Role of Thromboelastography Platelet Mapping and International Normalized Ratio in Defining "Normocoagulability" During Anticoagulation for Mechanical Circulatory Support Devices: A Pilot Retrospective Study.

Thromboembolic (TE) events and hemorrhagic complications continue to remain as frequent adverse events and causes of death after mechanical circulatory support device (MCSD) implantation. To counterbalance this postimplant multifactorial hypercoagulable state, antithrombotic therapy given postimplant must be individually tailored to keep patient adequately anticoagulated yet normocoagulable. Prior studies describing different anticoagulation protocols do not define normocoagulability for patients on MCSDs. We evaluated the role of thromboelastography platelet mapping (TEG PM) in defining "normocoagulability" for MCS patients on anticoagulant (warfarin) and antiplatelet agents. Ninety-eight MCSD patients who underwent TEG PM assay at our institution from 2012 to 2014 were included for retrospective analysis. Eleven (11.2%) subjects developed at least one TE event during the study period. Of the 13 TE events, 8 occurred in patients with total artificial heart (TAH). TEG parameters closest to the event or when patient was clinically adequately anticoagulated and corresponding international normalized ratio (INR) were measured. Thromboelastography coagulation index (CI) appears to be the single most statistically significant parameter that can be used to designate a patient as normocoagulable. Based on our results, patients with HeartMate II (HM II) and Heart Ware (HW) devices should be maintained at a CI value of less than or equal to 1.5 whereas patients with TAH devices should be maintained at a CI less than or equal to 1.2. The CI should be correlated with the degree of Vitamin K-dependent coagulation factor inhibition that is achieved using device-specific goal INR ranges. A recent modification, TEG PM assesses the effects of antiplatelet drug. Maximal amplitude arachidonic acid (MA-AA) < 50 and maximal amplitude adenosine diphosphate (MA-ADP) < 50 are desired for normocoagulable state.

Performance-enhancing drugs: understanding the risks.

To help clinicians understand the risks associated with performance-enhancing drugs, this overview covers prohibited lists of substances and methods, therapeutic use exemptions, the legitimate indications and adverse effects, including for megadose and polypharmacy doping of stimulants, anabolic steroids, erythropoiesis-stimulating agents, and growth hormone and ways in which physicians or patients risk committing anti-doping rule violations inadvertently.

Characteristics and trends of drug and dietary supplement inquiries by college athletes.

OBJECTIVE: To characterize the types of drug and dietary supplement inquiries submitted to the National Center for Drug Free Sport through the Resource Exchange Center (REC). DESIGN: Cross-sectional study. SETTING: United States, from July 2009 through June 2010. PARTICIPANTS: Athletes and athletic personnel associated with the National Collegiate Athletic Association (NCAA). INTERVENTION: Tabulation and classification of drugs and dietary supplement inquiries. MAIN OUTCOME MEASURE: Characteristics and trends of drug and dietary supplement inquiries. RESULTS: Inquiries for prescription medications for albuterol inhalers, methylphenidate, amphetamines, and prednisone were the most common using a drug lookup function. The most common inquiries for over-the-counter medications included pseudoephedrine, loratadine, cetirizine, and caffeine. Among dietary supplements, inquiries for amino acids/metabolites, vitamins and minerals, and herbal products occurred most frequently. One dietary supplement, N.O.-Xplode (Bio-Engineered Supplements and Nutrition, Inc.), accounted for the majority of individual dietary supplement inquiries. Banned substances accounted for 30% of all inquiries submitted to the REC and 18% of medications searched in a drug lookup database. CONCLUSION: Almost 25,000 inquiries were submitted to the REC. Pharmacists can use this information to advise, counsel, and refer NCAA athletes regarding the use of banned and permitted substances. Education programs regarding stimulants, dietary supplements, and the risk of using substances such as animal byproducts are needed, and pharmacists can participate in these programs.

Efficacy and safety of ingredients found in preworkout supplements.

