Homeostasis & Steroids - Dr. Shweta Yadav - Oral and Maxillofacial Surgery
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This document provides an overview of homeostasis and steroids. It discusses the history of steroids, defines homeostasis, and classifies steroids based on function and duration of action. The document outlines the biosynthesis, basal secretion, and components of the homeostatic system. It describes the mechanisms of action of glucocorticoids, including their effects on carbohydrate and fat metabolism, calcium levels, and the inflammatory response. The document also discusses the hypothalamic-pituitary-adrenal axis and negative feedback mechanism, adverse effects of steroids, contraindications, and the rule of two for dental treatment. It concludes by listing some uses of steroids in oral and maxillofacial surgery.
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Homeostasis & Steroids - Dr. Shweta Yadav - Oral and Maxillofacial Surgery
- 1. HOMEOSTASIS & STEROIDS Guided by Dr. S.R.Shenoi (Prof. & HOD) Guided by Dr. Kshitij Bang (Asso.Prof. & Guide) Presented by Dr. Shweta Yadav (Junior Resident) Department of Oral & Maxillofacial Surgery VSPM Dental College, Nagpur
- 2. Content Introduction History Definition Classification Functional Anatomy Biosynthesis Components of homeostatic system Mechanism of Action Pharmacological Action of Gluco- & Mineralocorticosteroids HPAAxis & Negative Feedback Mechanism Adverse Effects Contraindication Rule of Two Uses in Oral and Maxillofacial Surgery Conclusion Reference
- 3. Introduction • Steroidal hormones regulate body function to bring about a programmed pattern of life events and maintain homeostasis in the face of markedly variable external or internal environment. • The term ‘corticosteroid’ or ‘corticoid’ includes natural gluco- and mineralo-corticoids and their synthetic analogues. • Adrenal Cortex is more important than medulla. Tripathi KD. Essentials of pharmacology for dentistry. jaypee; 2016.
- 4. History • Sir Thomas Addison (1855) on ‘The Clinical Picture of Adrenal Destruction’ • Sir Hans Selye relationship between Adrenal cortex and Stress • Sir Hench (1949) jointly with Sir Kendall and Sir Reichstein – Rheumatoid Arthritis, got Nobel Prize in 1950 Satoskar RS, Rege N, Bhandarkar SD. Pharmacology and Pharmacotherapeutics-E-Book. Elsevier Health Sciences; 2015 Jul 27.
- 5. Definition • Homeostasis: the co-ordinated physiological process which maintains most of the steady states of the organism (Sir Walter Cannon). • The stability of the “milieu interieur” is the primary condition for freedom and independence of existence (Sir Claude Bernard); i.e. body systems act to maintain internal constancy. Truskett P. Bailey and Love's Short Practice of Surgery. ANZ Journal of Surgery. 2014 Mar 1;84(3).
- 6. Classification • Based on Function STEROIDS CORTICOSTEROIDS GLUCOCORTICOIDS HYDROCORTISONE, CORTISONE, PREDNISOLONE, METHYL PREDNISOLONE, TRIAMCINOLONE, DEXAMETHASONE, BETAMETHASONE, PARAMETHASONE MINERALOCORTICOIDS ALDOSTERONE, FLUDROCORTISONE, DEOXYCORTICOSTERONE ACETATE (DOCA) SEX HORMONE ANDROGEN, ESTROGEN, PROGESTERONE ANABOLIC STEROIDS
- 7. Classification of Glucocorticoid Short Acting • Hydrocortisone (Cortisol) • Cortisone Intermediate Acting • Triamcinolone • Prednisone • Prednisolone • Methylprednisolone • Fludrocortisone Long Acting •Dexamethasone •Betamethasone •Paramethasone • Based on Duration of Action Zandi M. The role of corticosteroids in today's oral and maxillofacial surgery. InGlucocorticoids-new recognition of our familiar friend 2012 Nov 28.
- 8. Essentials Of Medical Physiology-6th Edition-K Sembulingam, Prema Sembulingam
- 9. Biosynthesis Tripathi KD. Essentials of pharmacology for dentistry. jaypee; 2016.
