💊Pharmacology for Nurses Unit 26 – Hypothalamic, Pituitary & Adrenal Drug Therapy

Key Concepts

• Hypothalamic-pituitary-adrenal (HPA) axis plays a crucial role in regulating stress response, metabolism, and immune function
• Negative feedback loops maintain homeostasis by adjusting hormone secretion based on circulating levels
• Disorders of the HPA axis can lead to hormonal imbalances, causing a wide range of symptoms and health issues
• Pharmacological interventions target specific hormones, receptors, or enzymatic pathways to restore balance and alleviate symptoms
• Nurses must understand the actions, side effects, and interactions of HPA axis medications to ensure safe and effective patient care
• Patient education is essential for promoting adherence, monitoring for adverse reactions, and optimizing treatment outcomes

Anatomy and Physiology Review

• Hypothalamus serves as the primary control center, integrating signals from the nervous and endocrine systems
  • Releases hormones that stimulate or inhibit the anterior pituitary gland (corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH))
  • Produces antidiuretic hormone (ADH) and oxytocin, which are stored and released by the posterior pituitary gland
• Pituitary gland consists of two main lobes: anterior (adenohypophysis) and posterior (neurohypophysis)
  • Anterior pituitary secretes several hormones in response to hypothalamic stimulation (adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), growth hormone (GH))
  • Posterior pituitary releases ADH and oxytocin directly into the bloodstream
• Adrenal glands are located atop the kidneys and have two distinct regions: cortex and medulla
  • Adrenal cortex produces glucocorticoids (cortisol), mineralocorticoids (aldosterone), and androgens in response to ACTH stimulation
  • Adrenal medulla secretes catecholamines (epinephrine and norepinephrine) in response to sympathetic nervous system activation

Major Hormones and Their Functions

• Corticotropin-releasing hormone (CRH) stimulates ACTH release from the anterior pituitary, initiating the HPA axis response
• Adrenocorticotropic hormone (ACTH) promotes the synthesis and secretion of glucocorticoids, primarily cortisol, from the adrenal cortex
• Cortisol is a key glucocorticoid that regulates metabolism, inflammation, and stress response
  • Increases blood glucose levels by promoting gluconeogenesis and insulin resistance
  • Suppresses immune function and inflammation
  • Helps maintain blood pressure and cardiovascular function
• Aldosterone is the main mineralocorticoid that regulates fluid and electrolyte balance
  • Promotes sodium retention and potassium excretion in the kidneys
  • Contributes to blood pressure regulation
• Androgens, such as dehydroepiandrosterone (DHEA), are produced in small amounts by the adrenal cortex and play a role in sexual development and function

Common Disorders and Diseases

• Cushing's syndrome results from chronic exposure to excessive glucocorticoids, either endogenous or exogenous
  • Symptoms include weight gain, central obesity, moon face, buffalo hump, skin changes (thinning, bruising, striae), and mood disturbances
  • Can lead to complications such as hypertension, diabetes, osteoporosis, and increased risk of infections
• Addison's disease is caused by primary adrenal insufficiency, resulting in deficient glucocorticoid and mineralocorticoid production
  • Presents with fatigue, weight loss, hypotension, hyperpigmentation, and electrolyte imbalances (hyponatremia, hyperkalemia)
  • Acute adrenal crisis can be life-threatening and requires immediate treatment with glucocorticoids and fluid resuscitation
• Secondary adrenal insufficiency occurs due to pituitary or hypothalamic dysfunction, leading to decreased ACTH secretion and cortisol deficiency
  • Causes include pituitary tumors, traumatic brain injury, and abrupt withdrawal of long-term glucocorticoid therapy
• Congenital adrenal hyperplasia (CAH) is an inherited disorder characterized by enzyme deficiencies in cortisol synthesis pathways
  • Classic CAH presents in infancy with ambiguous genitalia, salt-wasting crisis, and virilization
  • Non-classic CAH may manifest later in life with signs of androgen excess (hirsutism, acne, menstrual irregularities)

Drug Classes and Mechanisms

• Glucocorticoids (synthetic analogues of cortisol) are used to treat adrenal insufficiency and various inflammatory or autoimmune conditions
  • Mechanism: Bind to glucocorticoid receptors and regulate gene transcription, suppressing inflammation and immune responses
  • Examples: Hydrocortisone, prednisone, dexamethasone
• Mineralocorticoid receptor antagonists block the effects of aldosterone and are used to treat hypertension and heart failure
  • Mechanism: Compete with aldosterone for binding to mineralocorticoid receptors, reducing sodium retention and blood pressure
  • Examples: Spironolactone, eplerenone
• Steroidogenesis inhibitors target enzymes involved in the synthesis of adrenal hormones and are used to treat Cushing's syndrome and CAH
  • Mechanism: Block the activity of enzymes such as 11β-hydroxylase or 17α-hydroxylase, reducing the production of cortisol or androgens
  • Examples: Ketoconazole, metyrapone, abiraterone
• ACTH analogues are used in diagnostic testing to assess adrenal function
  • Mechanism: Mimic the effects of endogenous ACTH, stimulating cortisol production
  • Example: Cosyntropin (synthetic ACTH)

