Transcript Document
Various Endocrine Glands of the Body Types of Hormones • Proteins, peptides and amino acid derivatives – Proteins are large molecules made of many amino acids – Peptides are smaller molecules typically made of a few amino acids – Amino acid derivatives are molecules derived from a single amino acid Lipid Hormones • Steroid hormones – Derived from cholesterol – All similar in structure, but small differences confer different effects – Similarities responsible for some cross reactivity • Eicosanoids – Derived from arachadonic acid (fat) The hypothalamus • Integrates information and many functions of the nervous system • The hypothalamus controls the function of the pituitary gland in two ways • It can secrete releasing hormones that act on the pituitary to stimulate secretion of stimulating hormones • It can also stimulate the release of hormones from the posterior pituitary via nervous input The Pituitary • Divided into two halves • The anterior portion is comprised of epithelial cells that act primarily as a glandular structure • The posterior portion has extensive innervation and responds to nervous sytem input from the hypothalamus The hypothalamus and the Pituitary Table. 10.3a Table. 10.3b Hormones of the Pituitary • Growth hormone – Controls growth and glucose metabolism – Mediated via the somatomedins • ACTH – Acts on the adrenal gland to stimulate the release of cortisol • Gonadotropins – Leutinizing hormone- ovulation, secretion of sex hormones – Follicle stimulating hormone – development of follicles and sperm cells • Prolactin – stimulates breasts to develop milk • Melanocyte stimulating hormone – Causes synthesis of melanin Hormones of the Posterior Pituitary • Antidiuretic hormone (aka vasopressin) – Causes the retention of fluid in the urine – Combats dehydration • Oxytocin – Causes lactation – Contractions during child birth The Thyroid Gland • Secretes two hormones that regulate metabolic rate – Thyroxine (T4) – contains four iodine atoms – Triiodothyronine (T3) – contains three iiodine atoms – Insufficient iodine impairs T3 and T4 synthesis The Parathyroid Gland • Primarily responsible for calcium homeostasis • Parathyroid hormone – Causes increased production of vitamin D and increased absorption of calcium in the intestine – Also causes resorption of calcium from the bones – Increased retention of calcium in the kidneys Regulation of the Thyroid Gland Clinical Indication Thyroid Hormones: Replacement or supplement in hypothyroidism of any cause • cretinism- mental & physical retardation in • children with chronic untreated hypothyroidism • nontoxic goiter in adults • myxedema in adults Thyroid Hormones Hormones (proteins) secreted from the thyroid gland include: • Triiodothyronine (T3) • Thyroxine (T4) • and Thyrocalcitonin TSH (Thyroid Stimulating Hormone) • Is secreted from the anterior pituitary gland in response to changes in the blood levels of T3 and T4 • Triggers T3, T4 secretion from the thyroid gland Thyroid Hormones T3, T4- concerned with muscle and nerve tissue growth • stimulates protein synthesis • increases the intestinal absorption of glucose • increases glycogen synthesis • mobilizes fatty acids • decreases serum cholesterol • increases BMR (basal metabolic rate) Adverse Effects Related to Overdosing Symptoms are dose and time dependent and characteristic of hyperthyroidism and increase in sympathetic tone: • • • • • • • • • • • Mental confusion to psychotic behavior Increased blood pressure Increased heart rate Diarrhea Weight loss Sweating Menstrual irregularities Tremors Headache Nervousness Anginal episodes Cautions and Contraindications Thyroid hormone therapy • is contraindicated in patients with myocardial infarction • is not recommended for weight reduction in the management of obesity • should be used with caution in patients – With cardiovascular disease, diabetes, adrenal insufficiency – Who are elderly Antithyroid Drugs Clinical Indication Treatment of hypersecretory conditions of the thyroid in order to: inactivate overactive tissue inhibit production of T3 and T4 Effects of Hypersecretion or Hyperthyroidism May be caused by tumors on the thyroid (thyrotoxic crisis), pituitary, or hypothalamus or Autoimmune disease (Grave’s Disease) – LATS (long-acting thyroid stimulating protein) not the same as TSH but same responses occur Symptoms are dose and time dependent and characteristic of hyperthyroidism especially increased sympathetic autonomic tone Antithyroid Drugs Mechanism of action Accumulate within the thyroid and destroy overactive tissue or inhibit the incorporation of iodine for production of T3 and T4 • Radioactive Iodide (immediate onset) • Methimazone (requires time to see effect) • Propylthiouracil (requires time to see effect) Antithyroid Drugs Special Considerations & Contraindications • Cross the placenta and affect fetal thyroid development • Abrupt discontinuation of iodide may cause thyroid storm • Iodide should be discontinued if fever, rash, soreness in gums & teeth occur • Iodide-containing drugs are contraindicated in patients with pulmonary edema • Radioactive iodide is present in the saliva and urine 24 hours after dosing Calcium Homeostasis Parathyroid Hormones Calcium ions • Essential for neuromuscular and endocrine function • Serum levels strictly regulated by two polypeptide hormones – calcitonin (thyroid) – parathormone (parathyroid) Calcium Homeostasis Parathormone Stimulated when serum calcium levels are low Stimulates bone resorption to mobilize calcium Increases intestinal and renal reabsorption of calcium Calcitonin Stimulated when serum calcium levels are high Inhibits bone resorption No effect on the intestine or kidney Antagonizes parathormone Calcium Disorders & Treatment • Hypocalcemia Parathyroid damage during surgery Treatment: calcium salts and vitamin D • Hypercalcemia Neoplasms, multiple myeloma, renal dysfunction Treatment: diuretics to increase the renal clearance of calcium calcitonin and bisphosphonates Degenerative Bone Disease & Treatment • Osteoporosis Decreased bone mass Decreased mineral deposition Increased bone resorption Treatment: Bisphosphonates, estrogen • Paget’s Disease Hyperactive bone metabolism Fragile bone and microfractures Treatment: Calcitonin, bisphosphonates Bisphosphonates • Alendronate • Etidronate • Pamidronate Poorly absorbed, not metabolized, excreted in urine The Adrenal Glands • Adrenal medulla responsible for the hormonal fight or flight response • Adrenal medulla releases epinephrine (adrenaline) and small amounts of norepinephrine Fight or Flight Hormones • Increases breakdown of glycogen to glucose in the liver • Increase heart rate – Increases cardiac output to the tissues • Increases blood pressure • Increases metabolic rate in skeletal muscle, cardiac muscle and nervous tissue The Adrenal Cortex • Produces gluccocorticoids – Cortisol • Regulates blood glucose levels • Causes amino acids to be converted to glucose in the liver • Cortisol secreted in times of stress to maintain glucose and energy levels Clinical Indication Glucocorticoids Replacement therapy in adrenal insufficiency (Addison’s Disease) Interrupt moderate to severe pain associated with conditions of inflammation Mineralocorticoids Replacement therapy in adrenalectomy or adrenal tumors Glucocorticoids • Adrenal cortex secretes glucocorticoids • Typically referred to as steroids • Regulate the metabolism of carbohydrates and proteins • Demand for cortisol rises during stress and tissue repair (e.g. wound healing) • Produce and conserve glucose • Promote protein catabolism and gluconeogenesis • Some mineralocorticoid activity i.e., sodium retention Corticosteroids Source of steroids-natural & synthetic cortisone, hydrocortisone, prednisone, methylprenisolone, triamcinolone, betamethasone, dexamethasone Vary in duration of action and potency Antiinflammatory action stabilize cell membranes prevent edema Systemic use in patients with normal adrenal function arthritis, collagen disease, rheumatic disorders, respiratory disease, spinal cord injury Topical use for skin irritation, rashes, itching Corticosteroids Adverse Effects Associated with high doses and chronic use • Exaggeration of steroid symptoms of Cushing’s disease mood changes insomnia weight gain, obesity protein catabolism, muscle weakness, wasting osteoporosis decreased wound healing increased infections fat deposition, moon facies • Steroid addiction personality changes- “steroid psychosis” psychological dependency (falacy) Steroid