- 10. Basal secretion Group Hormone Daily Glucocorticoids Cortisol Cortisone 5 – 30 mg 2 – 5 mg Mineralocorticoids Aldosterone 11- Deoxycorticosterone 0.12 mg Trace Sex Hormones Androgen Progestogen Oestrogen DHEA Progesterone Oestradiol 15 – 30 mg 0.4 – 0.8 mg Trace
- 11. Components of homeostatic system Essentials Of Medical Physiology-6th Edition-K Sembulingam, Prema Sembulingam
- 12. Mechanism of Action of Glucocorticoid Mehta AB, Nadkarni NJ, Patil SP, Godse KV et al. Topical corticosteroids in dermatology.Indian J Dermatol Venereol Leprol 2016;82:371-8
- 13. Actions of Glucocorticoids 1. Carbohydrate & protein metabolism 2. Fat metabolism 3. Calcium metabolism 4. Water excretion 5. Cardiovascular system 6. Skeletal muscles 7. Central nervous system 8. Stomach 9. Lymphoid tissue & blood cells 10. Inflammatory responses 11. Immunological & allergic responses Satoskar RS, Rege N, Bhandarkar SD. Pharmacology and Pharmacotherapeutics-E-Book. Elsevier Health Sciences; 2015 Jul 27.
- 15. Skeletal system Ilias I, Zoumakis E, Ghayee H. An Overview of Glucocorticoid Induced Osteoporosis. 2018 Jul 10.
- 16. • Promotes glycogen deposition in liver by- 1. Hepatic glycogen synthetase induction 2. Gluconeogenesis 3. Inhibition of glucose utilization by peripheral tissues 4. Increase glucose release from liver • Protein breakdown. • Mobilization of amino acid from peripheral tissue (used in gluconeogenesis, formation of plasma proteins, excessive urea production & nitrogen imbalance). • Muscle wasting, thinning of skin, lympholysis, loss of osteoid from bone. • Permissive action. • Promote : lipolysis • Ketogenic effect • Fat deposition occurs differently in different areas of the body. Redistribution of body fat. • Extremities - loose fat • Deposited over – face, neck & shoulder, abdomen, causing – moon face, fish mouth, buffalo hump.
- 17. • Inhibit intestinal absorption & decreases renal excretion of Ca++ • Loss of osteoid negative calcium balance ,Hypercalcemia, Spongy bone. • Independent of Na+ transport ,Water retention – in adrenal insufficiency. Enhances secretory activity of renal tubules. • Restrict capillary permeability. Maintain tone of arteriole & myocardial contractility. Permissive action on pressor effect of adrenaline & angiotensin. In adrenal insuffiency – hypovolumia & circulatory collapse. • Optimal level of glucocorticoid is required. Hypocorticism – weakness due to hypodynamic circulation. Hypercorticism – weakness due to muscle wasting & hypokalemia. • Mild euphoria, Increased motor activity, insomnia, anxiety or depression. Maintains the level of sensory perception & neuronal excitability. High doses lower the seizure threshold. • Blockade of prostaglandin (protective for gastric mucosa). Secretion of gastric acid & pepsin is increased. May aggravate the peptic ulcer.
- 19. Molecular mechanism of Anti-inflammatory effect • A. Transactivation mechanism: up-regulate the expression of anti-inflammatory proteins (lipocortin I). • B. Transrepression mechanism: down-regulate the expression of proinflammatory proteins (NF-кB, Fos, IL-1, TNF- α) • Transcriptional machinery (TM) • transcription factors (TF). Mechanism of Anti-Inflammatory Effect • Suppress T-cell activation and cytokine production • Suppress mast cell degranulation • Decrease capillary permeability indirectly by inhibiting mast cells and basophils • Reduce the expression of cyclooxygenase II and prostaglandin synthesis • Reduce prostaglandin, leukotriene and platelet activating factor levels by altering phospholipase A2 activity
- 20. Truskett P. Bailey and Love's Short Practice of Surgery. ANZ Journal of Surgery. 2014 Mar 1;84(3). The metabolic stress response :the ‘ebb and flow’ model
- 22. Negative feedback mechanism Regulation of corticosteroid production and response to stress which overrides the negative feedback regulation of ACTH release. Hypothalamo-pituitary-adrenal (HPA) axis
- 23. Excess mineralocorticoid Hypertension Fluid retention Oedema Hypokalemia Alkalosis Promote myocardial fibrosis & associated progression of the disease Tripathi KD. Essentials of pharmacology for dentistry. jaypee; 2016.
