Drugs affecting the Endocrine SystemNursing 3703PharmacologyBy Linda Self

Hypothalamic, Pituitary, Parathyroid, and Adrenal HormonesHypothalamus secretes releasing hormones affecting both the anterior and posterior pituitaryPosterior pituitary secretes ADH and OxytocinADH conserves water, Oxytocin functions in childbirth and lactation

Anterior pituitary hormones and target tissuesGH---most body tissuesACTH (corticotropin)adrenal cortexglucocorticoids, mineralocorticoids, androgensTSHthyroid--thyroxine

4. FSH and LHovaryestrogen and progesterone5. LH in malestestistestosterone6. Prolactinaffects the breast7. Melanocyte stimulating hormone--melanocytes

Parathyroid and calcium regulationParathyroidparathormone. Regulates calcium and phosphate metabolism. When serum levels increase, phosphorus decreasesIn concert with calcitonin and vitamin D, PTH regulates normal serum levels of calciumAffects GI absorption of calcium, movement of calcium to and from bone, and calcium excretion via kidneys

Parathyroid and calcium50% of calcium is bound, the other 50% is free.The unbound portion is instrumental in the normal function of all cellsCalcium constantly shifting between bone and serum

Parathyroid and calciumCalcium regulates:Cell membrane permeabilityNerve cell excitability and transmissionContraction of cardiac, skeletal and smooth muscleBlood coagulationHormone secretionCatecholamine releaseEnzyme activity

Parathyroid, calcium and phosphorusPhosphorus combines with calcium in bones and teeth as CaPO4Phosphorus functions:For cellular production of energyAs coenzyme with B vitaminsPhosphate buffer systemPhospholipidsPart of DNA and other nucleic acids so is necessary for growth and reproduction

CalcitoninSecreted by thyroidResponds to high serum levels of calciumLowers serum calcium by decreasing movement of calcium from bone to serum and increasing urinary excretion of calciumShort-acting

Vitamin DFat soluble vitamin that functions as a hormoneFunctions in regulation of calcium levels by increasing intestinal absorption of calcium and mobilizing calcium from boneMust be converted to intermediate metabolite in liver then to calcitriol in kidneys

Vitamin DPTH and adequate hepatic and renal function necessary to produce calcitriol the active form of vitamin D (1,25 dihydroxyvitamin D)

Adrenal HormonesAldosterone is the primary and most potent mineralocorticoidConserves sodium through its action on cells in distal nephronRegulated by the renin-angiotensin-aldosterone systemProtein bound amounts of aldosterone serve as depot or storage

Effects of MineralocorticoidsConserve sodium and water and eliminating potassiumSecretion of aldosterone is largely controlled by kidneysInadequate secretion of aldosterone causes hyperkalemia, hyponatremia and ECF volume deficit. Hypotension, shock and death may ensue.

Effects of Mineralocorticoids cont.Excessive secretion of aldosterone produces hypokalemia, hypernatremia and ECF volume excess (water intoxication). Edema and hypertension will result.

Hypothalamic HormonesGenerally must be given by injection or intranasally as will be broken down by GI systemAre equivalent to gonadotropin releasing hormonesChronic administration inhibits gonadotropin secretionGonadorelin (Factrel)used for diagnostic testing of gonadotropic function Goserelin (Zoladex)endometriosis, metastatic breast and prostate cancer

Hypothalamic HormonesLeuprolide (Lupron)used in advanced prostatic cancer, central precocious puberty, endometriosis, uterine fibroid tumorsAdverse effects are those of estrogen or testosterone deficiency; may cause depression, bone pain and difficulty in urinating

Hypothalamic and Pituitary AgentsOctreotide (Sandostatin)pharmacologically similar to somatostatin. Administration of this drug reduces blood levels of growth hormone and insulin-like growth factor; carcinoid tumors, thus diarrhea and flushing; and vasoactive intestinal peptide tumors, also relieving diarrhea

Octreotide cont.Used to treat diarrhea in patients with AIDS

Anterior Pituitary HormonesCorticotropin (Acthar Gel, or ACTH)diagnostic test of adrenal functionSomatrem (Protropin)synthesized growth hormone. Promotes growth in children whose growth is impaired 2ndary to deficient GH or in those with renal failure. Tissue wasting with AIDS.HCG (Chorex, Choron, Pregnyl) cryptorchidism, diagnostic test of testosterone production

Anterior Pituitary HormonesMenotropins (Pergonal)-a gonadotropin preparation obtained from the urine of postmenopausal women. Contains both LH and FSH. Usually combined with HCG to induce ovulation.Thyrotropin (Thytropar) used as diagnostic agent to distinguish between primary and secondary hypothyroidism

Posterior Pituitary HormonesDesmopressin (DDAVP, Stimate) and vasopressin (Pitressin). Synthetic equivalents of ADH. Useful in Diabetes Insipidus.Parenteral desmopressin used as hemostatic agent in hemophilia and Von Willebrands Disease. Treatment for bleeding esophageal varices. Desmopressin also can be inhaled; vasopressin is only injectable

Posterior Pituitary HormonesOxytocin (Pitocin)promotes uterine contractility and is used to induce labor and in the postpartum period to control bleeding.