PURPOSE: Published evidence on common ingredients of "energy drinks" and other dietary supplements widely used by consumers in hopes of enhancing athletic performance is reviewed. SUMMARY: Preworkout products- unregulated dietary supplements- typically contain "proprietary blends" of multiple ingredients, including caffeine, dimethylamylamine, creatine, arginine, ß-alanine, taurine, and phosphates. While some dietary supplement labels instruct consumers to seek the advice of a health care professional before using the products, the labels usually do not disclose all ingredients or their precise amounts, and evidence to support the purported performance-enhancing benefits is generally lacking. There is limited evidence to support the use of some preworkout supplement ingredients. For example, in one small placebo-controlled study (n = 12), the use of the energy drink Red Bull (containing caffeine and taurine) 40 minutes before a simulated cycling time trial appeared to provide a meaningful ergogenic benefit; in another small study (n = 12), the use of a similar caffeine-containing product (Redline) by strength-trained athletes was found to improve reaction time, energy, and mental focus relative to placebo use. However, published evidence on the use of the other ingredients listed above is scant, inconclusive, or conflicting. Adverse effects reported in association with preworkout supplements include gastrointestinal symptoms, cardiac arrhythmia, blood pressure increases, and potential effects on lipids and blood glucose. CONCLUSION: Although evidence exists to support the performance-enhancement efficacy of some preworkout ingredients as standalone agents, published data on combination products are scant, inconclusive, or conflicting. The safety of these products may be compromised if users consume larger-than-recommended amounts or use more than one product.

Evaluation of a pediatric continuous-infusion vancomycin therapy guideline.

PURPOSE: An institutional guideline for converting pediatric patients to continuous-infusion vancomycin (CIV) therapy if therapeutic targets are not achieved with intermittent i.v. dosing was evaluated. METHODS: All patients within a specified age range (>6 months but <19 years) who were converted to CIV therapy for pneumonia or osteomyelitis during the 2 years after guideline implementation were included in the evaluation. The guideline calls for conversion to CIV therapy if goals for trough serum vancomycin concentration (SVC) are not attained with escalating intermittent-infusion vancomycin (IIV) dosing. Primary outcome measures included the rate of attainment of the goal steady-state trough SVC (15-20 mg/L), preferably within 24-48 hours, the adequacy of an empirical dosing strategy, and adverse events. Secondary study outcomes included final vancomycin doses and the time to attainment of therapeutic SVCs. RESULTS: Within 24-48 hours after conversion to CIV therapy, the mean initial plateau SVC in the evaluated cases (n = 15) was 20.2 mg/L; the mean of all SVCs was 19.1 mg/L. The range of dosages required to achieve a plateau SVC of 15 mg/L was 23.8-65.4 mg/kg/day (median, 41 mg/kg/day). The mean ± S.D. vancomycin dosage at the end of CIV therapy was 44.3 ± 12.8 mg/kg/day. Monitoring of serum creatinine, urine output, and glomerular filtration rate indicated that no patients developed nephrotoxicity during CIV therapy. CONCLUSION: Conversion from IIV to CIV therapy in selected pediatric patients appeared to be safe and well tolerated, with few adverse effects noted. Using the institutional CIV dosing guideline, goal plateau SVC values were attained in most patients within 24-48 hours.

Availability of tobacco and alcohol products in Los Angeles community pharmacies.

The availability of tobacco and alcohol products in community pharmacies contradicts the pharmacists' Code of Ethics and presents challenges for a profession that is overwhelmingly not in favor of the sale of these products in its practice settings. The primary aim of this study was to estimate the proportion of pharmacies that sell tobacco products and/or alcoholic beverages and to characterize promotion of these products. The proportion of pharmacies that sell non-prescription nicotine replacement therapy (NRT) products as aids to smoking cessation also was estimated. Among 250 randomly-selected community pharmacies in Los Angeles, 32.8% sold cigarettes, and 26.0% sold alcohol products. Cigarettes were more likely to be available in traditional chain pharmacies and grocery stores than in independently-owned pharmacies (100% versus 10.8%; P < 0.001), and traditional chain drug stores and grocery stores were more likely to sell alcoholic beverages than were independently-owned pharmacies (87.5% vs. 5.4%; P < 0.001). Thirty-four (41.5%) of the 82 pharmacies that sold cigarettes and 47 (72.3%) of the 65 pharmacies that sold alcohol also displayed promotional materials for these products. NRT products were merchandised by 58% of pharmacies. Results of this study suggest that when given a choice, pharmacists choose not to sell tobacco or alcohol products.

Educational opportunities and anti-doping roles and responsibilities for pharmacists.

