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Current Opinion in Critical Care Aug 2016A complex network of hormones and other effectors characterize the hypermetabolic response in critical illness; these mediators work together to induce numerous... (Review)
Review
PURPOSE OF REVIEW
A complex network of hormones and other effectors characterize the hypermetabolic response in critical illness; these mediators work together to induce numerous pathophysiologic alterations. Increased incidence of infection, multiorgan failure, long-term debilitation, delays in rehabilitation, and death result from an inability to meet the prohibitively elevated protein and energy requirements, which occur during illness and can persist for several years. Pharmacologic interventions have been successfully utilized to attenuate particular aspects of the hypermetabolic response; these modalities are a component of managing critically ill patients - including those patients with severe burns. Here, we review recent advances in pharmacologically attenuating the hypermetabolic and catabolic responses.
RECENT FINDINGS
Propranolol, a nonspecific β-adrenergic receptor antagonist, is one of the most widely used anticatabolic therapies. Oxandrolone, testosterone, and intensive insulin therapy represent anabolic pharmacological strategies. Promising therapies, such as metformin, glucagon-like peptide 1, peroxisome proliferator-activated receptor agonists, are currently being investigated.
SUMMARY
Profound metabolic derangements occur in critically ill patients; this hypermetabolic response is a major contributor to adverse outcomes. Despite the pharmacological therapies currently available to counteract this devastating cascade, future studies are warranted to explore new multimodality agents that will counteract these effects while maintaining glycemic control and preventing unfavorable complications.
Topics: Adrenergic beta-Antagonists; Anabolic Agents; Critical Care; Critical Illness; Humans; Insulin; Oxandrolone; Propranolol
PubMed: 27272101
DOI: 10.1097/MCC.0000000000000330 -
Clinics in Plastic Surgery Jul 2017Severe burn injury is followed by a profound hypermetabolic response that persists up to 2 years after injury. It is mediated by up to 50-fold elevations in plasma... (Review)
Review
Severe burn injury is followed by a profound hypermetabolic response that persists up to 2 years after injury. It is mediated by up to 50-fold elevations in plasma catecholamines, cortisol, and glucagon that lead to whole-body catabolism, elevated resting energy expenditures, and multiorgan dysfunction. Modulation of the response by early excision and grafting of burn wounds, thermoregulation, control of infection, early and continuous enteral nutrition, and pharmacologic treatments aimed at mitigating physiologic derangements have markedly decreased morbidity.
Topics: Body Temperature Regulation; Burns; Catecholamines; Energy Metabolism; Humans
PubMed: 28576243
DOI: 10.1016/j.cps.2017.02.013 -
Best Practice & Research. Clinical... Jun 2015Besides growth hormone, several pharmaceutical products have been investigated for efficacy and safety in increasing short term growth or adult height. Short-term... (Review)
Review
Besides growth hormone, several pharmaceutical products have been investigated for efficacy and safety in increasing short term growth or adult height. Short-term treatment with testosterone esters in boys with constitutional delay of growth and puberty is efficacious in generating secondary sex characteristics and growth acceleration. The addition of oxandrolone to growth hormone (GH) in Turner syndrome has an additive effect on adult height gain. Treatment with GnRH analogs is the established treatment of central precocious puberty, and its addition to GH therapy appears effective in increasing adult height in GH deficient children, and possibly short children born SGA or with SHOX deficiency, who are still short at pubertal onset. Aromatase inhibitors appear effective in several rare disorders, but their value in increasing adult height in early pubertal boys with GH deficiency or idiopathic short stature is uncertain. A trial with a C-natriuretic peptide analog offers hope for children with achondroplasia.
Topics: Achondroplasia; Androgens; Aromatase Inhibitors; Dwarfism, Pituitary; Gonadotropin-Releasing Hormone; Growth Disorders; Human Growth Hormone; Humans; Natriuretic Agents; Natriuretic Peptide, C-Type; Oxandrolone; Puberty, Precocious; Recombinant Proteins; Testosterone; Turner Syndrome
PubMed: 26051296
DOI: 10.1016/j.beem.2015.01.003 -
Drug Testing and Analysis Jan 2022Oxandrolone is an anabolic-androgenic steroid with favourable anabolic to androgenic ratio, making it an effective anabolic agent with less androgenic side effects....
