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.

8. • 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.

9. Examples of systemic steroids
• Short-Acting
– Cortisol (hydrocortisone)
– Cortisone
– Prednisone
– Prednisolone
– Methylprednisolone
• Intermediate-Acting
– triamcinolone
• Long-Acting
– Betamethasone
– Dexamethasone

10. Systemic steroid hormone replacement therapy
Trophic 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.)

11. 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,

12. 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

13. INDICATION OF SYSTEMIC STEROIDS IN
DENTAL SURGERY
• Lichen planus
• Aphthous ulcers
• Benign mucous membrane pemphigoid
• Pemphigus vulgaris

14. 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

15. 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.

16. 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?

17. 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

18. 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

19. 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.

20. procedure premedication Intra- and post-op Resumption of
Steroid cover for 100
Simple procedures Hydrocortisone
operative procedures
Immediately if no
normal maintenance
(e.g. gastroscopy, mg i.m complications
simple dental and eating normally
extractions)
Minor surgery Hydrocortisone 100 Hydrocortisone 20 After 24 h if no
(e.g. laparoscopic mg i.m. mg orally 6-hourly complications
surgery or 50 mg i.m.
veins, hernias) every
6 hour s for 24 h if
not eating
Major surgery Hydrocortisone 100 Hydrocortisone After 7 2 h if normal
(e.g. hip mg i.m. 50-100 mg i.m progress
replacement, ever y 6 hours for and no complications
vascular surgery) 72 h Perhaps double
normal dose for
next 2-3 days
Gl tract surgery or Hydrocortisone 100 Hydrocortisone When patient eating
major thoracic mg i.m. 100 mg i.m. normally
surgery eve ry 6 hours for again Until then,
(not eating or 72 h or higher doses
ventilated) longer if still (to 50 mg 6-hourly)

21. THANKS