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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phenylpropanolamine (PPA) is contained in about 106 products, over half of which are available over-the-counter (OTC). Most are cough/cold remedies; nine are OTC diet aids. More than nine million Americans were using OTC diet aids in 1981, making PPA the fifth most used drug in the United States, responsible for over $200 million in revenues. The safety of PPA remains controversial. Although most controlled studies indicate minimal pressor effects with recommended doses, adverse drug reactions (ADRs) continue to be documented. Since 1965, 142 ADRs have been reported in 85 studies, 69% of these in North America. Many such cases may go unrecognized. About two thirds of all ADRs occurred in females and in patients under 30. Of ADRs attributed to legitimately sold PPA products, 85% occurred after consumption of OTC products versus only 15% after prescription drugs. The PPA product often contained combination ingredients, or PPA was consumed along with additional drugs. An overdose of PPA was taken in about a third of the cases. After ingestion of non-overdose amounts, 82% of the ADRs were severe. The most frequent side effects involved symptoms compatible with acute hypertension, with severe headache the most common complaint. Twenty-four intracranial hemorrhages, eight seizures, and eight deaths (most due to stroke) were associated with PPA ingestion. We have summarized these data in an effort to alert clinicians to the prevalence of usage of PPA products and the potential for adverse effects. In patients who present with elevated blood pressure or signs of acute hypertension, especially hypertensive encephalopathy of undetermined origin, we recommend inquiry about recent ingestion of PPA-containing diet aids and cough/cold products and suggest having such patients remain upright rather than supine.
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PMID:Adverse drug effects attributed to phenylpropanolamine: a review of 142 case reports. 220 Feb 64

Phenylpropanolamine (PPA) is the major ingredient in more than 70 over-the-counter preparations including diet pills, nasal decongestants, and the legal "look-alike" stimulants. Structurally and functionally similar to amphetamine and ephedrine, PPA has recently been associated with several neurological manifestations including psychosis, stroke, severe headache, seizures, and intracerebral hematoma. We report a case of intracerebral hematoma and subarachnoid hemorrhage in a young woman with angiographic and biopsy-proven vasculitis of the central nervous system (CNS) induced by PPA in her diet pills. From review of the literature, we distinguish drug-induced vasculitis as a separate entity from primary CNS vasculitis, both clinically and pathologically. This report should alert physicians, in general, to this potentially fatal side effect of PPA, a commonly used over-the-counter drug. Also, neurosurgeons in particular should consider the possibility of drug-induced vasculitis when faced with cases of intracerebral or subarachnoid hemorrhage without apparent cause.
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PMID:Phenylpropanolamine: an over-the-counter drug causing central nervous system vasculitis and intracerebral hemorrhage. Case report and review. 295 31

Phenylpropanolamine (PPA) overdose can cause severe hypertension, intracerebral hemorrhage, and death. We studied the efficacy and safety of propranolol in the treatment of PPA-induced hypertension. Subjects received propranolol either by mouth for 48 hours before PPA or as a rapid intravenous infusion after PPA. PPA, 75 mg alone, increased blood pressure (31 +/- 14 mm Hg systolic, 20 +/- 5 mm Hg diastolic), and propranolol pretreatment antagonized this increase (12 +/- 10 mm Hg systolic, 10 +/- 7 mm Hg diastolic). Intravenous propranolol after PPA also decreased blood pressure. Left ventricular function (assessed by echocardiography) showed that PPA increased the stroke volume 30% (from 62.5 +/- 20.9 to 80.8 +/- 22.4 ml), the ejection fraction 9% (from 64% +/- 10% to 70% +/- 7%), and cardiac output 14% (from 3.6 +/- 0.6 to 4.1 +/- 1.0 L/min). Intravenous propranolol reversed these effects. Systemic vascular resistance was increased by PPA 28% (from 1710 +/- 200 to 2190 +/- 700 dyne X sec/cm5) and was further increased by propranolol 22% (to 2660 +/- 1200 dyne X sec/cm5). We conclude that PPA increases blood pressure by increasing systemic vascular resistance and cardiac output, and that propranolol antagonizes this increase by reversing the effect of PPA on cardiac output. That propranolol antagonizes the pressor effect of PPA is in contrast to the interaction in which propranolol enhances the pressor effect of norepinephrine. This is probably because PPA has less beta 2 activity than does norepinephrine.
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PMID:Propranolol antagonism of phenylpropanolamine-induced hypertension. 398 72