Oxandrolone is an anabolic-androgenic steroid with favourable anabolic to androgenic ratio, making it an effective anabolic agent with less androgenic side effects. Although its metabolism has been studied in humans, its phase I and II metabolism has not been previously reported in the horse. The purpose of this study was to investigate the in vitro metabolism of oxandrolone (using both equine liver microsomes and S9) and in vivo metabolism following oral administration (three daily doses of 50 mg of oxandrolone to a single Thoroughbred horse), using both gas and liquid chromatography-mass spectrometry techniques. The in vitro phase I transformations observed included 16-hydroxylated (two epimers), 17-methyl-hydroxylated and 16-keto metabolites. In addition to parent oxandrolone and these hydroxylated metabolites, the 17-epimer and a 17,17-dimethyl-18-norandrost-13-ene analogue were detected in biological samples following the administration. 16-keto-oxandrolone was only observed in urine. The 16- and 17-methyl-hydroxylated oxandrolone metabolites were predominantly excreted as sulfate conjugates in urine, whereas parent oxandrolone, its epimer and 17,17-dimethyl-18-norandrost-13-ene derivative were found predominantly in the unconjugated urine fraction. The most abundant analyte detected in both plasma and urine was parent oxandrolone. However, the longest detection period using the developed analytical method was provided by 17-hydroxymethyl-oxandrolone in both matrices. The results of this study provided knowledge of how best to detect the use of oxandrolone in regulatory samples.
Topics: Anabolic Agents; Androgens; Animals; Chromatography, Liquid; Doping in Sports; Gas Chromatography-Mass Spectrometry; Horses; Male; Mass Spectrometry; Microsomes, Liver; Oxandrolone; Substance Abuse Detection
PubMed: 34378336
DOI: 10.1002/dta.3139 -
Allergologie Select 2018The aim of treatment of hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency (HAE-C1-INH) is either treating acute attacks or preventing attacks by using... (Review)
Review
The aim of treatment of hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency (HAE-C1-INH) is either treating acute attacks or preventing attacks by using prophylactic treatment. For treating acute attacks, plasma-derived C1 inhibitor (C1-INH) concentrates, a bradykinin B2 receptor antagonist, and a recombinant human C1-INH are available in Europe. In the United States, a plasma-derived C1-INH concentrate, a bradykinin B2 receptor antagonist, and a plasma kallikrein inhibitor were approved for the treatment of acute attacks. Fresh frozen plasma is also available for treating acute attacks. Short-term prophylactic treatment focuses on C1-INH and attenuated androgens. Long-term prophylactic treatments include attenuated androgens such as danazol, stanozolol, and oxandrolone, antifibrinolytics, and a plasma-derived C1-INH concentrate. Plasma-derived C1-INH and a bradykinin B2 receptor antagonist are admitted for self-administration and home therapy. So the number of management options increased considerably within the last few years thus helping to diminish the burden of HAE.
PubMed: 31826031
DOI: 10.5414/ALX1561E -
Journal of Plastic, Reconstructive &... Aug 2022Major thermal injury induces a complex pathophysiological state characterized by burn shock and hypercatabolism. Steroids are used to modulate these post-injury...
BACKGROUND
Major thermal injury induces a complex pathophysiological state characterized by burn shock and hypercatabolism. Steroids are used to modulate these post-injury responses. However, the effects of steroids on acute post-burn outcomes remain unclear.
METHODS
In this study of 52 thermally injured adult patients (median total burn surface area 42%, 33 males and 19 females), the effects of corticosteroid and oxandrolone on mortality, multi-organ failure (MOF), and sepsis were assessed individually. Clinical data were collected at days 1, 3, 7, and 14 post-injury.
RESULTS
Twenty-two (42%) and 34 (65%) burns patients received corticosteroids and oxandrolone within the same cohort, respectively. Following separate analysis for each steroid, corticosteroid use was associated with increased odds of in-hospital mortality (OR 3.25, 95% CI: 1.32-8•00), MOF (OR 2.36, 95% CI: 1.00-1.55), and sepsis (OR 5.95, 95% CI: 2.53-14.00). Days alive (HR 0.32, 95% CI: 0.18-0.60) and sepsis-free days (HR 0.54, 95% CI: 0.37-0.80) were lower among corticosteroid-treated patients. Oxandrolone use was associated with reduced odds of 28-day mortality (OR 0.11, 95% CI: 0.04-0.30), in-hospital mortality (OR 0.19, 95% CI: 0.08-0.43), and sepsis (OR 0.24, 95% CI: 0.08-0.69). Days alive, at 28 days (HR 6.42, 95% CI: 2.77-14.9) and in-hospital (HR 3.30, 95% CI: 1.93-5.63), were higher among the oxandrolone-treated group. However, oxandrolone was associated with increased MOF odds (OR 7.90, 95% CI: 2.89-21.60) and reduced MOF-free days (HR 0.23, 95% CI: 0.11-0.50).