- 24. Mineralocorticoid deficiency Decreases Na+ resorptive capacity (even in Na+ deficient state) Absorb water without attended Na+ (to maintain ECF) Dilutional hyponatremia Excessive water enters in the cell Decrease blood volume & increased hematocrit Fluid electrolyte imbalance Circulatory collapse Tripathi KD. Essentials of pharmacology for dentistry. jaypee; 2016.
- 25. Adverse effects of corticosteroids • Cushing’s habitus • Fragile skin, purple striae • Hyperglycaemia • Muscular weakness • Delayed healing • Peptic ulceration • Osteoporosis • Cataract • Growth retardation • Foetal abnormalities • Psychiatric disturbances • Suppression of hypothalamo- pituitary-adrenal (HPA) axis Tripathi KD. Essentials of pharmacology for dentistry. jaypee; 2016.
- 26. RULE OF 2 • Adrenal suppression may occur if a patient is taking 20 mg of cortisone or its equivalent daily, for 2 weeks within 2 years of dental treatment. • Withdrawal “Cold turkey”: if glucocorticoid therapy of less than 2 weeks duration. • Taper off: if Glucocorticoid therapy of greater than 2 weeks duration.
- 27. Uses in Oral and Maxillofacial Surgery • Temporomandibular disorders (TMDs) • Oral ulcerative and vesiculobullous lesions • Keloid and hypertrophic scars • Central giant cell granuloma • Bell's palsy • Hypersensitivity Reaction • Others
- 28. Contraindications 1. Peptic ulcer 2. Diabetes mellitus 3. Hypertension 4. Viral and fungal infections 5. Tuberculosis and other infections 6. Osteoporosis 7. Psychosis 8. Epilepsy 9. Renal failure Tripathi KD. Essentials of pharmacology for dentistry. jaypee; 2016.
- 29. Conclusion • Emphasis is laid on why knowledge of these events is important to understand the rationale for modern ‘stress-free’ perioperative and critical care. • Resuscitation, surgical intervention and critical care can return the severely injured patient to a situation in which homeostasis becomes possible once again.
- 30. References • Tripathi KD. Essentials of pharmacology for dentistry. jaypee; 2016. • Satoskar RS, Rege N, Bhandarkar SD. Pharmacology and Pharmacotherapeutics-E-Book. Elsevier Health Sciences; 2015 Jul 27. • Truskett P. Bailey and Love's Short Practice of Surgery. ANZ Journal of Surgery. 2014 Mar 1;84(3). • Essentials Of Medical Physiology-6th Edition-K Sembulingam, Prema Sembulingam • Kent S, Hennedige A, McDonald C, Henry A, Dawoud B, Kulkarni R, Logan G, Gilbert K, Exely R, Basyuni S, Kyzas P. Systematic review of the role of corticosteroids in cervicofacial infections. British Journal of Oral and Maxillofacial Surgery. 2019 Feb 13. • The Role of Corticosteroids in Today's Oral and Maxillofacial Surgery 2012 http://dx.doi.org/10.5772/48655 Mohammad Zandi • Ilias I, Zoumakis E, Ghayee H. An Overview of Glucocorticoid Induced Osteoporosis. 2018 Jul 10. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK278968/
- 31. THANK YOU
Editor's Notes
- Hormone (hormaein = to stir up) is a substance of intense biological activity that is produced by specific cells in the body and is transported through the circulation to act on is target cells. Cortex produces hormones that are vital to life, such as cortisol (which helps regulate metabolism and helps your body respond to stress) and aldosterone (which helps control blood pressure)
- Clinical importance of Adrenal Gland was 1st described by – Stimulated extensive research work in adrenal physiology. Great therapeutic potential was opened by
- A corticosteroid with predominantly sodium retaining effects is called a mineralocorticoid e.g. aldosterone and desoxycorticosterone. A corticosteroid with predominantly liver glycogen depositing and neoglucogenetic actions is called a glucocorticoid e.g. hydrocortisone, cortisone and most of the newer synthetic steroids. The term cortisol refers to the native hormone of the adrenal cortex present in the biological fluids; whereas the term hydrocortisone is used to refer to the synthetic substance used therapeutically.
