DRUGS ACTING ON THE ENDOCRINE SYSTEM PDF

○ E.g., estrogen – enters cells and influences DNA, causing longer-term effects HYPOTHALAMUS- THE MA...

○ E.g., estrogen – enters cells and influences DNA, causing longer-term effects HYPOTHALAMUS- THE MASTER GLAND The hypothalamus coordinates both nervous and endocrine responses to maintain homeostasis It monitors body functions, including temperature, thirst, hunger, water retention, blood pressure, and emotional reactions Known as the "master gland" for its role in ENDOCRINE SYSTEM regulating the pituitary gland The endocrine system, alongside the nervous system, maintains internal homeostasis It integrates the body’s response to both Located at the base of the forebrain and internal and external environments connected to the pituitary gland Often referred to as the "neuroendocrine Regulates a range of body functions through system" due to their interconnected functions the autonomic, endocrine, and nervous systems Responds to both internal and external stimuli to maintain homeostasis Endocrine glands produce and secrete hormones into the bloodstream Hormones serve as chemical messengers The hypothalamus produces releasing hormones: affecting various bodily functions Growth hormone-releasing hormone (GH-RH) The system helps regulate growth, Thyrotropin-releasing hormone (TRH) metabolism, reproduction, and electrolyte Gonadotropin-releasing hormone (GnRH) balance Corticotropin-releasing hormone (CRH) Prolactin-releasing hormone (PRH) HORMONES Inhibiting Hormones Produced in small amounts and secreted GH release-inhibiting factor (somatostatin) directly into the bloodstream Prolactin-inhibiting factor (PIF) (possibly dopamine) Travel to specific receptor sites in the body Regulate metabolic processes and act to COMMUNICATION BETWEEN THE HYPOTHALAMUS either increase or decrease cellular functions AND PITUITARY Are broken down immediately after their action The hypothalamus connects to the pituitary via two networks: ○ Vascular network for releasing factors Membrane-bound Hormones: to the anterior pituitary ○ E.g., insulin – acts quickly by ○ Neural network for ADH and oxytocin interacting with cell receptors to the posterior pituitary Intracellular Hormones: This system ensures hormones are released as needed to maintain balance GROUP M  The hypothalamus regulates the release of Melanocyte-Stimulating Hormone (MSH): hormones from the pituitaryC ○ Important for skin color changes in Pituitary hormones then stimulate other animals endocrine glands in the body ○ May play a role in nerve growth and The hypothalamus can suppress hormone development in humans production when levels become too high Lipotropins: ○ Stimulate fat mobilization, but their role in humans is not fully understood PITUITARY GLAND Located in the skull in the bony sella turcica, under a layer of dura mater Stores and releases two hormones produced Divided into three lobes: anterior, posterior, and by the hypothalamus: intermediate ○ Antidiuretic Hormone (ADH): Historically known as the "master gland," but Also known as vasopressin now considered under the regulation of the Released in response to hypothalamus increased plasma osmolarity or decreased blood volume Increases water retention in Anterior Lobe: Produces and secretes key the kidneys to regulate blood hormones osmolarity Posterior Lobe: Stores and releases hormones ○ Oxytocin produced by the hypothalamus Stimulates uterine Intermediate Lobe: Produces endorphins and contractions during labor enkephalins in response to pain and stress Causes milk "let-down" in lactating women Released in response to hormonal and neurological stimuli Produces six major hormones: ○ Growth Hormone (GH) ○ Adrenocorticotropic Hormone (ACTH) Produces endorphins and enkephalins ○ Follicle-stimulating hormone (FSH) ○ Released in response to severe pain or ○ Luteinizing Hormone (LH) stress ○ Prolactin (PRL) ○ Bind to specific receptors in the ○ Thyroid-stimulating hormone (TSH, brainstem to block pain perception also called thyrotropin) Also produced in peripheral tissues and other Regulates growth, reproduction, and parts of the brain metabolism Triggered by factors like pain, sympathetic stimulation, guided imagery, and exercise Rhythmic secretion: Release of hormones PITUITARY GLAND AND THE HYPOTHALAMUS varies throughout the day (diurnal rhythm) ○ E.g., ACTH secretion peaks early The hypothalamus regulates the pituitary morning (6-9 AM) through feedback mechanisms Influenced by: ○ The hypothalamus sends signals to ○ Activity in the CNS the pituitary to release hormones ○ Hypothalamic hormones ○ This coordination allows the pituitary ○ Peripheral endocrine gland hormones to control many endocrine functions in ○ Drugs and diseases the body GROUP M  The hypothalamus is considered the "master ○ TRH Release: gland" due to its greater regulatory control Hypothalamus releases TRH over the endocrine system to anterior pituitary ○ TSH Production: Anterior pituitary releases Overproduction or underproduction of pituitary TSH hormones can lead to disorders: ○ Thyroid Gland Activation: ○ Growth disorders (e.g., dwarfism, TSH stimulates thyroid to gigantism) produce