Adrenal Steroids and Related Drugs Flashcards
Glucocorticoids - MoA
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
Glucocorticoids - Clinical use
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
Glucocorticoids - Special considerations
Protein and potassium-rich diet during treatment
Give with Vit D and calcium
Glucocorticoids - Contraindications
Psychosis, peptic ulcers, heart disease, hypertension, diabetes, osteoporosis, and certain infections (varicella, tuberculosis) or glaucoma
Glucocorticoids - Adverse effects
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
Symptoms of withdrawal of glucocorticoids
Anorexia, nausea, vomiting, weight loss, lethargy, headache, fever, joint & muscle pain, and postural hypotension.
Low potency steroids
Hydrocortisone
Desonide
Dexamethasone (when administered topically)
Hydrocortisone - MoA
Has a small mineralocorticoid effect.
Cortisone is rapidly metabolized to hydrocortisone by the liver after oral adm.
Hydrocortisone - Clinical use
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.
Hydrocortisone - Special consideration
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)
Hydrocortisone - Adverse effects
Hypertension
Loss of potassium
Sodium retention
Synthetic corticosteroids - MoA
Same as cortisol, except: increased half-life and duration of action, decreased salt-retaining, better penetration of lipid membranes
Synthetic corticosteroids - Clinical use and Special consideration
Primary generalized glucocorticoid resistance (Chrousos) syndrome
Not used in primary adrenal insufficiency
Prednisone, Prednisolone Methylprednisolone and Triamcinolone - Clinical use
Cancer, inflammation, allergy, autoimmune disorders
SLE, Polyarthritis nodosa, MS, Scleroderma, RA.
Prednisone, Prednisolone and Methylprednisolone Special consideration
Salt-retaining activity, used for systemic treatment.
Prednisone rapidly converted to prednisolone.
Triamcinolone - Special considerations
NO salt retaining activity, used for systemic treatment
Dexamethasone - Clinical use
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)
Dexamethasone - Special considerations
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
Antiinflammatory effects of Glucocorticoids
- Suppress the activation of T lymphocytes by interleukins and nuclear factor kB (NF- kB) –> no inflammatory cytokines.
- Suppress production of cytokines by activated helper T cells
- 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.
- Stabilize lysosomal membranes of neutrophils and prevent the release of catabolic enzymes (acid phosphatase) from these organelles, and this limit cytotoxic effects of inflammation.
- Cause vasoconstriction by inhibiting phospholipase A2, leading to decreased prostacyclin.
- They decrease activation of macrophages and decrease the synthesis and release of cytokines from these cells.
Short-Acting Drugs
Hydrocortisone
Cortisone
Fludrocortisone
Intermediate-Acting Drugs
Methylprednisolone
Prednisone
Triamcinolone
Long-Acting Drugs
Dexamethasone
Betamethasone
Budesonide
