losartan-potassium and Substance-Related-Disorders

The present review provides a comprehensive overview on the erythropoietic and non-erythropoietic effects of rHuEpo on human sport performance, paying attention to quantifying numerically how rHuEpo affects exercise performance and describing physiological changes regarding the most important exercise variables. Much attention has been paid to treatment schedules, in particular, to assess the effects of microdoses of rHuEpo and the prolonged effects on sport performance following withdrawal. Moreover, the review takes into account non-erythropoietic ergogenic effects of rHuEpo, including cognitive benefits of rHuEpo. A significant increase in both Vo2max and maximal cycling power was evidenced in studies taken into account for this review. rHuEpo, administered at clinical dosage, may have significant effects on haematological values, maximal and submaximal physiological variables, whereas few reports show positive effects on exercise perfomance. However, the influence of micro-dose rHuEpo on endurance performance in athletes is still unclear and further studies are warranted.

Topics: Athletes; Athletic Performance; Cognition; Doping in Sports; Dose-Response Relationship, Drug; Erythropoietin; Exercise; Exercise Test; Hematology; Humans; Oxygen Consumption; Sports; Substance Withdrawal Syndrome; Substance-Related Disorders

The administration of recombinant human erythropoietin (rhEPO) increases the maximum oxygen consumption capacity, and is therefore abused as a doping method in endurance sports. The detection of erythropoietin (EPO) abuse is based on direct pharmacological and indirect haematological approaches, both of which have several limitations. In addition, current detection methods cannot cope with the emerging doping strategies of EPO mimicry, analogues and gene doping, and thus novel detection strategies are urgently needed. Direct detection methods for EPO misuse can be either pharmacological approaches that identify exogenous substances based on their physicochemical properties, or molecular methods that recognise EPO transgenes or gene transfer vectors. Since direct detection with molecular methods requires invasive procedures, it is not appropriate for routine screening of large numbers of athletes. In contrast, novel indirect methods based on haematological and/or molecular profiling could be better suited as screening tools, and athletes who are suspect of doping would then be submitted to direct pharmacological and molecular tests. This article reviews the current state of the EPO doping field, discusses available detection methods and their shortcomings, outlines emerging pharmaceutical and genetic technologies in EPO misuse, and proposes potential directions for the development of novel detection strategies.

Topics: Doping in Sports; Erythropoietin; Genomics; Humans; Substance Abuse Detection; Substance-Related Disorders

The use of drugs and supplements to enhance performance has become a part of mainstream athletics. Many team physicians and sports medicine practitioners are unfamiliar with the benefits and risks of these products and thus are unable to educate young athletes on this topic. In spite of numerous reports on the health risks of anabolic steroid use, 1 to 3 million Americans have used them. Human growth hormone has been tried by up to 5% of 10th graders, although no scientific study has shown that it is an effective performance-enhancing drug. Amphetamines and similar compounds may be the most widely abused drug in baseball; recently, they have come under increased scrutiny in sport. Erythropoietin is a highly effective aerobic enhancer that has been linked to multiple deaths in cyclists and other endurance athletes. The neutraceutical industry, led by supplements such as creatine, ephedra, and androstenedione, remains unregulated by the Food and Drug Administration and has serious issues with quality and side effects. An understanding of these products is essential for the sports medicine practitioner to provide sound, safe advice to the athlete.

Topics: Amphetamines; Anabolic Agents; Doping in Sports; Erythropoietin; Health Policy; Human Growth Hormone; Humans; Physical Endurance; Sports Medicine; Substance-Related Disorders; United States; United States Food and Drug Administration

Neuropsychiatric side effects are common with interferon-based therapy for chronic hepatitis C, and their prompt recognition and management is essential to effective patient care. Depression induced by interferon has been a significant cause of early treatment discontinuation in clinical trials. The need to monitor for and treat interferon-induced depression is well established, but whether to use antidepressants prophylactically remains controversial. Nonetheless, clinicians should maintain a low threshold for antidepressant therapy. Other significant neuropsychiatric side effects include anxiety, hypomania or mania, fatigue, and cognitive dysfunction. These can be additional sources of patient distress during interferon therapy and require appropriate intervention through patient education, psychotropic medications, support, and behavioral techniques.