thyroid hormone ○ Thyroid dysfunction (e.g., ○ Feedback Loop: hypothyroidism, hyperthyroidism) Rising thyroid hormone levels ○ Reproductive issues (e.g., infertility, signal hypothalamus to stop menstrual irregularities) TRH release, reducing TSH production ENDOCRINE REGULATION Hormones & Homeostasis ○ Hormones regulate body functions to Feedback on Multiple Levels maintain homeostasis ○ Hypothalamus may also sense TRH ○ Released in small amounts to meet and TSH levels directly the body’s needs ○ Anterior pituitary may adjust TSH ○ Regulated through feedback systems release based on thyroid hormone (mainly negative feedback levels ○ Multiple backup controls to ensure proper regulation Complications in Hormone Therapy ○ Exogenous hormone administration Negative Feedback Mechanisms can disrupt the normal feedback loop ○ Most hormones are regulated through negative feedback ○ When hormone levels are adequate, Growth Hormone (GH) & Prolactin (PRL) production slows down ○ Do not follow typical feedback ○ When hormone levels fall, production systems increases ○ Regulated directly by the HYPOTHALAMIC-PITUITARY AXIS (HPA) hypothalamus through inhibiting factors: Role of the Hypothalamus Somatostatin: Inhibits GH ○ Stimulated by light, emotion, cortex release activity, chemicals PIF (Prolactin Inhibiting ○ Works with the pituitary gland to Factor): Inhibits PRL release regulate hormones Negative Feedback in the HPA ○ The hypothalamus secretes releasing hormones to stimulate the pituitary Pancreas ○ Pituitary releases stimulating ○ Insulin, glucagon, and somatostatin hormones that act on target glands released in response to blood glucose ○ Hormones return to hypothalamus to levels stop further release when levels are Parathyroid Glands sufficient ○ Release parathyroid hormone based on local calcium levels Example of Negative Feedback: Thyroid Hormone Kidneys Regulation Thyroid Hormone Regulation Process GROUP M  ○ Erythropoietin and renin released in response to blood pressure and oxygenation levels GI Hormones ○ Released in response to local stimuli (acid, proteins, calcium) Thyroid Gland ○ Calcitonin released in response to blood calcium levels Sympathetic Nervous System & ACTH ○ Stress response triggers ACTH and adrenocorticoid hormone release Aldosterone ○ Released in response to ACTH and high potassium levels ENDOCRINE & NERVOUS SYSTEM INTERACTION Interconnected Systems ○ Endocrine and nervous systems work closely to maintain homeostasis ○ Medications affecting either system can have broad, unexpected effects Clinical Relevance ○ Nurses should understand these interactions when administering drugs ○ Adverse effects often involve both endocrine and nervous systems GROUP M  Cetrorelix (Cetrotide): GnRH antagonist for fertility Degarelix (Firmagon): Blocks GnRH for cancer treatment Ganirelix Acetate (Antagon): GnRH antagonist THERAPEUTIC ACTIONS & INDICATIONS Goserelin, Histrelin, Leuprolide, Nafarelin: Used to suppress gonadotropin secretion and decrease sex hormones Tesamorelin: Stimulates GH release to decrease abdominal fat in HIV patients with lipodystrophy ENDOCRINE SYSTEM FUNCTION Cetrorelix, Degarelix, Ganirelix: Block GnRH to The endocrine system maintains homeostasis treat conditions like prostate cancer and through glandular hormone regulation fertility disorders Disruptions in hormone levels can lead to PHARMACOKINETICS disorders affecting overall body function Absorption Slow absorption via IM, subcutaneous, or depot forms Nafarelin is administered via nasal spray Drugs that interact with hypothalamic and Metabolism & Excretion pituitary hormones are used to treat and Metabolized by endogenous hormonal replace deficient hormones pathways Most are excreted in urine HYPOTHALAMIC HORMONES Crosses Placenta & Breast Milk Due to their hormone-like properties, these drugs can pass into the placenta and breast milk Contraindications and Cautions GHRH: Growth Hormone-Releasing Hormone TRH: Thyrotropin-Releasing Hormone CONTRAINDICATIONS GnRH: Gonadotropin-Releasing Hormone Hypersensitivity to the drug or its CRH: Corticotropin-Releasing Hormone components PRH: Prolactin-Releasing Hormone Pregnancy and lactation due to potential harm to fetus or baby Cautions Use with caution in: Somatostatin (GH-IH): Inhibits growth ○ Renal Impairment: May affect hormone release excretion PIF: Prolactin-Inhibiting Factor ○ Peripheral Vascular Disorders: Can alter drug absorption ○ Rhinitis: Alters absorption when using Nafarelin nasal spray ADVERSE EFFECTS OF AGONIST Hypothalamic-Releasing Hormones Agonist Effects (e.g., Goserelin, Leuprolide) Goserelin (Zoladex): Synthetic GnRH Increased Sex Hormones: Histrelin (Vantas): GnRH as an Initial stimulation can cause: antineoplastic agent ○ Ovarian Leuprolide (Lupron) and Nafarelin (Synarel): overstimulation Potent GnRH agonists (women) Tesamorelin (Egrifta): Stimulates GH ○ Flushing and fluid release, used in HIV-related lipodystrophy retention GROUP MWA  ○ Increased Growth Hormone Replacement Therapy temperature and appetite Historical Treatment ○ Originally extracted from cadavers, Long-term Use: Continued suppression of limiting supply and increasing cost gonadotropin