Corticosteroids; Uses, Side Effects, Drug Interactions, Pregnancy

Corticosteroids, Corticosteroids; Uses, Side Effects, Drug Interactions, Pregnancy, Rx Harun








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Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogs of these hormones. Two main classes of corticosteroids, glucocorticoids, and mineralocorticoids are involved in a wide range of physiological processes, including stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior.

Types of Corticosteroids

  1.  According to synthetic names

  • Glucocorticoids such as cortisol affect carbohydrate, fat, and protein metabolism, and have anti-inflammatory, immunosuppressive, antiproliferative, and vasoconstrictive effects. Anti-inflammatory effects are mediated by blocking the action of inflammatory mediators(transrepression) and inducing anti-inflammatory mediators (transactivation). Immunosuppressive effects are mediated by suppressing delayed hypersensitivity reactions by direct action on T-lymphocytes. Anti-proliferative effects are mediated by inhibition of DNA synthesis epidermal cell turnover. Vasoconstrictive effects are mediated by inhibiting the action of inflammatory mediators such as histidine.
  • Mineralocorticoids such as aldosterone are primarily involved in the regulation of electrolyte and water balance by modulating ion transport in the epithelial cells of the renal tubules of the kidney.
  • Systemic corticosteroids refer to corticosteroids that are given orally or by injection and distribute throughout the body. It does not include corticosteroids used in the eyes, ears, or nose, on the skin or that are inhaled, although small amounts of these corticosteroids can be absorbed into the body.

Naturally occurring corticosteroids, hydrocortisone, and cortisone are produced by the outer portion of the adrenal gland known as the cortex (hence the name, corticosteroid). Corticosteroids are classified as either

Function of Corticosteroids

  1. glucocorticoids (anti-inflammatory) which suppress inflammation and immunity and assist in the breakdown of fats, carbohydrates, and proteins, or as
  2. mineralocorticoids (salt-retaining) that regulate the balance of salt and water in the body.

Examples of synthetic corticosteroids include:

  • betamethasone,
  • prednisone
  • prednisolone
  • triamcinolone
  • methylprednisolone
  • dexamethasone

Some glucocorticoids also in addition to their anti-inflammatory actions have salt-retaining properties but they are used mostly for their anti-inflammatory effects. Fludrocortisone, a synthetic mineralocorticoid has strong salt-retaining effects with significant anti-inflammatory actions and is used mostly for its salt-retaining capabilities.

What are some examples of systemic (oral and injectable) corticosteroids

The following is a list of the systemic (oral and injectable) corticosteroids that are available in the United States:

Glucocorticoids

  • hydrocortisone
  • cortisone
  • ethamethasoneb
  • prednisone
  • prednisolone
  • triamcinolone Methylprednisolone
  • dexamethasone

Mineralocorticoid

  • Fludrocortisone

2.  According to the chemical source structure

By chemical structure – In general, corticosteroids are grouped into four classes, based on chemical structure. Allergic reactions to one member of a class typically indicate an intolerance of all members of the class. This is known as the “Coopman classification”.The highlighted steroids are often used in the screening of allergies to topical steroids.

  • Group A – Hydrocortisone peHydrocortisone, methylprednisolone, prednisolone, prednisone, and triamcinolone (short- to medium-acting glucocorticoids).
  • Group B – Acetonides  – (and related substances)Amcinonide, budesonide, desonide, fluocinolone acetonide, fluocinonide, halcinonide, and triamcinolone acetonide.
  • Group C – Betamethasone type Beclometasone, betamethasone, dexamethasone, fluocortolone, halometasone, and mometasone.
  • Group D1 – Halogenated (less labile) Alclometasone dipropionate, betamethasone dipropionate, betamethasone valerate, clobetasol propionate, clobetasone butyrate, fluprednidene acetate, and mometasone furoate.
  • Group D2 – Labile prodrug esters – Ciclesonide, cortisone acetate, hydrocortisone aceponate, hydrocortisone acetate, hydrocortisone buteprate, hydrocortisone butyrate, hydrocortisone valerate, prednicarbate, and tixocortol pivalate.
  • By route of administration
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Topical steroids

Further classification of topical steroids

USA system

The USA system utilizes 7 classes, which are classified by their ability to constrict capillaries and cause skin blanching. Class I is the strongest, or superpotent. Class VII is the weakest and mildest.

