Corticosteroids: Uses, Side Effects, and Treatment

• Corticosteroids are a rapid-acting class of drugs that can reduce inflammation and decrease the overactive immune system responses. They can be:
  • Glucocorticosteroids: The main corticosteroid here is cortisol, also known as the stress hormone, which is required to maintain stress.
  • Mineralocorticoids:  Aldosterone is the main mineralocorticoid, which causes sodium and water retention, which is required to maintain blood pressure.
• The cortex of the Adrenal gland releases Mineralocorticoids, Glucocorticoids, and Sex steroids.
• The medulla of the Adrenal gland releases Adrenaline and Noradrenaline.

Mineralocorticoids

• Aldosterone:
  • Causes Na+ and water retention
  • Increases BP
  • Causes edema
  • Decreases K+
  • Produces ventricular remodeling and increases mortality in chronic CHF patients.
• Hence, the activity of aldosterone is suppressed in chronic CHF patients. 
• Most of the endogenous substances are short-acting and cannot be used; hence, preparations are used.

Preparations of Mineralocorticoid

• Aldosterone cannot be used in therapy because it is very short-acting.
• Fludrocortisone uses:
  • Used in the treatment of Addison’s disease (Hydrocortisone + Fludrocortisone).
  • To manage Hypotension.

Glucocorticoids

Actions In CNS

• Increases mood changes and behavioral changes (Contraindicated in Psychosis)
• Decreases seizure threshold (Contraindicated in Epilepsy).
• Reduces cerebral edema (Dexamethasone is the drug of choice)

Actions In CVS

• It causes Na+ and water retention, leading to a rise in BP and edema.
• These are contraindicated in Hypertension and CHF patients
• They have permissive action on Adrenaline and Angiotensin 2.
• Steroids are added to increase the permissive action on Adrenaline and Angiotensin 2, which in turn increases the effect.

Actions In Respiratory System

• They are known to decrease inflammation and Production of Prostaglandins, Histamines, and Leukotriene.
• It is used in the management of Bronchial asthma.
• They are known to increase beta 2 responsiveness, causing bronchodilation, and are used in Status asthmaticus (I.V. Hydrocortisone is preferred here).
• It is known to increase pulmonary surfactant and is used in preterm delivery cases.

Actions On Immunity (bone Marrow)

• Steroids suppress T cells more than B cells.
• Cell-mediated immunity is suppressed more than Humoral immunity.
• Steroids are Immunosuppressant drugs.
• Immunosuppressants are used in organ transplant patients and in autoimmune diseases such as rheumatoid arthritis, where a person's immune system attacks their body's own cells.
• The adverse effects of immunosuppressants include opportunistic infections.
• Used in the treatment of leukemia and lymphoma because the increased T cells and B cells can be suppressed. 
• These are contraindicated in Kaposi’s sarcoma.
• Kaposi's sarcoma is a cancer of HIV patients as the steroids can worsen the immunosuppression.
• They increase neutrophils.
• Steroids increase RBC and hence are used in the treatment of Autoimmune Hemolytic Anemia.
• They also increase thrombocytes.
• Steroids decrease monocytes, Eosinophils, and Basophils and hence are used in the treatment of allergic conditions like Loeffler’s syndrome and Bronchial Asthma as in asthma patients, the eosinophilic activity is high.

Anti-inflammatory Action Of Steroids

• They decrease IL- Interleukin 1,2,6
• They also decrease ICAM: Intracellular Adhesion Molecule 
• They decrease ELAM: Endothelial leukocyte adhesion molecule
• Annexin 1 is produced by steroids, which inhibits the enzyme phospholipase A2 (PLA2).
• Membrane phospholipids (MP) are converted into arachidonic acid (AA) with the help of phospholipase 2.
• Arachidonic acid is acted upon by two enzymes, COX (cyclo-oxygenase) and LOX (lipoxygenase).
• Prostaglandins (PGs) and leukotrienes (LTs) are inflammatory mediators.
• Steroids also inhibit the chemotaxis of neutrophils.
• Uses:
  • Rheumatoid arthritis
  • Gout
  • Steroids suppressed the inflammatory process in Covid-19 (Cytokinin storm). Steroids are the only drugs that reduced mortality in Covid-19.
• Adverse effect is poor wound healing is seen as healing is an inflammatory process.

Actions On Skeletal Muscles

• Steroids increase the protein breakdown in the muscles causing myopathy

Actions On Bone

• They decrease calcium absorption and increase calcium elimination leading to Osteoporosis
• Drug of choice for steroid induced Osteoporosis is Bisphosphonates

Effects Of Steroids On Metabolism

Preparations Of Glucocorticoids

• Prednisone is a prodrug that gets converted to prednisolone.
• If 20 mg of hydrocortisone is used, the equivalent dose of prednisolone will be 5 mg.
• The lower the dose, the more potent the drug.
• So, here, the most potent is dexamethasone (0.8 mg).
• In cases of cerebral edema, dexamethasone is used. In case of hydrocortisone, which has a mineralocorticoid activity of 1, causes sodium and water retention, worsening the edema.
• In Addison's disease or crises, hydrocortisone is used as it has both glucocorticoid and mineralocorticoid activity of 1:1.