CONCLUSION
Steroid therapies following major thermal injury may significantly affect patient prognosis. Oxandrolone was associated with better outcomes except for MOF. Adverse effects of corticosteroids and oxandrolone should be considered when managing burn patients.
Topics: Adult; Anabolic Agents; Cohort Studies; Female; Hospital Mortality; Humans; Male; Oxandrolone; Sepsis
PubMed: 35599217
DOI: 10.1016/j.bjps.2022.04.007 -
American Journal of Men's Health 2020During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass.... (Review)
Review
During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass. Testosterone is the most abundant testicular androgen, but some effects are mediated by its conversion to the more potent androgen dihydrotestosterone (DHT) or to estradiol. Androgen deficiency, requiring replacement therapy, may occur due to a primary testicular failure or secondary to a hypothalamic-pituitary disorder. A very frequent condition characterized by a late activation of the gonadal axis that may also need androgen treatment is constitutional delay of puberty. Of the several testosterone or DHT formulations commercially available, very few are employed, and none is marketed for its use in adolescents. The most frequently used androgen therapy is based on the intramuscular administration of testosterone enanthate or cypionate every 3 to 4 weeks, with initially low doses. These are progressively increased during several months or years, in order to mimic the physiology of puberty, until adult doses are attained. Scarce experience exists with oral or transdermal formulations. Preparations containing DHT, which are not widely available, are preferred in specific conditions. Oxandrolone, a non-aromatizable drug with higher anabolic than androgenic effects, has been used in adolescents with preserved testosterone production, like Klinefelter syndrome, with positive effects on cardiometabolic health and visual, motor, and psychosocial functions. The usual protocols applied for androgen therapy in boys and adolescents are discussed.
Topics: Adolescent; Androgens; Child; Clinical Protocols; Disorders of Sex Development; Hormone Replacement Therapy; Humans; Klinefelter Syndrome; Male; Outcome Assessment, Health Care; Puberty
PubMed: 32448030
DOI: 10.1177/1557988320922443 -
Bone Research 2015Severe burn injury triggers the body's nonspecific adaptive responses to acute insult, including the systemic inflammatory and stress responses, as well as the... (Review)
Review
Severe burn injury triggers the body's nonspecific adaptive responses to acute insult, including the systemic inflammatory and stress responses, as well as the sympathetic response to immobilization. These responses trigger inflammatory bone resorption followed by glucocorticoid-induced apoptosis of osteoblasts and probably osteocytes. Because these patients are catabolic, they suffer concomitant muscle wasting and negative nitrogen balance. The use of anabolic agents such as recombinant human growth hormone and oxandrolone results in improved bone mineral content and muscle strength after approximately 1 year. Use of bisphosphonates within the first 10 days of a severe burn completely blocks the resorptive bone loss and has the added advantage of appearing to preserve muscle protein from excessive breakdown. The mechanism for the protective effect on muscle is not currently known. However, if the effect of bisphosphonates on muscle can be confirmed, it raises the possibility that bone communicates with muscle.
PubMed: 26273535
DOI: 10.1038/boneres.2015.2 -
The Cochrane Database of Systematic... Jul 2015Inclusion body myositis (IBM) is a late-onset inflammatory muscle disease (myopathy) associated with progressive proximal and distal limb muscle atrophy and weakness.... (Review)
Review
BACKGROUND
Inclusion body myositis (IBM) is a late-onset inflammatory muscle disease (myopathy) associated with progressive proximal and distal limb muscle atrophy and weakness. Treatment options have attempted to target inflammatory and atrophic features of this condition (for example with immunosuppressive and immunomodulating drugs, anabolic steroids, and antioxidant treatments), although as yet there is no known effective treatment for reversing or minimising the progression of inclusion body myositis. In this review we have considered the benefits, adverse effects, and costs of treatment in targeting cardinal effects of the condition, namely muscle atrophy, weakness, and functional impairment.
