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Corticosteroids

Corticosteroids are exogenous glucocorticoids important in immunosuppresion in a variety of illnesses.

can possess both glucocorticoid and mineralcorticoid activity, though a reduction on MC activity is desirable.

These drugs are synthesized from cholic acid isolated from cattle or plants.

uses
mechanisms
preparations
delivery routes
adverse drug reactions
metabolism and excretion
dependency

Uses

Lungs

Corticosteroids

increase surfactant and stabilize cell membranes
decrease prostaglandin and leukotrienes
increases pulmonary microvasculature
increases vitamin A

Immune System

Corticosteroids have profound effects on inflammation, reducing the concentration, distribution, and function of leukocytes and suppressing inflammatory cytokines and chemokines.

Following a dose of short-acting steroid, the number of circulating neutrophils increases, due to bone marrow mobilization and decreased extravasation, while the number of circulating lymphocytes, monocytes, eosinophils, and basophils decreases as they return to lymphoid tissue.

Macrophages and other APCs reduce their function

Skin

Topical steroids cause vasoconstriction, possibly by attenuating mast cell degranulation. Capillary permeability is also decreased through the reduction of histamine release.

Transplants

Corticosteroids help control transplant rejection by reducing antigen expression in grafted tissue, delaying revascularization, and interfering with T cell sensitization and B cell activation.

Mechanism

Like endogenous glucocorticoids, corticosteroids' effects are mediated by nuclear receptors, inhibiting the function of transcription factors such as AP1 or NF-kB. These TFs have broad action on regulation of growth factors and proinflammatory cytokines.

Corticosteroids influence most cells of the body. Major metabolic impacts are due to direct action of these drugs on the cell, but other important effects are mediated by insulin and glucagon.

Mediate many anti-inflammatory and immunosuppressive effects by inhibiting IL1beta, ppase A2, COX-2

Glucocorticoids must be activated by 11beta HSD1 (hydroxysteroid dehydrogenase).

Preparations

Hydrocortisone is a short acting molecule (8-12h) with both GC and MC activity
Prednisone is intermediate acting (12-36h) with stronger GC and weaker MC activity
Dexamethasone is long acting (24-72h) with very strong GC and no MC activity

stability is affected by C1,2 double bond, C9 F, and C16 hydroxylation or methylation

Delivery Routes

Oral: rapidly absorbed and distributed to tissues,
Topical: increased absorption on damaged skin; distributed throughout area of application; metabolized in skin
Inhalant: systemic absorption of 30-50% through the oral and esophageal mucosa
Injection: onset and duration from 2days-3 weeks
Opthalmic: minimal systemic distribution

Adverse Drug Reactions

The side effects of corticosteroids are numerous and serious.

They include:

infection (especially fungal and viral) and poor wound healing
increased risk of peptic ulcers when used with NSAIDs
osteoporosis and osteonecrosis, especially of the femoral head
hypertension
obesity, especially central weight gain
depression, euphoria, mood swings, or psychosis
skin thinning and striae
adrenal insufficiency
Cushing's like syndromes

50 mg for more than 7 days is bad for some reason.

neonates

cerebral palsy
immunosuppression, leading to frequent RSV infection
Cushning's - diabetes, hypertension, weight loss
adrenal suppression (Addison's)
GI perforation

Contraindications and Drug Interactions

-induced potassium loss can cause digoxin toxicity
can increase or decrease anticoagulant action

CBG levels are increased by estrogen, hyperthyroidism, diabetes

CBG levels are decreased by genetics, hypothyroidism, and protein deficiency states

Corticosteroid metabolism increased by barbiturates, phenytoin, mitotane, aminoglutethmide, rifampin.

Metabolism and Excretion

Dependency

Rapid reduction in corticosteroid