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Adrenal Suppression (adrenal + suppression)
Selected AbstractsEvaluation of Adrenal Suppression of a Lipid Enhanced, Topical Emollient Cream Formulation of Hydrocortisone Butyrate 0.1% in Treating Children with Atopic DermatitisPEDIATRIC DERMATOLOGY, Issue 1 2007Lawrence Eichenfield M.D. In the pediatric population however, the potential impact of adrenal suppression is always an important safety concern. Twenty boys and girls, 5,12 years of age, with normal adrenal function and a history of atopic dermatitis were maximally treated three times daily with a lipid-rich, moisturizing formulation of hydrocortisone butyrate 0.1% for up to 4 weeks. At the conclusion of the 4-week treatment period, cosyntropin injection stimulation testing showed no evidence of adrenal suppression. In addition, the therapy was noted to be highly efficacious, with a clinical success rate of 80% (Physician Global Score of (0) clear or (1) almost clear). No local side effects associated with prolonged use of topical corticosteroids were reported. In summary, this study supports the contention that this lipid-rich, moisturizing formulation of hydrocortisone butyrate 0.1% was a well-tolerated and beneficial treatment for atopic dermatitis, demonstrating no adrenal suppression in the pediatric population aged 5,12 years. The relevance of these findings for children below 5 years of age, because of difference in body mass/surface area ratios, remains to be determined. [source] Should we be testing for adrenal suppression prior to discontinuation of steroids in patients with inflammatory bowel disease?INFLAMMATORY BOWEL DISEASES, Issue 3 2000Kim L. Isaacs M.D., Ph.D. No abstract is available for this article. [source] Adrenal toxicology: a strategy for assessment of functional toxicity to the adrenal cortex and steroidogenesisJOURNAL OF APPLIED TOXICOLOGY, Issue 2 2007Philip W. Harvey Abstract The adrenal is the most common toxicological target organ in the endocrine system in vivo and yet it is neglected in regulatory endocrine disruption screening and testing. There has been a recent marked increase in interest in adrenal toxicity, but there are no standardised approaches for assessment. Consequently, a strategy is proposed to evaluate adrenocortical toxicity. Human adrenal conditions are reviewed and adrenocortical suppression, known to have been iatrogenically induced leading to Addisonian crisis and death, is identified as the toxicological hazard of most concern. The consequences of inhibition of key steroidogenic enzymes and the possible toxicological modulation of other adrenal conditions are also highlighted. The proposed strategy involves an in vivo rodent adrenal competency test based on ACTH challenge to specifically examine adrenocortical suppression. The H295R human adrenocortical carcinoma cell line is also proposed to identify molecular targets, and is useful for measuring steroids, enzymes or gene expression. Hypothalamo-pituitary-adrenal endocrinology relevant to rodent and human toxicology is reviewed (with an emphasis on multi-endocrine axis effects on the adrenal and also how the adrenal affects a variety of other hormones) and the endocrinology of the H295R cell line is also described. Chemicals known to induce adrenocortical toxicity are reviewed and over 60 examples of compounds and their confirmed steroidogenic targets are presented, with much of this work published very recently using H295R cell systems. In proposing a strategy for adrenocortical toxicity assessment, the outlined techniques will provide hazard assessment data but it will be regulatory agencies that must consider the significance of such data in risk extrapolation models. The cases of etomindate and aminoglutethimide induced adrenal suppression are clearly documented examples of iatrogenic adrenal toxicity in humans. Environmentally, sentinel species, such as fish, have also shown evidence of adrenal endocrine disruption attributed to exposure to chemicals. The extent of human sub-clinical adrenal effects from environmental chemical exposures is unknown, and the extent to which environmental chemicals may act as a contributory factor to human adrenal conditions following chronic low-level exposures will remain unknown unless purposefully studied. Copyright © 2007 John Wiley & Sons, Ltd. [source] Topical corticosteroids in psoriasis: strategies for improving safetyJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2 2010EJ Horn Abstract Corticosteroids are a mainstay of topical therapy for psoriasis. While efficacious and relatively safe when used carefully, the potential for side effects, notably skin atrophy and adrenal suppression, have been associated with excesses in potency, prolonged or widespread use. The International Psoriasis Council Working Group on Topical Therapy has reviewed the efficacy and safety of topical corticosteroids and recommends strategies for safe, long-term use of these agents. [source] US4 Pharmacotherapy complicating dental surgeryORAL DISEASES, Issue 2006Boras Planning dental treatments for patients taking antithrombotic can be difficult for the general dental practitioner, particularly when surgical interventions are needed. The drugs employed in the long-term treatment of such patients include platelet aggregation inhibitors and oral anticoagulants. Platelet aggregation inhibitors do not represent a contraindication to oral surgery. The activity of oral anticoagulants can be affected by many substances, for this reason it is necessary to monitor by INR the patients taking those drugs. When INR is within therapeutic limits for the more common conditions, most of the oral surgery interventions