Corticosteroids
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Introduction
Corticosteroids are exogenous glucocorticoids important in immunosuppresion in a variety of illnesses. There
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.
- 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
Indications
- lungs
- immune system
- skin
- transplants
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).
Common Medications
- overview
- prednisone
- topical steroids
- Tab 2
Overview
Short- and medium-acting glucocorticoids
- 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
- prednisolone
- methylprednisolone
Intermediate-acting
- traimcinolone
- fluprednisolone
Long-acting
- betamethasone
- dexamethasone: 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
Prednisone
- very similar to cortisone
- given as prednosone; metabolized in the liver into prednisolone
- prednisolone travels in blood bound to cortisone-bindign proteins
- crosses plasma membrane alone
- binds to receptors, activates transcription after binding to HREs
- increases serum glucose, increasing insulin and lipogenesis
- inhibits glucose uptake in muscle while stimulating hormone sensitive lipase, causing lipolysis
- increased neutrophils, decreased B and T cells, monocytes, eosinophils and basophils
- decreased IL-12 and IFN-gamma
- complement
- antibody production decreased by large doses but not by moderate
- affects NCS - insomnia, euphoria
- affects pituitary, suppresses ACTH
- get peptic ulcers
- decreases vitamin D
- inhibits wound healing
topical steroids
potency ranking: group I: highest potency
ointments are usually strnger than a cream
Adverse Effects
The side effects of corticosteroids are numerous and can be serious. 50 mg for more than 7 days is bad for some reason.
short term
- hyperglycemia
- insomnia
- depression, euphoria, mood swings, or psychosis
long term
- infection (especially fungal and viral) and poor wound healing
- increased risk of peptic ulcers when used with NSAIDs
- hypertension
- skin thinning and striae
- Cushing's-like syndrome
- adrenal insufficiency
- huge appetite; weight gain (especially centrally)
- osteoporosis and osteonecrosis, especially of the femoral head
- sodium retention
- neutrophilia
- glaucoma (cataracts)
- diabetes type II
- increased risk of infection
- gingival hyperplasia
- altered hair growth
- growth suppression in children
neonates
- cerebral palsy
- immunosuppression, leading to frequent RSV infection
- Cushning's - diabetes, hypertension, weight loss
- adrenal suppression (Addison's)
- GI perforation
Contraindications
fungal/other infections
- -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.
Guidance on Use
- glucocorticoids are absorbed rapidly when given orally
- prednisolone has a half-life of about one hour
- alternate day dosing decreases side effects and keeps ACTH production going
Dependency
- very difficult to stop; must be decreased gradually
- stopping too quickly can cause some serious side effects as natural cortisol is shut down and must be revamped
Resources and References
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