IN THE NAME OF GOD

 Side effects from glucocorticoids are mostly seen with oral and injectable glucocorticoids, but can be seen with inhaled and topical steroids at higher doses.  glucocorticoid toxicity is related to both the average dose and cumulative duration of use.

Toxicity of Glucocorticoids

 Mild hirsutism  Bruising  Facial erythema  Increased sweating  Thin, fragile skin  Impaired wound healing  Striae  Acne

 moon face  buffalo hump  central obesity  Truncal and peripheral adipocytes vary in sensitivity to the glucocorticoid facilitated lipolytic effect—that is, the peripheral adipocytes are more sensitive to this effect than the central adipocytes.

 Cataract  Glaucoma  Exophthalmos  Swelling of lids and ocular muscle

 Ischemic heart disease  Heart failure  Atherosclerosis  Hypertension

 The pathogenesis is multifactorial,involving increased peripheral vascular sensitivity to adrenergic agonists, increased hepatic production of angiotensinogen (renin substrate), and activation of renal mineralocorticoid receptors.

 Glucocorticoids increase hepatic glucose production (in part by increasing substrate availability through proteolysis and lipolysis); they also induce insulin resistance and hyperinsulinemia and inhibit glucose transport into the cells.  New-onset diabetes occurs in patients with underlying impaired glucose tolerance or subclinical diabetes.

 Serum lipids, both triglycerides and cholesterol, may be increased during corticosteroid therapy.

 Peptic ulcer disease  Candidiasis  Pancreatitis  Fatty liver  Viseral perforation

 There was no increased incidence of PUD in those taking corticosteroids alone but there was an increased risk in those taking non- steroidal anti-inflammatory drugs.  when a patient is prescribed corticosteroid treatment who has risk factors for PUD such as a past history of PUD; smoking; high alcohol intake; or receiving ulcerogenic drugs(NSAIDS ) should be given a prophylactic agent for GI bleeding.

 Polycythemia is a feature of Cushing’s syndrome but does not appear to be a feature of corticosteroid therapy.

 The total white blood count is increased in patients on corticosteroids. The various classes of white blood cells are affected in the following ways:  Polymorphonuclear leucocytes increased  Lymphocytes decreased; T cells are reduced to a greater extent than B cells although immunoglobulin synthesis is also decreased  Monocytes decreased  Eosinophils decreased

 Steroids act in multiple ways to inhibit the immune system and so their use is associated with an increased susceptibility to infection.

 Corticosteroid use is associated with sodium and water retention; this can be reduced by recommending a low salt diet.

 The greatest rate of bone loss occurs in the first 6 months and is thought to continue at a lower rate for as long as steroids are used.  Bone loss is greatest in trabecular (cancellous) bone, which is more metabolically active but also occurs in cortical bone.

 Reduced osteoblast activity resulting in reduced bone formation  Increased bone resorption due to increased osteoclast activity  Reduced intestinal absorption of calcium and phosphate  Reduced renal reabsorption of calcium  Secondary hyperparathyroidism  Reduced sex hormones

 A substantial increase in fracture risk can occur within 3-6 months of steroid treatment. If steroids are discontinued, bone improves substantially after 6-24 months. It seems that bone loss is related to the dose of glucocorticoids.

 During corticosteroid use there is a reduction in muscle protein synthesis and protein catabolism; therefore, muscle weakness and loss of bulk can occur. In its extreme form a steroid myopathy may develop, affecting the proximal muscles in upper and lower extremities.

 Osteonecrosis (avascular necrosis) is a serious complication of corticosteroid.The risk increases with both dose and duration of treatment but it is not possible to predict who will be affected.  The femoral head is most frequently involved but other large joints may be affected. Joint pain and stiffness are the earliest symptoms.

 Mood swings  Euphoria  Depression  Delirium  Memory impairment  Suicide attempts  Sleep disturbance, insomnia and unpleasant dreams

 Psychosis has been reported and usually develops within 2 weeks of starting treatment, particularly with doses of >40 mg/day prednisolone. Symptoms respond to tapering of the corticosteroids, usually within 3 weeks.

 Exogenous glucocorticoids can lead to HPA suppression and secondary adrenal insufficiency (isolated glucocorticoid deficiency with normal aldosterone secretion). The abrupt cessation, or too rapid withdrawal, may cause symptoms of AI.

 Any patient with Cushingoid appearance  Any one who has received more than 20 mg prednisone daily (or equivalent) for more than 3 weeks  Any one who has received an evening dose of prednisone (even physiologic) for more than 3 weeks

 No need for testing, and these patients should be treated like any patient with secondary AI by giving stress dose of glucocorticoids perioperatively.

 Any patient who has received any dose of glucocorticoids for less than 3 weeks  Any patient on less than 5 mg prednisone, provided that it is not taken in the evening  Alternate glucocorticoid therapy

 We try to limit the adverse effects of glucocorticoids by the following steps:  Use of the lowest dose of glucocorticoids for the shortest period of time needed to achieve the treatment goals  Treatment of those pre-existing comorbid conditions that may increase risk when glucocorticoids are required  Monitoring of patients under treatment for adverse effects that may benefit from additional intervention

 Pre-existing conditions or risk factors for adverse effects that should be assessed or treated when glucocorticoids are to be instituted include :  Diabetes mellitus  Hyperlipidemia  Hypertension  Heart failure

 Glaucoma and Cataract  Low bone density or Osteoporosis  Peptic ulcer disease  Use of non-steroidal anti-inflammatory drugs  Presence of infection

 During treatment with glucocorticoids and depending upon individual risk factors such as dose and duration of glucocorticoids usage,other medications being used,and comorbidities,particular attention should be given to  Body weight  Blood pressure  Heart failure and peripheral edema  Serum lipid  Diabetes or glucose intolerance  Glaucoma  Fracture risk

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