do not need any special precaution. Evidence indicates that suspending antithrombotic drugs is not indicate, as complications following a thrombotic accident are more frequent and serious than bleedings following oral surgery. It is well known that systemic corticosteroid therapy due to the effect on adrenal suppression can interfere with dental surgical procedures. However, that is largely dependent on the type and dose of corticosteroid that patient is currently taking, or has been taking in the last 12 months and on the type and extent of surgical procedure which is to be performed. Surgical management of dental patients with history of systemic corticosteroid therapy is proposed from the existing literature. [source] Evaluation of Adrenal Suppression of a Lipid Enhanced, Topical Emollient Cream Formulation of Hydrocortisone Butyrate 0.1% in Treating Children with Atopic DermatitisPEDIATRIC DERMATOLOGY, Issue 1 2007Lawrence Eichenfield M.D. In the pediatric population however, the potential impact of adrenal suppression is always an important safety concern. Twenty boys and girls, 5,12 years of age, with normal adrenal function and a history of atopic dermatitis were maximally treated three times daily with a lipid-rich, moisturizing formulation of hydrocortisone butyrate 0.1% for up to 4 weeks. At the conclusion of the 4-week treatment period, cosyntropin injection stimulation testing showed no evidence of adrenal suppression. In addition, the therapy was noted to be highly efficacious, with a clinical success rate of 80% (Physician Global Score of (0) clear or (1) almost clear). No local side effects associated with prolonged use of topical corticosteroids were reported. In summary, this study supports the contention that this lipid-rich, moisturizing formulation of hydrocortisone butyrate 0.1% was a well-tolerated and beneficial treatment for atopic dermatitis, demonstrating no adrenal suppression in the pediatric population aged 5,12 years. The relevance of these findings for children below 5 years of age, because of difference in body mass/surface area ratios, remains to be determined. [source] Anti-inflammatory treatment for recurrent wheezing in the first five years of lifePEDIATRIC PULMONOLOGY, Issue 4 2003Athanasios G. Kaditis MD Abstract Medications identified for the treatment of recurrent wheezing in preschool children by the Expert Panel Report of the NHLBI Guidelines for the Diagnosis and Management of Asthma include inhaled corticosteroids, chromones, theophylline, and leukotriene pathway modifiers. However, these various agents differ in their mechanism, extent of action on the airway inflammatory process, and degree of clinical efficacy. Inhaled corticosteroids can control symptoms in many young children with even severe persistent wheezing, but data on their long-term safety when administered in preschool-age children are scarce. There is some information on the uninterrupted use of inhaled corticosteroids in school-age children and the absence of an adverse effect on ultimate adult height. Despite laboratory evidence of adrenal suppression in some studies, few pediatric cases of clinical adrenal insufficiency have been reported. Low-dose inhaled corticosteroid (<400 mcg/day for beclomethasone), which is adequate for controlling mild persistent symptoms, is generally safe. Chromones have a remarkable safety profile, but they are most effective for symptoms of mild severity. Promising data have been published on the efficacy and safety of leukotriene pathway modifiers when used in young children with persistent symptoms. It is uncertain whether early introduction and long-term administration of inhaled corticosteroids prevent development of irreversible airway obstruction. Nevertheless, they may be especially useful for patients with moderate to severe disease in whom other agents (chromones or leukotriene pathway modifiers) will most likely fail to control symptoms. Pediatr Pulmonol. 2003; 35:241,252. © 2003 Wiley-Liss, Inc. [source] A Prospective Observational Study of the Effect of Etomidate on Septic Patient Mortality and Length of StayACADEMIC EMERGENCY MEDICINE, Issue 1 2009Karis L. Tekwani MD Abstract Objectives:, Etomidate is known to cause adrenal suppression after single-bolus administration. Some studies suggest that when etomidate is used as an induction agent for intubation of septic patients in the emergency department (ED), this adrenal suppression leads to increased mortality, vasopressor requirements, and length of hospital stay. The authors sought to determine differences in the in-hospital mortality and hospital length of stay (LOS) between septic patients given etomidate and patients given alternative or no induction agents for rapid-sequence intubation in our ED. Methods:, This was a nonrandomized, prospective observational study of all patients meeting sepsis criteria who were intubated in an ED over a 9-month period. Times of patient presentation, intubation, admission, discharge, and/or death were recorded, as well as the intubation agent used, if any, and corticosteroid use. The authors also recorded relevant laboratory and demographic variables to determine severity of illness using the Mortality in Emergency Department Sepsis (MEDS) score. Mortality and survivor LOS between the patients given etomidate and those given alternative or no induction agents were compared. Results:, A total of 106 patients with sepsis were intubated over the study period. Of these, 74 patients received etomidate, while 32 patients received ketamine, benzodiazepines, propofol, or no induction agents. Age in years (median = 78; interquartile range [IQR] = 67 to 83), gender (45% male), MEDS score (median = 