Class IVery potent: up to 600 times stronger than hydrocortisone

  • Clobetasol propionate 0.05%
  • Betamethasone dipropionate 0.25%
  • Halobetasol propionate 0.05%
  • Diflorasone diacetate 0.05%

Class II

  • Fluocinonide 0.05%
  • Halcinonide 0.05%
  • Amcinonide 0.05%
  • Desoximetasone 0.25%

Class III

  • Triamcinolone acetonide 0.5%
  • Mometasone furoate 0.1%
  • Fluticasone propionate 0.005%
  • Betamethasone dipropionate 0.05%
  • Halometasone 0.05%

Class IV

  • Fluocinolone acetonide 0.01-0.2%
  • Hydrocortisone valerate 0.2%
  • Hydrocortisone butyrate 0.1%
  • Flurandrenolide 0.05%
  • Triamcinolone acetonide 0.1%
  • Mometasone furoate 0.1%

Class V

  • Fluticasone propionate 0.05%
  • Desonide 0.05%
  • Fluocinolone acetonide 0.025%
  • Hydrocortisone valerate 0.2%

Class VI

  • Alclometasone dipropionate 0.05%
  • Triamcinolone acetonide 0.025%
  • Fluocinolone acetonide 0.01%
  • Desonide 0.05%

Class VII

The weakest class of topical steroids. Has poor lipid permeability, and cannot penetrate mucous membranes well.

  • Hydrocortisone 2.5% (Hytone cream, lotion, ointment)
  • Hydrocortisone 1% (Many over-the-counter brands)

Class IV

Very potent (up to 600 times as potent as hydrocortisone)

  • Clobetasol propionate
  • Betamethasone dipropionate

Class III

Potent (50-100 times as potent as hydrocortisone)

  • Betamethasone valerate
  • Betamethasone dipropionate
  • Diflucortolone valerate
  • Hydrocortisone 17-butyrate
  • Mometasone furoate
  • Methylprednisolone aceponate
  • Halometasone 0.05%

Class II

Moderate (2-25 times as potent as hydrocortisone)

  • Clobetasone butyrate
  • Triamcinolone acetonide

Class I

Mild

  • Hydrocortisone 0.5-2.5%
Allergy associations

The highlighted steroids are often used in the screening of allergies to topical steroid and systemic steroids. When one is allergic to one group, one is allergic to all steroids in that group.

Group A

  • Hydrocortisone,
  • Hydrocortisone acetate,
  • Cortisone acetate,
  • Tixocortol pivalate,
  • Prednisolone,
  • Methylprednisolone, and
  • Prednisone

Group B

  • Triamcinolone acetonide,
  • Triamcinolone alcohol,
  • Amcinonide,
  • Budesonide,
  • Desonide,
  • Fluocinonide,
  • Fluocinolone acetonide, and
  • Halcinonide

Group C

  • Betamethasone,
  • Betamethasone sodium phosphate,
  • Dexamethasone,
  • Dexamethasone sodium phosphate, and
  • Fluocortolone

Group D

  • Mometasone furoate Hydrocortisone-17-butyrate,
  • Hydrocortisone-17-valerate,
  • Alclometasone dipropionate,
  • Betamethasone valerate,
  • Betamethasone dipropionate,
  • Prednicarbate, clobetasone-17-butyrate,
  • Clobetasol-17 propionate,
  • Fluocortolone caproate,
  • Fluocortolone pivalate,
  • Fluprednidene acetate, and
  • Mometasone furoate
  • For use topically on the skin, eye, and mucous membranes.Topical corticosteroids are divided in potency classes I to IV in most countries (A to D in Japan). Seven categories are used in the United States to determine the level of potency of any given topical corticosteroid.

Inhaled steroids

For nasal mucosa, sinuses, bronchii, and lungs. This group includes:

  • Flunisolide
  • Fluticasone furoate
  • Fluticasone propionate
  • Triamcinolone acetonide
  • Beclomethasone dipropionate
  • Budesonide

Oral forms

  • Such as – prednisone, prednisolone, methylprednisolone, or dexamethasone.

Systemic forms

Available in injectables for intravenous and parenteral routes.