OBJECTIVES
To assess the effects of treatment for IBM.
SEARCH METHODS
On 7 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, and EMBASE. Additionally in November 2014 we searched clinical trials registries for ongoing or completed but unpublished trials.
SELECTION CRITERIA
We considered randomised or quasi-randomised trials, including cross-over trials, of treatment for IBM in adults compared to placebo or any other treatment for inclusion in the review. We specifically excluded people with familial IBM and hereditary inclusion body myopathy, but we included people who had connective tissue and autoimmune diseases associated with IBM, which may or may not be identified in trials. We did not include studies of exercise therapy or dysphagia management, which are topics of other Cochrane systematic reviews.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures.
MAIN RESULTS
The review included 10 trials (249 participants) using different treatment regimens. Seven of the 10 trials assessed single agents, and 3 assessed combined agents. Many of the studies did not present adequate data for the reporting of the primary outcome of the review, which was the percentage change in muscle strength score at six months. Pooled data from two trials of interferon beta-1a (n = 58) identified no important difference in normalised manual muscle strength sum scores from baseline to six months (mean difference (MD) -0.06, 95% CI -0.15 to 0.03) between IFN beta-1a and placebo (moderate-quality evidence). A single trial of methotrexate (MTX) (n = 44) provided moderate-quality evidence that MTX did not arrest or slow disease progression, based on reported percentage change in manual muscle strength sum scores at 12 months. None of the fully published trials were adequately powered to detect a treatment effect. We assessed six of the nine fully published trials as providing very low-quality evidence in relation to the primary outcome measure. Three trials (n = 78) compared intravenous immunoglobulin (combined in one trial with prednisone) to a placebo, but we were unable to perform meta-analysis because of variations in study analysis and presentation of trial data, with no access to the primary data for re-analysis. Other comparisons were also reported in single trials. An open trial of anti-T lymphocyte immunoglobulin (ATG) combined with MTX versus MTX provided very low-quality evidence in favour of the combined therapy, based on percentage change in quantitative muscle strength sum scores at 12 months (MD 12.50%, 95% CI 2.43 to 22.57). Data from trials of oxandrolone versus placebo, azathioprine (AZA) combined with MTX versus MTX, and arimoclomol versus placebo did not allow us to report either normalised or percentage change in muscle strength sum scores. A complete analysis of the effects of arimoclomol is pending data publication. Studies of simvastatin and bimagrumab (BYM338) are ongoing. All analysed trials reported adverse events. Only 1 of the 10 trials interpreted these for statistical significance. None of the trials included prespecified criteria for significant adverse events.
AUTHORS' CONCLUSIONS
Trials of interferon beta-1a and MTX provided moderate-quality evidence of having no effect on the progression of IBM. Overall trial design limitations including risk of bias, low numbers of participants, and short duration make it difficult to say whether or not any of the drug treatments included in this review were effective. An open trial of ATG combined with MTX versus MTX provided very low-quality evidence in favour of the combined therapy based on the percentage change data given. We were unable to draw conclusions from trials of IVIg, oxandrolone, and AZA plus MTX versus MTX. We need more randomised controlled trials that are larger, of longer duration, and that use fully validated, standardised, and responsive outcome measures.
PubMed: 35658164
DOI: 10.1002/14651858.CD001555.pub5 -
Cureus Jan 2021Anabolic-androgenic steroids (AAS) are commonly used among both competitive athletes and recreational athletes in order to gain a performance edge. Unfortunately, AAS...
Anabolic-androgenic steroids (AAS) are commonly used among both competitive athletes and recreational athletes in order to gain a performance edge. Unfortunately, AAS generally carries a broad range of short term and long term adverse effects. These include endocrinological abnormalities, cardiovascular risks, psychological issues, and largely adverse effects on every organ system in the human body. While testosterone, and at times oxandrolone, are used for clinical purposes, AAS generally encompasses a very broad range of synthetic compounds that are used at high doses. In this case report, we look at a patient who has used the vast majority of common anabolic steroids over the past three decades and how these compounds may affect long-term metabolic and cardiovascular health. The purpose is to provide a primary care approach to this patient population.
PubMed: 33564503
DOI: 10.7759/cureus.12492