Drug use and abuse by athletes has become a common problem. Pharmacists can assist by managing the legitimate medication needs of athletes to prevent them from accidentally using a banned substance. Pharmacists can also educate athletes and the public about the health consequences of using performance-enhancing substances. Pharmacists can play a variety of roles to assist with anti-doping. Such roles include educating, advising, dispensing and monitoring medications and supplements; and working with anti-doping agencies. There are few established educational opportunities for pharmacists and pharmacy students. Educational programs in sports pharmacy and doping control need to be developed for instruction in the classroom, for post-graduate training and for experiential programs. Classroom instruction should include information about performance-enhancing substances and general principles of doping control. Student activities for an established advanced pharmacy practice experience include education on performance-enhancing substances and assay technologies, preparing and providing presentations to athletes and others regarding these substances, performing literature research on drugs and dietary supplements used to improve athletic performance, writing a monograph on these substances, and participating in doping control programs.

Development needs of volunteer pharmacy practice preceptors.

OBJECTIVE: To determine the training needs and interests of volunteer pharmacy preceptors. METHODS: Volunteer preceptors (n=576) were surveyed on various aspects of precepting and their needs related to additional training. RESULTS: Two hundred thirty-six preceptors (40.9%) responded. Preceptors were less confident about enforcing attendance policies, identifying and managing unmotivated or failing students, identifying dishonesty or plagiarism, and handling conflict. While only 29.5% of respondents agreed that having an APPE student decreased their overall workload, approximately half (48.1%) indicated that student pharmacists helped them complete their daily tasks and 67.8% agreed that APPE students extended patient care. Respondents who had received training were significantly more confident than preceptors who had not received training in their abilities to clarify expectations, evaluate a student's knowledge, and foster skills related to critical thinking and problem solving. CONCLUSIONS: Training programs for pharmacy preceptors are effective; however, important areas in which additional training is needed or desired were identified among both new and experienced preceptors.

Estimating aminoglycoside clearance and creatinine clearance in underweight patients.

PURPOSE: An adjustment factor (AF) was developed and evaluated to determine the best method for estimating aminoglycoside clearance (CL(amino)) and creatinine clearance (CL(cr)) in underweight patients. METHODS: This study was a retrospective, multicenter, chart analysis of aminoglycoside pharmacokinetic data obtained between January 2000 and August 2006 at the University of Southern California University Hospital and Cedars-Sinai Medical Center. Adult patients were included in this study if they had received inpatient aminoglycoside therapy, were at least 60 inches tall, and were at least 10% below their ideal body weight (IBW). CL(cr) and CL(amino) were estimated and compared to actual CL(amino) using the Cockcroft-Gault equation with actual serum creatinine (SCr) (CG(SCr)), Cockcroft-Gault equation with SCr rounded to 1 mg/dL (CG(rnd)), and Cockcroft-Gault equation multiplied by an AF (CG(AF)). Results An AF of 0.69 was determined from 52 patients and tested in 53 separate patients. The CG(AF) method was more precise and less biased than the CG(SCr) equation; the CG(rnd) equation was less biased than the CG(SCr) equation; the CG(AF) method was more precise and less biased than the CG(rnd) equation, but this difference was not statistically significant. In underweight patients with an SCr concentration of > or = 1 mg/dL, the CG(AF) method had less bias compared with the CG(SCr) equation. CONCLUSION: Both the CG(rnd) and CG(AF) methods of predicting CL(amino) in underweight patients were superior to the CG(SCr) equation. The CG(AF) method was more accurate in patients exhibiting greater differences between IBW and actual body weight.

Pharmacy students' perceptions of a required senior research project.

OBJECTIVES: To determine pharmacy students' perceptions of a required research project in a doctor of pharmacy curriculum. METHODS: A survey instrument was administered to senior pharmacy students to determine their perceptions of the project advisor and overall project experience and their postgraduation employment plans. RESULTS: Two-hundred twenty-nine (81.5%) students completed a survey instrument. The majority agreed or strongly agreed that the project provided a valuable learning experience (88.2%), provided a competitive advantage for postgraduate job opportunities (73.2%), and should be a continued graduation requirement (74.2%). Respondents with plans for a residency or fellowship were more likely than those entering a community or hospital/institutional pharmacy to agree that completion of the project made them more qualified or marketable and should be continued as a graduation requirement (p < 0.05). CONCLUSIONS: A required research project was perceived by pharmacy students to be a beneficial experience. Students pursuing residency or fellowship were more likely to feel the project was beneficial than students entering the workforce.