secretion decreases sex Modern Treatment hormone production ○ Somatropin (synthetic human GH), produced through recombinant DNA ADVERSE EFFECTS OF ANTAGONIST (rDNA) technology Antagonist Effects (e.g., Cetrorelix, Degarelix) ○ Brand Names: Humatrope, Nutropin, Male Side Effects: Decreased Saizen, Genotropin, Zorbtive, etc. testosterone levels may lead to: THERAPEUTIC ACTIONS AND INDICATIONS ○ Loss of energy ○ Reduced sperm count and Primary Use activity ○ GH Replacement: Used in children ○ Altered secondary sex with short stature (dwarfism) and characteristics (e.g., muscle adults with somatotropin deficiency mass, voice pitch) syndrome (SDS) Female Side Effects: Reduced sex hormones can lead to: ○ Lack of menstruation Other Indications ○ Fluid and electrolyte ○ Growth failure in children with GH imbalances deficiency ○ Insomnia and irritability ○ Certain conditions like HIV-related lipodystroph ANTERIOR PITUITARY HORMONES PHARMACOKINETICS Role of the Anterior Pituitary Administration Secretes hormones essential for growth, metabolism, and reproductive function Typically injected Agents affecting pituitary hormones mimic or Peak levels: Reach peak within 7 hours after antagonize the effects of these hormones injection Therapeutic Use Distribution Used for replacement therapy (e.g., growth Widely distributed throughout the body, hormone deficiency) and diagnostic purposes particularly in liver and kidneys Main Anterior Pituitary Hormones Excretion Growth Hormone (GH) Excreted in urine and feces Luteinizing Hormone (LH) Follicle-Stimulating Hormone (FSH) Considerations Thyroid-Stimulating Hormone (TSH) Reduced clearance in patients with liver or Adrenocorticotropic Hormone (ACTH) renal dysfunction, potentially increasing drug concentrations CONTRAINDICATIONS AND CAUTIONS Contraindications Responsible for: Known allergy to somatropin or its ingredients Linear skeletal growth Closed epiphyses (in children whose growth Growth of internal organs plates have fused) Protein synthesis Cranial lesions, abdominal surgery, and acute Deficiency can lead to hypopituitarism illness (e.g., complications post-heart surgery) and dwarfism Caution in Pregnancy & Lactation Common Causes of GH Deficiency Potential risks to the fetus Developmental abnormalities, pituitary tumors, circulatory disturbances, trauma, etc In adults: Often due to pituitary tumors or treatment for childhood GH deficiency GROUP MWA ADVERSE EFFECTS OF GROWTH HORMONE Not used directly for GH excess due to AGONISTS multiple effects (inhibits gastrin, glucagon, insulin) Antibody formation to GH, leading to inflammation and autoimmune-type reactions (swelling, joint pain) Endocrine Effects: Hypothyroidism and insulin resistance Octreotide acetate and Lanreotide: More Swelling and joint pain are common in some potent than somatostatin in inhibiting GH patients Less effect on insulin release CLINICALLY IMPORTANT DRUG–DRUG Used to treat acromegaly in patients INTERACTIONS unresponsive to surgery or radiation Lanreotide: Given as monthly subcutaneous Cytochrome P450 Interaction injection ○ GH may interact with drugs metabolized by the cytochrome P450 enzyme system, leading to altered Mechanism of Action: metabolism of other medications ○ A semisynthetic ergot alkaloid that Monitoring Required inhibits GH secretion ○ Careful monitoring is needed when ○ Increases somatostatin release from combining GH therapy with other the hypothalamus drugs affecting liver enzymes ○ May be used alone or in combination with radiation therapy for acromegaly Effect in Normal Individuals: ○ In normal individuals, dopamine agonists can increase GH release (opposite effect) Caused mainly by pituitary tumors Can occur at any age, leading to hyperpituitarism Effects of GH Hypersecretion In Children (Before Epiphyseal Plate Closure) MECHANISM OF ACTION: ○ Gigantism: Increased height (7-8 ft) ○ Pegvisomant is a GH analogue that with normal body proportions binds to GH receptors on cells, In Adults (After Plate Closure) blocking GH's effects ○ Acromegaly: Enlargement of hands, ○ Used for patients who don’t respond to feet, and internal organs (e.g., heart) other treatments (surgery, radiation, ○ Linear growth stops, but peripheral octreotide) body growth continues ○ Administered daily via subcutaneous Treatment Options injection Surgical and Radiation Therapy PHARMACOKINETICS ○ Often used for pituitary tumors Octreotide & Lanreotide Drug Therapy ○ Octreotide: Rapidly absorbed, widely For patients who cannot undergo surgery or distributed; excreted 30% unchanged radiation in urine Medications: ○ Lanreotide: Depot form, slow release, ○ Dopamine agonists (e.g., half-life of 25-30 days Bromocriptine) Bromocriptine ○ Somatostatin analogues (e.g., ○ Administered orally, absorbed from the Octreotide acetate, Lanreotide) GI tract, extensively metabolized in the ○ GH analogue (e.g., Pegvisomant) liver ○ Excreted in bile Pegvisomant ○ Subcutaneous injection; peak effect within 33-77 hours Naturally inhibits GH release from the ○ Half-life of 6 days, excreted in urine hypothalamus GROUP MWA CONTRAINDICATIONS AND CAUTIONS Increased toxicity with erythromycin ○ (avoid combination) Bromocriptine ○ Decreased effectiveness with ○ Contraindicated in pregnancy and phenothiazines (monitor closely) lactation due to effects on the fetus Pegvisomant and lactation inhibition ○ May require higher doses if used with Octreotide, Lanreotide, and Pegvisomant opioids (mechanism unclear) ○ No adequate studies in pregnancy or lactation; use only if benefits outweigh DRUGS AFFECTING THE ANTERIOR PITUITARY risks HORMONES ○ Caution in endocrine disorders (e.g., diabetes, thyroid dysfunction), as GH Chorionic Gonadotropin antagonists may worsen these Cosyntropin conditions Pasireotide Thyrotropin Alpha ADVERSE EFFECTS Octreotide & Lanreotide ○ GI complaints: Constipation, diarrhea, nausea, flatulence Mechanism of Action: ○ Serious effects: Acute cholecystitis, biliary tract obstruction, pancreatitis Acts like Luteinizing Hormone (LH) ○ Cardiac effects: Sinus bradycardia, Stimulates testosterone production in males arrhythmias and progesterone production in females ○ Injection site reactions: Pain, discomfort, inflammation Indications: ○ Blood glucose changes: Monitor Male: Treatment of hypogonadism, to glucose levels, especially with stimulate testosterone production Lanreotide Female: Used in fertility treatments to support Bromocriptine ovulation ○ GI disturbances: Nausea, constipation ○ Dopamine-blocking effects: Related Drug: Chorionic Gonadotropin Alpha (Ovidrel) Drowsiness, postural hypotension – Used as a fertility drug to induce ovulation in women ○ Lactation inhibition Pegvisomant ○ Injection site pain and inflammation ○ Liver function changes, increased infection risk, nausea, and diarrhea DRUG-DRUG INTERACTIONS Mechanism of Action: Bromocriptine A synthetic form of ACTH ○ Increased toxicity with erythromycin (Adrenocorticotropic Hormone) (avoid combination) Stimulates the adrenal glands to produce ○ Decreased effectiveness with cortisol phenothiazines (monitor closely) Indications: Pegvisomant ○ May require higher doses if used with Diagnostic use to test adrenal function and opioids (mechanism unclear) adrenal gland responsiveness Not used therapeuticallyRapid onset, short duration of action DRUGS AFFECTING THE ANTERIOR PITUITARY Nursing Implications: Primarily used in endocrine HORMONES diagnostics Chorionic Gonadotropin Cosyntropin Pasireotide Thyrotropin Alpha Mechanism of Action: DRUG-DRUG INTERACTIONS A somatostatin analog that inhibits the release of ACTH from the pituitary Bromocriptine Acts on somatostatin receptors in the adrenal gland GROUP MWA Indications: Pasireotide Cushing's Disease: Reduces ACTH secretion in Available in long-acting injectable (LAR) form patients with Cushing’s disease Half-life of 12-15 hours Acromegaly: Suppresses GH in patients who do not respond to other therapies Thyrotropin Alpha Administration: Available in long-acting release (LAR) Administered IM or subcutaneously (SC) form for monthly injections Half-life of 24 hours Mechanism of Action: CONTRAINDICATIONS AND CAUTIONS A synthetic version of TSH Chorionic Gonadotropin (Thyroid-Stimulating Hormone) Contraindicated in pregnancy and active Stimulates the thyroid to produce thyroid ovarian cysts hormones Cosyntropin Indications: Use cautiously in patients with adrenal Adjunctive treatment for radioiodine ablation insufficiency of thyroid tissue Contraindicated in severe cardiovascular Used in patients who have undergone disease near-total to total thyroidectomy for thyroid cancer Pasireotide Helps locate thyroid remnants by stimulating iodine uptake Contraindicated in pregnancy and lactation Caution with liver dysfunction, as it may cause THERAPEUTIC USES OF THESE DRUGS liver enzyme changes Chorionic Gonadotropin Thyrotropin Alpha Used in fertility treatments for both men Contraindicated in patients with iodine allergy (testosterone stimulation) and women Caution in patients with cardiovascular issues (ovulation induction) or hyperthyroidism Cosyntropin Used for diagnostic testing of adrenal function ADVERSE EFFECTS Chorionic Gonadotropin Pasireotide Headache, fatigue, irritability Treats Cushing's disease and acromegaly Possible ovarian hyperstimulation Thyrotropin Alpha Cosyntropin Fluid retention, hypokalemia, increased blood Aids in post-thyroidectomy management and pressure radioiodine ablation Hyperglycemia in diabetic patients Pasireotide PHARMACOKINETICS GI symptoms: Nausea, diarrhea, abdominal discomfort Chorionic Gonadotropin Elevated liver enzymes, glucose intolerance Administered intramuscularly (IM) Fatigue and headache Half-life: Several hours, depending on the Thyrotropin Alpha formulation Injection site reactionsFlu-like symptoms (e.g., fever, chills) Cosyntropin CLINICAL CONSIDERATIONS Administered IV for diagnostic purposes Chorionic Gonadotropin Short duration of action Monitor ovarian response during fertility treatment Ensure proper timing for ovulation induction GROUP MWA Cosyntropin DRUGS AFFECTING ADH Only used for diagnostic testing of adrenal Desmopressin (DDAVP) insufficiency ○ Synthetic ADH used for Diabetes Pasireotide Insipidus Regular monitoring of liver function and ○ Available as oral, IV, subcutaneous, glucose levels is essential and nasal forms Thyrotropin Alpha