DOCSLIB.ORG

Effects of Prednisolone and Dexamethasone in Vivo and in Vitro: Studies of Insulin Binding, Deoxyglucose Uptake and Glucose Oxidation in Rat Adipocytes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Effects of Prednisolone and Dexamethasone in Vivo and in Vitro: Studies of Insulin Binding, Deoxyglucose Uptake and Glucose Oxidation in Rat Adipocytes Diabetologia (1981) 21:149-153 Diabetologia Springer-Verlag 1981 Effects of Prednisolone and Dexamethasone in Vivo and in Vitro: Studies of Insulin Binding, Deoxyglucose Uptake and Glucose Oxidation in Rat Adipocytes R. De Pirro 1, A. Green, M. Yung-Chin Kao, and J. M. Olefsky Department of Medicine, University of Colorado Health Sciences Center, Division of Endocrinology, Denver, CO 80262, USA Summary. We have studied the effects of dexa- glucose uptake and metabolism [5]. In addition to methasone and prednisolone in vitro and in vivo on their effects on glucose metabolism, administration insulin binding, deoxyglucose uptake and glucose of glucocorticoids in vivo may also impair insulin oxidation in rat adipocytes. In the studies in vivo, rats binding to target cells, and this could provide another were treated for 22 h with dexamethasone (30 ~tg/kg) cause for glucocorticoid-induced insulin resistance. or prednisolone (200 ~tg/kg). Following sacrifice, The results of several studies support this hypothesis. adipocytes were prepared and the results demon- Thus, it has been demonstrated that treatment of rats strated that cells from prednisolone treated rats with dexamethasone decreases the insulin binding showed a 17% increase in insulin binding and capacity of hepatocytes and adipocytes [6, 7]. How- increased rates of basal and insulin stimulated deoxy- ever, Beck-Nielsen et al. [8] have demonstrated that glucose uptake and glucose oxidation. Conversely, administration of prednisone in man produces an dexamethasone administration resulted in a 22% increase in the insulin binding capacity of circulating decrease in insulin binding, and decreased rates of monocytes. These apparently conflicting results raise deoxyglucose uptake and glucose oxidation by the the possibility that different glucocorticoids can pro- cells. Thus, prednisolone and dexamethasone had duce divergent effects on both insulin binding and opposite effects in vivo. In contrast to the opposite glucose metabolism. In order to test this hypothesis effects of the two glucocorticoids in vivo, dexa- we have studied the effects of prednisolone and dexa- methasone and prednisolone (each at a concentration methasone on insulin binding and insulin action on of 1 ~mol/1) had similar effects on adipocytes in vitro. rat adipocytes both in vivo and in vitro. Incubation of adipocytes with the steroids did not alter insulin binding, while both agents led to a com- parable decrease in the rates of basal and insulin Materials and Methods stimulated deoxyglucose uptake and glucose oxida- tion. Thus, dexamethasone and prednisolone have Materials opposite effects on adipocyte glucose metabolism in Porcine highly-purified insulin was generously supplied by Dr. vivo but have similar effects in vitro. Ronald Chance of Eli Lilly, Indianapolis. Bovine serum albumin (fraction V) was purchased from Armour, Phoenix, Arizona; col- Key words: Insulin, adipocytes, prednisolone, dexa- methasone, insulin binding, deoxyglucose transport, glucose oxidation Table 1. Plasma glucose, non-ester• fatty acid and insulin con- centration in rats treated with dexamethasone or prednisolone for 22 h Plasma Control Dexamethasone Prednisolone Insulin resistance is a well documented consequence Glucose (mmol/1) 7.9+0.2 (7) 8.0_+0.1 (7) 7.6+0.2 (6) of glucocorticoid administration both in man [1, 2] NEFA (gmol/1) 176• (7) 274_+24c (7) 250+-34b (5) and rats [3, 4]. One cause of this insulin resistance is Insulin (mU/l) 16_+2 (7) 21+4 e (7) 11• a (6) the well known