Characteristics of drug and dietary supplement inquiries by college athletes.

BACKGROUND: In the United States, the National Center for Drug Free Sport manages the drug-testing programs for athletes of the National Collegiate Athletic Association (NCAA). Through its Resource Exchange Center (REC), Drug Free Sport supports athletic staff and athletes with information regarding drugs and dietary supplements. PURPOSE: To characterize the types of drug-related and dietary supplement-related inquiries submitted to Drug Free Sport through the REC. STUDY DESIGN: Cross-sectional study. METHODS: All inquiries submitted to the REC for the period of September 1, 2005, through June 30, 2006, were reviewed. The data were categorized by the method of inquiry submission; the name of the substance in question; the sex, sport, and NCAA division of the athlete involved; the nature of the inquiry; and the response provided by the REC regarding the NCAA's status of the substance in question. RESULTS: Pseudoephedrine, acetaminophen/hydrocodone, and albuterol were the most commonly self-searched medications; stimulants accounted for the majority of banned medications. Dietary supplements accounted for 80% of all inquiries submitted to the REC via the Banned Drug Inquiry Form. Among all dietary supplements, creatine was the most commonly inquired. Banned substances accounted for 29% of all inquiries. CONCLUSIONS: There were more than 10 000 inquiries regarding the status of medications, dietary supplements, and other substances for NCAA athletes during the 2005-2006 academic year. It is helpful for athletes to have resources that help them navigate banned-substance lists and so avoid the inadvertent use of banned substances. CLINICAL RELEVANCE: Educating athletes regarding the stimulant content of various dietary supplements and addressing the lack of clinical trials to support stated claims and safety appear critical.

Use of duloxetine in pregnancy and lactation.

OBJECTIVE: To report a case of a woman who used duloxetine during pregnancy and breast-feeding. CASE SUMMARY: A 29-year-old woman was treated with duloxetine for depression during the second half of an uncomplicated gestation. She gave birth at term to a healthy female infant. A cord blood sample was obtained at birth. The mother continued the antidepressant while exclusively breast-feeding her infant. One month later, we collected blood and milk samples from the mother and a single blood sample from the infant. All samples were analyzed for the presence and concentrations of duloxetine. DISCUSSION: Duloxetine crosses the placenta at term and is excreted into breast milk. No evidence of developmental or other type of toxicity was observed in the infant at birth or during the first 32 days after birth. The published literature detailing human pregnancy experience with this antidepressant is limited to 11 cases in which women became pregnant while taking duloxetine. In 10 cases, the drug was discontinued when pregnancy was diagnosed and no outcome data were reported. In the eleventh case, an infant exposed to duloxetine 90 mg/day developed neonatal behavioral syndrome. One study examined the excretion of duloxetine into breast milk, but the mothers discontinued nursing for the study. In the present case, no adverse effects from exposure to the drug in milk were noted in the exclusively breast-fed infant. The possibility of functional/neurobehavioral deficits appearing later in life cannot be excluded because long-term follow-up has not been conducted in infants exposed to duloxetine in utero or during nursing. CONCLUSIONS: No developmental toxicity or other signs of toxicity were observed in an infant exposed to duloxetine during the second half of gestation and during breast-feeding in the first 32 days after birth. However, the possibility of functional/neurobehavioral deficits appearing later in life cannot be excluded.

High-dose carisoprodol during pregnancy and lactation.

OBJECTIVE: To report a case of use of high-dose carisoprodol during pregnancy and breast-feeding. CASE SUMMARY: A 28-year-old woman with severe back muscle spasm took carisoprodol 2800 mg/day before and throughout an uncomplicated pregnancy and while exclusively breast-feeding her infant during the first month after birth. Serum drug concentrations of carisoprodol and the active metabolite meprobamate were measured in the mother and infant. Concentrations of these agents also were measured in breast milk. Developmental toxicity was not observed in the near-term infant, whose birth weight was at the 10th percentile for gestational age. Only slight sedation was noted in the infant during breast-feeding, and no signs or symptoms of withdrawal were noted when nursing was stopped. DISCUSSION: Carisoprodol and meprobamate are excreted into breast milk. Although the published human pregnancy data are limited to 15 cases, carisoprodol does not appear to cause developmental toxicity (growth restriction, structural anomalies, functional/neurobehavioral deficits, or death), even when the mother is taking high doses. No signs or symptoms of withdrawal were noted in our infant or in a previously published case when breast-feeding was stopped. Long-term follow-up has not been conducted in exposed infants, and the possibility of functional/neurobehavioral l deficits appearing later in life cannot be excluded. CONCLUSIONS: Except for mild sedation, no other toxicity was observed in a near-term infant exposed to carisoprodol throughout gestation and during breast-feeding in the first month after birth.

