Exam 2 - Endocrine Pharmacology: Adrenocorticoids

Endocrine Pharmacology: Adrenocorticoids

• Adrenocorticoids are a class of drugs that affect the adrenal glands, which are located above the kidneys.
• Adrenal glands have two parts: the cortex and the medulla.
• The adrenal cortex secretes various hormones, including mineralocorticoids (e.g., aldosterone) and glucocorticoids (e.g., cortisol).
• Aldosterone regulates sodium balance.
• Cortisol modulates metabolism.
• The hormones from the adrenal glands have related, but distinct effects.
• The hypothalamus has a significant role in regulating the function of the anterior pituitary gland, and in turn hormones.

Hypothalamus-Pituitary-Endocrine Axes

• The hypothalamus produces releasing hormones to stimulate/inhibit pituitary hormones.
• The pituitary gland synthesizes and releases hormones into circulation.
• Circulating hormones act on specific endocrine glands/tissues, producing various biological effects.
• The hypothalamus-pituitary-thyroid (HPT) axis is an example of this axis.

Normal Anatomy of the Adrenal Glands

• Adrenal glands are small yellowish structures located at the top of each kidney.
• They are situated in the perirenal space, positioned superior and anterior to the kidneys.

Adrenal Glands: Medulla and Cortex

• Adrenal glands have two functional regions: the adrenal medulla and the adrenal cortex.
• Different regions of the Adrenal cortex have varying functions.
• The adrenal cortex produces hormones with various functions, including mineralocorticoids (e.g., aldosterone) and glucocorticoids (e.g., cortisol).

The Adrenal Cortex

• The adrenal cortex acts like a typical endocrine gland.
• It primarily secretes steroid hormones including aldosterone, cortisol, and sex hormones.
• These steroids are produced through a complex series of enzymatic steps.

Synthesis of Adrenocortical Hormones

• Adrenocortical hormones are derived from cholesterol and synthesized through enzymatic reactions.
• Various enzymes are involved at various stages of hormone creation.
• The different pathways create different types.

Drugs Covered in this Section: Glucocorticoids and Mineralocorticoids

• Synthetic corticosteroids like prednisone, prednisolone, triamcinolone, betamethasone, and dexamethasone are involved.
• Natural corticosteroids like hydrocortisone are part of the therapy.
• Mineralocorticoids like aldosterone, deoxycorticosterone, and fludrocortisone are included.
• Specific categories of antagonists such as inhibitors of synthesis and receptor blockers are included.

Cellular Response of Steroid Signaling

• Steroid hormones bind to specific intracellular receptors.
• This leads to changes in gene expression and subsequent cellular effects.
• Glucocorticoids, for instance, can regulate glucose metabolism.

Drug Interactions with Glucocorticoids

• Glucocorticoids (GCs) can interact with other drugs.
• Some drugs increase or inhibit the activity of the enzymes metabolizing GCs.
• Other drugs might be affected by the GCs.

Glucocorticoid Structure and Activity

• Specific structural features of glucocorticoids are critical for their activity.
• The structure dictates how a specific glucocorticoid acts in the body.
• Structural modifications can impact both potency and activity of the hormone.

Glucocorticoids: Structures

• Different structures of glucocorticoids and some relevant metabolites are described and compared.

Prednisone

• Prednisone is a synthetic glucocorticoid.
• Prednisone's mechanism of action mimics the effects of natural glucocorticoids.
• Prednisone has a specific metabolism and excretion profile distinct from others.
• Prednisone is frequently used in various conditions to treat inflammatory and immune responses.

Hydrocortisone (Cortisol)

• Hydrocortisone, or cortisol, is a naturally occurring glucocorticoid.
• It has a significant amount of action and affects multiple body systems.
• Hydrocortisone's action and metabolism have effects on bodily functions.

Adrenal Gland Diseases

• Congenital adrenal hyperplasia (CAH) is often caused by a deficiency of an enzyme involved in steroid synthesis.
• Adrenocortical insufficiency can manifest as Addison's disease, characterized by insufficient production of glucocorticoids and mineralocorticoids.
• Cushing's syndrome is caused by overproduction of cortisol.
• Primary aldosteronism results from overactivity of the adrenal gland producing aldosterone.
• Secondary aldosteronism results from overactivity of the renin-angiotensin-aldosterone system.
• Pheochromocytoma is a tumor of the adrenal medulla that typically produces excess catecholamines.

Diagnosing Adrenal Gland Conditions

• Various tests are used to help diagnose different adrenal conditions.
• These tests typically focus on evaluating hormone levels and responses.

Treatment of Adrenal Gland Conditions

• Treatment strategies vary based on the specific adrenal condition.
• These can involve hormone replacement, surgery, or other methods.

Mineralocorticoids (Aldosterone, Deoxycorticosterone, Fludrocortisone)

• Mineralocorticoids (e.g., aldosterone) are crucial for regulating sodium and potassium balance.
• They affect sodium reabsorption and potassium secretion.
• Fludrocortisone is a synthetic mineralocorticoid used to treat mineralocorticoid deficiency.

Mineralocorticoid Antagonists

• Drugs such as spironolactone, eplerenone, drospirenone, and finerenone are mineralocorticoid antagonists.
• These agents block the effects of aldosterone and reduce sodium retention.
• These antagonists have varied mechanisms and clinical uses to treat various conditions.