Adrenal steroids
description
Transcript of Adrenal steroids
![Page 1: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/1.jpg)
Adrenal steroids
Dr Sanjeewani Fonseka
Department of Pharmacology
![Page 2: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/2.jpg)
Objectives• Recall the physiological effect of adrenocortical steroids
• Describe the anti- inflammatory and immunosuppressive effects of glucocorticoids
• Compare the relative potency, glucocorticoid/mineralocorticoid activity and duration of action of commonly available steroid drugs
• List clinical uses and adverse effects of glucocorticoid drugs
• Explain the principles underling replacement therapy in adrenocortical insufficiency
• Describe the precautions that can be taken to minimize the adverse effects of long-term steroid therapy
![Page 3: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/3.jpg)
![Page 4: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/4.jpg)
![Page 5: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/5.jpg)
Endogenous Glucocorticoids
Hydrocortisone
Corticosterone
![Page 6: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/6.jpg)
![Page 7: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/7.jpg)
Corticosteroids are Gene-Active
![Page 8: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/8.jpg)
![Page 9: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/9.jpg)
![Page 10: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/10.jpg)
GlucocorticoidsKinetics:• Well absorbed orally
• Bound to corticosteroid-binding globulin and albumin
• Distributed all over the body & passes the BBB
• In the liver, cortisol is reversibly converted to cortisone & conjugated with glucuronic & sulfuric acid
• Excreted in urine as 17-hydroxy corticosteroids
![Page 11: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/11.jpg)
Action of glucocorticoids
• Metabolic
• Anti-inflammatory
• Immunosuppressive
![Page 12: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/12.jpg)
Actions
1. Carbohydrate
2. Protein
3. Lipid
4. Electrolyte and
H2O
5. CVS
6. Skeletal Muscle
7. CNS
8. Stomach
9. Blood
10. Anti-inflammatory
11. Immunosuppressant
12.Growth and Cell
Division
13. Calcium metabolism
![Page 13: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/13.jpg)
Carbohydrate metabolism
• Gluconeogenesis– Peripheral actions (mobilize glucose and glycogen)
– Hepatic actions
• Peripheral utilization of glucose
• Glycogen deposition in liver(activation of hepatic glycogen synthase)
hyperglycemia
![Page 14: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/14.jpg)
protein metabolism
Negative nitrogen balance
• Decreased protein synthesis
• Increased protein breakdown
![Page 15: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/15.jpg)
Addison's disease: weakness and fatigue is due to
Prolonged use:
Skeletal Muscles
Needed for maintaining the normal function of Skeletal muscle
inadequacy of circulatory system
Steroid myopathy
![Page 16: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/16.jpg)
• Redistribution of Fat
Lipid metabolism
![Page 17: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/17.jpg)
Electrolyte and water balance
Act on DT and CD of kidney
– Na+ reabsorption
– Urinary excretion of K+ and H+
![Page 18: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/18.jpg)
• Direct– Mood– Behavior– Brain excitability
• Indirect– maintain glucose, circulation and electrolyte
balance
CNS
![Page 19: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/19.jpg)
– Acid and pepsin secretion
– immune response to H.Pylori
Stomach
![Page 20: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/20.jpg)
RBC: Hb and RBC content
(erythrophagocytosis)
WBC: Lymphocytes, eosinophils, monocytes, basophils
Polymorphonucleocytes
Blood
![Page 21: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/21.jpg)
Actions on inflammatory cells
• Recruitment of N, monocytes, macrophage into affected area
• Action of fibroblasts
• T helper action
• Osteoblast
• osteoclast
![Page 22: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/22.jpg)
Inflammatory mediators
• Reduced cytokines
• Reduced complement
• Reduced histamine
![Page 23: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/23.jpg)
Anti-inflammatory actions of corticosteroids
Corticosteroid inhibitory effect
![Page 24: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/24.jpg)
• Inhibit cell division or synthesis of DNA
• Delay the process of healing
• Retard the growth of children
Growth and Cell division
![Page 25: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/25.jpg)
• Intestinal absorption
• Renal excretion
• Excessive loss of calcium from bones (e.g., vertebrae, ribs, etc)
• Osteoporosis
Calcium metabolism
![Page 26: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/26.jpg)
Pharmacological Actions
• synthetic glucocorticoids are used because they have a higher affinity for the receptor
• have little or no salt-retaining properties.
![Page 27: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/27.jpg)
Clinical uses
• Replacement therapy
• Immunosuppressive / anti-inflammatory therapy
• Neoplastic disease
![Page 28: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/28.jpg)
Types of Steroids
Replacement Therapy
• glucocorticoid (hydrocortisone)
• mineralocorticoid (fludrocortisone)
![Page 29: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/29.jpg)
Anti-inflammatory Therapy
• Short acting: hydrocortisone
• Intermediate acting: prednisolone, methylprednisolone, triamcinolone
• Long acting: dexamethasone
![Page 30: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/30.jpg)
PreparationsDrug Anti-inflam. Salt retaining Topical
Cortisol 1 1.0 1Cortisone 0.8 0.8 0Prednisone 4 0.8 0Prednisolone 5 0.3 4Methylpredni- solone
5 0 5
Intermediate actingTriamcinolone 5 0 5Paramethasone 10 0 -Fluprednisolone 15 0 7
![Page 31: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/31.jpg)
PreparationsDrug Anti-inflam. Salt retaining Topical
Long actingBetamethasone 25-40 0 10Dexamethasone 30 0 10
MineralocorticoidsFludrocortisone 10 250 10DOCA 0 20 0
![Page 32: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/32.jpg)
Side effects
• Not seen in replacement therapy
• Seen if used for anti-inflammatory property
• Excess of physiological actions
![Page 33: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/33.jpg)
Iatrogenic Cushing’s syndrome
![Page 34: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/34.jpg)
Adverse effects (long term)
• Glucose intolerance
• Acne
• Hypertension, edema
• Susceptibility to infection (TB, fungal)
• Myopathy
• Behavior & mood changes
![Page 35: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/35.jpg)
![Page 36: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/36.jpg)
![Page 37: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/37.jpg)
![Page 38: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/38.jpg)
Adverse effects (long term)
• Avascular necrosis of bone
• Cataract
• Peptic ulcer
• Skin atrophy, delayed wound healing
• Growth retardation (children)
• Suppression of HPA axis
![Page 39: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/39.jpg)
![Page 40: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/40.jpg)
Drug interactions
• Estrogens - decrease prednisone clearance
• Phenobarbital, phenytoin, and rifampicin - increase metabolism of glucocorticoids
• May cause digitalis toxicity secondary to hypokalemia
• Monitor for hypokalemia with co-administration of diuretics
![Page 41: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/41.jpg)
Read
Monitoring while on steroids
Pregnancy and steroids
Infections and long term steroid
Surgery and steroids
![Page 42: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/42.jpg)
Summary
![Page 43: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/43.jpg)
![Page 44: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/44.jpg)
long term steroids
• Monitor BP, electrolyte and blood sugar
• Advise moderate exercise
• Bone protection measures
• Gastric protection if needed
![Page 45: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/45.jpg)
• Give morning dose
• Every other day
• Minimum effective dose
• Steroid sparing agents
![Page 46: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/46.jpg)
![Page 47: Adrenal steroids](https://reader035.fdocuments.us/reader035/viewer/2022062500/568152ae550346895dc0d18b/html5/thumbnails/47.jpg)
Read
• Mineralocorticoids – action, side effects, clinical uses