Pharmacology of Steroids Notes

Learning Outcomes

  • Understanding Steroids:
    • Definition of steroids and their natural production by adrenal glands via the HPA axis.
    • Circadian rhythm of cortisol and the role of steroids in the body.
  • Mechanism and Impact:
    • Mechanism of action of steroids and their physiological effects.
    • Major therapeutic uses of steroids.
  • Health Risks and Considerations:
    • Side effects and contraindications related to steroid use.
    • Importance of tapering off steroids; risks of sudden cessation.
  • Specific Uses:
    • Clinical applications of inhaled and topical steroids along with their side effects.
    • Use of Steroid Cards to manage treatment protocols.

What are Steroids?

  • Definition:
    • Steroids are hormones that can be produced by the adrenal cortex, playing significant roles in the regulation of various physiological functions.

Corticosteroids vs Glucocorticoids

  • Corticosteroids: A collective term for steroid medications.
  • Glucocorticoids: Refers to steroid hormones (like cortisol) produced in the Zona Fasciculata of the adrenal cortex.

Steroid Physiology

  • Adrenal Cortex Zones:
    • Zona Glomerulosa: Produces mineralocorticoids (e.g., Aldosterone).
    • Zona Fasciculata: Produces glucocorticoids (Cortisol).
    • Zona Reticularis: Produces androgen precursors.
  • Functions:
    • Provides resistance to stressors and increases serum glucose availability.

HPA Axis and Steroid Release

  • Mechanism:
    • Stress activates the hypothalamus to secrete Corticotrophin-Releasing Hormone (CRH).
    • CRH stimulates the anterior pituitary to release Adrenocorticotrophic Hormone (ACTH), which acts on the adrenal cortex to release cortisol.
  • Physiology Under Stress:
    • Stressors like trauma or hypoglycemia stimulate the release of CRH/ACTH resulting in corticosteroid production.

Circadian Rhythms of Cortisol

  • Parameters:
    • Cortisol exhibits circadian rhythms influencing blood pressure and heart rate.
  • Importance:
    • Understanding these rhythms is crucial for dosing and managing steroid therapies effectively.

Mechanism of Action of Steroids

  • Lipid Solubility:
    • Cortisol required transport proteins for distribution:
    • Corticosteroid-binding globulin (80-90%).
    • Albumin (10-15%).
  • Tissue Impact:
    • Steroids act on various tissues affecting inflammation, immune response, and metabolism.

Physiological Effects of Steroids

  • Anti-inflammatory Actions:
    • Inhibition of APC migration, reduction of prostaglandin synthesis, fibroblast proliferation, mast cell activation.
    • Inhibition and stimulation of various cytokines impacting immune response.
  • Metabolic Effects:
    • Increased serum glucose levels.

Clinical Use of Steroids

  • Categories:
    • Endocrine: Replacement therapy for adrenal insufficiency.
    • Anti-inflammatory: Treatment of conditions like asthma, arthritis, and allergies.
    • Immunosuppressive: Managing autoimmune diseases.

Pharmacokinetics of Steroids

  • Key Points:
    • Absorption: Depends on administration route.
    • Distribution: ~95% bound to proteins.
    • Metabolism: Occurs in the liver.
    • Elimination: Primarily through kidneys.
  • Half-lives:
    • Short: Hydrocortisone (8-12 hours).
    • Intermediate: Prednisolone (18-36 hours).
    • Long: Dexamethasone (35-56 hours).

Side Effects of Steroids

  • Common Issues:
    • Cushing's syndrome, hypertension, diabetes, insomnia, depression, and anxiety.
    • Long-term Consequences:
    • Osteoporosis, increased infection risk, delayed wound healing, and HPA axis suppression.
  • Relative Contraindications:
    • Caution in pregnant women, children, patients with diabetes, head injuries, or gastric issues.

Long-term Use Considerations

  • Tapering:
    • Gradual weaning prevents adrenal crisis.
  • Additional Support:
    • Patients may require extra steroid cover prior to surgical procedures.

Respiratory Steroids

  • Asthma Management:
    • Reduces inflammation by inhibiting leukotrienes and prostaglandins.
    • Inhibits release of pro-inflammatory cytokines.

Inhaled Steroids - Side Effects

  • Common adverse effects include:
    • Oral thrush, voice problems, diabetes induction, adrenal suppression (particularly in children), osteoporosis, and glaucoma.
  • Management:
    • Gradual weaning of dosage necessary when discontinuing.

Topical Steroids

  • Mechanism:
    • Decrease inflammation by downregulating inflammatory mediators.
  • Types/Preparations:
    • Vary by potency: Mild (Hydrocortisone 1%) to Very Potent (Clobetasol propionate 0.05%).

Common Adverse Reactions of Topical Steroids

  • Possible Issues:
    • Infections, skin thinning, bruising, tachyphylaxis, stretch marks, and rebound syndrome from abrupt withdrawal.

Considerations for Steroid Use

  • Steroid Cards:
    • Documentation required for patients on long-term steroid therapy to prevent adrenal crisis emergencies.
  • Monitoring:
    • Regular checks for glycosuria, blood pressure adjustments, and immune response evaluations.

Steroid Emergency Protocols

  • Emergency Actions:
    • Immediate treatment for adrenal crisis with hydrocortisone.
    • Importance of recognizing symptoms like vomiting and shock.

Summary

  • Understanding the pharmacology of steroids is crucial for safe and effective therapeutic use. Key aspects include recognizing their physiological roles, mechanisms of action, potential side effects, and proper management protocols for long-term treatment.