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Systemic steroids

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  • 1. SYSTEMIC STEROIDS JONATHAN OLESU
  • 2. ANATOMY AND PHYSIOLOGY• The adrenal glands are located on the superior aspect of each kidney and• consist of two defined portions• The outer portion of the gland, the adrenal cortex, produces three groups of steroid hormones: – glucocorticoids, – mineralocorticoids, – androgens.• They are derived from cholesterol and share a common core structure.
  • 3. • The adrenal cortex has three zones.• The outermost zona glomerulosa produces mineralocorticoids, primarily aldosterone• The zona fasciculata and the innermost• zona reticularis secrete glucocorticoid,cortisol, and androgens.• The inner portion of the gland, adrenal medulla,produces catecholamines, – epinephrine (adrenaline), and – norepinephrine (noradrenaline).
  • 4. • aldosterone, – for sodium and potassium balance and extracellular fluid volume.• Cortisol – essential for metabolism, – anti-inflammatory properties, and – maintenance of homeostasis during periods of physical or emotional stress.
  • 5. • Cortisol secretion is regulated by the hypothalamic- pituitary-adrenal axis. The circadian rhythm, mediated by the CNS, and responses to stress stimulate the hypothalamus to release corticotropin-releasing hormone (CRH), which stimulates the production and secretion of adrenocorticotropic hormone (ACTH) by the anterior pituitary.• The adrenal cortex is stimulated by ACTH to produce and secrete cortisol. Circulating plasma cortisol levels are elevated within minutes after stimulation in a normally functioning gland.
  • 6. • The increased levels of cortisol act to inhibit the production of CRH and ACTH, and thereby decrease the output of cortisol• This process constitutes the negative feedback loop of cortisol regulation.• The normal pattern of cortisol secretion usually peaks about the time of awakening in the morning and is lowest in the afternoon and evening.• During a 24-hour period, approximately 20 mg of cortisol are secreted. Stress from trauma, illness, and emotional concerns can enhance this secretion.
  • 7. • Aldosterone secretion is regulated by – renin-angiotensin system, – ACTH, sodium, and – potassium levels .• When renal blood pressure decreases, – renin is released, which – stimulates release of angiotensin and – activates the secretion of aldosterone• via a negative feedback loop.
  • 8. Examples of systemic steroids• Short-Acting – Cortisol (hydrocortisone) – Cortisone – Prednisone – Prednisolone – Methylprednisolone• Intermediate-Acting – triamcinolone• Long-Acting – Betamethasone – Dexamethasone
  • 9. Systemic steroid hormone replacement therapyTrophic Hormone Deficit Hormone Replacement Hydrocortisone (10–20 mg A.M.; 5–10 mg P.M.)ACTH Cortisone acetate (25 mg A.M.; 12.5 mg P.M.) Prednisone (5 mg A.M.; 2.5 mg P.M.)
  • 10. Uses and problems of therapeutic steroid therapy• Apart from their use as therapeutic replacement for endocrine deficiency states, synthetic glucocorticoid s are widely used for many non-endocrine conditions• Short-term use (e.g. for acute asthma) carries only small risks of significant side- effects except for the simultaneous suppression of immune responses. The danger lies in their continuance, often through medical oversight or patient default. In general, therapy for 3 weeks or less, or a dose of prednisolone less than 1 0 mg per day, will not result in significant long-term suppression of the normal adrenal axis.• Long-term therapy with synthetic or natural steroids will, in most respects, mimic endogenous Cushings syndrome. Exceptions are the relative absence of hirsutism, ac ne, hypertension and severe sodium retention, a s the common synthetic steroids have low androgenic and mineralocorticoid activity.• Excessive doses of steroids may also be absorbed from skin when strong dermatological preparations are used, but inhaled steroids rarely cause Cushings syndrome,
  • 11. Common therapeutic uses of glucocorticoids• Respiratory disease • Rheumatological disease• Asthma,COPD,sarcoidosis,hayfever,prevention and • SLE,polymyalgia rheumatica, cranial arteritis,juvenile treatment of ARDS. idiopathic arthritis, vasculitides,rheumatoid arthritis• Cardiac disease • Neurological disease• Post-myocardial infarction syndrome • Cerebral oedema• Renal • Skin disease• Some nephrotic syndromes, some • Pemphigus,eczema glomerulonephritides • Tumours• GI disease • Hodgkin’s lymphoma, other lymphomas• Ulcerative colitis• Crohn’s disease • Transplantation• Autoimmune hepatitis • Immunosuppression• THE MOST COMMON INDICATION FOR STEROID USE IS AS AN ANTI-INFLAMMATORY DRUG
  • 12. INDICATION OF SYSTEMIC STEROIDS IN DENTAL SURGERY• Lichen planus• Aphthous ulcers• Benign mucous membrane pemphigoid• Pemphigus vulgaris
  • 13. Major adverse effects of corticosteroid therapy• Physiological • Endocrine• Adrenal and/or pituitary suppression • Weight gain ,Glycosuria/hyperglycaemia/ diabetes ,Impaired growth• Pathological Cardiovascular • Amenorrhoea• Increased blood pressure • Bone and muscle• Gastrointestinal • Osteoporosis, Proximal myopathy and wasting ,Aseptic• Peptic ulceration exacerbation necrosis of the hip, Pathological fractures• Pancreatitis • Skin• Renal • Thinning, Easy bruising• Polyuria• Nocturia • Eyes • Cataracts (including inhaled drug)• Central nervous• Depression • Increased susceptibility to infection• Euphoria • (signs and fever are frequently masked ), Septicaemia, Fungal• Psychosis • Infections, Reactivation of TB Skin (e.g. fungi)• Insomnia
  • 14. Supervision of steroid therapy1. Long-term steroid therapy must never be stopped suddenly.2. Doses should be reduced very gradually, with most being given in the morning at the time of withdrawal — this minimizes adrenal suppression.Many authorities believe that alternate-day therapy produces lesssuppression.3. Doses need to be increased in times of serious inter-current illness(defined as presence of a fever), accident and stress. Double doses shouldbe taken during these times.4. Other physicians, anaesthetists and dentists must be told about steroidtherapy.5. Patients should also be informed of potential side-effects and all thisinformation should be documented in the clinical record.6. Regular supervision including, e.g. DXA scan.
