Sympathomimetic activity of a Hoodia gordonii product: a possible mechanism of cardiovascular side effects.

Hoodia gordonii, a popular appetite suppressant, is widely used as an ingredient in many food supplements despite the fact that supporting scientific evidence is scarce. Recently alarming side effects of H. gordonii products (increased blood pressure and elevated pulse rate) have been reported. The aim of our study was to elucidate the underlying mechanism of these symptoms. A H. gordonii-containing product was tested for sympathomimetic activity. Isolated organ experiments on rat uterine rings revealed smooth muscle relaxant effect with a substantial component mediated through ß -adrenergic receptors. Chromatographic comparison of the analyzed product and authentic plant material confirmed that the herbal product contained Hoodia spp. extract, and its cardiovascular effects may be linked to the compounds of the plant.

Hemorrhagic stroke in young healthy male following use of sports supplement Jack3d.

A 26-year-old male was presented to a military treatment facility in Afghanistan shortly after taking a weight-lifting supplement called Jack3d with a severe headache and was subsequently found to have suffered a Dejerine-Roussy variant right thalamic hemorrhagic stroke. Jack3d active ingredients include geranamine, schizandrol A, caffeine, beta-alanine, creatine monohydrate, and L-arginine alpha-ketoglutarate. A literature search revealed case reports suggesting some of the constituent ingredients may predispose to stroke and hemorrhage and also revealed a substantial paucity of data existed regarding schizandrol A, a herb used in traditional eastern medicine. The product has no readily apparent disclaimer or warning regarding the risks or lack of data regarding the components. Jack3d is sold as a nutritional supplement and is therefore not subject to same FDA regulation and scrutiny that a pharmaceutical receives. The potential adverse effect was reported to the FDA via MedWatch in accordance with the recently passed Dietary Supplement and Nonprescription Drug Consumer Protection Act.

Case reports: Death of active duty soldiers following ingestion of dietary supplements containing 1,3-dimethylamylamine (DMAA).

Dietary supplements and their associated adverse events are not uncommon in the U.S. military, and selected dietary supplements have been associated with a number of nontraumatic deaths in service members. Specific ingredients and dietary supplement products in the civilian community are often associated with multiple adverse events and some have subsequently been removed from the marketplace; the most notable in the last decade is ephedra. We present case reports for two soldiers who were taking commercially available dietary supplements containing multiple ingredients to include the sympathomimetic, 1,3-dimethylamylamine (DMAA); both collapsed during physical exertion from cardiac arrest and ultimately died. A presentation of their clinical courses and a discussion of the history and pharmacology of dietary supplement ingredients, including DMAA, are provided. Our cases highlight concerns that DMAA in combination with other ingredients may be associated with significant consequences, reminiscent of previous adverse events from other sympathomimetic drugs previously removed from the market.

Ischemic stroke associated with cough and cold preparation containing methylephedrine and supplement containing Chinese herbal drugs.

Methylephedrine is generally harmless and is contained in many cough and cold preparations. Likewise, Chinese herbal drugs are considered to be effective and to have few side effects. A 32-year-old woman experienced ischemic stroke attributed to concomitant administration of a cough and cold preparation containing methylephedrine and a supplement containing Chinese herbal drugs. Computed tomography and magnetic resonance imaging of the brain showed acute infarctions bilaterally in the cerebellum. Conventional angiography and magnetic resonance angiography showed transient stenosis of the left vertebral artery. These findings suggested vasospasm or dissection, presumably related to hypertension and/or angiitis or vasoconstriction of large cerebral arteries leading to local thrombosis as a result of stasis and sympathomimetic-induced platelet activation. Combining methylephedrine and Chinese herbal drugs might carry a risk of stroke.

Effects of Muntingia calabura L. on isoproterenol-induced myocardial infarction.

