Glucocorticoids: Functions and Types

Study Notes

Glucocorticoids are steroid hormones produced naturally by the adrenal glands in the body, also known as cortisol.
They have powerful anti-inflammatory effects, but are also immunosuppressive.

Glucocorticoids can be synthetically made and taken orally or injected, examples include hydrocortisone and prednisone.
Synthetic glucocorticoids are used to relieve pain quickly, especially in sports medicine.

Glucocorticoids are lipid-soluble and need a carrier protein called trans Cortin to transport them around the body.
They go inside cells, bind to glucocorticoid receptors, and upregulate or downregulate certain genes.
Glucocorticoids inhibit nuclear factor Kappa B's activity, suppressing inflammation and the production of inflammatory cytokines.

Glucocorticoids inhibit the formation of inflammatory mediators by inhibiting enzymes phospholipase a2 and Cox.
They reduce the production of prostaglandins, leucotrienes, and thromboxanes, which are inflammatory mediators.

Synthetic glucocorticoids are used as replacement therapy for people with Addison's disease, where the adrenal glands produce low levels of cortisol.

Long-term use of glucocorticoids can lead to immunosuppression, making people more prone to infection.
It can also lead to Cushing syndrome, characterized by weight gain, obesity, and fluid retention.
Glucocorticoids can affect bone health, leading to osteoporosis by inhibiting osteoblast activity and stimulating osteoclast activity.

Glucocorticoids are steroid hormones produced by the adrenal glands, also known as cortisol, with powerful anti-inflammatory effects and immunosuppressive properties.

Synthetic glucocorticoids can be taken orally or injected, examples include hydrocortisone and prednisone, and are used to relieve pain quickly, especially in sports medicine.

Glucocorticoids require a carrier protein called trans Cortin for transportation around the body due to their lipid-soluble nature.
They bind to glucocorticoid receptors inside cells, upregulating or downregulating certain genes.
Glucocorticoids inhibit nuclear factor Kappa B's activity, suppressing inflammation and the production of inflammatory cytokines.

Glucocorticoids inhibit the formation of inflammatory mediators by inhibiting enzymes phospholipase a2 and Cox.
They reduce the production of prostaglandins, leucotrienes, and thromboxanes, which are inflammatory mediators.

Synthetic glucocorticoids are used as replacement therapy for people with Addison's disease to supplement low cortisol levels.

Long-term use of glucocorticoids can lead to immunosuppression, making people more prone to infection.
Prolonged use can cause Cushing syndrome, characterized by weight gain, obesity, and fluid retention.
Glucocorticoids can negatively impact bone health, leading to osteoporosis by inhibiting osteoblast activity and stimulating osteoclast activity.

Tissue injury or irritation releases phospholipase A2, converting phospholipids into arachidonic acid.
Arachidonic acid is a substrate for cyclooxygenase (COX) and 5-lipoxygenase (5-LOX).

COX enzyme has two forms: COX-1 and COX-2.
COX-1 is constantly expressed throughout the body, responsible for:
- Producing thromboxane and prostaglandins, which stimulate normal body functions.
- Regulating gastric acid, promoting platelet aggregation, and maintaining renal blood flow.
COX-2 is induced at sites of inflammation, leading to:
- Production of prostaglandins that mediate inflammation, pain, and fever.

NSAIDs act by inhibiting COX enzymes, decreasing prostaglandin production, resulting in:
- Anti-inflammatory effects.
- Antipyretic effects.
- Analgesic effects.
NSAIDs can be divided into three categories based on COX enzyme selectivity:
- Selective COX-1 inhibitors.
- Relatively non-selective COX inhibitors.
- Selective COX-2 inhibitors.

Common adverse effects occur in the gastrointestinal tract due to:
- Inhibition of COX-1-mediated production of PGE2 and PGI2, increasing risk of GI bleeding and peptic ulcers.
- Agents with higher COX-1 selectivity have a higher risk.
Inhibition of COX-1-mediated production of TXA2 leads to:
- Antiplatelet effect and increased risk of bleeding.
- Aspirin-induced antiplatelet effect persists even after therapy is stopped.
Adverse effects on the kidney result from:
- Decreased production of renal prostaglandins, increasing risk of kidney injury in susceptible patients.
Adverse effects on the cardiovascular system result from:
- Agents with high COX-1 selectivity having a protective cardiovascular effect.
- Agents with high COX-2 selectivity increasing the risk of cardiovascular events.

Prostaglandin analogs interact with specific G-protein coupled prostaglandin receptors, harnessing beneficial effects.
Examples of prostaglandin analogs include:
- Alprostadil (erectile dysfunction and ductus arteriosus).
- Lubiprostone (chronic constipation).
- Misoprostol (stomach ulcers and inducing labor).
- Bimatoprost, Latanoprost, and Travoprost (open-angle glaucoma).
- Iloprost and Treprostinil (pulmonary arterial hypertension).