- Short Acting (Biological t1/2 8-12 hrs) Intermediate Acting (Biological t1/2 12-36 hrs) Long Acting (Biological t1/2 36- 72 hrs) Metabolizes primarily in liver. Excreted in urine(75 %) and in bile & feces (25%) . t1/2 = 1.5 hour, but biological t1/2 is longer because of action through intracellular receptors & regulation of protein synthesis. Synthetic derivatives are more resistance to metabolism, so are longer acting
- Corticosteroids are 21 carbon compounds. Synthesized in adrenal cortical cells from cholesterol. Steroidogenesis takes place under the influence of ACTH, which makes the cholesterol available for conversion into Pregnenolone
- COMPONENTS OF HOMEOSTATIC SYSTEM Homeostatic system in the body acts through selfregulating devices, which operate in a cyclic manner This cycle includes four components: 1. Sensors or detectors, which recognize the deviation 2. Transmission of this message to a control center 3. Transmission of information from the control center to the effectors for correcting the deviation Transmission of the message or information may be an electrical process in the form of impulses through nerves or a chemical process mainly in the form of hormones through blood and body fluids 4. Effectors, which correct the deviation
- steroids are metabolised in the liver and the metabolites are excreted in the urine as conjugates with sulfuric and glucuronic acids. The corticosteroids being water insoluble, are excreted in the urine only in traces. Mechanism of action: Glucocorticoids act by a complex mechanism involving cytosolicnuclear actions and membrane bound receptors, thus producing genomic and nongenomic actions, respectively. They enter the cell as free molecules and bind to cytosolic steroid receptors. The complex translocates to the nucleus and the steroid binds to the glucocorticoid responsive element (GRE) in the regulatory region of the concerned gene. The interaction is responsible for the genomic effects, executed through activation or repression of DNA transcription. Repression of DNA transcription is believed to be responsible for anti-inflammatory actions of glucocorticoids while up-regulation of gene. transcription which occurs with higher doses is believed to cause undesirable effects
- http://tmedweb.tulane.edu/pharmwiki/doku.php/glucocorticoid_pharmacology
- Overview of the mechanisms of glucocorticoid-induced osteoporosis (GCOP). Osteoporosis results from an imbalance between osteoblast and osteoclast activity. BMP-2: bone morphogenic protein-2; Cbfa1: core binding factor a1; Bcl-2: B-cell leukemia/lymphoma-2 apoptosis regulator; Bax: BCL-2-associated X protein; IGF-I: insulin-like growth factor-I; IGFBP: IGF binding protein; IGFBP-rPs: IGFBP-related proteins; HGF: hepatocyte growth factor; RANKL: receptor activator of the nuclear factor-κB ligand; CSF-1: colony-stimulating factor-1; OPG: osteoprotegerin; PGE2: Prostaglandin E 2; PGHS-2 prostaglandin synthase-2
- The hypothalamic-pituitary-adrenal axis (HPA or HTPA axis) is also known as the limbic-hypothalamic-pituitary-adrenal axis and is a complex set of interactions between the hypothalamus, the pituitary gland, and the adrenal (also called “suprarenal”) glands.
- the rate of release of ACTH regulate the rates of secretion of cortisol and corticosterone. The plasma level of cortisol modulates the rate of release of CRH and in turn that of ACTH by negative feedback mechanism. Thus, increased plasma level of cortisol inhibits ACTH release and reduces its store in the adenohypophysis. Under stressful situations, neuronal impulses from higher centres stimulate release of CRH which ultimately elevates the output of cortisol to meet the increased demands of the body. This important homeostatic mechanism which overrides the diurnal variations in ACTH secretion as well as its regulation by plasma cortisol level is deranged in various disease states and in the functional suppression of the HPA complex by glucocorticoid administration
- IN DCT ↑ Na+ reabsorption ↑ K+ & H+ excretion
- IN DCT ↑ Na+ excretion ↑ K+ & H+ retention hyponatremia hyperkalemia acidosis Hematocrit :the ratio of the volume of red blood cells to the total volume of blood.