Conivaptan (Vaprisol) Monitor thyroid function following radioiodine ○ Vasopressin receptor antagonist used therapy to treat SIADH Ensure that the patient does not have residual ○ Administered via IV infusion thyroid cancer Tolvaptan (Samsca) ○ Another Vasopressin receptor antagonist used for hyponatremia and POSTERIOR PITUITARY HORMONES SIADH ○ Given orally Hormones Produced in the Posterior Pituitary Antidiuretic Hormone (ADH): Also known as THERAPEUTIC ACTIONS AND INDICATIONS Vasopressin Desmopressin Oxytocin: Stimulates milk ejection and uterine ○ ADH replacement therapy for DI contractions ○ Increases water reabsorption in Disorders Related to ADH kidneys Diabetes Insipidus (DI): Insufficient ADH Vasopressin Receptor Antagonists secretion (Conivaptan, Tolvaptan) Syndrome of Inappropriate ADH (SIADH): ○ Used to block ADH effects in Excessive ADH secretion conditions like SIADH ○ Increase urine output and raise serum sodium levels ○ Used under hospital supervision due Characteristics: to rapid shifts in fluid balance ○ Excessive production of dilute urine (polyuria) PHARMACOKINETICS ○ Polydipsia (excessive thirst) due to Desmopressin dehydration Rapid absorption and metabolism ○ Blood becomes concentrated with Excreted by the liver and kidneys high sodium levels Available via oral, IV, subcutaneous, or nasal Causes routes ○ Head trauma, surgery, pituitary tumors, Tolvaptan or injuries Orally absorbed, half-life of 12 hours ○ Can be acute or chronic Conivaptan Treatment Administered IV with a half-life of 5 hours ○ ADH replacement therapy with Excreted via urine and feces Desmopressin (DDAVP) CONTRAINDICATIONS AND CAUTIONS Desmopressin Contraindicated in severe renal dysfunction and hypersensitivity Characteristics Caution in vascular disease, epilepsy, and ○ Fluid retention and dilution of blood asthma ○ Can lead to hyponatremia (low sodium Should not be used during pregnancy or levels) lactation Causes ○ Metastatic cancer, sepsis, brain injury, Vasopressin Antagonists (Conivaptan, Tolvaptan) or medications Contraindicated in patients with Treatment hypersensitivity and severe renal impairment ○ Vasopressin receptor antagonists Use caution in patients with vascular disease (e.g., Conivaptan, Tolvaptan) to block and electrolyte imbalances ADH ADVERSE EFFECTS Desmopressin Water intoxication: Drowsiness, headache, nausea, convulsions GROUP MWA  GI issues: Abdominal cramps, nausea, flatulence Local irritation with nasal or injection forms Hypersensitivity: Rash, bronchial constriction Vasopressin Antagonists (Conivaptan, Tolvaptan) Rapid volume shifts: Polyuria, hypotension, arrhythmias Electrolyte imbalance: Hyperkalemia, hyperglycemia GI symptoms: Constipation, dry mouth, and thirst Clinically Important Drug–Drug Interactions Desmopressin Increased antidiuretic effects when combined with carbamazepine or chlorpropamide Tolvaptan and Conivaptan Caution with digoxin, ACE inhibitors, ARBs, and potassium-sparing diuretics (risk of hyperkalemia). Tolvaptan should not be combined with telithromycin (risk of severe toxicity) GROUP MWA  Mineralocorticoids Adrenal corticosteroids Androgens: Affect electrolytes, stímulate protein production Glucocorticoids: Regulate metabolism, immune function, and inflammation Mineralocorticoids: Regulate sodium and potassium balance (aldosterone) · Used pharmacologically for hypogonadism, protein growth, and immune suppression ADRENOCORTICAL AGENTS Control of Corticosteroid Release Controlled by ACTH (adrenocorticotropic hormone) from the pituitary gland CRH (corticotropin-releasing hormone) from the hypothalamus stimulates ACTH Widely used to suppress immune system and - Diurnal Rhythm relieve symptoms of inflammation - High cortisol levels in the morning - Important: Do not cure inflammatory - Lower levels at night, influenced by disorders sleep/wake cycles and light exposure Currently reserved for short-term use (acute inflammation or replacement therapy) Stress and Corticosteroid Secretion Not used for long-term chronic conditions Stress triggers SNS activation and bypasses the normal diurnal rhythm Results in release of ACTH and corticosteroids Physiological effects of corticosteroids in - Two adrenal glands sit on top of the kidneys stress: Glands have two main components: - Increase blood volume (aldosterone - Adrenal Medulla (inner core) effect) - Adrenal Cortex (outer shell) - Release glucose for energy - Inhibit protein production to conserve energy - Suppress inflammation and immune response - Part of the Sympathetic Nervous System (SNS) - Releases epínephríne bloodstream Effects of Prolonged Corticosteroid Use - Supports fight-or-flight response by acting as a Adverse reactions during prolonged use: backup for SNS stimulation - Decreased healing (protein breakdown - Hormones reach specific receptor sites, inhibition) creating systemic effects (e.g., increased heart - Increased infection risk (immune rate) suppression) For optimal results, short-term use is advised to avoid complications Adrenal cortex produces corticosteroids Three types of corticosteroids: Androgens (male sex hormones like Aldosterone also secreted in response to high testosterone) potassium