An advanced pharmacy practice experience in sports pharmacy.

OBJECTIVE: To establish and evaluate an advanced pharmacy practice experience (APPE) in sports pharmacy. DESIGN: Students actively participated in a variety of activities for this new 6-week elective APPE, including drug-testing collections, delivering presentations, and providing drug information. Students also learned about assays, compounding, and dispensing medications specifically for athletes, and visited various athletic medical facilities. Student were given written and practical certification examinations for drug-testing collections, and their specimen measurements were compared to those obtained by the testing laboratory for validation; satisfaction surveys were obtained from testing sites; and presentation evaluations were obtained from audience participants. ASSESSMENT: Students were able to accurately measure pH and specific gravity of urine samples and all students passed the certification examination. Students rated the APPE very high. Also, students received high satisfaction ratings on surveys administered to the officials of the schools where they tested and members of the groups to whom they gave presentations. CONCLUSION: Students gained experience and insight into the various roles of pharmacists in sports pharmacy and developed confidence in their ability to conduct drug-testing collections.

Accuracy of oral liquid measuring devices: comparison of dosing cup and oral dosing syringe.

BACKGROUND: Previous studies have found that teaspoons are commonly used to administer liquid medications to children. The capacity of household teaspoons ranges from 1.5 mL to 9 mL, potentially leading to errors in dosing. There are few studies evaluating alternative measuring devices. OBJECTIVE: To assess adult consumers' previous experience with measuring devices for oral liquids, compare the accuracy of an oral syringe with that of a dosing cup, and determine consumer perceptions of accuracy and ease of use of an oral syringe and a dosing cup. METHODS: Individuals at least 18 years of age were shown a picture of 5 commonly used measurement devices and asked their perceptions of and experience with the devices. They were then asked to measure a 5 mL (1 teaspoon) dose of Tylenol (acetaminophen) suspension, using the EZY Dose oral syringe and the dosing cup provided by the manufacturer. An acceptable dose was defined as 5.0 +/- 0.5 mL. Following the measurement, participants completed a 5 item survey that assessed their perceptions of the accuracy and ease of use of the syringe and dosing cup. RESULTS: A total of 96 subjects completed the study. Participants more commonly reported use of droppers (68%), dosing cups (67%), and teaspoons (62%) versus cylindrical spoons (49%) or oral syringes (49%) for measuring oral liquids. Sixty-four (66.7%) subjects measured an acceptable dose using the syringe versus 14 subjects (14.6%) using the cup (p < 0.001). The mean volumes +/- SD measured with the syringe and cup were 4.5 +/- 0.7 mL and 6.3 +/- 0.7 mL, respectively (p < 0.001). After using both devices, the majority of subjects believed that the syringe (80%) and cup (71%) would measure an accurate dose. Most (87%) participants perceived that the cup was easy to use; 63% believed that the syringe was easy to use. CONCLUSIONS: Droppers and dosing cups were the most commonly used devices in the home for measuring liquid medications. Subjects were more likely to measure an acceptable dose with an oral syringe when compared with a dosing cup. However, a large proportion of study participants were unable to measure an accurate dose with either device. Community pharmacists should educate caregivers on the selection and proper use of measuring devices to improve the accuracy of medication administration in the home.

Drug interaction between oral contraceptives and St. John's Wort: appropriateness of advice received from community pharmacists and health food store clerks.