  • 15. Pharmacologic Clinical Uses of Adrenal Steroids• The widespread use of glucocorticoids emphasizes the need for a thorough understanding of the metabolic effects of these agents. Before adrenal hormone therapy is instituted, the expected gains should be weighed against undesirable effects. Several important questions should be addressed before initiating therapy.• First, how serious is the disorder (the more serious, the greater the likelihood that the risk/benefit ratio will be positive)?• Second, how long will therapy be required (the longer the therapy, the greater the risk of adverse side effects)?• Third, does the individual have preexisting conditions that glucocorticoids may exacerbate ? – If so, then a careful risk/benefit assessment is required to ensure that the ratio is favorable given the increased likelihood of harm by steroids in these patients.• Fourth, which preparation is best?
  • 16. Table 336-9 A Checklist Prior to the Administration of Glucocorticoids in Pharmacologic DosesPresence of tuberculosis or other chronic infection (chest x-ray, tuberculin test)Evidence of impaired glucose intolerance, history of gestational diabetes, or strong family history oftype 2 diabetes mellitus in first-degree relativeEvidence of preexisting (or high risk for) osteoporosis (bone density assessment in organ transplantrecipients or postmenopausal patients)History of peptic ulcer, gastritis, or esophagitis (stool guaiac test)Evidence of hypertension, cardiovascular disease, or hyperlipidemia (triglyceride level)History of psychological disorders
  • 17. Supplementary Measures to Minimize Undesirable Metabolic Effects of GlucocorticoidsDiet Monitor caloric intake to prevent weight gain. Diabetic diet if glucose intolerant. Restrict sodium intake to prevent edema and minimize hypertension. Provide supplementary potassium if necessary.Consider antacid, H2 receptor antagonist, and/or H+, K+,-ATPase inhibitor therapy
  • 18. Institute all-day steroid schedule, if possible Patients receiving steroid therapy over a prolonged period (months) should have an appropriate increase inhormone level during periods of acute stress. A rule of thumb is to double the maintenance dose.Minimize loss of bone mineral density Consider administering gonadal hormone replacement therapy in post-menopausal women: 0.625–1.25 mg conjugated estrogens given cyclically with progesterone, unless the uterus is absent(testosterone replacement in hypogonadal men). Ensure adequate calcium intake (should be ~1200 mg/d elemental calcium). Administer a minimum of 800–1000 IU/d supplemental vitamin D. Measure blood levels of calciferol and 1,25(OH)2 vitamin D. Supplement as needed. Consider administering bisphosphonate prophylactically, orally, or parenterally in high-risk patients.
  • 19. procedure premedication Intra- and post-op Resumption of Steroid cover for 100Simple procedures Hydrocortisone operative procedures Immediately if no normal maintenance(e.g. gastroscopy, mg i.m complicationssimple dental and eating normallyextractions)Minor surgery Hydrocortisone 100 Hydrocortisone 20 After 24 h if no(e.g. laparoscopic mg i.m. mg orally 6-hourly complicationssurgery or 50 mg i.m.veins, hernias) every 6 hour s for 24 h if not eatingMajor surgery Hydrocortisone 100 Hydrocortisone After 7 2 h if normal(e.g. hip mg i.m. 50-100 mg i.m progressreplacement, ever y 6 hours for and no complicationsvascular surgery) 72 h Perhaps double normal dose for next 2-3 daysGl tract surgery or Hydrocortisone 100 Hydrocortisone When patient eatingmajor thoracic mg i.m. 100 mg i.m. normallysurgery eve ry 6 hours for again Until then,(not eating or 72 h or higher dosesventilated) longer if still (to 50 mg 6-hourly)
  • 20. THANKS