effect Of these drugs to inhibit tissue Results are means • SEM for number of rats shown in parenthe- ses. The statistical significance of differences between the treated I Present address: 2 Clinica Medica, Policlinico Umberto 1, groups and controls are indicated by a(p <0.05), b(p <0.01) and 1-00145 Roma, Italy C(p <0.001) 0012-186X/81/0021/0149/$01.00 150 R. De Pirro et al.: Glucocorticoid Effects on Adipocytes lagenase from Worthington Biochemicals, Freehold, New Jersey; This assay measures the total uptake of the radiolabelled 2-deoxy- [125I]Na, 2-deoxy-[1-3H]-glucose (16.1 Ci/mmol), L-[1-3H[-glu - glucose and is based on the principle that, although 2-deoxyglu- cose (10.7 Ci/mmol), [1-14C]-glucose (61 Ci/mmol) from New cose can be phosphorylated like D-glucose, it cannot be further England Nuclear, Cambridge, Massachusetts; dexamethasone and metabolised [17]. The assay was terminated at the end of 3 min by prednisolone from Sigma, St. Louis; silicone oil (6428-R15) from transferring 200 ~d aliquots from the assay mixture to plastic mi- Arthur H. Thomas, Philadelphia. crotubes containing 100 ~tl silicone oil. The tubes were centrifuged for 30 s in a Beckman microfuge, and the assay was considered terminated when centrifugation begins. In experiments in which Animals the stimulatory effect of insulin on uptake was measured, the cells were preincubated with insulin for 60 min at 24 ~ The amount of Male Sprague-Dawley rats (160-170 g) were used for all experi- sugar trapped in the extracellular water space of the cell layers was ments. Animals were injected SC three times (at 1500, 2300 and determined using L-[1-3H]-glucose, and was 0.033 _+ 0.001% 0700h) with saline (0.154mol/I), dexamethasone (30 [xg/kg) or (mean _+ SEM). prednisolone (200 ~tg/kg) and then stunned by a blow to the head and decapitated at 1300 h. Thus, each rat was killed 6 h after the last injection (22 h after the first injection). The injection volume was 0.4 ml and steroids were freshly prepared from stock solutions Glucose Oxidation in ethanol by drying the desired amount under nitrogen and resus- The ability of adipocytes to oxidize glucose was determined pending in saline. All rats had free access to standard rat chow and according to the method of Rodbell [9]. Adipocytes were incu- water. No weight differences were found between any of the bated at 37 ~ with [1J4C]-glucose (2 retool/l) in Krebs-Ringer groups. bicarbonate buffer (pH 7.4) containing BSA (40 mg/ml). After 1 h of incubation the generated a4CO2 was collected and counted in a liquid scintillation counter. Preparation of Isolated Adipocytes Isolated fat cells were prepared from epididymal fat pads by shak- Analytical Methods ing at 37 ~ for 60 rain in Krebs-Ringer bicarbonate buffer (pH 7.4) containing collagenase (3 mg/ml) and bovine serum albumin Plasma glucose was determined by the glucose oxidase method (BSA) (40 mg/ml) according to the method of Rodbell [9]. Cells using a Beckman glucose analyser. Plasma insulin was determined were filtered through 250 ~tM nylon mesh, centrifuged at 400 rev/ by the double antibody radioimmunoassay [ 18], and non-esterified min for 4 min and washed twice in buffer. Adipocyte counts were fatty acid (NEFA) by the method of Chlouverakis and Hojnicki performed according to a modification of method III of Hirsch and [19]. Gallian [10] in which the cells were fixed in 2% osmium tetroxide in 0.05 mol/1 collidine buffer (made up to physsiological osmolality with saline) for 24 h at 37 ~ and then taken up in a known volume of 0.154 mmol/1 NaC1 for counting with a Coulter Counter Model Statistical Analysis ZB. Results are presented as mean _+ SEM. Analysis of variance was used to test for significant changes. Iodination of Insulin [125I]insulin was prepared at a specific activity of 170-190 ~tCi/~tg according to a modification [11] of the method of Hunter and Results Greenwood [12]. Studies in Vivo Binding Studies The effects of 22 h dexamethasone or prednisolone Isolated fat cells were suspended in a buffer containing 35 mmol/1 treatment on plasma glucose, NEFA and insulin con- Tris, 120mmol/1 NaC1, 1.2mmol/1 MgSO4, 5mmol/1 KC1, centrations are presented in Table 1. As can be seen, 10 mmol/1 glucose, 2 mmol/1 CaC12; 24 retool/1 Na acetate and dexamethasone treatment led to an increase, whilst 10mg/ml BSA, pH 7.6, and incubated with [125I]insulin and unlabelled insulin in plastic flasks in a 24 ~ shaking water bath as prednisolone led to a decrease in plasma insulin con- previously described [13]. Optimal steady-state binding conditions centration. Neither steroid had any statistically sig- are achieved at 24 ~ after 60 min of incubation. The incubations nificant effect on plasma glucose concentration, were terminated by removing 200 ~tl aliquots from the cell suspen- whereas plasma NEFA concentrations were elevated sion and rapidly centrifuging the cells in plastic microtubes to which 100 ~tl silicone oil had been added [14]. The cells were then in both treatment groups. It should be noted that removed and the radioactivity determined. All studies were car- food intake and body weight were the same in con- ried out in triplicate. trols and both experimental groups over the treat- ment period. 2-Deoxyglucose Uptake Insulin Binding: Prednisolone and dexamethasone These studies were performed using the same cell centrifugation had opposite effects on the ability of adipocytes to technique as described for the binding studies, and the details of bind insulin. Cells from control rats bound 2.09 + this method have been previously reported [15, 16]. Unless other- wise stated, isolated adipocytes were incubated with 2-deoxy- 0.09% of a tracer concentration (0.2 ng/ml) of insu- [1-3H]-D-glucose at a concentration of 0.125 mmol/1 in Krebs- lin per 2 • 105 cells. Administration of prednisolone Ringer bicarbonate (pH 7.4) containing BSA (10 mg/ml) at 24 ~ resulted in an increase to 2.41 + 0.15% per 2 • l0 s R. De Pirro et al.: Glucocorticoid Effects on Adipocytes 151 cells, whilst dexamethasone led to a decrease to 1.64 ~ 2.52 + 0.10% per 2 • l0 s cells in binding.
Load more

Recommended publications
  • The National Drugs List
    ^ ^ ^ ^ ^[ ^ The National Drugs List Of Syrian Arab Republic Sexth Edition 2006 ! " # "$ % &'() " # * +$, -. / & 0 /+12 3 4" 5 "$ . "$ 67"5,) 0 " /! !2 4? @ % 88 9 3: " # "$ ;+<=2 – G# H H2 I) – 6( – 65 : A B C "5 : , D )* . J!* HK"3 H"$ T ) 4 B K<) +$ LMA N O 3 4P<B &Q / RS ) H< C4VH /430 / 1988 V W* < C A GQ ") 4V / 1000 / C4VH /820 / 2001 V XX K<# C ,V /500 / 1992 V "!X V /946 / 2004 V Z < C V /914 / 2003 V ) < ] +$, [2 / ,) @# @ S%Q2 J"= [ &<\ @ +$ LMA 1 O \ . S X '( ^ & M_ `AB @ &' 3 4" + @ V= 4 )\ " : N " # "$ 6 ) G" 3Q + a C G /<"B d3: C K7 e , fM 4 Q b"$ " < $\ c"7: 5) G . HHH3Q J # Hg ' V"h 6< G* H5 !" # $%" & $' ,* ( )* + 2 ا اوا ادو +% 5 j 2 i1 6 B J' 6<X " 6"[ i2 "$ "< * i3 10 6 i4 11 6! ^ i5 13 6<X "!# * i6 15 7 G!, 6 - k 24"$d dl ?K V *4V h 63[46 ' i8 19 Adl 20 "( 2 i9 20 G Q) 6 i10 20 a 6 m[, 6 i11 21 ?K V $n i12 21 "% * i13 23 b+ 6 i14 23 oe C * i15 24 !, 2 6\ i16 25 C V pq * i17 26 ( S 6) 1, ++ &"r i19 3 +% 27 G 6 ""% i19 28 ^ Ks 2 i20 31 % Ks 2 i21 32 s * i22 35 " " * i23 37 "$ * i24 38 6" i25 39 V t h Gu* v!* 2 i26 39 ( 2 i27 40 B w< Ks 2 i28 40 d C &"r i29 42 "' 6 i30 42 " * i31 42 ":< * i32 5 ./ 0" -33 4 : ANAESTHETICS $ 1 2 -1 :GENERAL ANAESTHETICS AND OXYGEN 4 $1 2 2- ATRACURIUM BESYLATE DROPERIDOL ETHER FENTANYL HALOTHANE ISOFLURANE KETAMINE HCL NITROUS OXIDE OXYGEN PROPOFOL REMIFENTANIL SEVOFLURANE SUFENTANIL THIOPENTAL :LOCAL ANAESTHETICS !67$1 2 -5 AMYLEINE HCL=AMYLOCAINE ARTICAINE BENZOCAINE BUPIVACAINE CINCHOCAINE LIDOCAINE MEPIVACAINE OXETHAZAINE PRAMOXINE PRILOCAINE PREOPERATIVE MEDICATION & SEDATION FOR 9*: ;< " 2 -8 : : SHORT -TERM PROCEDURES ATROPINE DIAZEPAM INJ.
