Corticosteroids Pharmacology!

Corticosteroids Pharmacology

Corticosteroids are among the most widely prescribed drug classes – used to treat a wide variety of allergic, inflammatory, and autoimmune disorders, as well as a range of malignancies. Here, we review the must-know facts about corticosteroids pharmacology that you need to know.

There are two classes of corticosteroid:

• Glucocorticoids
• Mineralocorticoids

Mineralocorticoids are involved in the regulation of bodily electrolyte and water balance. Fludrocortisone is a synthetic mineralocorticoid that is used in the treatment of Addison’s disease and adrenogenital syndrome. Aldosterone is an example of an endogenous mineralocorticoid that regulates electrolyte and water balance by modulating ion transport in the epithelial cells of the kidney’s renal tubules.

Glucocorticoids – such as cortisol – impact protein, fat, and carbohydrate metabolism. Their wide-ranging effects include anti-inflammatory, anti-proliferative, and immunosuppressant properties. In addition, by inhibiting the mediator, histidine, glucocorticoids also have vasoconstrictive effects. Examples of synthetic glucocorticoids include:

• Prednisone (converted by the liver into prednisolone)
• Prednisolone
• Methylprednisolone
• Hydrocortisone
• Dexamethasone
• Beclomethasone
• Budesonide
• Fluticasone
• Betamethasone
• Triamcinolone
• Clobetasol
• Mometasone
• Loteprednol

There are three broad categories of corticosteroid use:

• Systemic – prednisolone, hydrocortisone, dexamethasone

Allergic and inflammatory disorders; suppression of autoimmune disease; used as part of a wider chemotherapy regimen; hormone replacement in conditions such as adrenal insufficiency.

• Inhaled – beclomethasone, budesonide, fluticasone

In the treatment of asthma and chronic obstructive pulmonary disease (COPD).

• Topical – hydrocortisone, betamethasone, triamcinolone, mometasone

Treating inflammatory skin diseases, such as eczema and other skin flare-ups.

Dexamethasone and betamethasone are also used to promote fetal lung maturation in cases of premature birth. More recently, dexamethasone has proven effective in cases of severe COVID-19 infection.

Loteprednol is used in the treatment of ophthalmic inflammatory conditions.

Mechanism of action

Glucocorticoids work by modulating gene expression.

Glucocorticoids achieve this by binding to receptors in cytosol – known as glucocorticoid receptors (GR). By binding, the receptor passes into the nucleus to bind to glucocorticoid-response elements. This influences gene expression by:

• Upregulation of anti-inflammatory genes
• Downregulation of pro-inflammatory genes

Glucocorticoids also have metabolic effects. For example – they increase gluconeogenesis from circulating fats and amino acids that have come about through the catabolism (or breakdown) of muscle and fat.

For systemic inflammatory disorders, this has an enormous impact. Glucocorticoids also impact circulating monocytes and eosinophils, suppressing their effects.

Inhaled corticosteroids exert their effects on the respiratory tract – reducing mucosal inflammation, widening airways, eliminating mucus secretion, and reducing the number of flare-ups in patients with COPD.

Topical corticosteroids have a more local effect. However, prolonged use of high doses can trigger systemic side effects.

Side effects

Side effects with glucocorticoids vary depending upon which route of administration is required.

For example, systemically administered corticosteroids cause more serious, systemic effects whereas inhaled and topical routes cause less serious, local effects.

Side effects with glucocorticoids include:

• Immunosuppression – increasing risk of infection
• Steroid-induced diabetes – due to increased gluconeogenesis
• Bone effects – steroid-induced osteoporosis
• Muscle weakness – thin skinning and easy bruising
• Mood alterations – depression, psychosis, confusion, insomnia
• Mineralocorticoid effects – hypertension, edema and hypokalemia
• Increased appetite and weight gain
• Increased risk of heart attack and stroke

Oral candidiasis, thrush, and hoarse voice are common effects of inhaled corticosteroids. Inhaled corticosteroids, when taken by children, have been linked to growth retardation – the highest risk of which is with inhaled fluticasone.

Side effects of topical corticosteroids include skin thinning, striae, dermatitis, and worsening acne.

Psychiatric side effects occur in approximately 5 percent of patients taking corticosteroids, particularly prednisolone.

Clinical Pharmacology

When we talk about the clinical pharmacology of corticosteroids, we must consider the following factors:

• When taken with NSAIDs, glucocorticoids increase the risk of gastrointestinal bleeding and peptic ulceration.
• When taken with loop diuretics, thiazide diuretics or beta-2 agonists, glucocorticoids increase the risk of hypokalemia.
• Corticosteroids increase the risk of fracture – with this risk highest in older patients.
• Due to their immunosuppressive effects, corticosteroids increase the risk of infections. Corticosteroids also limit the efficacy of certain vaccines, too.
• Sudden withdrawal from chronic glucocorticoid therapy can induce Addisonian crisis. Patients should be gradually withdrawn from these drugs to help the adrenal gland recover its normal function.
• Co-administration with other drugs – such as proton-pump inhibitors or bisphosphonates – may be warranted to offset the chronic potential side effects of glucocorticoids (stomach irritation / decreased bone density etc.).
• Once-daily glucocorticoid treatment should be taken in the morning. This helps to emulate the body’s natural circadian rhythm and reduces the risk of sleep disturbances.
• Prolonged use of high-dose inhaled corticosteroids – such as fluticasone – should be used with caution in children given the risk of growth retardation.
• Topical corticosteroids should not be applied where an active infection is present. This can increase the risk of the infection worsening and/or spreading.
• Topical corticosteroids should be applied very thinly to the skin and only to the affected area – otherwise skin damage may occur.
• To reduce the risk of oral candidiasis and hoarse voice with inhaled corticosteroids, patients are counseled to gargle their mouth after use.

That concludes our review of corticosteroids pharmacology. Check back to our pharmacy blog soon for more exclusive content to help you master the science of drugs and medicines!