Phenylpropanolamine (PPA) is a drug that has been associated with serious side effects including stroke. It is often combined with caffeine in diet preparations and "look-alike" pills. In order to determine if PPA/caffeine can lead to stroke in normotensive and/or hypertensive rats, we administered the combination in six times the allowed human dose calculated on a per weight basis for the rats two times per day for five days. Subarachnoid and cerebral hemorrhage was noted in 18% of the hypertensive rats. A single PPA/caffeine administration (same dose) lead to acute hypertension in both the normotensive and hypertensive animals. These results suggest that PPA/caffeine can lead to cerebral hemorrhage in previously hypertensive animals when administered in greater than the allowed dosage. An acute elevation in blood pressure may be a contributing factor.
Stroke
PMID:Cerebral hemorrhage associated with phenylpropanolamine in combination with caffeine. 669 15

Phenylpropanolamine (PPA) is the major ingredient of many over-the-counter cold remedies and diet pills. Use or abuse of PPA may cause hemorrhagic stroke or cerebral vasculitis similar to the clinical and angiographic picture associated with amphetamine use or abuse. We report a 32-year-old Taiwanese women who developed sudden onset of severe headache, nausea and vomiting on the seventh day of oral ingestion of 75 mg PPA per day. Cerebral angiograms showed multiple areas of alternating focal constriction and dilatation ("beading" appearance) in the anterior and posterior cerebral arteries consistent with cerebral arteritis. This case should alert medical practitioners to the potential hazards of over-the-counter drugs like PPA.
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PMID:Cerebral arteritis associated with oral use of phenylpropanolamine: report of a case. 761 35

The relative toxicity of ephedra-containing dietary supplements is disputed. In order to ascertain the magnitude of the problem, we reviewed all autopsies in our Medical Examiner's jurisdiction, from 1994 to 2001, where ephedrine or any its isomers (E+) were detected. Toxicology testing results were tabulated and anatomic findings in E+ cases were compared to those in a control group of drug-free trauma victims. Of 127 E+ cases identified, 33 were due to trauma. Decedents were mostly male (80.3%) and mostly Caucasian (59%). Blood ephedrine concentrations were <0.49 mg/l in 50% of the cases, range 0.07-11.73 mg/l in trauma victims, and 0.02-12.35 mg/l in non-trauma cases. Norephedrine (NE) was present in the blood of 22.8% (mean of 1.81 mg/l, S.D.=3.14 mg/l) and in the urine of 36.2% (mean of 15.6 mg/l, S.D.=21.50mg/l). Pseudoephedrine (PE) was present in the blood of 6.3% (8/127). More than 88% (113/127) of the decedents also tested positive for other drugs, the most common being cocaine (or its metabolites) and morphine. The most frequent pathologic diagnoses were hepatic steatosis (27/127) and nephrosclerosis (22/127). Left ventricular hypertrophy was common, and coronary artery disease (CAD) detected in nearly one third of the cases. The most common findings in E+ deaths are those generally associated with chronic stimulant abuse, and abuse of other drugs was common in those with CAD. There were no cases of heat stroke or rhabdomyolysis. In most cases, norephedrine was not detected, suggesting it plays no role in ephedrine toxicity.
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PMID:Demographic, pathologic, and toxicological profiles of 127 decedents testing positive for ephedrine alkaloids. 1468 75