    [Show full text]
  • Prednisolone Versus Dexamethasone for Croup: a Randomized Controlled Trial Colin M
    Prednisolone Versus Dexamethasone for Croup: a Randomized Controlled Trial Colin M. Parker, MBChB, DCH, MRCPCH, FACEM,a,b Matthew N. Cooper, BCA, BSc, PhDc OBJECTIVES: The use of either prednisolone or low-dose dexamethasone in the treatment of abstract childhood croup lacks a rigorous evidence base despite widespread use. In this study, we compare dexamethasone at 0.6 mg/kg with both low-dose dexamethasone at 0.15 mg/kg and prednisolone at 1 mg/kg. METHODS: Prospective, double-blind, noninferiority randomized controlled trial based in 1 tertiary pediatric emergency department and 1 urban district emergency department in Perth, Western Australia. Inclusions were age .6 months, maximum weight 20 kg, contactable by telephone, and English-speaking caregivers. Exclusion criteria were known prednisolone or dexamethasone allergy, immunosuppressive disease or treatment, steroid therapy or enrollment in the study within the previous 14 days, and a high clinical suspicion of an alternative diagnosis. A total of 1252 participants were enrolled and randomly assigned to receive dexamethasone (0.6 mg/kg; n = 410), low-dose dexamethasone (0.15 mg/kg; n = 410), or prednisolone (1 mg/kg; n = 411). Primary outcome measures included Westley Croup Score 1-hour after treatment and unscheduled medical re-attendance during the 7 days after treatment. RESULTS: Mean Westley Croup Score at baseline was 1.4 for dexamethasone, 1.5 for low-dose dexamethasone, and 1.5 for prednisolone. Adjusted difference in scores at 1 hour, compared with dexamethasone, was 0.03 (95% confidence interval 20.09 to 0.15) for low-dose dexamethasone and 0.05 (95% confidence interval 20.07 to 0.17) for prednisolone.
    [Show full text]
  • Mifepristone
    1. NAME OF THE MEDICINAL PRODUCT Mifegyne 200 mg tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains 200-mg mifepristone. For the full list of excipients, see section 6.1 3. PHARMACEUTICAL FORM Tablet. Light yellow, cylindrical, bi-convex tablets, with a diameter of 11 mm with “167 B” engraved on one side. 4. CLINICAL PARTICULARS For termination of pregnancy, the anti-progesterone mifepristone and the prostaglandin analogue can only be prescribed and administered in accordance with New Zealand’s abortion laws and regulations. 4.1 Therapeutic indications 1- Medical termination of developing intra-uterine pregnancy. In sequential use with a prostaglandin analogue, up to 63 days of amenorrhea (see section 4.2). 2- Softening and dilatation of the cervix uteri prior to surgical termination of pregnancy during the first trimester. 3- Preparation for the action of prostaglandin analogues in the termination of pregnancy for medical reasons (beyond the first trimester). 4- Labour induction in fetal death in utero. In patients where prostaglandin or oxytocin cannot be used. 4.2 Dose and Method of Administration Dose 1- Medical termination of developing intra-uterine pregnancy The method of administration will be as follows: • Up to 49 days of amenorrhea: 1 Mifepristone is taken as a single 600 mg (i.e. 3 tablets of 200 mg each) oral dose, followed 36 to 48 hours later, by the administration of the prostaglandin analogue: misoprostol 400 µg orally or per vaginum. • Between 50-63 days of amenorrhea Mifepristone is taken as a single 600 mg (i.e. 3 tablets of 200 mg each) oral dose, followed 36 to 48 hours later, by the administration of misoprostol.
