IN THE NAME OF GOD

Systemic Effects of Oral Glucocorticoids

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

Skin and soft tissue

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.

Cushingoid appearance and weight gain

Cataract Glaucoma Exophthalmos Swelling of lids and ocular muscle

Eye

Ischemic heart disease Heart failure Atherosclerosis Hypertension

Cardiovascular disease

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.

Hypertension

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.

Hyperglycemia

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

Hyperlipidemia

Peptic ulcer disease Candidiasis Pancreatitis Fatty liver Viseral perforation

Gastrointestinal disease

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 .

Gastrointestinal disease

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

Hematologic

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

Hematologic

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

Immune response

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

Fluid and electrolyte balance

Musculoskeletal

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.

Osteoporosis

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

Mechanism of steroid induced bone loss

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 .

MYOPATHY

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.

OSTEONECROSIS

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

unpleasant dreams

Behavioural changes

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.

Behavioural changes

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.

Adrenal Insufficiency

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

Patients at high risk for HPA suppression include:

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

Patients who are unlikely to have HPA suppression include:

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

Guideline

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

Guideline

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

drugs Presence of infection

continue

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

Guideline

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