SYSTEMIC STEROIDS

JONATHAN OLESU

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.

• 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).

• 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.

• 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.

• 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.

• 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.

Examples of systemic steroids

• Short-Acting– Cortisol (hydrocortisone)– Cortisone– Prednisone– Prednisolone– Methylprednisolone

• Intermediate-Acting– triamcinolone

• Long-Acting– Betamethasone – Dexamethasone

Systemic steroid hormone replacement therapy

Trophic Hormone Deficit Hormone Replacement

ACTHHydrocortisone (10–20 mg A.M.; 5–10 mg P.M.)Cortisone acetate (25 mg A.M.; 12.5 mg P.M.)Prednisone (5 mg A.M.; 2.5 mg P.M.)

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 Cushing's 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 Cushing's syndrome,

Common therapeutic uses of glucocorticoids

• Respiratory disease• Asthma,COPD,sarcoidosis,hayfever,prevention and

treatment of ARDS.

• Cardiac disease• Post-myocardial infarction syndrome

• Renal• Some nephrotic syndromes, some glomerulonephritides

• GI disease• Ulcerative colitis• Crohn’s disease• Autoimmune hepatitis

• THE MOST COMMON INDICATION FOR STEROID USE IS AS AN ANTI-INFLAMMATORY DRUG

• Rheumatological disease• SLE,polymyalgia rheumatica, cranial

arteritis,juvenile idiopathic arthritis, vasculitides,rheumatoid arthritis

• Neurological disease• Cerebral oedema

• Skin disease• Pemphigus,eczema

• Tumours• Hodgkin’s lymphoma, other lymphomas

• Transplantation• Immunosuppression

INDICATION OF SYSTEMIC STEROIDS IN DENTAL SURGERY

• Lichen planus• Aphthous ulcers• Benign mucous membrane pemphigoid• Pemphigus vulgaris

Major adverse effects of corticosteroid therapy

• Physiological • Adrenal and/or pituitary suppression

• Pathological Cardiovascular • Increased blood pressure

• Gastrointestinal • Peptic ulceration exacerbation • Pancreatitis

• Renal • Polyuria • Nocturia

• Central nervous • Depression • Euphoria • Psychosis • Insomnia

• Endocrine • Weight gain ,Glycosuria/hyperglycaemia/

diabetes ,Impaired growth • Amenorrhoea

• Bone and muscle • Osteoporosis, Proximal myopathy and wasting ,Aseptic

necrosis of the hip, Pathological fractures

• Skin • Thinning, Easy bruising

• Eyes • Cataracts (including inhaled drug)

• Increased susceptibility to infection • (signs and fever are frequently masked ), Septicaemia,

Fungal • Infections, Reactivation of TB Skin (e.g. fungi)

Supervision of steroid therapy 1. 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 less suppression.

3. Doses need to be increased in times of serious inter-current illness (defined as presence of a fever), accident and stress. Double doses should be taken during these times. 4. Other physicians, anaesthetists and dentists must be told about steroid therapy. 5. Patients should also be informed of potential side-effects and all this information should be documented in the clinical record. 6. Regular supervision including, e.g. DXA scan.

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?

Table 336-9 A Checklist Prior to the Administration of Glucocorticoids in Pharmacologic Doses

Presence of tuberculosis or other chronic infection (chest x-ray, tuberculin test)

Evidence of impaired glucose intolerance, history of gestational diabetes, or strong family history of type 2 diabetes mellitus in first-degree relative

Evidence of preexisting (or high risk for) osteoporosis (bone density assessment in organ transplant recipients 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

Supplementary Measures to Minimize Undesirable Metabolic Effects of Glucocorticoids

Diet

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

Institute all-day steroid schedule, if possible

Patients receiving steroid therapy over a prolonged period (months) should have an appropriate increase in hormone 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.

Steroid cover for operative proceduresprocedure premedication Intra- and post-op Resumption of

normal maintenanceSimple procedures (e.g. gastroscopy, simple dental extractions)

Hydrocortisone 100 mg i.m

Immediately if no complications and eating normally

Minor surgery (e.g. laparoscopic surgeryveins, hernias)

Hydrocortisone 100 mg i.m.

Hydrocortisone 20 mg orally 6-hourly or 50 mg i.m. every 6 hour s for 24 h if not eating

After 24 h if no complications

Major surgery (e.g. hip replacement, vascular surgery)

Hydrocortisone 100 mg i.m.

Hydrocortisone 50-100 mg i.m ever y 6 hours for 72 h

After 7 2 h if normal progressand no complications Perhaps double normal dose for next 2-3 days

Gl tract surgery or major thoracic surgery (not eating or ventilated)

Hydrocortisone 100 mg i.m.

Hydrocortisone 100 mg i.m. eve ry 6 hours for 72 h or longer if still unwell

When patient eating normally again Until then, higher doses (to 50 mg 6-hourly) may be needed

THANKS