    [Show full text]
  • Opposing Effects of Dehydroepiandrosterone And
    European Journal of Endocrinology (2000) 143 687±695 ISSN 0804-4643 EXPERIMENTAL STUDY Opposing effects of dehydroepiandrosterone and dexamethasone on the generation of monocyte-derived dendritic cells M O Canning, K Grotenhuis, H J de Wit and H A Drexhage Department of Immunology, Erasmus University Rotterdam, The Netherlands (Correspondence should be addressed to H A Drexhage, Lab Ee 838, Department of Immunology, Erasmus University, PO Box 1738, 3000 DR Rotterdam, The Netherlands; Email: [email protected]) Abstract Background: Dehydroepiandrosterone (DHEA) has been suggested as an immunostimulating steroid hormone, of which the effects on the development of dendritic cells (DC) are unknown. The effects of DHEA often oppose those of the other adrenal glucocorticoid, cortisol. Glucocorticoids (GC) are known to suppress the immune response at different levels and have recently been shown to modulate the development of DC, thereby influencing the initiation of the immune response. Variations in the duration of exposure to, and doses of, GC (particularly dexamethasone (DEX)) however, have resulted in conflicting effects on DC development. Aim: In this study, we describe the effects of a continuous high level of exposure to the adrenal steroid DHEA (1026 M) on the generation of immature DC from monocytes, as well as the effects of the opposing steroid DEX on this development. Results: The continuous presence of DHEA (1026 M) in GM-CSF/IL-4-induced monocyte-derived DC cultures resulted in immature DC with a morphology and functional capabilities similar to those of typical immature DC (T cell stimulation, IL-12/IL-10 production), but with a slightly altered phenotype of increased CD80 and decreased CD43 expression (markers of maturity).
    [Show full text]
  • Mitigations in Selected Haemostatic Parameters in Administration of Graded Doses of Dexamethasone and Its Blockers in Wister
    ogy iol : Cu ys r h re P n t & R Anatomy & Physiology: Current y e s m e o a t Nwangwa et al., Anat Physiol 2018, 8:2 r a c n h A Research DOI: 10.4172/2161-0940.1000297 ISSN: 2161-0940 Research Article Open Access Mitigations in Selected Haemostatic Parameters in Administration of Graded Doses of Dexamethasone and its Blockers in Wister Rats Nwangwa EK and Odigie OM* Department of Human Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Delta State University, Abraka, Delta State, Nigeria *Corresponding author: Odigie OM, Department of Human Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Delta State University, Abraka, Delta State, Nigeria, E-mail: [email protected] Received date: May 07, 2018; Accepted date: May 25, 2018; Published date: May 29, 2018 Copyright: © 2018 Nwangwa EK, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Clinical trials have shown that an even newer compound, dexamethasone (Dex), might be more potent and less likely to cause side-effects than any other known corticosteroid medication. This study investigated the possible changes in selected haemostatic parameters [clotting time, bleeding time, platelets count and fibrinogen level] in albino wistar rats, following administration of graded doses of Dex. Forty-two male albino Wistar rats were randomly grouped into seven of six rats each. With Group A receiving normal diets (Control), Groups B-G were respectively given 0.1 mg/Kg of Dex, 0.3 mg/Kg of Dex, 0.1 mg/Kg of Dex +33 mg/Kg of Ketokonazol (Keto), 0.3 mg/Kg of Dex +33 mg/Kg of Keto, 0.1 mg/Kg of Dex+Vitamin (Vit) E and 0.1 mg/Kg of Dex.