Phenylpropanolamine (PPA) recently has been publicly implicated as a cause of stroke and other neurologic events. In November of 2000, the Food and Drug Administration (FDA) requested a voluntary recall of the product from all manufacturers. However, medications containing PPA still can be found in many homes of those unaware of the voluntary recall. We present a case of stroke after PPA ingestion that occurred 4 months after the recall in an 8-year-old boy on chronic peritoneal dialysis. The patient developed occipital infarcts and was found to have extremely elevated levels of PPA in his blood and dialysis fluid. Though the voluntary recall was in effect, the family already had a bottle of the medication at home. Physicians must be aware that the public is still ingesting the drug and remain rigorous in including its toxicity in the differential diagnosis of acute neurologic events.
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PMID:Cerebral infarcts in a pediatric patient secondary to phenylpropanolamine, a recalled medication. 1502 28

Phenylpropanolamine (dl-norephedrine) was one of the most widely used therapeutic agents to act on the sympathetic nervous system. Because of concerns regarding incidents of stroke, its use as a nasal decongestant was discontinued. Although considered an alpha1-adrenergic agonist, the vascular adrenergic pharmacology of phenylpropanolamine was not fully characterized. Unlike most other circulations, the vasculature of the nasal mucosa is highly enriched with constrictor alpha2-adrenoceptors. Therefore, experiments were performed to determine whether phenylpropanolamine activates vascular alpha2-adrenoceptors. Mouse tail and mesenteric small arteries and human small dermal veins were isolated and analyzed in a perfusion myograph. The selective alpha1-adrenergic agonist phenylephrine caused constriction of tail and mesenteric arteries and human veins. The selective alpha2-adrenergic agonist UK14,304 [5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine] caused constriction in tail arteries and in human veins, but not mesenteric arteries. The lack of constriction to UK14,304 was also observed in endothelium-denuded mesenteric arteries. Phenylpropanolamine constricted both types of artery but was 62-fold more potent in tail arteries. In mesenteric arteries, constriction to phenylpropanolamine was not affected by the selective alpha2-adrenergic antagonist, rauwolscine (10(-7) M) but was abolished by the selective alpha1-adrenergic antagonist, prazosin (3 x 10(-7) M). In contrast, constriction to phenylpropanolamine in tail arteries and in human veins was inhibited by rauwolscine but not prazosin. Therefore, phenylpropanolamine is a preferential alpha2-adrenergic agonist. At low concentrations, it constricts blood vessels that express functional alpha2-adrenoceptors, whereas at much higher concentrations, phenylpropanolamine also activates vascular alpha1-adrenoceptors. This action likely contributed to phenylpropanolamine's therapeutic activity, namely constriction of the nasal vasculature.
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PMID:Phenylpropanolamine constricts mouse and human blood vessels by preferentially activating alpha2-adrenoceptors. 1560 85

Over the past several years, the pharmacologic treatment of obesity has undergone changes in safety, efficacy, and therapeutic targeting. The prevalence of cardiac valvulopathy associated with treatment with phentermine, fenfluramine, and dexfenfluramine is now becoming clarified with the publication of longer-term studies. Phenylpropanolamine, a well-known over-the-counter appetite suppressant, was recently removed from the market in the United States because of an increased risk of hemorrhagic stroke in women. In contrast, two currently approved medications, sibutramine and orlistat, have been shown to be safe and moderately effective for weight loss with documented beneficial effects on cardiovascular risk factors. Three other drugs, bupropion, topiramate, and ciliary neurotrophic factor, are undergoing clinical trials for obesity based on empirical observations. Most promising are the advances in genetics and molecular biology that are beginning to elucidate new targets for controlling appetite and energy utilization. These therapeutic agents will likely herald a second generation of anti-obesity medications over the next decade.
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PMID:Obesity pharmacology: past, present, and future. 1703 90

Phenylpropanolamine-induced vasculitis and related intracerebral hemorrhage has moved from the spotlight it occupied following its withdrawal from the market at the end of 2000 after the Food and Drug Administration ruled that it was not safe and effective, but the risk from medicines purchased prior to that time and still in the possession of the public can still pose a health hazard. We present the case of a patient who developed intracerebral hemorrhage following phenylpropanolamine ingestion post-partum 4 years following the recall, as well as her difficult recovery process. This case emphasizes the point that physicians should consider phenylpropanolamine when evaluating young females with few risk factors for stroke.
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PMID:Postpartum Phenylpropanolamine-Induced Intracerebral Hemorrhage. 2784 20


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