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Medical uses

Medical conditions treated with systemic corticosteroids

  • Allergy and respirology medicine
    • Asthma (severe exacerbations)
    • Chronic obstructive pulmonary disease (COPD)
    • Allergic rhinitis
    • Atopic dermatitis
    • Hives
    • Angioedema
    • Anaphylaxis
    • Food allergies
    • Drug allergies
    • Nasal polyps
    • Hypersensitivity pneumonitis
    • Sarcoidosis
    • Eosinophilic pneumonia
    • Some other types of pneumonia (in addition to the traditional antibiotic treatment protocols)
    • Interstitial lung disease
  • Dermatology
    • Pemphigus Vulgaris
    • Contact dermatitis
  • Endocrinology (usually at physiologic doses)
    • Addison’s Disease
    • Adrenal insufficiency
    • Congenital adrenal hyperplasia
  • Gastroenterology
    • Ulcerative colitis
    • Crohn’s disease
    • Autoimmune hepatitis
  • Hematology
    • Lymphoma
    • Leukemia
    • Hemolytic anemia
    • Idiopathic thrombocytopenic purpura
    • Multiple Myeloma
  • Rheumatology/Immunology
    • Rheumatoid arthritiseas
    • Systemic lupus erythematosus
    • Polymyalgia rheumatica
    • Polymyositis
    • Dermatomyositis
    • Polyarteritis
    • Vasculitis
  • Ophthalmology
    • Uveitis
    • Keratoconjunctivitis
  • Other conditions
    • Multiple sclerosis
    • Organ transplantation
    • Nephrotic syndrome
    • Chronic hepatitis (flare-ups)
    • Cerebral edema
    • IgG4-related disease
    • Prostate cancer
    • Tendinosis
    • Lichen planus

Topical formulations are also available for the skin, eyes (uveitis), lungs (asthma), nose (rhinitis), and bowels. Corticosteroids are also used supportively to prevent nausea, often in combination with 5-HT3 antagonists.

Side Effects of Corticosteroids

The most common

Common 

Side effects of corticosteroids may include

Rare

Drug Interactions of Corticosteroids

  • Certain drugs such as troleandomycin erythromycin and clarithromycin and ketoconazole can reduce the ability of the liver to metabolize (breakdown) corticosteroids and this may lead to an increase in the levels and side effects of corticosteroids in the body.
  • On the other hand, phenobarbital, ephedrine, phenytoin, and rifampin may reduce the blood levels of corticosteroids by increasing the breakdown of corticosteroids by the liver. This may necessitate an increase of corticosteroid dose when they are used in combination with these drugs.
  • Estrogens have been shown to increase the effects of corticosteroids possibly by decreasing their breakdown by the liver.
  • Corticosteroid effects on warfarin can vary; therefore when taking warfarin along with corticosteroids, there may be the increased need for monitoring coagulation levels more closely.
  • Low blood potassium (hypokalemia) and a higher chance of heart failure can result from combining corticosteroids with drugs that reduce potassium in the blood (for example, diuretics, amphotericin B).
  • Anticholinesterase drugs (for example, physostigmine) may cause severe weakness in some patients with myasthenia gravis when prescribed with corticosteroids.
  • Corticosteroids can increase blood glucose, so close monitoring of blood sugar and higher doses of diabetes medications may be needed.
  • Cholestyramine (Questran, Questran Light) can decrease the absorption of oral corticosteroids from the stomach and this could reduce the blood levels of corticosteroids.
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Pregnancy Catagory of Corticosteroids

FDA Pregnancy Risk Category: C

The U.S. Food & Drug Administration has classified all medications into categories based on their safety for the mother and baby. Medicine is rated A, B, C, D and X, where A is the safest and X is not safe. All medicines approved since 1980 are classified in one of these categories, and here are the categories relating to asthma medicines.

  • Category A
    These are the medicines for which adequate, well-controlled studies in pregnant women have not shown an increased risk of fetal abnormalities. No medicines used to treat asthma fall into this category.
  • Category B
    Category B indicates animal studies have revealed no evidence of harm to the fetus, however, there are no adequate and well-controlled studies in pregnant women. Some asthma medications fall in this category, and category B asthma drugs are generally considered safe for both mother and child.
  • Category C
    Category C is one in which animal studies have shown an adverse effect and there are no adequate and well-controlled studies in pregnant women; or, no animal studies have been conducted and there are not adequate and well-controlled studies in pregnant women. Most of the medicine used to treat asthma fall into this category, and are generally considered safe for both mother and child.

References

 

Corticosteroids, Corticosteroids; Uses, Side Effects, Drug Interactions, Pregnancy, Rx Harun

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