13; IQR = 10 to 15), and receipt of supplemental corticosteroids (56%) were statistically similar between the two groups. In-hospital mortality of patients given etomidate (38%; 95% confidence interval [CI] = 28% to 49%) was similar to those receiving alternatives (44%; 95% CI = 28% to 61%). Surviving patients had a median hospital LOS after receiving etomidate of 10 days compared to those receiving alternatives (7.5 days; p = 0.08). Conclusions:, No statistically significant increase in hospital LOS or mortality in patients given etomidate for rapid-sequence intubation was found. Suggestions that the use of etomidate for intubation in the ED be abandoned are not supported by these data. [source] Pharmacodynamics of glucose regulation by methylprednisolone.BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2009II. normal rats Abstract A physiologic pharmacodynamic model was developed to jointly describe the effects of methylprednisolone (MPL) on adrenal suppression and glycemic control in normal rats. Six groups of animals were given MPL intravenously at 0, 10 and 50,mg/kg, or by subcutaneous 7 day infusion at rates of 0, 0.1 and 0.3,mg/kg/h. Plasma concentrations of MPL, corticosterone (CST), glucose and insulin were determined at various times up to 72,h after injection and 336,h after infusion. The pharmacokinetics of MPL was described by a two-compartment model. A circadian rhythm for CST was found in untreated rats with a stress-altered baseline caused by handling, which was captured by a circadian harmonic secretion rate with an increasing mesor. All drug treatments caused CST suppression. Injection of MPL caused temporary increases in glucose over 4,h. Insulin secretion was thereby stimulated yielding a later peak around 6,h. In turn, insulin can normalize glucose. However, long-term dosing caused continuous hyperglycemia during and after infusion. Hyperinsulinemia was achieved during infusion, but diminished immediately after dosing despite the high glucose concentration. The effects of CST and MPL on glucose production were described with a competitive stimulation function. A disease progression model incorporating reduced endogenous glucose uptake/utilization was used to describe glucose metabolism under different treatments. The results exemplify the roles of endogenous and exogenous hormones in mediating glucose dynamics. The pharmacokinetic/pharmacodynamic model is valuable for quantitating diabetogenic effects of corticosteroid treatments and provides mechanistic insights into the hormonal control of the metabolic system. Copyright © 2009 John Wiley & Sons, Ltd. [source] In vivo comparison of the relative systemic bioavailability of fluticasone propionate from three anti-static spacers and a metered dose inhalerBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2009Arun Nair WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Conventional spacers help overcome problems with co-ordination and may improve lung deposition and decrease oropharyngeal impaction. , Antistatic spacers eliminate electrostatic charge and may hence improve respirable dose delivery. , The systemic bioavailability of inhaled fluticasone propionate is primarily dependent on delivery by the pulmonary route and hence the performance of antistatic spacers can be evaluated using adrenal suppression as a sensitive surrogate for relative bioavailability to the lung after an inhalation. WHAT THIS STUDY ADDS , This study compares the relative bioavailability to the lung of inhaled fluticasone delivered via conventional pressurized metered dose inhalers (pMDI) and three antistatic spacers (plastic Zerostat-V, plastic Aerochamber Max, and metal Nebuchamber) in patients with asthma. , All three antistatic spacers when compared with pMDI significantly increased the relative bioavailability to the lungs of inhaled fluticasone in terms of relative adrenal suppression, and there were no significant differences between the plastic and metal antistatic spacers. AIMS The systemic bioavailability of inhaled fluticasone propionate (FP) depends primarily on lung absorption and can be quantified by measuring suppression of overnight and early morning urinary cortisol/creatinine (OUCC and EMUCC, respectively). The aim of the study was to determine the relative bioavailability of hydrofluoroalkane (HFA) FP to the lungs via anti-static plastic (Zerostat-V and Aerochamber Max), metal (Nebuchamber) anti-static spacers and metered dose inhaler [Flixotide Evohaler (EH) (pMDI)]. METHODS A randomized, double-blind, double-dummy, four-way crossover design was used. Eighteen mild to moderate asthmatics received single doses of placebo/HFA-FP 2 mg via the 280-ml Zerostat-V (ZS); 250-ml Nebuchamber (NC); 197-ml Aerochamber Max (AC); and pMDI (EH). Measurements of OUCC and EMUCC were made at baseline and 10 h after each dose. RESULTS Significant suppression of OUCC and EMUCC occurred from baseline with all three spacers, but not Evohaler (geometric mean fold suppression, 95% confidence interval): ZS, 2.74 (1.75, 4.30), P < 0.001; NC, 3.31 (1.81, 6.06), P < 0.001; AC, 4.98 (3.39, 7.31), P < 0.001; and for EH this was 1.42 (0.92, 2.21), P= 0.169 (equating to a 64, 70, 80 and 30% fall in OUCC via the ZS, NC, AC and EH devices, respectively). There were significant differences between all three spacers vs. EH. When compared with the Evohaler, the Zerostat V resulted in 48% greater suppression (P= 0.009); the Nebuchamber 57% greater suppression (P= 0.001); and the Aerochamber Max 71% greater suppression of OUCC (P < 0.001). CONCLUSION All three antistatic spacers significantly increased the relative systemic bioavailability of HFA-FP compared with the standard pMDI. [source] | ||||||||||