Drugs used for Calcium and Bone DisordersBisphosphonatesalendronate (Fosamax), risedronate (Actonel) and zoledronate (Zometa)Bind to bone and inhibit calcium resorptionPoorly absorbed from GI tractTake on empty stomach, with water, 30 minutes before other intake

Drugs Used for Calcium and Bone DisordersCalcitonin-salmon (Calcimar, Miacalcin)Used in treatment of hypercalcemia, Pagets Disease (osteitis deformans) and osteoporosis. Inhibits bone resorption and slows the rate of bone turnover. May help with bone pain.

Drugs used for Calcium and bone DisordersSymptomatic hypcalcemia, calcium gluconate may be given intravenouslyOral preparations (e.g. calcium citrate or carbonate) available. For nutritional deficiency of calcium and for osteopenia.

Drugs used for calcium and bone disordersCorticosteroids inhibit cytokine release, by direct cytolytic effects of some bone tumors, and by inhibiting calcium absorption from the intestine and by increasing calcium excretion in the urine.Used in the treatment of hypercalcemia due to malignancies or vitamin D intoxication.

Cont. drugs for bone, calcium disordersEstrogens and AntiestrogensEstrogens most beneficial immediately after menopause when there is a period of accelerated bone loss. Decrease bone breakdown, increase calcium absorption from gut and increase calcitriol (active form of Vitamin D)

Bone and calciumRaloxifen (Evista) and tamoxifen (Nolvadex) act like estrogen in some tissues and prevent the action of estrogen in other body tissues.Raloxifen is classified as a selective estrogen receptor modulator and is approved for postmenopausal osteoporosis

Cont.Tamoxifen (Nolvadex) is classified as an antiestrogen. Is used to prevent and treat breast cancer. Also has estrogenic effects so can be used to prevent osteoporosis and cardiosvascular disease.

Cont. Bone and calciumTeriparatide (Forteo) is a recombinant DNA version of parathormone. Actually increases bone formation by increasing osteoblasts. Increases serum levels of calcium and calcitriol. Metabolized and excreted by liver, kidneys and bone. Not felt to cause osteosarcoma. Not known to cause deposition of calcium in soft tissues.

Bone and calciumVitamin D (400 IU for those 6months to 24 years; 200 IU in those 25 years and older)Furosemide (Lasix) useful in hypercalcemia as causes increased excretion of calciumSodium chloride solution useful as inhibits reabsorption of calcium in renal tubules

Bone and calciumNeutro-phos inhibits intestinal absorption of calcium and increases deposition in bone. Effective in tx any kind of hypercalcemia. Can cause soft tissue calcification. Ensure renal function is normal and that phosphorus level is low before administering this drug. Monitor.

Adrenal Agent

Adrenal cortex produces glucocorticoids, mineralocorticoids and adrenal sex hormonesFludrocortisone (Florinef, Apothecon) only mineralocorticoid described in text. Used in conjunction with a glucocorticoid.

PearlsThiazide diuretics are contraindicated in patients with hypercalcemia as they decrease urinary excretion of calciumMust consider albumin levels when looking at calcium levelsFor children on growth hormone, must follow bone growth and epiphysial closure, record ht. and wt. weekly

PearlsDietary calcium is superior to supplementalMenopausal women on HRT should have 1000mg of calcium daily, for those not taking hormones, should have 1500mg per day

PearlsVasopressinwatch for water intoxication, chest pain, MI, hypertension, nausea and diarrheaOxytocincan result in uterine ruptureOctreotide can cause arrhkythmias, bradycardia, headache, hyperglycemia, injection site pain and symptoms of gallstones

Acute hypercalcemiaMedical emergencyFor severe symptoms or level >12mg/dL, rehydrateIV salineLasixAlendronate (Fosamax) or zolendronate (Zometa)Monitor serum calcium levelsCalcium channel blockers not so effective when hypercalcemic

Thyroid and Antithyroid DrugsThyroid produces thyroxine, triidothyronine, and calcitoninThyroxine is called T4 (has 4 atoms of iodine)Triidothyronine has 3 atoms of iodine so is called T3

ThyroidRequired for normal growth and development and are critical for brain and skeletal development and maturationIncrease rate of cellular metabolism and oxygen consumptionIncrease heart rate, force of contraction and cardiac output