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Antiviral Agents; Anxiety; Bipolar Disorder; Clinical Trials as Topic; Cognition Disorders; Comorbidity; Depression; Erythropoietin; Fatigue; Hepatitis C, Chronic; Humans; Interferons; Mental Disorders; Psychotropic Drugs; Recombinant Proteins; Risk Factors; Substance-Related Disorders

Topics: Deferoxamine; Doping in Sports; Erythropoietin; Growth Hormone; Humans; Hydroxyethyl Starch Derivatives; Substance Abuse Detection; Substance-Related Disorders

r-HuEPO: Ever since it was first produced, illicit use recombinant human erythropoietin (r-HuEPO), a human polypeptide which accelerates production and maturation of red cells and consequently improves aerobic potential, has been observed in athletic competitions. IMPORTANCE OF SCREENING: Unfortunately, abuse of r-HuEPO can have severe adverse effects, particularly on the cardiovascular system. Screening methods capable of detecting exogenous erythropoietin were thus developed not only to detect illicit drug use in sports competition, but also to preserve athletesí health. THEORETICAL POSSIBILITIES: Several methods have been explored. Direct methods using electrophoresis or indirect methods measuring different biological parameters (fibrin degradation products, number of soluble transferrin receptors) as well specific hematology tests (red cell morphology, hematocrit...) can theoretically detect exogenous erythropoietin. METHODS TO VALIDATE: It would be advisable to examine all of the available work on the proposed methods to develop a reliable diagnostic method for detecting r-HuEPO. Soluble transferrin receptor counts appear to be the most promising method, but specificity is not totally satisfactory.

Topics: Erythropoietin; Female; Humans; Male; Mass Screening; Recombinant Proteins; Sports; Substance-Related Disorders; Transferrin

The purpose of this article is to review and summarize the literature regarding the effects of medications and other substances on blood pressure. Many substances are known to cause or exacerbate hypertension, including sodium chloride, substances of abuse, nonprescription sympathomimetics, nonsteroidal anti-inflammatory drugs, sex steroids, immunosuppressive therapies, erythopoietin, antidepressants, ergot alkaloids, anesthetic agents, and other substances. With the population aging, the increasing incidence of polypharmacy, and the growth of over-the-counter pharmacological agents, including those which were previously available only by prescription, drug-induced hypertension is assuming heightened importance. Furthermore, these agents represent an important modifiable cause of secondary hypertension, and it is imperative that clinicians recognize this causal relationship.

Topics: Adrenergic Agents; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Antihypertensive Agents; Ergot Alkaloids; Erythropoietin; Gonadal Steroid Hormones; Humans; Hypertension; Immunosuppressive Agents; Lead; Sodium Chloride; Substance-Related Disorders

To summarize the literature describing the epidemiology, pharmacology, efficacy, and adverse effects associated with growth hormone (GH), caffeine, aerobic metabolism facilitator (AMF), and sympathomimetic use among athletes.. Relevant articles were identified from a MEDLINE search using the search terms "Doping in Sports," "Blood," "Caffeine," "Cocaine," "Erythropoietin," "Somatotropin," and "Sympathomimetics (exploded)." Additional references were found in bibliographies of these articles.. We reviewed studies of ergogenic drug (ED) use among athletes. Interpretation of these studies is difficult because of poor research design and the paucity of information available. This necessitated the inclusion of many anecdotal or conjectural reports in our review.. There are no studies documenting an ergogenic effect associated with GH use in humans or animals. It is still unknown whether GH abuse causes adverse effects in healthy adults, although GH-induced acromegaly has been suspected. Amphetamines, cocaine, and caffeine are thought to improve performance via enhanced concentration among athletes. Amphetamines and cocaine may increase aggressiveness. The ergogenic effects of other sympathomimetics including ephedrine and phenylpropanolamine are unclear. AMFs (e.g., blood doping, epoetin) enhance aerobic metabolism and endurance by increasing the oxygen-carrying capacity of the blood. Risks associated with excessive AMF use include increased blood viscosity and clotting.. Athletes view EDs as an essential component for success. Without adequate intervention measures, ED abuse is likely to continue unchecked.