Contraindications • Patients with systemic fungal infections • Local viral herpes infections • Topical application to the eyes or orbital area • Live virus vaccinations The Pancreas • The pancreas produces insulin and glucagon – The primary blood glucose regulatory hormones • Insulin produced in the beta cells of the islets of Langerhans • Glucagon produced in the alpha cells Insulin • The primary glucoregulatory hormone • Elevated in response to increased blood glucose or amino acids • Inhibited when blood glucose is low • Diabetes results from perturbed insulin metabolism Diabetes • Type 1- insulin dependent diabetes – The individual does not produce insulin • Type II- non-insulin dependent diabetes mellitus (adult onset) – The individual does not respond appropriately to insulin Clinical Indication Maintain circulating glucose levels sufficient to promote intracellular glucose transport and provide a source of energy for cells Pancreatic Endocrine Function The pancreas secrets two polypeptide hormones that regulate carbohydrate metabolism and blood glucose levels • Insulin Promotes glucose movement into cells and carbohydrate storage • Glucagon Increases glucose in the blood by stimulating glycogen breakdown Insulin & Glucagon Secretion Insulin is secreted by beta cells in response to elevated glucose levels • Mobilizes glucose into skeletal, heart, fat cells • Promotes storage of fat and protein Glucagon is secreted by alpha cells in response to low glucose levels • Stimulates glyocogenolysis (breakdown) • Mobilizes glucose into the circulation Diabetes Mellitus (DM) • • • • Defect in beta cell function Deficiency in insulin production and secretion Type I DM is insulin dependent (juvenile diabetes) genetic predisposition Type II DM relative insulin deficiency (maturity-onset) aging, improper diet, obesity Diabetes Mellitus Symptoms • • • • • • • • • • Persistently high blood glucose levels Spill over into high urine glucose (glycosuria) Volume of water excreted (polyuria) Dehydration and thirst Excessive fluid intake (polydipsia) Excessive food intake (polyphagia) Fat breakdown produces ketosis Neuropathy, retinal hemorrhage Renal dysfunction Atherosclerosis Treatment of Diabetes Mellitus Correct the metabolic imbalance with diet adjustment and administration of • Insulins • Oral sulfonylureas acetohexamide, glipizide, glyburide, tolazamide, tolbutamide • Glucose absorption inhibitors acarbose, miglitol • Antihyperglycemic drugs Metformin, troglitazone Treatment of Diabetes Mellitus Insulin (Type I, II DM) • Sources: animal or recombinant DNA • Onset of action varies with each insulin type • Provides single peak of glucose activity • Requires multiple daily doses • Injected 15 to 30 minutes before meals • Juice or sugar can reverse hypoglycemia • Salicylates, beta-blockers, MAOI potentiate insulin-induced hypoglycemia Treatment of Diabetes Mellitus Oral sulfonylureas (oral hypoglycemics) • Type II DM only • Enter the beta cells and cause insulin release • Vary in onset and duration of action • Delay in onset related to absorption • Not a substitute for insulin • Prolonged action sustains hypoglycemia • Cause gastrointestinal irritation, nausea, diarrhea, weakness, fatigue, dizziness, hypersensitivity reactions (rash), elevated serum liver enzymes, leukopenia, thrombocytopenia & anemia Contraindications & Drug Interactions with Oral Hypoglycemics Contraindicated in patients: • With a known hypersensitivity • With complications of fever, ketoacidosis or coma • With liver or renal disease, peptic ulcers • Who are pregnant Drug Interactions occur because of • Protein binding displacement • Liver enzyme inhibition • Inhibition of glucose metabolism Treatment of Diabetes Mellitus Glucose Absorption Inhibitors • Do not reduce blood glucose levels • Do not release insulin • Interfere with dietary carbohydrate digestion • Delay a peak in glucose absorption after meals • Are ingested with meals • Do not impair liver enzymes • Cause flatulence, diarrhea, and abdominal pain • Contraindicated in patients with ketoacidosis, impaired absorption, or hypersensitivity reaction Treatment of Diabetes Mellitus Antihyperglycemic Drugs • Do not reduce blood glucose levels or release insulin • Keep glucose blood