OBJECTIVE: To estimate the extent to which community pharmacists and health food store clerks provide appropriate advice regarding a drug interaction between oral contraceptives and St. John's wort (SJW). DESIGN: Cross-sectional study. SETTING: Three community pharmacy chains and three health food store chains in four highly populated counties in California. PARTICIPANTS: Community pharmacists (n=99) and health food store clerks (n=84). INTERVENTION: Investigators, posing as consumers, telephoned pharmacists and health food store clerks and asked the following question: "Is there a problem with taking SJW with birth control pills?" MAIN OUTCOME MEASURES: Respondents were classified based on their ability to correctly identify the drug interaction (yes or no) and on the overall appropriateness (i.e., the absence of incorrect advice) of their advice. Comparisons were made between men and women respondents and between pharmacists and health food store clerks. RESULTS: Community pharmacists were more likely than health food store clerks to correctly identify the drug interaction (50.5% versus 10.9%; Xchi(1 df) = 54.32, P < 0.001). Overall, 31.8% of respondents provided inappropriate advice that implied the absence of a drug interaction (26.3% of 99 pharmacists and 34.8% of 184 health food store clerks; Xchi(1 df) = 2.15, P = 0.14). Appropriateness of advice varied significantly among the three pharmacy chains (P < 0.001) and the three health food store chains (P < 0.05). Responses did not differ by gender of respondents (P = 0.18). CONCLUSION: Lack of awareness of the potentially serious drug interaction between SJW and oral contraceptives by those who sell these products places the public at risk. Training and education, more comprehensive product labeling, and policies to refer consumers to drug information centers are needed.

Response of CEDIA amphetamines assay after a single dose of bitter orange.

Bitter orange has recently been substituted as an ingredient in many "ephedra-free" dietary supplements used for weight loss. The primary active ingredient in bitter orange is synephrine. Previous reports have documented false-positive results from ephedrine with urine amphetamine assays. Because of the similarity in chemical structure of ephedrine and synephrine, it is hypothesized that ingestion of a bitter orange supplement may have the potential to cause false-positive results with urine amphetamine assays. The purpose of this study was to determine the response of the CEDIA Amphetamines Assay after ingestion of bitter orange. Six healthy adult male volunteers were administered a single oral dose of Nature's Way Bitter Orange, a 900-mg dietary supplement extract standardized to 6% synephrine. Urine specimens were collected at baseline and 3 and 6 hours post-administration. Additional urine specimens were collected from 1 subject at 9, 12, and 15 hours after administration. All specimens were analyzed by the CEDIA Amphetamines Assay. Urine specific gravity and pH also were measured. All urine specimens demonstrated a negative response to the CEDIA Amphetamines Assay. Urine specific gravity ranged from 1.007 to 1.028, and pH ranged from 5.0 to 7.0; thus, reducing the possibility that the negative results were caused by diluted specimens or reduced excretion of synephrine into alkaline urine. This information will be of value when health care providers or those who interpret drug screens are asked to provide consultation regarding the interference of bitter orange supplements with the CEDIA Amphetamines Assay. A single-dose of Nature's Way Bitter Orange was not found to cause a false-positive response to the CEDIA Amphetamines Assay in 6 healthy adult male volunteers.

Blood pressure and heart rate effects following a single dose of bitter orange.

BACKGROUND: The ingredients of numerous "ephedra-free" dietary supplements used for weight loss include bitter orange, which contains sympathomimetic alkaloids such as synephrine. Due to the similarity in chemical structure to ephedrine and the potential sympathomimetic effects of synephrine, it is hypothesized that bitter orange may increase blood pressure (BP) and heart rate (HR). OBJECTIVE: To determine the effects on BP and HR after a single dose of bitter orange in healthy adults. METHODS: In a prospective, randomized, double-blind, placebo-controlled, crossover study, 15 young, healthy, adult subjects received either a single dose of Nature's Way Bitter Orange--a 900 mg dietary supplement extract standardized to 6% synephrine--or matching placebo, with a one week washout period. Systolic BP (SBP), diastolic BP (DBP), and HR were measured at baseline and every hour for 6 hours after administration. RESULTS: SBP after bitter orange was significantly increased versus placebo at hours 1-5 (p < 0.0001); the peak difference was 7.3 +/- 4.6 mm Hg. Although the baseline DBP was higher than after administration of both placebo and bitter orange, DBP after bitter orange was significantly increased versus placebo at hours 4 and 5 (p < or = 0.02); the peak difference was 2.6 +/- 3.8 mm Hg. HR was significantly increased after bitter orange versus placebo for hours 2-5 (p < 0.01); the peak difference was 4.2 +/- 4.5 beats/min. CONCLUSIONS: SBP, DBP, and HR were higher for up to 5 hours after a single dose of bitter orange versus placebo in young, healthy adults.