Topics: Amphetamines; Caffeine; Cocaine; Doping in Sports; Erythropoietin; Growth Hormone; Humans; Male; Metabolism; Substance-Related Disorders; Time Factors

Topics: Biotechnology; Erythropoietin; Growth Hormone; Humans; Illicit Drugs; Recombinant Proteins; Sports; Substance-Related Disorders; United States

The detection of recombinant human erythropoietin (r-HuEPO) abuse by athletes remains problematic. The main aim of this study was to demonstrate that the five indirect markers of altered erythropoiesis identified in our earlier work were reliable evidence of current or recently discontinued r-HuEPO use. A subsidiary aim was to refine weightings of the five markers in the initial model using a much larger data set than in the pilot study. A final aim was to verify that the hematologic response to r-HuEPO did not differ between Caucasian and Asiatic subjects.. Recreational athletes resident in Sydney, Australia (Sydney, n = 49; 16 women, 33 men) or Beijing, China (Beijing, n=24; 12 women, 12 men) were randomly assigned to r-HuEPO or placebo groups prior to a 25 day administration phase. Injections of r-HuEPO (or saline) were administered double-blind at a dose of 50 IU/kg three times per week, with oral iron (105 mg) or placebo supplements taken daily by all subjects. Blood profiles were monitored during and for 4 weeks after drug administration for hematocrit (Hct), reticulocyte hematocrit (RetHct), percent macrocytes (%Macro), serum erythropoietin (EPO) and soluble transferrin receptor (sTfr), since we had previously shown that these five variables were indicative of r-HuEPO use.. The changes in Hct, RetHct, %Macro, EPO and sTfr in the Sydney trial were qualitatively very similar to the changes noted in our previous administration trial involving recreational athletes of similar genetic origin. Statistical models developed from Fisher's discriminant analysis were able to categorize the user and placebo groups correctly. The same hematologic response was demonstrated in Beijing athletes also administered r-HuEPO.. This paper confirms that r-HuEPO administration causes a predictable and reproducible hematologic response. These markers are disturbed both during and for several weeks following r-HuEPO administration. This work establishes an indirect blood test which offers a useful means of detecting and deterring r-HuEPO abuse. Ethnicity did not influence the markers identified as being able to detect athletes who abuse r-HuEPO.

Topics: Adult; Australia; Biomarkers; China; Doping in Sports; Double-Blind Method; Erythropoiesis; Erythropoietin; Female; Humans; Male; Recombinant Proteins; Substance-Related Disorders

The use of recombinant human erythropoietin (r-HuEPO) to enhance athletic performance is prohibited. Existing tests cannot readily differentiate between exogenous and endogenous EPO. Therefore the aim of our study was to investigate possible indirect detection of r-HuEPO use via blood markers of altered erythropoiesis.. Twenty-seven recreational athletes were assigned to three groups prior to a 25 day drug administration phase, with the following protocols: EPO+IM group (n = 10), 50 Ukg(-1) r-HuEPO at a frequency of 3wk(-1), 100 mg intramuscular (IM) iron 1wk(-1) and a sham iron tablet daily; EPO+OR group (n = 8), 50 U.kg(-1) r-HuEPO 3wk(-1), sham iron injection 1wk(-1) and 105 mg of oral elemental iron daily; placebo group (n = 9), sham r-HuEPO injections 3wk(-1), sham iron injections 1wk(-1) and sham iron tablets daily. Each group was monitored during and for 4 weeks after drug administration.. Models incorporating combinations of the variables reticulocyte hematocrit (RetHct), serum EPO, soluble transferrin receptor, hematocrit (Hct) and % macrocytes were analyzed by logistic regression. One model (ON-model) repeatedly identified 94-100% of r-HuEPO group members during the final 2 wk of the r-HuEPO administration phase. One false positive was recorded from a possible 189. Another model (OFF-model) incorporating RetHct, EPO and Hct was applied during the wash-out phase and, during the period of 12-21 days after the last r-HuEPO injection, it repeatedly identified 67-72% of recent users with no false positives.. Multiple indirect hematologic and biochemical markers used simultaneously are potentially effective for identifying current or recent users of r-HuEPO.

Topics: Adult; Analysis of Variance; Biomarkers; Blood Gas Analysis; Diagnosis, Computer-Assisted; Doping in Sports; Double-Blind Method; Erythrocytes; Erythropoietin; False Positive Reactions; Female; Ferritins; Hematocrit; Hemoglobins; Humans; Iron; Male; Receptors, Transferrin; Recombinant Proteins; Reticulocytes; Substance-Related Disorders

The author argues that drug testing of U.S. high school students for performance-enhancing substance misuse is invasive, expensive, and the low number of positive test results do not justify the costs, especially in financially strapped school districts where this money would be better spent on injury prevention for athletes and the education of all students.