    [Show full text]
  • The Effects of Dehydroepiandrosterone Sulfate on Counterregulatory Responses During Repeated Hypoglycemia in Conscious Normal Rats Darleen A
    The Effects of Dehydroepiandrosterone Sulfate on Counterregulatory Responses During Repeated Hypoglycemia in Conscious Normal Rats Darleen A. Sandoval, Ling Ping, Ray Anthony Neill, Sachiko Morrey, and Stephen N. Davis ␮ ⅐ ؊1 ⅐ ؊1 We previously determined that both antecedent hy- mol/l kg min ; P < 0.05). In summary, day-1 poglycemia and elevated cortisol levels blunt neu- antecedent hypoglycemia blunted neuroendocrine and roendocrine and metabolic responses to subsequent metabolic responses to next-day hypoglycemia. How- hypoglycemia in conscious, unrestrained rats. The adre- ever, simultaneous DHEA-S infusion during antecedent nal steroid dehydroepiandrosterone sulfate (DHEA-S) hypoglycemia preserved neuroendocrine and metabolic has been shown in several studies to oppose corticoste- counterregulatory responses during subsequent hypo- roid action. The purpose of this study was to determine glycemia in conscious rats. Diabetes 53:679–686, 2004 if DHEA-S could preserve counterregulatory responses during repeated hypoglycemia. We studied 40 male Sprague-Dawley rats during a series of 2-day protocols. he Diabetes Control and Complications Trial Day 1 consisted of two 2-h episodes of 1) hyperinsuline- mic (30 pmol ⅐ kg؊1 ⅐ min؊1) euglycemia (6.2 ؎ 0.2 established that intensive glucose control in type ANTE EUG), 2) hyperinsulinemic eug- 1 diabetic patients can slow the progression or ;12 ؍ mmol/l; n -plus simultaneous Tsignificantly reduce the onset of diabetic micro (8 ؍ lycemia (6.0 ؎ 0.1 mmol/l; n intravenous infusion of DHEA-S (30 mg/kg; ANTE EUG vascular complications (e.g., retinopathy, nephropathy, ؉ DHEA-S), 3) hyperinsulinemic hypoglycemia (2.8 ؎ neuropathy) (1). Unfortunately, the study also established ANTE HYPO), or 4) hyperinsulinemic that intensive glucose treatment causes an approximate ;12 ؍ mmol/l; n 0.1 -with simulta- threefold increase in the frequency of severe hypoglyce (8 ؍ hypoglycemia (2.8 ؎ 0.1 mmol/l; n neous intravenous infusion of DHEA-S (30 mg/kg; ANTE mia (2).
    [Show full text]
  • And Function by Progesterone TLR4-Mediated Dendritic Cell
    Differential Modulation of TLR3- and TLR4-Mediated Dendritic Cell Maturation and Function by Progesterone This information is current as Leigh A. Jones, Shrook Kreem, Muhannad Shweash, of September 23, 2021. Andrew Paul, James Alexander and Craig W. Roberts J Immunol 2010; 185:4525-4534; Prepublished online 15 September 2010; doi: 10.4049/jimmunol.0901155 http://www.jimmunol.org/content/185/8/4525 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2010/09/13/jimmunol.090115 Material 5.DC1 http://www.jimmunol.org/ References This article cites 56 articles, 12 of which you can access for free at: http://www.jimmunol.org/content/185/8/4525.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on September 23, 2021 • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2010 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Differential Modulation of TLR3- and TLR4-Mediated Dendritic Cell Maturation and Function by Progesterone Leigh A.
    [Show full text]
  • Decadron® (Dexamethasone Tablets, Usp)
    NDA 11-664/S-062 Page 3 TABLETS DECADRON® (DEXAMETHASONE TABLETS, USP) DESCRIPTION DECADRON* (dexamethasone tablets, USP) tablets, for oral administration, are supplied in two potencies, 0.5 mg and 0.75 mg. Inactive ingredients are calcium phosphate, lactose, magnesium stearate, and starch. Tablets DECADRON 0.5 mg also contain D&C Yellow 10 and FD&C Yellow 6. Tablets DECADRON 0.75 mg also contain FD&C Blue 1. The molecular weight for dexamethasone is 392.47. It is designated chemically as 9-fluoro-11β,17,21- trihydroxy-16α-methylpregna-1,4-diene-3,20-dione. The empirical formula is C22H29FO5 and the structural formula is: Dexamethasone, a synthetic adrenocortical steroid, is a white to practically white, odorless, crystalline powder. It is stable in air. It is practically insoluble in water. CLINICAL PHARMACOLOGY Glucocorticoids, naturally occurring and synthetic, are adrenocortical steroids that are readily absorbed from the gastrointestinal tract. Glucocorticoids cause varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli. Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have sodium-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs including dexamethasone are primarily used for their anti-inflammatory effects in disorders of many organ systems. At equipotent anti-inflammatory doses, dexamethasone almost completely lacks the sodium-retaining property of hydrocortisone and closely related derivatives of hydrocortisone. INDICATIONS AND USAGE Allergic states: Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in asthma, atopic dermatitis, contact dermatitis, drug hypersensitivity reactions, perennial or seasonal allergic rhinitis, and serum sickness.