- Glucocorticoid 1. Cushing’s habitus: characteristic appearance with rounded face, narrow mouth, supraclavicular hump, obesity of trunk with relatively thin limbs. 2. Fragile skin, purple striae—typically on thighs and lower abdomen, easy bruising, telangiectasis, hirsutism. Cutaneous atrophy localized to the site occurs with topical application as well. 3. Hyperglycaemia, may be glycosuria, precipitation of diabetes. 4. Muscular weakness: proximal (shoulder, arm, pelvis, thigh) muscles are primarily affected. Myopathy occurs occasionally, warrants withdrawal of the corticoids. 5. Susceptibility to infection: this is nonspecific for all types of pathogenic organisms. Latent tuberculosis may flare; opportunistic infections with low grade pathogens (Candida, etc.) set in. 6. Delayed healing: of wounds and surgical incisions. 7. Peptic ulceration: risk is doubled; bleeding and silent perforation of ulcers may occur. Dyspeptic symptoms are frequent with high dose therapy. 8. Osteoporosis: especially involving vertebrae and other flat spongy bones. Compression fractures of vertebrae and spontaneous fracture of long bones can occur, especially in the elderly. Radiological evidence of osteoporosis is an indication for withdrawal of corticoid therapy. Corticosteroid induced osteoporosis can be prevented/arrested by calcium supplements + vit D, and by estrogen/raloxifene or androgen replacement therapy in females and males respectively. However, bisphosphonates are the most effective drugs in this regard. Avascular necrosis of head of femur, humerous, or knee joint is an occasional abrupt onset complication of high dose corticosteroid therapy. 9. Posterior subcapsular cataract may develop after several years of use, especially in children. 10. Glaucoma: may develop in susceptible individuals after prolonged topical therapy. 11. Growth retardation: in children occurs even with small doses if given for long periods. Large doses do inhibit GH secretion, but growth retardation may, in addition, be a direct cellular effect of corticoids. Recombinant GH given concurrently can prevent growth retardation, but risk/benefit of such use is not known. 12. Foetal abnormalities: Cleft palate and other defects are produced in animals, but have not been encountered on clinical use in pregnant women. The risk of abortion, stillbirth or neonatal death is not increased, but intrauterine growth retardation can occur after prolonged therapy, and neurological/ behavioral disturbances in the offspring are feared. Prednisolone appears safer than dexa/ beta methasone, because it is metabolized by placenta, reducing foetal exposure. There is no evidence of foetal growth retardation occurring after short term use in the mother. Prolonged corticosteroid therapy during pregnancy increases the risk of gestational diabetes, pregnancy induced hypertension and preeclampsia. 13. Psychiatric disturbances: mild euphoria frequently accompanies high dose steroid treatment. This may rarely progress to manic psychosis. Nervousness, decreased sleep and mood changes occur in some patients. Rarely a depressive illness may be induced after long-term use. 14. Suppression of hypothalamo-pituitary-adrenal (HPA) axis: occurs depending both on dose and duration of therapy. In time, adrenal cortex atrophies and stoppage of exogenous steroid precipitates withdrawal syndrome consisting of malaise, fever, anorexia, nausea, postural hypotension, electrolyte imbalance, weakness, pain in muscles and joints and reactivation of the disease for which they were used. Subjected to stress, these patients may go into acute adrenal insufficiency leading to cardiovascular collapse.
- Withdrawal “Cold turkey”: if glucocorticoid therapy of less than 2 weeks duration Taper off: if Glucocorticoid therapy of greater than 2 weeks duration. Rate of taper should be proportional to duration of prior therapy. The longer the original therapy, the slower the rate of dose reduction. Withdrawal syndrome: hypotension, hypoglycemia, myalgia and fatigue, joint pain, muscle stiffness, muscle tenderness , or fever.
- Resuscitation: the action or process of reviving someone from unconsciousness or apparent death