levels Glucocorticoids (e.g., cortisol) GROUP M  Stimulates kidneys to reabsorb sodium and excrete potassium, restoring electrolyte balance Anti-inflammatory and immunosuppressive effects Block arachidonic acid metabolism, reducing Adrenal Excess (Cushing Syndrome) prostaglandins and leukotrienes Cushing Disease: Caused by excessive - Impair movement of phagocytes and adrenocortical hormones (e.g., ACTH-secreting inhibit lymphocyte function tumor, steroid use) Common uses: - Symptoms: Short-term treatment for inflammatory disorders ➔ Moon face, central obesity, - Cancer, hematological disorders, and hypertension, osteoporosis neurological infections ➔ Hirsutism (excessive hair growth) in - Replacement therapy for adrenal insufficiency females Pharmacokinetics Adrenal Insufficiency - Well absorbed from many sites Causes: - Metabolized in the liver, excreted in urine; Cross - Adrenal gland damage (e.g., Addison the placenta and enter breast milk disease) - Use in pregnancy and lactation only if benefits - Prolonged corticosteroid use (results in outweigh risks gland atrophy) - Available in various forms: oral, topical, - ACTH suppression leads to adrenal intranasal, inhaled, intra-articular, and parenteral atrophy, delaying hormone production recovery Adrenal Crisis Hydrocortisone: Topical, ophthalmic use; has Occurs during extreme stress in patients with adrenal both glucocorticoid and mineralocorticoid insufficiency effects - Symptoms of adrenal crisis: Prednisone: Oral only, commonly used for ➔ Physiological exhaustion, hypotension, inflammation fluid shift, shock, and possible death Beclomethasone: Respiratory inhalant, used for ➔ Treatment involves massive steroid asthma infusion and life support measures Betamethasone: Long-acting, used in acute situations Preventing Adrenal Crisis Weaning off corticosteroids is crucial after prolonged use to prevent adrenal atrophy Methylprednisolone: Available in multiple Short-term use with gradual tapering of forms, used in inflammation corticosteroids allows adrenal recovery Contraindications: - Known allergy to steroid preparations - Acute infection (immune suppression risk) Stimulate glucose production for energy - Lactation (may pass to baby) Caution in: Therapeutic Actions - Diabetes (can elevate glucose levels) - Increase protein breakdown, decrease - Peptic ulcers (can worsen ulcers) protein formation (preserving energy) - Endocrine disorders (imbalances may occur) - Promote lipogenesis (fat formation for - Pregnancy (possible fetal effects) energy storage) Adverse Effects Common glucocorticoids: Methylprednisolone may cause increased - Beclomethasone, Betamethasone, Prednisone, toxicity in African Americans Hydrocortisone, Dexamethasone, Methylprednisolone, etc. GROUP M  - Children: Risk for growth retardation - Infection (impairs adrenal response) due to hypothalamic-pituitary - High sodium intake (can cause hypernatremia) suppression - Local use: Inflammation, infections, burning, and stinging - Systemic effects include hypertension, Adverse Effects osteoporosis, and immunosuppression - Sodium and water retention: - Headache, edema, hypertension, heart failure Drug-Drug Interactions - Hypokalemia (low potassium levels) Increased effects when combined with: - Allergic reactions: Skin rash, anaphylaxis - Erythromycin, ketoconazole, troleandomycin - Decreased effects when combined with: Drug-Drug Interactions Salicylates, barbiturates, phenytoin, - Decreased effectiveness when combined with: rifampin - Salicylates, barbiturates, rifampin, anticholinesterases - |f combination therapy is necessary, close monitoring and dose adjustments may be required Regulate electrolyte levels and homeostasis Classic example: Aldosterone, Fludrocortisone, cortisone, and hydrocortisone (at high doses) are examples of mineralocorticoids Aldosterone has been phased out for pharmacological use Therapeutic Actions - Increase sodium reabsorption in renal tubules, leading to water retention - Cause potassium excretion Fludrocortisone: Preferred for replacement therapy in adrenal insufficiency Used for salt-wasting adrenogenital syndrome when combined with glucocorticoids Pharmacokinetics - Absorbed slowly and distributed throughout the body - Metabolized in the liver to inactive forms; cross placenta and enter breast milk - Should be avoided during pregnancy and lactation due to potential fetal effects Contraindications and Cautions - Known allergy to the drug - Severe hypertension, heart failure, cardiac disease (due to sodium/water retention) - Lactation (risk to baby) Caution in: - Pregnancy (potential fetal harm) GROUP M  Thyroid Dysfunction Hypothyroidism (Underactive Thyroid) - Causes: Iodine deficiency, autoimmune disease (e.g., Hashimoto's), pituitary problems - Symptoms: Fatigue, weight gain, cold intolerance - Treatment: Thyroid hormone replacement Hyperthyroidism (Overactive Thyroid) - Causes: Graves' disease, goiter - Symptoms: Weight loss, anxiety, heat intolerance - Treatment: Antithyroid drugs, surgery, radioactive iodine THYROID AGENTS Types of Thyroid Agents Location: Middle of the neck, surrounding the trachea - Thyroid Hormones (Replacement