    [Show full text]
  • Dexamethasone: an All Purpose Agent? 65
    Dexamethasone: An All Purpose Agent? 65 Dexamethasone: An All Purpose Agent? KARA ALLEN MBBS (Hons), BMedSci (Hons) ATY2, St Vincent’s Hospital, Melbourne Dr Kara Allen is an ATY2 at St Vincent's Hospital Melbourne. Her interests include regional anaesthesia and ultrasound and she is currently undertaking a pilot study into perioperative dexamethasone use. SUMMARY Dexamethasone is a synthetic glucocorticosteroid which has minimal mineralocorticoid activity. It is a potent anti-inflammatory drug with 25-50 times the potency of hydrocortisone and is up to sixteen times as potent as prednisolone. Dexamethasone is utilised frequently in the perioperative setting, including prophylaxis against postoperative nausea and vomiting, reduction of airway and cerebral oedema, and it may be useful in the management of acute and chronic pain. This review is intended to outline some of the perioperative uses of dexamethasone and elucidate areas where further research is needed. PHARMACOLOGY Like all glucocorticoids, dexamethasone acts on the glucocorticoid receptor which is a member of the nuclear receptor superfamily, subfamily 3C. Multiple signalling pathways are involved following binding of the steroid to the receptor, including direct DNA binding which results in changes to gene transcription. This results in changes to carbohydrate, protein and fat metabolism as well as changes to gluconeogenesis. Of interest in the perioperative setting is the decreased release of bradykinin, tumour necrosis factor, interleukin-1, interleukin-2 and interleukin-6 and decreased production of prostaglandins 1. There is decreased transmission of impulses in C fibres. Binding of steroid ligands to the glucocorticoid receptor also alters the half life of mRNA which have already been produced within the cell 2.
    [Show full text]
  • Pharmacologic Characteristics of Corticosteroids 대한신경집중치료학회
    REVIEW J Neurocrit Care 2017;10(2):53-59 https://doi.org/10.18700/jnc.170035 eISSN 2508-1349 Pharmacologic Characteristics of Corticosteroids 대한신경집중치료학회 Sophie Samuel, PharmD1, Thuy Nguyen, PharmD1, H. Alex Choi, MD2 1Department of Pharmacy, Memorial Hermann Texas Medical Center, Houston, TX; 2Department of Neurosurgery and Neurology, The University of Texas Medical School at Houston, Houston, TX, USA Corticosteroids (CSs) are used frequently in the neurocritical care unit mainly for their anti- Received December 7, 2017 inflammatory and immunosuppressive effects. Despite their broad use, limited evidence Revised December 7, 2017 exists for their efficacy in diseases confronted in the neurocritical care setting. There are Accepted December 17, 2017 considerable safety concerns associated with administering these drugs and should be limited Corresponding Author: to specific conditions in which their benefits outweigh the risks. The application of CSs in H. Alex Choi, MD neurologic diseases, range from traumatic head and spinal cord injuries to central nervous Department of Pharmacy, Memorial system infections. Based on animal studies, it is speculated that the benefit of CSs therapy Hermann Texas Medical Center, 6411 in brain and spinal cord, include neuroprotection from free radicals, specifically when given Fannin Street, Houston, TX 77030, at a higher supraphysiologic doses. Regardless of these advantages and promising results in USA animal studies, clinical trials have failed to show a significant benefit of CSs administration Tel: +1-713-500-6128 on neurologic outcomes or mortality in patients with head and acute spinal injuries. This Fax: +1-713-500-0665 article reviews various chemical structures between natural and synthetic steroids, discuss its E-mail: [email protected] pharmacokinetic and pharmacodynamic profiles, and describe their use in clinical practice.