Adverse Effects

• Glaucoma is caused by topical use (eye drops), while cataract is a side effect of systemic use.
• In pregnant women, prednisolone is used because it cannot cross the placenta.
• Peptic ulcers can occur in the GIT due to decreased PGs production.

Hypothalamus-Pituitary-Adrenal Axis 

• Hypothalamus-Pituitary-Adrenal (HPA) Axis.
• The hypothalamus releases the cortisol-releasing hormone, which acts on the pituitary, and the pituitary releases ACTH. ACTH acts on the adrenal gland, and the adrenal gland releases corticosteroids.
• The excess of steroids (long term) can control and inhibit the HPA axis. So, when the steroids are stopped, the axis is not activated and corticosteroids are not released, and the patient can experience stress, low BP, and cardiovascular abnormalities, and may go into a coma.
• Therefore, to avoid such incidents, the HPA axis must be activated.
• HPA axis suppression occurs when 20-25 mg of hydrocortisone or its equivalent is given for 2–3 weeks.

How To Avoid Hpa Axis Suppression?

• The drug should be Given every alternative day
• Wherever possible, local steroids are preferred over systemic steroids.
• Start with a low dose.
• Short acting steroids are preferred over long acting steroids.
• The dose is not divided and it is given early in the morning.
• When steroids are stopped, they should be gradually tapered.

Contraindications Of Steroids

• Epilepsy: decreases seizure threshold.
• Psychosis: causes behavior changes.
• CHF, Hypertension and edema: increased sodium and water retention.
• Viral and fungal infections: decreased immunity can flare up viral and fungal infections. In Covid-19, in the first week, antiviral drugs were used and steroids were started in the second week.
• Ileocecal TB: steroids increase the risk of perforation.
• Peptic ulcer: Steroids decrease the gastroprotective prostaglandins. 
• Renal Failure: There is increased sodium and water retention, and the kidneys also eliminate steroids, increasing the levels of the steroids.
• Osteoporosis
• Kaposi sarcoma
• Glaucoma

Uses Of Steroids

Diagnostic Use 

• Dexamethasone suppression test:
  • To check the integrity of the HPA axis.
  • Diagnose Cushing syndrome.

Replacement Use

• Addisonian crisis (emergency)- I.V Hydrocortisone is used
• Addison’s disease (Chronic)- Hydrocortisone + Fludrocortisone is used.
• Pregnancy- 
  • Preterm delivery 
    • In the case of preterm delivery, steroids increase lung surfactant production, decrease respiratory stress, and also decrease the risk of patent ductus arteriosus which can develop after the birth.
    • Betamethasone 12 mg given I.M, 12 mg repeated after 24 hours.
    • Dexamethasone 6 mg I.M, four doses given 12 hours apart
  • Congenital adrenal hyperplasia (CAH)
  • Steroids have also been shown to decrease necrotizing endocarditis in the newborn.

Congenital Adrenal Hyperplasia

• In this condition, there is a 21 hydroxylase deficiency (the most common), the enzyme required for steroid synthesis.
• Corticosteroid synthesis is inhibited due to an enzyme deficiency, and the hypothalamus and pituitary keep increasing pressure on the adrenal gland for steroid synthesis, resulting in adrenal hyperplasia.
• Babies born will have low BP, low Na+, and high K+.
• Due to 21 hydroxylase deficiency, cholesterol biosynthesis will move towards more and more testosterone synthesis.
• CAH also has virilization features, resulting in ambiguous features, particularly in female fetuses.
• The treatment is done with hydrocortisone, as it has both glucocorticoids as well as mineralocorticoid activity.

• If a woman gives birth to a child with CAH and is pregnant for the second time (risk of CAH).
• Dexamethasone should be given in the sixth week of pregnancy or as soon as the pregnancy is diagnosed.
• If the fetus is male, the drug can be stopped, but if the fetus is female, the drug should be continued till delivery.

OTHER THERAPEUTIC USES

• Rheumatoid arthritis
• Gout
• Psoriasis
• Allergy
• BA: Bronchial Asthma
• Organ transplant
• Leukemia
• Lymphoma
• GVHD: Graft versus host disease (Dexamethasone is preferred)
• CINV: Chemotherapy-induced nausea vomiting (Dexamethasone is preferred)
• Duchenne muscular dystrophy: The drug used is Deflazocort.
• T.B. meningitis: steroids are used because if inflammation is not suppressed, the patient may end up with seizures.
• For neurocysticercosis, antihelminthic drugs like albendazole are used. These drugs lead to the release of larvae, increasing inflammation and causing seizures; hence, steroids are used.
• COVID-19 (decreases mortality).
• Lepra Reaction: In both types 1 and 2, the drug of choice is steroids.

Download the PrepLadder app now and unlock a 24-hour FREE trial of premium high-yield content. Access Video Lectures, digital notes, QBank, and Mock Tests for FREE to ace your NEET PG preparation. Elevate your study experience and gear up for success. Start your journey with PrepLadder today!