ephedrine preparations were included as generally recognized safe and effective for use as bronchodilators in the final monograph for OTC bronchodilator drug products on October 2, 1986. Between 1986 and 1993, several additional case reports appeared in the literature, including another case of ephedrine-induced cerebral hemorrhage in 1990, and three case reports of ephedrine consumption associated with stroke which appeared in the journal Neurology in 1993.
The 1993 case reports were the result of an investigation initiated in 1991 after a 37 year old male presented with cerebral infarction at the Albuquerque Veterans Affairs Medical Center. The patient had ingested 10 "white-cross" ephedrine tablets daily for weight loss, a dose equivalent to approximately 150 mg/day. A review of records of the New Mexico office of the Medical Investigator 1981 to 1991 revealed a single case of fatal stroke in a 42 year old male who had hypertensive cerebral vasculopathy and a history of taking 10 - 20 white-cross tablets daily (150 - 300 mg/day) for 23 years. On autopsy, evidence of cerebral atherosclerosis, arteriolosclerosis and arteriolonephrosclerosis was found, with blood concentration of 2.7 µg/ml ephedrine.
The New Mexico case review also revealed two other cases of fatal stroke involving ingestion of a combination of caffeine, phenylpropanolamine, and ephedrine. The third report in that case series was identified from an investigation of 17 fatal intracranial hemorrhages in Connecticut during the period April 1989 to April 1990; this case was an 84 year old female whose blood on autopsy was positive for the presence of ephedrine.
The authors hypothesized that ephedrine-induced hypertension caused these three cases, but the disparity between them illustrates the uncertainty in identifying a causal chain, and sets the stage for the unbridled marketing of botanical ephedrine products that occurred after the Dietary Supplement Health and Education Act was passed in 1994. The first case had not significantly exceeded the normal daily therapeutic dose, although the duration is not mentioned. The second case appears to be one of significant long-term abuse; the high consumption of ephedrine over 23 years was a likely cause of the case's predisposition to stroke and the eventual fatality. The conditions surrounding the third case are much less clear; like the younger man in the second case, this patient had signs of cerebral atherosclerosis, atherosclerosis, and arteriolonephrosclerosis. But this was an 84 year old woman, and her history of medication was not evident. While it was possible that her stroke was precipitated by the vasoconstricting and hypertensive effect of ephedrine, it is difficult to determine with any confidence. Nonetheless, it was during the time this case series was being prepared that New Mexico became one of the first states to enact a regulation banning the sale of any OTC product containing ephedrine.