ThyroidIncrease fat metabolism including metabolism of cholesterolInhibition of pituitary secretion of TSH

Thyroid DisordersGoiter is an enlargement of the thyroid possibly due to a lack of iodine in the diet; thyroiditis, inflammation from infection, tumors, or hyper or hypofunction of the thyroidTo compensate for the iodine deficiency, the pituitary secretes more TSH; thyroid enlarges producing more hormone; possibly effecting a normal hormone level

Goiter cont.If insufficient amount of hormone, hypothyroidism will resultCorrection of goiter involves replacing iodine;replacement of thyroid hormone; may have some regression of goiter or may need excision

HypothyroidismOccurs secondary to disease or destruction of thyroid gland resulting in insufficient production of thyroid hormonesCauses include: Hashimotos thyroiditis, previous exposure to radiation, treatment with amiodarone, lithium or iodine.

HypothyroidismCongenital (Cretinism)may occur with a lack of iodine in the mothers diet. Symptoms will be manifested in infancy and if left unchecked, will result in severe mental retardationHypothyroidismmay be subclinical but may progress. May have mildly elevated TSH with normal thyroxine levels.

HypothyroidismSigns and symptoms initially vague thenbecome progressively more pronounced and include:Cold intolerance, elevated cholesterol, constipation, fatigue, aches and pains, puffy appearance of face and eyelids, mental sluggishness, lethargy, capillary fragility, decreased BP, anemia, bradycardia

HypothyroidismTreatment is exogenous replacement of thyroxine Replacement indicated if TSH level is higher than 10 microunits/L

HypothyroidismMyxedema coma is severe hypothyroidismCharacterized by hypothermia, cardiovascular collapse, coma, hyponatremia, hypoglycemia, and lactic acidosisPredisposing factors include: cold, infection, CNS depressants.

HypothyroidismTreatment=replacement of thyroid hormone. Synthetic levothyroxine is the drug of choice. If subclinical, tx if TSH is higher than 10 microunits/L. Controversial if should start tx at levels between 5-10 mu/LIn myxedema coma, tx will be with IV levothyroxine.

HyperthyroidismCharacterized by excessive secretion of thyroid hormone.May be associated with overtx w/thyroid drugs, nodular goiter, thyroiditis, functioning thyroid cancer, pituitary adenoma resulting in excess TSH secretion.

HyperthyroidismSubclinical hyperthyroidism is defined as a reduced TSH (below 0.1 microunit/L) and normal thyroixine and triiodthyronine levels. Most common cause is excess thyroid hormone replacementGreatly increases the risk for atrial fibrillation and for osteoporosis

HyperthyroidismThyroid storm or thyrotoxic crisis is a severe complication of hyperthyroidism resulting in: severe tachycardia, fever, dehydration, heart failure and coma.

HyperthyroidismTreatment depends on cause. May warrant surgery or radioactive iodine therapy. Graves diseaseradioactive iodine, subtotal thyroidectomy.Antithyroid drugs include thioamide derivatives (propylthioruracil and methimazole) and iodine preparations.

Drugs used in HypothyroidismLevothyroxine (synthroid, Levothroid) a synthetic preparation of T4. Uniform potency and dosing. Liotrix (Euthroid, Thyrolar) contains both levothyroxine and triiodthyronine in a 4:1 ratio approximating natural thyroid hormone.

Drugs used in HyperthyroidismPropylthiouracil (PTU) is the prototype of the thioamide antithyroid drugsCan be used alone or incombination with thyroidectomy and in the treatment of thyrotoxic crisisActs by inhibiting conversion of T4 to more active T3. Does not affect thyroid stores. Short acting requiring tid dosing.

Drugs used in hyperthyroidismMethimazole (Tapazole)similar to PTU Strong iodine solution (Lugols solution) and saturated solution of potassium iodide (SSKI)these drugs inhibit release of thyroid hormone, causing them to accumulate in the gland. Lugols decreases the size and vascularity of the thyroid before thyroidectomy.

Iodine preparations should not be followed by PTU, methimazole or radioactive iodine because the latter drugs cause release of stored thyroid hormone and can precipitate crisis.

Sodium iodide 131Radioactive isotope of iodine. Thyroid picks up the isotope from circulating blood. Act by emitting beta and gamma rays which destroy thyroid tissue and decrease production of thyroid hormones. Also used for diagnosis and in the treatment of cancer.Usually given in a single dose as outpatient. No special precautions. May be 6 months for therapeutic effects. During this time, on maintenance medications.

Antithyroid DrugsIodine preparations and thioamide antithyroid drugs are contraindicated during pregnancy as can lead to goitor and hypothyroidism in the fetus or newborn