Adrenal Steroids and Related Drugs

Question 1

Glucocorticoids - MoA

Answer 1

Activation of glucocorticoid receptors alters gene expression: increases blood glucose, muscle protein catabolism, and insulin secretion.
Lipolysis + lipogenesis.
Wasting of connective & lymphoid tissue, fat & skin.
Cell-mediated immunologic functions are inhibited. Increased Neutrophils, Decreased lymphocytes, decreased eosinophils, decreased basophils, decreased monocytes. Inh migration of leukocytes.
High dose: increased gastric acid

Question 2

Glucocorticoids - Clinical use

Answer 2

Adrenal insufficiency: Chronic (Addison disease), acute (shock, infection, trauma), congenital adrenal hyperplasia (CAH).
Primary: decreased cortisol and aldosterone
Secondary: decreased cortisol and androgens, but normal aldosterone.

Inflammation and autoimmune disorders: asthma, organ transplant rejection, Connective tissue diseases (SLE, Polymyositis, Polyarteritis nodosa), Thrombocytopenia purpura, rheumatic disorders, hematologic cancers, neurologic disorders, chemotherapy vomiting, hypercalcemia, mountain sickness, dermatologic (atopic/contact dermatitis, seborrheic dermatitis, and pruritis), ocular disorders. Ulcerative colitis.
Sarcoidosis (DOC).

Lymphomas and lymphocytic leukemias

Question 3

Glucocorticoids - Special considerations

Answer 3

Protein and potassium-rich diet during treatment

Give with Vit D and calcium

Question 4

Glucocorticoids - Contraindications

Answer 4

Psychosis, peptic ulcers, heart disease, hypertension, diabetes, osteoporosis, and certain infections (varicella, tuberculosis) or glaucoma

Question 5

Glucocorticoids - Adverse effects

Answer 5

Cushing syndrome: Redistribution of fat (Moon face, buffalo hump), hirsutism, weight gain, muscle wasting and weakness, acne, bruising, thinning of the skin, hyperglycemia, glucose intolerance, hypertension, osteoporosis, euphoria or psychosis, peptic ulcers, reduced secretion of TSH and FSH.

Cortisone and hydrocortisone: Sodium retention, potassium loss, and hypertension.

Long-term: Posterior subscapular cataracts and glaucoma, and masking of symptoms of mycotic and other infections. Growth retardation in children.

Hypokalemia, increased bone catabolism , antagonize effect of vit D, and decreased calcium absorption

Question 6

Symptoms of withdrawal of glucocorticoids

Answer 6

Anorexia, nausea, vomiting, weight loss, lethargy, headache, fever, joint & muscle pain, and postural hypotension.

Question 7

Low potency steroids

Answer 7

Hydrocortisone
Desonide
Dexamethasone (when administered topically)

Question 8

Hydrocortisone - MoA

Answer 8

Has a small mineralocorticoid effect.

Cortisone is rapidly metabolized to hydrocortisone by the liver after oral adm.

Question 9

Hydrocortisone - Clinical use

Answer 9

Preferred drug for chronic & acute adrenal insufficiency (if hyperkalemia persists add mineralocorticoid such as fludrocortisone),
CAH in combination with fludrocortisone (suppress corticotropin secretion).
Cushing syndrome: Large doses during and after surgery with slow reduction of dose and
Ulcerative colitis.

Question 10

Hydrocortisone - Special consideration

Answer 10

Salt-retaining activity.
Acute adrenal insufficiency (addisonian/adrenal crisis): intravenous adm
Chronic adrenal insufficiency oral adm (2/3 in morning, 1/3 in evening, may need combo with fludrocortisone)

Question 11

Hydrocortisone - Adverse effects

Answer 11

Hypertension
Loss of potassium
Sodium retention

Question 12

Synthetic corticosteroids - MoA

Answer 12

Same as cortisol, except: increased half-life and duration of action, decreased salt-retaining, better penetration of lipid membranes

Question 13

Synthetic corticosteroids - Clinical use and Special consideration

Answer 13

Primary generalized glucocorticoid resistance (Chrousos) syndrome

Not used in primary adrenal insufficiency

Question 14

Prednisone, Prednisolone Methylprednisolone and Triamcinolone - Clinical use

Answer 14

Cancer, inflammation, allergy, autoimmune disorders

SLE, Polyarthritis nodosa, MS, Scleroderma, RA.

Question 15

Prednisone, Prednisolone and Methylprednisolone Special consideration

Answer 15

Salt-retaining activity, used for systemic treatment.

Prednisone rapidly converted to prednisolone.

Question 16

Triamcinolone - Special considerations

Answer 16

NO salt retaining activity, used for systemic treatment

Question 17

Dexamethasone - Clinical use

Answer 17

Diagnostic: Dexamethasone suppression test (Cushing syndrome)Single low dose of dexamethasone is given orally 11pm, and cortisol levels in plasma are measured at 8am the following morning. In healthy individuals cortisol levels will be less than 5mcg/dL, while in cushing syndrome it will be more than 10mcg/dL. High doses can be used to differentiate adrenal hyperplasia from other causes of hyperandrogenism.
Prevention of emesis during chemotherapy,
Infectious & inflammatory disorders (if long & potent treatment needed)

Question 18

Dexamethasone - Special considerations

Answer 18

High anti-inflammatory effect,
no salt retaining activity.

Low Dose suppression test: cortisol measured before & after one dose –> Cushing will have no suppression.
High Dose suppression test: adrenal hyperplasia vs other causes

Question 19

Antiinflammatory effects of Glucocorticoids

Answer 19

1. Suppress the activation of T lymphocytes by interleukins and nuclear factor kB (NF- kB) –> no inflammatory cytokines.
2. Suppress production of cytokines by activated helper T cells
3. Decrease the release of histamine, prostaglandins and leukotrienes (by increasing transcription of annexin-1 previously named lipocortin-1, which inhibits phospholipase A2), and other substances from mast cells, eosinophils, and inflamed tissue.
4. Stabilize lysosomal membranes of neutrophils and prevent the release of catabolic enzymes (acid phosphatase) from these organelles, and this limit cytotoxic effects of inflammation.
5. Cause vasoconstriction by inhibiting phospholipase A2, leading to decreased prostacyclin.
6. They decrease activation of macrophages and decrease the synthesis and release of cytokines from these cells.

Question 20

Short-Acting Drugs

Answer 20

Hydrocortisone
Cortisone
Fludrocortisone

Question 21

Intermediate-Acting Drugs

Answer 21

Methylprednisolone
Prednisone
Triamcinolone

Question 22

Long-Acting Drugs

Answer 22

Dexamethasone
Betamethasone
Budesonide