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1、outlinesoutlines（1）Pharmacological effects，adverse effects of glucorticoids（2）mechanisms underlying anti-inflammatory reaction（3）the applications of glucorticoids cortisol secretion and modulationcortisol secretion and modulationPitutary glandPitutary glandadrenal glandadrenal glandHypothalamusHypot
2、halamusACTH:Adrenocorticotropic HormoneACTH:Adrenocorticotropic HormoneCRH:corticotropin releasing hormoneCRH:corticotropin releasing hormonecortisolcortisolsexual hormonesexual hormoneMineralocorticoidsMineralocorticoidsbiological effectsbiological effectsstressstressMorningMorningafternoonafternoo
3、nsteroids hormones：different pathwayslimited steps:cholesterol ester hydrolase DexamethasonehydrocortisoneBeclometasonePrednisonedrugs(1)blood glucose glycogenolysis gluconeogenesis.glucorticoids(2)negative nitrogen balanceprotein catabolism(3)lipolysisfree fattyTGketosisdiabetes or hyperglycemiawea
4、kly,dysfunction(4)sodiium andwater retentionenlarge blood volumehypertension Carbohydrate,Protein,Carbohydrate,Protein,and Fat Metabolismand Fat Metabolismfat depositionantianti-inflammation and inflammation and immune depressionimmune depressionglucorticoidsswellingpainheatitchfibroblastsscarinflam
5、mationgene expressionPLA2，COX2PGE2immune reactionmacrophageblood vesselNOSGREreceptoriL-6 and IL-AP-1NF-kBBellavance MA et al.The HPA-Immune Axis and the ImmunomodulatoryActions of Glucocorticoids in the Brain Front Immunol.2014 Mar 31;5:136.Read moreincrease the resistance increase the resistance t
6、o stressto stressInfectioninflammatoryinflammatoryimmune reactionimmune reactionblood glucosecardio vascular systemcardio vascular systemheart inhibitionheart inhibitionvessel dialationvessel dialationPGE2,cytokinesPGE2,cytokinesLPS,toleranceLPS,toleranceglucorticoidsglucorticoidsAlter blood cell le
7、vels Alter blood cell levels in plasmain plasmabasophilsbasophilseosinophilseosinophilslymphocyteslymphocytesmonocytesmonocyteshemoglobinhemoglobinerythrocytes erythrocytes plateletsplateletspolymorphonuclear polymorphonuclear leukocytesleukocytesfibrinogenfibrinogenglucorticoidsglucorticoidsImmune
8、surppressionImmune surppressionoxygen transportoxygen transportthrombosisthrombosisglucocorticoidsglucocorticoids Pharmacological effectsPharmacological effects Increase resistance to stress Increase resistance to stress Alter blood cell levels in plasmaAlter blood cell levels in plasma Affect other
9、 components of endocrineAffect other components of endocrine nervous systemnervous system Development of Fetal lung Development of Fetal lung Clinical usesClinical uses Replacement therapyReplacement therapy Primary adrenocortical insufficiencyPrimary adrenocortical insufficiency Secondary adrenocor
10、tical Secondary adrenocortical insufficiencyinsufficiency Diagnosis of adrenal dysfunctionDiagnosis of adrenal dysfunction Adrenocortical insufficiency Adrenocortical insufficiency Adrenocortical hypoAdrenocortical hypo-and hyperand hyper-functionfunction Use of GC for diagnostic purposesUse of GC f
11、or diagnostic purposesClinical use of Clinical use of glucocorticoidsglucocorticoidsAcute severe infectious diseases and Acute severe infectious diseases and inflammatory diseases(severe)inflammatory diseases(severe)SepsisSepsis toxic bacillary toxic bacillary dysenterydysentery tuberculoustuberculo
12、us pleuritispleuritisimmune diseasesimmune diseases Autoimmune diseases:SLE systemic lupus Autoimmune diseases:SLE systemic lupus erythematosuserythematosus transplantationtransplantation allergic diseaseallergic diseaseClinical uses of Clinical uses of glucocorticoidsglucocorticoids acceleration of
13、 lung maturation acceleration of lung maturation stimulation of lung maturation in the stimulation of lung maturation in the fetusfetus cortisolscortisols Stroke,traumatic brain injuryStroke,traumatic brain injuryadverse effects adverse effects Metabolic effects Metabolic effects a rounded,plethoric
14、 face(moon a rounded,plethoric face(moon facies)and trunk facies)and trunk muscle wasting,thinning,purple muscle wasting,thinning,purple striae,and easy bruising of the striae,and easy bruising of the skinskinpoor wound healingpoor wound healing O Osteoporosissteoporosis mental disordersmental disor
15、ders HHypertensionypertension diabetesdiabetesToxicity of cortisolToxicity of cortisol Others complicationsOthers complications Produce or worsen Peptic ulcersProduce or worsen Peptic ulcers Hypomania or acute psychosisHypomania or acute psychosis Sodium and fluid retention,loss of potassiumSodium a
16、nd fluid retention,loss of potassium Adrenal Adrenal suppresionsuppresion Iatrogenic Adrenal insufficiencyIatrogenic Adrenal insufficiency Tapered slowlyTapered slowlyContraindications and Contraindications and cautions cautions HyperglycemiaHyperglycemia Sodium retentionSodium retention Hypokalemia
17、Hypokalemia Peptic ulcerPeptic ulcer OsteoporosisOsteoporosis Hidden infectionsHidden infections How to avoid How to avoid these side effects these side effects and toxicityand toxicity Diagnosed Diagnosed accuratelyaccurately Select Select appropriatelyappropriately Kept dosage as Kept dosage as lo
18、w as possible low as possible Short duration of Short duration of therapy as therapy as possiblepossibleHow to use drugs How to use drugs appropriatelyappropriately acute or chronic,acute or chronic,dosage dosage and duration of and duration of therapytherapy Dosage Dosage Frequent intervals for inf
19、lammationFrequent intervals for inflammation Aggressively increase for severe autoimmuneAggressively increase for severe autoimmune StossStoss therapy therapy for acute serious diseasesfor acute serious diseases Replacement therapy for Adrenal insufficiencyReplacement therapy for Adrenal insufficien
20、cy Special dosage formsSpecial dosage forms Local therapy skin,asthma(inhale)Local therapy skin,asthma(inhale)MineralocorticoidsMineralocorticoids and and antagonist of antagonist of adrenocorticaladrenocorticalagentsagents MineralocorticoidsMineralocorticoids Sodium retention and loss of potassium
21、Sodium retention and loss of potassium antagonistantagonistmetyraponemetyrapone(antagonist)(antagonist)Selective inhibitor of steroid synthesisSelective inhibitor of steroid synthesis Diagnostic test Diagnostic test cushingscushings syndromesyndrome Ketoconazole Ketoconazole inhibitor of steroid synthesisinhibitor of steroid synthesis Breast cancer and Breast cancer and cushingscushings syndromesyndrome MitotaneMitotane“chemical scalpel”“chemical scalpel”Adrenal carcinoma Adrenal carcinoma