INTRODUCTION: This study was designed to scientifically evaluate the effects of an aqueous extract of Muntingia calabura L. (M. calabura), a medicinal herb, on isoproterenol-induced myocardial infarction (MI) in rat models. METHODS: Six groups of Wistar albino rats, each comprising six animals, were selected for this study. Group I served as a control, Group II rats were given isoproterenol (20 mg/100g, subcutaneously), and Group III rats were given M. calabura leaf extract (300 mg/kg). Groups IV, V and VI rats were given M. calabura leaf extract (100 mg/kg, 200 mg/kg and 300 mg/kg, respectively) and isoproterenol (20 mg/100g subcutaneously) prior to MI induction. The transaminases (aspartate transaminase and alanine transaminase), lactate dehydrogenase (LDH) and creatine phosphokinase (CK), were estimated in both the serum and heart tissues, and the serum uric acid level was also estimated. RESULTS: Isoproterenol significantly increased the activities of CK, LDH and the transaminases in serum with a concomitant decrease in these enzymes in tissue. Pretreatment with the aqueous leaf extract of M. calabura at a dose of 300 mg/kg body weight for 30 days had a significant effect on the activities of marker enzymes compared to the other groups. Serum uric acid level, which increased on isoproterenol administration, registered near normal values on treatment with the leaf extract under study. CONCLUSION: The study confirms the protective effects of M. calabura leaf extract against isoproterenol-induced biochemical alterations in rats.

Herbal drugs of abuse: an emerging problem.

Some herbal products are emerging as popular drugs for recreational abuse. Plant and herbal supplements used recreationally can have a wide spectrum of clinical effects ranging from euphoric and stimulant effects to hallucinogenic experiences. Despite the potential for abuse, addiction, and serious adverse effects, there may be a false perception that these products are all safe, legal, and organic. These perceptions and the ease of accessibility to herbal products could result in greater potential for recreational abuse and subsequent complications presenting to emergency departments. Health care professionals must be cognizant of this emerging problem as increased media coverage and marketing have made these products accessible and recognizable to many young adults and teenagers.

Unintended immunomodulation: part II. Effects of pharmacological agents on cytokine activity.

Cytokines are proteins that are produced by immune and non-immune cells, and they function as mediators to facilitate cellular communication. Their production is regulated by a complex network of co-stimulatory and feedback loops that responds to a variety of stimuli. Several pharmacological agents have been found to alter systemic concentrations and/or the activity of different cytokines via a variety of mechanisms, including changes in biosynthesis, secretion, and/or stability. Many of the agents that modulate cytokine levels commonly are used in the management of critically ill patients. Catecholamines for example, have been found to promote the secretion of anti-inflammatory cytokines, and, therefore, may alter acute inflammatory processes such as sepsis. Antimicrobials have multiple effects on cytokine production, either secondary to the release of endotoxins from gram-negative bacteria or via direct activity on cytokine expression at the transcriptional and/or post-transcriptional level. Pentoxifylline has multiple effects on the immune system, but inhibition of pro-inflammatory cytokine release predominates. The reminder of the known drug-cytokine interactions and their effect on the inflammatory process are discussed. Information on the pharmacodynamic effect of drugs is limited, and our understanding of the clinical significance of these observations awaits further investigation. This review was designed to provide intensivists and other clinicians with useful information regarding the effect of medications on cytokine activity. It is also intended to help researchers and clinicians to optimize the design of studies of pharmacotherapeutic modulation of cytokines and to avoid the use of some agents in clinical circumstances in which cytokine manipulation is undesirable.

Hypersensitivity myocarditis associated with ephedra use.

BACKGROUND: Ephedrine has previously been described as a causative factor of vasculitis but myocarditis has not yet been associated with either ephedrine or its plant derivative ephedra. CASE REPORT: A 39-year-old African American male with hypertension presented to Rush Presbyterian St. Luke's Medical Center with a 1-month history of progressive dyspnea on exertion, orthopnea, and dependent edema. He was taking Ma Huang (Herbalife) 1-3 tablets twice daily for 3 months along with other vitamin supplements, pravastatin, and furosemide. Physical examination revealed a male in mild respiratory distress. The lung fields had rales at both bases without audible wheezes. Internal jugular venous pulsations were 5 cm above the sternal notch. Medical therapy with intravenous furosemide and oral enalapril was initiated upon admission. Cardiac catheterization with coronary angiography revealed normal coronary arteries, a dilated left ventricle, moderate pulmonary hypertension, and a pulmonary capillary wedge pressure of 34 mm Hg. The patient had right ventricular biopsy performed demonstrating mild myocyte hypertrophy and an infiltrate consisting predominantly of lymphocytes with eosinophils present in significantly increased numbers. Treatment for myocarditis was initiated with azothioprine 200 mg daily and prednisone 60 mg per day with a tapering course over 6 months. Anticoagulation with warfarin and diuretics was initiated and angiotensin-converting enzyme inhibition was continued. Hydralazine was added later. One month into therapy, an echocardiogram demonstrated improved left ventricular function with only mild global hypokinesis. A repeat right ventricular biopsy 2 months after the first admission showed no evidence of myocarditis. At 6 months, left ventricular ejection fraction was normal (EFN 50%) and the patient asymptomatic. CONCLUSION: Ephedra (Ma Huang) is the suspected cause of hypersensitivity myocarditis in this patient due to the temporal course of disease and its propensity to induce vasculitis.