Therapy): For hypothyroidism Function: Regulates metabolism, heat production, and - Antithyroid Agents: For hyperthyroidism calcium homeostasis (Thioamides, Iodine solutions) Hormones Produced: Thyroid Hormones - Thyroid hormones (T3, T4) Levothyroxine (T4): - Calcitonin (regulates calcium levels) - Most commonly used for hypothyroidism STRUCTURE Liothyronine (T3): ANATOMY: - Faster onset, used for more immediate needs - Two lobes connected by an isthmus - Follicular cells produce T3 and T4 Liotrix: - Parafollicular cells produce calcitonin - Combination of T4 and T3 in a 4:1 ratio Hormone Production: Indications: - Iodine from diet is crucial for T3 and T4 Hypothyroidism production Myxedema coma Thyroid Hormones: T3 & T4 Prevention of goiter T3 (Triiodothyronine): - Contains 3 iodine atoms; more active form PHARMACOKINETICS T4 (Thyroxine): - Contains 4 iodine atoms; converted to T3 in Absorption: Well absorbed from the GI tract tissues Functions: Binding: Bind to serum proteins - Regulates metabolism, oxygen consumption, Elimination: Primarily in bile and growth - Affects heart rate, body temperature, and Effects during Pregnancy: Thyroid hormone therapy enzyme systems should continue during pregnancy Thyroid Hormone Regulation Regulation via Hypothalamic-Pituitary Axis: CONTRAINDICATIONS & CAUTION - Hypothalamus releases TRH → Stimulates anterior pituitary to release TSH → Stimulates Contraindications: thyroid hormone production Allergy to thyroid agents - Negative feedback loop: High thyroid hormone Acute thyrotoxicosis or myocardial infarction levels inhibit TRH and TSH production Cautions: GROUP M  Use in lactation (can enter breast milk) - Preoperative treatment Caution in cardiac conditions and adrenal - Radiation emergencies insufficiency ADVERSE EFFECTS - Iodine Solutions ADVERSE EFFECTS - Hypothyroidism - Iodism (metallic taste, sore gums, diarrhea) Common Side Effects DRUG-DRUG INTERACTIONS Skin reactions Hair loss (especially during the first months) - Monitor drug levels in patients switching from Symptoms of hyperthyroidism (arrhythmias, hyperthyroid to euthyroid states nervousness, anxiety) Monitoring: Regular thyroid function tests ANTITHYROID AGENTS Thioamides (e.g., Methimazole, - Four small glands behind the thyroid gland Propylthiouracil) - Produce Parathyroid Hormone (PTH) — - Inhibit thyroid hormone production regulates serum calcium levels - Used for hyperthyroidism treatment - Essential for maintaining calcium Mechanism homeostasis in the body - Prevents thyroid hormone formation LOCATION & STRUCTURE - Inhibit T4 to T3 conversion Location Indications - Located on the back of the thyroid gland - Treatment of hyperthyroidism Structure - Pre-surgical preparation - Examples: Methimazole, Propylthiouracil (PTU) - Small groups of glandular tissue - Two pairs: superior and inferior parathyroid ADVERSE EFFECTS glands - Liver toxicity (especially with PTU) FUNCTION: - Bone marrow suppression (with methimazole) - Nausea, rash, and GI complaints PTH Actions - Stimulates osteoclasts to release calcium DRUG-DRUG INTERACTIONS from bones - Increased bleeding risk with oral - Increases calcium absorption in the intestines anticoagulants - Enhances calcium reabsorption in the kidneys - Changes in serum levels of theophylline and - Stimulates production of calcitriol (active digoxin Vitamin D) in the kidneys PTH VS CALCITONIN: CALCIUM REGULATION Iodine Solutions (e.g., Potassium Iodide, ❖ PTH: Elevates serum calcium levels Radioactive Iodine) ❖ Calcitonin: Reduces serum calcium levels - High doses block thyroid function - Balance: PTH increases calcium levels, and - Used in severe hyperthyroidism or as adjuncts calcitonin lowers them, maintaining to surgery homeostasis Mechanism Calcium Homeostasis - High iodine doses block thyroid hormone Importance of Calcium: production - Essential for nerve function, muscle - Radioactive iodine destroys thyroid tissue contraction, blood clotting - Must be maintained within a normal range Indications Control of Calcium: - Hyperthyroidism GROUP M  - PTH and calcitonin work together to regulate - Vitamin D (Calcitriol): Regulates calcium serum calcium absorption in the intestine Factors Affecting PTH Secretion PHARMACOKINETICS Magnesium: Affects PTH release Calcitriol: Phosphate: High phosphate levels stimulate - Absorbed in the GI tract, stored in liver and PTH release bones, half-life 5-8 hours Feedback Loop: PTH release is inhibited when Teriparatide: calcium levels are high and stimulated when - Subcutaneous injection, rapid absorption, calcium levels are low half-life ~1 hour Natpara: Parathyroid Dysfunction - Administered subcutaneously, peak in 30 Hypoparathyroidism: minutes, half-life ~3 hours - Absence of PTH leads to hypocalcemia CONTRAINDICATIONS - Common after thyroid surgery - Treated with calcium and Vitamin D General: ❖ Cause: Most often after parathyroid removal during thyroid surgery - Avoid in patients with high calcium levels ❖ Symptoms: Low calcium levels, muscle (hypercalcemia) cramps, spasms - Caution in patients with renal issues or a ❖ Treatment: Calcium and Vitamin D therapy history of kidney stones Hyperparathyroidism: Pregnancy & Lactation: - Overproduction of PTH leads to hypercalcemia - Use with caution during pregnancy, only if - Can result from tumors or genetic disorders benefits outweigh risks - Includes primary and secondary forms (related - Avoid during lactation due to potential adverse to kidney disease) effects on infants ❖ Cause: Excessive PTH production, often due to ADVERSE EFFECTS parathyroid tumors ❖ Symptoms: High calcium levels, kidney stones, Common Effects bone pain - Gastrointestinal: Metallic taste, nausea, constipation Types: - CNS: Weakness, headache, irritability - Primary: Occurs more in women aged 60-70 - Possible kidney or liver dysfunction with - Secondary: Associated with chronic renal prolonged use failure DRUG INTERACTIONS Management: Surgical intervention or medication Parathyroid Hormone Agents PARATHYROID HORMONE AGENTS - Avoid magnesium-containing antacids (increased risk of hypermagnesemia) - Monitor digoxin levels carefully (risk of toxicity with hypercalcemia) - Reduced absorption with cholestyramine or mineral oil Teriparatide (Forteo): - Stimulates bone formation Natpara: - Replaces missing PTH for hypoparathyroidism Calcitriol (Rocaltrol): Bisphosphonates: - Active form of Vitamin D - Function: Slows bone resorption, helps lower Abaloparatide (Tymlos): serum calcium - Used for osteoporosis treatment - Includes alendronate, risedronate, zoledronic THERAPEUTIC ACTIONS acid PTH Analogues: Calcitonins: - Stimulate bone formation, increase serum - Function: Inhibit bone resorption, lower calcium, decrease phosphorus calcium levels - Teriparatide: Increases bone mass, reduces fracture risk GROUP M  - Available as calcitonin salmon (nasal spray or injection) PHARMACOKINETICS Bisphosphonates: Well absorbed in the intestine, excreted in urine Calcitonins: Metabolized in tissues, excreted by kidneys, peak effects within 40 minutes CONTRAINDICATIONS & CAUTIONS Bisphosphonates: Not for use in hypocalcemia, caution in renal or GI issues Calcitonins: Avoid in patients allergic to fish, caution with renal dysfunction ADVERSE EFFECTS Bisphosphonates: GI distress, esophageal erosion, bone pain Calcitonins: Flushing, skin rash, nausea, injection site irritation GROUP M  Endocannabinoid System ○ Affects metabolism, insulin sensitivity, fat storage Stress Response ○ SNS, corticosteroids, and growth hormone all alter glucose regulation Loss of Blood Glucose Control Hyperglycemia ○ Results in glycosuria (sugar in urine), fatigue, polyphagia (increased hunger), and polydipsia (increased thirst) Lipolysis and Ketosis Diabetes Mellitus ○ Breakdown of fat for energy, leading to Metabolic disorder affecting glucose, fat, and ketone production and acidosis protein metabolism Protein Breakdown Affects multiple organ systems, leading to ○ Leads to elevated nitrogen waste and cardiovascular disease, neuropathy, difficulty in healing nephropathy, and retinopathy Goal of treatment is to regulate blood glucose Type Of Diabetes using insulin and antidiabetic drugs. Type 1: ○ Insulin-dependent, rapid onset, often in Pancreas and Hormonal Regulation younger people, requires insulin Pancreatic islets (alpha, beta, delta cells) replacement regulate blood glucose Type 2: ○ Alpha cells ○ Insulin resistance, often linked to Release glucagon in response lifestyle factors, more common in to low blood sugar adults but increasing in younger ○ Beta cells populations Release insulin in response to high blood sugar ○ Delta cells Release somatostatin, which inhibits both insulin and Basement Membrane Changes: Thickening of blood glucagon vessel walls, leading to: If the diabetes is not controlled it will continue Insulin’s Action to progress leading to: ○ Atherosclerosis (heart disease and Stimulates glucose uptake into cells stroke risk) (facilitated diffusion) ○ Retinopathy (vision loss) Promotes glycogen storage in liver and ○ Neuropathy (nerve damage, muscles particularly in feet and legs) Increases fat storage and protein synthesissis ○ Nephropathy (kidney dysfunction) Release triggered by increased blood glucose or food intake Diagnosis Other Factors Affecting Glucose Fasting Blood Glucose (FBS) Adiponectin ○ >126 mg/dL is diagnostic ○ Secreted by fat cells; increases insulin Oral Glucose Tolerance Test (OGTT) sensitivity and protects blood vessels ○ Measures body's response to glucose challenge GROUP M 1  HbA1c Test HYPERGLYCEMIA (High Blood Sugar) ○ Reflects 3-month average glucose levels, goal is 126 mg/dL diabetes (fasting) Classifications Fatigue Type 1 Diabetes Glycosuria ○ Insulin deficiency due to beta cell Symptoms Polyphagia destruction, typically requires lifelong Polydipsia Itchy skin insulin therapy Type 2 Diabetes Ketoacidosis: ○ Characterized by insulin resistance, - Fruity breath, initially managed by lifestyle changes Serious dehydration, (diet, exercise) Complications Kussmaul respirations CNS Effects: - Confusion - Coma Lifestyle Modifications ○ Diet control, weight loss, and exercise Treatment Immediate insulin administration Medications ○ Oral agents to stimulate insulin production, increase receptor sensitivity, or control glucose HYPOGLYCEMIA (Low Blood Sugar) absorption Definition Blood glucose level