level from rising too fast • Decrease liver glucose production and intestinal glucose absorption • Promote smoother distribution of glucose to tissues • Causes diarrhea, nausea, vomiting and flatulence • May cause lactic acidosis leading to respiratory and cardiovascular distress • Contraindicated in patients with metabolic acidosis, renal disease or abnormal creatinine clearance The Testes and the Ovaries • The testes produce testosterone • The ovaries produce estrogen and progesterone Clinical Indication Female hormones Replacement therapy in hypogonadism and menopause, or fertility enhancement, and adjunctive therapy for cancer Prevent ovulation or implantation in the uterus Alleviate menstrual disorders in nonmenopausal women Female Sex Hormones Estrogens and Progestogens LH and FSH secreted from the anterior pituitary gland induce conditions for the secretion of estrogen and progesterone Estrogens secreted from developing cells in the ovaries stimulate • uterine lining and mammary glands • motility within the fallopian tubes • endometrium for implantation of a fertilized egg Progesterone secreted from the corpus luteum • completes development uterine lining for implantation • stimulates mammary ducts for lactation Pharmacological Actions Contraception Estrogen and progestogen combinations mimic the natural secretory cycle so that • FSH and LH secretions are suppressed • ovulation is blocked • cervical mucus is thickened decreasing the possibility of implantation Hormone Replacement Therapy (HRT) Estrogens interact with receptors to reduce • hot flashes, sweating, muscle & joint aches that occur during menopause • bone resorption and turnover that decreases bone mineral density in osteoporosis • coronary artery disease by decreasing blood pressure, LDL- lipoproteins and insulin Estrogen and Progestogens Adverse Effects • • • • • • • • • • • Nausea Vomiting Headache Dizziness Irritability Depression Fluid retention Breast tenderness Weight gain Thrombophlebitis (pain in legs, groin) Double-vision Female Sex Hormones Contraindications Use in pregnant women or those with a history of Thrombophlebitis Liver disease Breast tumors Estrogen-dependent cancers Undiagnosed vaginal bleeding Special considerations Use in women with a history of Diabetes High blood pressure Seizure disorders Male Sex Hormones - Androgens Clinical Indication In men Replacement therapy in hypogonadism, delayed puberty, and impotence due to androgen deficiency In women Adjunctive therapy for inoperable breast cancer and postpartum breast engorgement Androgens Pharmacologic Action Anabolic action - Stimulate protein synthesis Clinical benefit- Increase body weight and appetite Nontherapeutic use- Increase muscle mass and enhance athletic performance Erythropoiesis-Stimulate production of RBCs Clinical benefit- Reverse refractory anemia Inhibit tumor growth Clinical benefit- reduce pain & swelling in women with fibrocystic breast disease Adverse Effects Result from chronic high dose use Men may develop • Decreased sperm count • Increased breast tissue • Sustained erection • Tumors • Addiction syndrome Women may develop Hirsutism Menstrual irregularities Acne Men and women • Jaundice • Nausea • Vomiting • Diarrhea • Retention of sodium and water Deepening voice Androgens Special Considerations and Contraindications Contraindications Men breast or prostate cancer Pregnant women- virilization of fetus Special considerations Blood glucose levels may fluctuate in diabetic patients Bruising and localized hemorrhages may increase in patients also receiving anticoagulants Impotence Inability to achieve or maintain an erection Causes include • Nerve or spinal cord damage • Diminished blood flow to penis • Medication-induced reduction in nerve excitability during sexual performance Treatment Sildenafil (oral phosphodiesterase PDE inhibitor) Inhibits an enzyme (PDE) in muscle metabolism That increases blood flow and rigidity in the penis Sildenafil Adverse Effects • Headache • Flushing • Nasal congestion • Diarrhea • Rash • Upset stomach Sildenafil Contraindications • Patients taking nitrates may develop livethreatening hypotension and cardiovascular collapse • Patients predisposed to sustained erection (e.g., sickle cell anemia, leukemia)