Evaluation of intrinsic sympathomimetic activity of bucindolol and carvedilol in rat heart.

Many beta-adrenoceptor antagonists are weak partial agonists, possessing significant intrinsic sympathomimetic activity (ISA). Under certain conditions, ISA may be deleterious through stimulation of beta 1- and/or beta 2-adrenoceptors in the heart. Drugs with ISA are particularly problematic in the treatment of congestive heart failure since agents that activate cardiac beta-adrenoceptors, such as xamoterol, have been associated with increases in the incidence of arrhythmia and mortality. Carvedilol was recently approved for the treatment of congestive heart failure, and bucindolol is currently in large clinical trials for this indication. In the present study, the ISA of bucindolol and carvedilol was evaluated in a standard model used to investigate ISA, the pithed rat. Both compounds produced dose-dependent inhibition of the positive-chronotropic effects of the non-selective beta-adrenoceptor agonist, isoproterenol, confirming that these drugs are beta-adrenoceptor antagonists. However, cumulative administration of bucindolol (10-1,000 micrograms/kg i.v.) in the pithed rat produced a significant dose-related increase in heart rate. The maximal increase in heart rate produced by bucindolol was 44% of that obtained with isoproterenol (90 +/- 6vs. 205 +/- 11 bpm, respectively). In marked contrast, cumulative administration of carvedilol (10-1,000 micrograms/kg i.v.) had no significant effect on resting heart rate in the pithed rat. The maximal increase in heart rate elicited by bucindolol (1,000 micrograms/kg i.v.) was inhibited by treatment with the competitive beta-adrenoceptor antagonist, propranolol (99 +/- 8.7 vs. 26 +/- 2.6 bpm), confirming that the ISA observed with bucindolol was mediated through stimulation of myocardial beta-adrenoceptors. Carvedilol, which had no ISA, antagonized the ISA of bucindolol, and was as effective as propranolol in blocking the ISA of bucindolol (99 +/- 8.7 vs. 27 +/- 2.3 bpm). In summary, bucindolol and carvedilol are both potent beta-adrenoceptor antagonists in the pithed rat: however, only bucindolol possesses beta-adrenoceptor-mediated ISA.

Reversal of topical antiglaucoma medication effects on the conjunctiva.

OBJECTIVE: To determine whether the adverse effects of antiglaucoma medications could be reversed before filtration surgery, potentially reducing the risk of subsequent failure. METHODS: One month before surgery, 30 patients who were receiving multiple antiglaucoma medications underwent an inferior bulbar conjunctival biopsy, ceased using sympathomimetic drops, and began treatment with topical corticosteroid, (1% fluorometholone four times daily). At the time of surgery two conjunctival biopsy specimens were obtained, one from the operation site (superior bulbar region), and one from the inferior bulbar region. The biopsy specimens were quantitatively analyzed by light microscopy. In addition, the outcome of first trabeculectomy for 16 of these patients was compared with that of 16 matched patients who had not undergone an altered preoperative regimen of topical therapy. RESULTS: During a 1-month period a notable decrease occurred in the number of fibroblasts and inflammatory cells throughout the conjunctiva. Inferior bulbar conjunctiva was found to be representative of superior bulbar conjunctiva with respect to these changes. Furthermore, evidence comparing the matched patients suggested that the altered preoperative regimen may have improved the success rate of trabeculectomy. CONCLUSIONS: The preoperative regimen used reversed the adverse conjunctival effect of topical medication. The regimen may be of clinical benefit in improving the success rate of trabeculectomy.