Adrenocorticoids 11/18/2018 MEDC 603 Steroids

Adrenocorticoids Hydrocortisol Aldosterone (11b,17a,21-trihydroxy- pregn-4-ene-3,20-dione) Aldosterone (11b,21-dihydroxy- pregn-4-ene-3,18,20-trione) 11/18/2018 MEDC 603 Steroids

Adrenocorticoids Addison’s Disease  Disease States Cushing’s Disease Conn’s Syndrome  Disease States 11/18/2018 MEDC 603 Steroids

Adrenocorticoids  Selected Indications Allergic Rhinitis Rheumatoid Arthritis Asthma Multiple Sclerosis Carpal Tunnel Syndrome Dermatitis COPD Osteoarthritis Cystic Fibrosis Temporal Arteritis Gout Psoriasis Herniated Disc Shingles Inflammatory Bowel Disease Tennis Elbow Sinusitis Lupus Erythematosus 11/18/2018 MEDC 603 Steroids

Overall Equilibrium in Aldosterone Opened form hemi-acetal form Aldosterone 11/18/2018 MEDC 603 Steroids

3D structure of hydrocortisol Overall Structure of Adrenocorticoids ~ planar A ring Differences in the substitution pattern 3D structure of hydrocortisol 11/18/2018 MEDC 603 Steroids

Biochemical Mechanism of Action Cortisol Aldosterone Anti-inflammatory Action Mineralocorticoid Action Receptor Receptor Lipocortin Aldosterone- induced protein Phospholipase A2 Cell membrane phospholipids Prostaglandins leucotrienes Regulates Na+-K+-ATPase Pump Na+ Influx 11/18/2018 MEDC 603 Steroids

Metabolism of Adrenocorticoids Reduction C-20 Reduction C-4 Reduction C-3 11/18/2018 MEDC 603 Steroids

at C-3, C-4 and C-20 positions Metabolism of Adrenocorticoids Oxidation C-11 Reduction at C-3, C-4 and C-20 positions 11/18/2018 MEDC 603 Steroids

Structure-Activity Relationships Anti- Salt- Plasma inflammatory retaining half activity activity life Hydrocortisone 1 1 120 m Cortisone 0.8 0.8 30 m 11/18/2018 MEDC 603 Steroids

Structure-Activity Relationships Anti- Salt- Plasma inflammatory retaining half activity activity life Prednisone 4 1 60 m Prednisolone 4 0.6 115-212 m 11/18/2018 MEDC 603 Steroids

Structure-Activity Relationships Anti- Salt- Plasma inflammatory retaining half activity activity life 6a-methyl 4 0 78-188 m prednisolone Triamcinolone 5 0 200+ m 11/18/2018 MEDC 603 Steroids

Structure-Activity Relationships Anti- Salt- Plasma inflammatory retaining half activity activity life Dexamethasone 30 0 110-210 m Betamethasone 35 0 300+ m 11/18/2018 MEDC 603 Steroids

Structure-Activity Relationships Anti- Salt- Plasma inflammatory retaining half activity activity life Aldosterone 0.2 800 30 m 11-deoxy 0 40 60 m corticosterone Fludrocortisone 10 800 300+ m 11/18/2018 MEDC 603 Steroids