Specific Medications and Their Uses

• Hydrocortisone is the preferred glucocorticoid for treating adrenal insufficiency, as it closely mimics physiological cortisol secretion
  • Dosing aims to replicate the diurnal rhythm, with higher doses in the morning and lower doses in the afternoon/evening
  • Stress dosing is necessary during illness, surgery, or trauma to prevent adrenal crisis
• Fludrocortisone is a potent mineralocorticoid used to replace aldosterone in primary adrenal insufficiency
  • Helps maintain fluid and electrolyte balance, preventing hyponatremia and hyperkalemia
• Prednisone and prednisolone are commonly prescribed glucocorticoids for their anti-inflammatory and immunosuppressive effects
  • Used in the management of various conditions (rheumatoid arthritis, asthma, inflammatory bowel disease, multiple sclerosis)
  • Long-term use requires tapering to prevent adrenal suppression and withdrawal symptoms
• Dexamethasone is a potent, long-acting glucocorticoid with minimal mineralocorticoid activity
  • Used in high doses for the treatment of cerebral edema, cancer-related complications, and as a diagnostic tool in Cushing's syndrome
• Mifepristone is a glucocorticoid receptor antagonist approved for the treatment of Cushing's syndrome
  • Blocks the effects of excess cortisol at the receptor level, alleviating symptoms of hypercortisolism

Nursing Considerations and Patient Education

• Monitor patients for signs and symptoms of adrenal insufficiency, especially during stress or illness
  • Educate patients and caregivers on the importance of stress dosing and the use of emergency glucocorticoid injection kits
• Assess for adverse effects of glucocorticoid therapy, such as hyperglycemia, hypertension, osteoporosis, and mood changes
  • Encourage regular monitoring of blood glucose, blood pressure, bone density, and mental health
  • Advise patients on the importance of calcium and vitamin D supplementation to prevent osteoporosis
• Teach patients about the proper administration of medications, including the importance of taking doses at consistent times and not abruptly discontinuing therapy
  • Provide instructions on tapering schedules when discontinuing long-term glucocorticoid treatment
• Educate patients on the signs and symptoms of adrenal crisis (severe weakness, hypotension, abdominal pain, vomiting) and the need for immediate medical attention
  • Ensure patients wear medical alert bracelets or carry identification indicating their adrenal insufficiency diagnosis and glucocorticoid dependence
• Collaborate with the healthcare team to develop individualized treatment plans and monitor patient response to therapy
  • Communicate any changes in the patient's condition or medication regimen to ensure continuity of care

Clinical Applications and Case Studies

• Case 1: A 45-year-old woman presents with fatigue, weight gain, and easy bruising. Lab results reveal elevated cortisol levels and abnormal dexamethasone suppression test. She is diagnosed with Cushing's syndrome secondary to an adrenal tumor.
  • Treatment: Surgical resection of the adrenal tumor, followed by temporary glucocorticoid replacement therapy to prevent adrenal insufficiency
  • Nursing considerations: Monitor for signs of adrenal insufficiency post-operatively, educate the patient on stress dosing, and assess for resolution of Cushing's symptoms
• Case 2: A 25-year-old man is admitted to the emergency department with severe hypotension, hyponatremia, and hyperkalemia. He reports a history of autoimmune thyroiditis and recent fatigue, weight loss, and skin hyperpigmentation. Adrenal insufficiency is suspected.
  • Diagnostic tests: Cosyntropin stimulation test reveals inadequate cortisol response, confirming primary adrenal insufficiency (Addison's disease)
  • Treatment: Initiate intravenous hydrocortisone and fluid resuscitation, followed by long-term oral glucocorticoid and mineralocorticoid replacement therapy
  • Nursing considerations: Educate the patient on the importance of medication adherence, stress dosing, and wearing a medical alert bracelet; monitor electrolytes and blood pressure
• Case 3: A 6-year-old girl is evaluated for precocious puberty and virilization. Genetic testing confirms a diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
  • Treatment: Glucocorticoid replacement with hydrocortisone to suppress ACTH and control androgen excess; mineralocorticoid replacement with fludrocortisone to maintain electrolyte balance
  • Nursing considerations: Educate parents on the importance of regular medication administration, monitoring growth and development, and providing emotional support for the child and family
• Case 4: A 60-year-old woman with rheumatoid arthritis presents with Cushingoid features after long-term prednisone therapy. Her physician initiates a slow tapering schedule to prevent adrenal insufficiency.
  • Nursing considerations: Teach the patient about the tapering process and the potential for withdrawal symptoms; monitor for signs of adrenal insufficiency or disease flare during tapering; reinforce the importance of not abruptly discontinuing the medication
• Case 5: A 35-year-old man with a history of pituitary surgery develops secondary adrenal insufficiency. He is prescribed hydrocortisone replacement therapy and educated on stress dosing.
  • Nursing considerations: Assess the patient's understanding of stress dosing guidelines; provide education on the recognition and management of adrenal crisis; encourage the patient to inform all healthcare providers about his adrenal insufficiency diagnosis and treatment