Topics: Adolescent; Anabolic Agents; Athletes; Central Nervous System Stimulants; Cost-Benefit Analysis; Doping in Sports; Erythropoietin; Hematinics; Humans; Performance-Enhancing Substances; Schools; Students; Substance Abuse Detection; Substance-Related Disorders; United States

A 26-year-old male bodybuilder was admitted to the surgical department of a Danish community hospital for hematemesis. During the clinical interview, he revealed that he had recently finished a course of anabolic steroids and erythropoietin. The patient also had a previous history of infections and chronic ulcers due to paraffin-oil injections in both upper arms one year before. Over the course of the next few hours, the patient developed signs of multi-organ dysfunction, including pancreatitis, hemorrhagic gastritis, nephropathy with temporary anuria, and respiratory insufficiency, and was transferred to the ICU. After manometric monitoring on the patient's upper arms proved difficult, invasive blood pressure monitoring was used and revealed that the patient was in a state of hypertensive crisis. This case of multi-organ dysfunction was possibly caused by multi-substance-induced hypercalcemia.

Topics: Adult; Anabolic Agents; Critical Care; Denmark; Erythropoietin; Humans; Hypercalcemia; Male; Multiple Organ Failure; Substance-Related Disorders; Weight Lifting

Erythropoietin (Epo) is a glycoprotein hormone that promotes the production of red blood cells. Recombinant human Epo (rhEpo) is illicitly used to improve performance in endurance sports. Doping in sports is discouraged by the screening of athletes for rhEpo. Both direct tests (indicating the presence of exogeneous Epo isoforms) and indirect tests (indicating hematological changes induced by exogenous Epo administration) can be used for Epo detection. At present, the test adopted by the World Anti Doping Agency is based on a combination of isoelectric focusing and double immunoblotting, and distinguishes between endogenous and rhEpo. However, the adopted monoclonal anti-Epo antibodies are not monospecific. Therefore, the test can occasionally lead to the false-positive detection of rhEpo (epoetin-beta) in post-exercise, protein-rich urine, or in case of contamination of the sample with microorganisms. An improved preanalytical care may counteract a lot of these problems. Adaptation of the criteria may be helpful to further refine direct Epo testing. Indirect tests have the disadvantage that they require blood instead of urine samples, but they can be applied to detect a broader range of performance improving techniques which are illicitly used in sports.

Topics: Doping in Sports; Erythropoietin; Glycosylation; Humans; Isoelectric Focusing; Recombinant Proteins; Substance-Related Disorders

Information derived from blood analyses can assist in the detection and/or deterrence of blood doping in sport. We investigated whether comparing an athlete's hematologic values against his or her own historical baseline rather than population-derived thresholds enhanced the ability to detect blood doping.. We developed an approach whereby an athlete's true baseline value could be estimated with just one prior blood test. We also estimated a universal value for within-subject variability for key hematologic parameters using the highest value obtained among four separate cohorts of male athletes including 80 elite rowers, 124 endurance-trained or team-sport subjects, 288 professional football players and 630 athletes competing at national or international level. The (individual) baseline and (universal) variability were then incorporated so as to define expected thresholds for subsequent blood tests. The sensitivity of our approach was obtained by analyzing data from 49 recreational athletes administered either recombinant human erythropoietin (n=37) or placebo (n=12).. We found that removing within-subject variability by comparing new results against an historical baseline heightened the capacity to detect blood doping. It was possible to delineate the longitudinal changes in either hemoglobin (Hb) or the OFF-hr model score (an algorithm using both Hb and percent reticulocytes) caused by recombinant human erythropoietin treatment from the natural biological fluctuations found in subjects treated with placebo.. Our objective data supported the intuitive belief that longitudinal monitoring of athletes' blood profiles will help detect blood doping. This information could be used to instigate target-testing of suspicious athletes, or even warrant the exclusion from competition of athletes with aberrant variations in key hematologic values.

Topics: Cohort Studies; Doping in Sports; Erythropoietin; Humans; Male; Substance Abuse Detection; Substance-Related Disorders

Topics: Anabolic Agents; Creatine; Designer Drugs; Doping in Sports; Ephedra; Erythropoietin; Growth Hormone; Humans; Sports; Steroids; Substance-Related Disorders

Topics: Altitude; Erythropoietin; Ferritins; Humans; Iron; Receptors, Transferrin; Recombinant Proteins; Reference Values; Substance-Related Disorders