    [Show full text]
  • Early Refill Drug Utilization Review Drugs
    Early Refill Drug Utilization Review Drugs Published: 05/01/2012 Point-of-Sale Drug Authorization and Policy Drug Name Effective Date Override Override Center Override Acarbose X 11/8/2008 Acebutolol hydrochloride X 11/8/2008 acetaminophen X 11/8/2008 acetazolamide X 11/8/2008 acetazolamide sodium X 11/8/2008 acetylcholine X 11/8/2008 acetylcysteine X 11/8/2008 Acitretin X 11/8/2008 Acrivastine X 11/8/2008 activated charcoal X 11/8/2008 adalimumab X 11/8/2008 Adapalene X 11/8/2008 Adenosine X 11/8/2008 albumin human X 11/8/2008 Albuterol X 11/8/2008 albuterol sulfate X 11/8/2008 alclometasone dipropionate X 11/8/2008 aldesleukin X 11/8/2008 alendronate sodium X 11/8/2008 alfentanil hydrochloride X 11/8/2008 aliskiren hemifumarate X 11/8/2008 Alitretinoin X 11/8/2008 almotriptan malate X 11/8/2008 alosetron hydrochloride X 11/8/2008 Alprazolam X 1/6/2010 Aluminum X 11/8/2008 aluminum sulfate X 11/8/2008 amantadine hydrochloride X 11/8/2008 amcinonide X 11/8/2008 amino acids X 11/8/2008 aminophylline X 11/8/2008 amiodarone hydrochloride X 11/8/2008 amitriptyline hydrochloride X 11/8/2008 amlodipine besylate X 11/8/2008 Ammonium X 11/8/2008 Ammonium chloride X 11/8/2008 amobarbital X 1/6/2010 Point-of-Sale Drug Authorization and Policy Drug Name Effective Date Override Override Center Override Amoxicillin trihydrate X 11/8/2008 amphetamine X 1/6/2010 amyl nitrite X 11/8/2008 Amylase X 11/8/2008 apraclonidine hydrochloride X 11/8/2008 arformoterol tartrate X 11/8/2008 Arginine X 11/8/2008 arginine hydrochloride X 11/8/2008 aripiprazole X
    [Show full text]
  • Assessing Drug Interaction and Pharmacokinetics of Loxoprofen in Mice Treated with CYP3A Modulators
    pharmaceutics Article Assessing Drug Interaction and Pharmacokinetics of Loxoprofen in Mice Treated with CYP3A Modulators Sanjita Paudel 1, Aarajana Shrestha 2, Piljoung Cho 1, Riya Shrestha 1, Younah Kim 1, Taeho Lee 1, Ju-Hyun Kim 2 , Tae Cheon Jeong 2, Eung-Seok Lee 2 and Sangkyu Lee 1,* 1 BK21 Plus KNU Multi-Omics based Creative Drug Research Team, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea; [email protected] (S.P.); [email protected] (P.C.); [email protected] (R.S.); [email protected] (Y.K.); [email protected] (T.L.) 2 College of Pharmacy, Yeungnam University, Gyeongsan 38541, Korea; [email protected] (A.S.); [email protected] (J.-H.K.); [email protected] (T.C.J.); [email protected] (E.-S.L.) * Correspondence: [email protected]; Tel.: +82-53-950-8571; Fax: +82-53-950-8557 Received: 29 July 2019; Accepted: 12 September 2019; Published: 16 September 2019 Abstract: Loxoprofen (LOX) is a non-selective cyclooxygenase inhibitor that is widely used for the treatment of pain and inflammation caused by chronic and transitory conditions. Its alcoholic metabolites are formed by carbonyl reductase (CR) and they consist of trans-LOX, which is active, and cis-LOX, which is inactive. In addition, LOX can also be converted into an inactive hydroxylated metabolite (OH-LOXs) by cytochrome P450 (CYP). In a previous study, we reported that CYP3A4 is primarily responsible for the formation of OH-LOX in human liver microsomes. Although metabolism by CYP3A4 does not produce active metabolites, it can affect the conversion of LOX into trans-/cis-LOX, since CYP3A4 activity modulates the substrate LOX concentration.
    [Show full text]