Systemic steroids

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  • 1. SYSTEMIC STEROIDSJONATHAN OLESU

2. ANATOMY AND PHYSIOLOGY The adrenal glands are located on the superioraspect of each kidney and consist of two defined portions The outer portion of the gland, the adrenalcortex, produces three groups of steroidhormones: glucocorticoids, mineralocorticoids, androgens. They are derived from cholesterol and share acommon core structure. 3. The adrenal cortex has three zones. The outermost zona glomerulosa producesmineralocorticoids, primarily aldosterone The zona fasciculata and the innermost zona reticularis secrete glucocorticoid,cortisol, andandrogens. The inner portion of the gland, adrenalmedulla,produces catecholamines, epinephrine (adrenaline), and norepinephrine (noradrenaline). 4. aldosterone, for sodium and potassium balance andextracellular fluid volume. Cortisol essential for metabolism, anti-inflammatory properties, and maintenance of homeostasis during periods ofphysical or emotional stress. 5. Cortisol secretion is regulated by the hypothalamic-pituitary-adrenal axis. The circadian rhythm, mediatedby the CNS, and responses to stress stimulate thehypothalamus to release corticotropin-releasinghormone (CRH), which stimulates the production andsecretion of adrenocorticotropic hormone (ACTH) bythe anterior pituitary. The adrenal cortex is stimulated by ACTH to produceand secrete cortisol. Circulating plasma cortisol levelsare elevated within minutes after stimulation in anormally functioning gland. 6. The increased levels of cortisolact to inhibit the production ofCRH and ACTH, and therebydecrease the output of cortisol This process constitutes thenegative feedback loop ofcortisol regulation. The normal pattern of cortisolsecretion usually peaks aboutthe time of awakening in themorning and is lowest in theafternoon and evening. During a 24-hourperiod, approximately 20 mg ofcortisol are secreted. Stressfrom trauma, illness, andemotional concerns canenhance 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 ReplacementHydrocortisone (1020 mg A.M.; 510 mg P.M.)ACTHCortisone 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 therapeuticsteroid therapy Apart from their use as therapeutic replacement for endocrine deficiencystates, synthetic glucocorticoid s are widely used for many non-endocrineconditionsShort-term use (e.g. for acute asthma) carries only small risks of significant side-effects except for the simultaneous suppression of immune responses. The dangerlies in their continuance, often through medical oversight or patient default. Ingeneral, therapy for 3 weeks or less, or a dose of prednisolone less than 1 0 mgper day, will not result in significant long-term suppression of the normal adrenalaxis. Long-term therapy with synthetic or natural steroids will, in most respects, mimicendogenous Cushings syndrome. Exceptions are the relative absence ofhirsutism, ac ne, hypertension and severe sodium retention, a s the commonsynthetic steroids have low androgenic and mineralocorticoid activity. Excessive doses of steroids may also be absorbed from skin when strongdermatological preparations are used, but inhaled steroids rarely cause Cushingssyndrome, 11. Common therapeutic uses ofglucocorticoids Respiratory disease Rheumatological disease Asthma,COPD,sarcoidosis,hayfever,prevention and SLE,polymyalgia rheumatica, cranial arteritis,juveniletreatment 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,eczemaglomerulonephritides Tumours GI disease Hodgkins lymphoma, other lymphomas Ulcerative colitis Crohns disease Transplantation Autoimmune hepatitis Immunosuppression THE MOST COMMON INDICATION FOR STEROID USEIS 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 corticosteroidtherapy 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 themorning 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 AdrenalSteroids The widespread use of glucocorticoids emphasizes the need for athorough understanding of the metabolic effects of these agents.Before adrenal hormone therapy is instituted, the expected gainsshould be weighed against undesirable effects. Several importantquestions should be addressed before initiating therapy. First, how serious is the disorder (the more serious, the greater thelikelihood that the risk/benefit ratio will be positive)? Second, how long will therapy be required (the longer thetherapy, the greater the risk of adverse side effects)? Third, does the individual have preexisting conditions thatglucocorticoids may exacerbate ? If so, then a careful risk/benefit assessment is required to ensure thatthe ratio is favorable given the increased likelihood of harm by steroidsin 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: 0.6251.25 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 8001000 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 premedicationIntra- and post-op Resumption of Steroid cover for 100Simple procedures Hydrocortisone operative procedures Immediately if nonormal maintenance(e.g. gastroscopy,mg i.mcomplicationssimple dental and eating normallyextractions)Minor surgery Hydrocortisone 100 Hydrocortisone 20 After 24 h if no(e.g. laparoscopicmg i.m.mg orally 6-hourly complicationssurgeryor 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.mprogressreplacement, ever y 6 hours for and no complicationsvascular surgery)72 h Perhaps doublenormal dose fornext 2-3 daysGl tract surgery or Hydrocortisone 100 Hydrocortisone When patient eatingmajor thoracicmg i.m.100 mg i.m.normallysurgeryeve ry 6 hours for again Until then,(not eating or 72 h orhigher dosesventilated)longer if still(to 50 mg 6-hourly) 20. 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