This study investigated using reticulocyte (retic) parameters as indirect markers of human recombinant erythropoietin (r-HuEPO) abuse in elite athletes. Absolute reticulocyte count (# retic), the per cell haemoglobin content of reticulocytes (CHr), reticulocyte haemoglobin mass per litre of blood (RetHb) and red blood cell:reticulocyte haemoglobin (RBCHb:RetHb) ratio were assessed using flow cytometry. Venous blood was drawn from 155 elite athletes from six sports during regular training to establish reference ranges (95% confidence interval) for these parameters. The reference ranges were compared with those of a non-athletic population (n = 23), four groups of athletes (n = 24) before and after exposure to simulated altitudes (2,500-3,000 m for 11-23 nights), two groups of elite cyclists (n = 13) before and after four weeks of training at natural altitude (1,780 and 2,690 m), and with those of non-athletic subjects from a separate study (n =24) before and 1-2 days after they were injected with 1,200 U x kg(-1) r-HuEPO over a 9-10 day period. Generally the changes induced by r-HuEPO injection exceeded by approximately 100% the magnitude of the changes associated with natural altitude exposure. Simulated altitude exposure did not significantly alter the reticulocyte parameters. From the sample of 155 non-users and 24 r-HuEPO users, the population mean and variance, as well as the 95% confidence limits for the population mean and population variance, were estimated. Relative to arbitrarily chosen cut-off levels, the confidence limits for the rate of true positives and rate of true negatives were also calculated. Based on the lowest rate of false positives and highest rate of true positives, the best discriminator between r-HuEPO users and non-users was # retic, marginally superior to RBCHb: RetHb ratio and RetHb. At a cut-off for # retic of 221 x 10(9)x L(-1) we could be 95% sure that we would find no more than 7 false positives in every 100,000 tests. We would expect to pick up 51.8% of users, and could be 95% sure of picking up at least 38% of current or recent users. This result highlights the potential power of retic parameters for detecting r-HuEPO abuse among athletes. However, the efficacy of these cut-offs for detecting r-HuEPO abuse is unknown if an athlete is a chronic user or stops using r-HuEPO several weeks before being tested.

Topics: Bicycling; Boxing; Doping in Sports; Erythrocyte Count; Erythropoietin; False Positive Reactions; Hemoglobins; Humans; Male; Recombinant Proteins; Reticulocytes; Substance-Related Disorders; Swimming; Track and Field

Recombinant human erythropoietin (EPO) therapy in uremic patients raises the hematocrit (Hct) and increases physical exercise capacity (1,2) and quality of life (1). In general, partial correction of anemia to subnormal levels in uremic patients has proven to be safe with few serious adverse effects apart from hypertension (3). Ever since the advent of EPO the prospect of abuse of the hormone by sportsmen has been subject to scrutiny. Both maximal oxygen uptake and endurance capacity are increased after EPO treatment in healthy subjects (4). Moreover, EPO treatment in healthy subjects has been found to induce an accentuated blood pressure reaction after submaximal exercise (5). Previous studies have shown that extreme physical exertion can predispose to an increased intravascular coagulation (6). Moreover there is a significantly increased risk of thrombosis in patients with myeloproliferative disorders, particularly in polycythemia vera (7). An enhanced risk of cardiovascular events may therefore arise should sportsmen abuse EPO as a blood doping agent. The aim of this study was to examine the effects of an EPO-induced increase in Hct on the coagulation system in healthy subjects.

Topics: Adult; Antithrombin III; Blood Coagulation Tests; Erythropoietin; Fibrinopeptide A; Hematocrit; Humans; Male; Peptide Hydrolases; Recombinant Proteins; Reference Values; Risk; Sports Medicine; Substance-Related Disorders; Thromboembolism

Deliberate self-administration of recombinant human erythropoietin (rHuEpo) in a patient without anemia has never been documented. The case of a 62-year-old man who worked in an allied health care field and surreptitiously injected the drug, causing his hematocrit to increase to a dangerously high level is presented. Resultant complications of the misuse of erythropoietin in this patient included worsening hypertension, exacerbation of chronic lung disease and development of new onset angina. Medical management consisted of endotracheal intubation with mechanical ventilation, intravenous hydration, and serial phlebotomy. The unusual possibility of erythropoietin abuse must be added to the differential diagnosis with a patient with unexplained polycythemia. This case highlights the potential abuse of biological growth factors that may mask medical conditions.

Topics: Angina Pectoris; Bloodletting; Delusions; Diagnosis, Differential; Drug Overdose; Erythropoietin; Fluid Therapy; Hematocrit; Humans; Hypertension; Lung Diseases, Obstructive; Male; Middle Aged; Polycythemia; Respiration, Artificial; Self Medication; Substance-Related Disorders

Topics: Doping in Sports; Erythropoietin; Humans; Substance-Related Disorders