Drugs affecting the Endocrine

System
Nursing 3703
Pharmacology
By Linda Self
Hypothalamic, Pituitary,
Parathyroid, and Adrenal
Hormones
Hypothalamus secretes releasing
hormones affecting both the anterior
and posterior pituitary
Posterior pituitary secretes ADH and
OxytocinADH conserves water,
Oxytocin functions in childbirth and
lactation
Anterior pituitary hormones and target
tissues
1. GH---most body tissues
2. ACTH (corticotropin)adrenal cortex
glucocorticoids, mineralocorticoids,
androgens
3. TSHthyroid--thyroxine
4. FSH and LHovaryestrogen and
progesterone
5. LH in malestestistestosterone
6. Prolactinaffects the breast
7. Melanocyte stimulating hormone--
melanocytes
Parathyroid and calcium regulation
Parathyroidparathormone. Regulates calcium
and phosphate metabolism. When serum levels
increase, phosphorus decreases
In concert with calcitonin and vitamin D, PTH
regulates normal serum levels of calcium
Affects GI absorption of calcium, movement of
calcium to and from bone, and calcium excretion
via kidneys
Parathyroid and calcium
50% of calcium is bound, the other 50% is
free.
The unbound portion is instrumental in the
normal function of all cells
Calcium constantly shifting between bone
and serum
Parathyroid and calcium
Calcium regulates:
1. Cell membrane permeability
2. Nerve cell excitability and transmission
3. Contraction of cardiac, skeletal and smooth
muscle
4. Blood coagulation
5. Hormone secretion
6. Catecholamine release
7. Enzyme activity
Parathyroid, calcium and
phosphorus
Phosphorus combines with calcium in bones
and teeth as CaPO4
Phosphorus functions:
1. For cellular production of energy
2. As coenzyme with B vitamins
3. Phosphate buffer system
4. Phospholipids
5. Part of DNA and other nucleic acids so is
necessary for growth and reproduction

Calcitonin
Secreted by thyroid
Responds to high serum levels of calcium
Lowers serum calcium by decreasing
movement of calcium from bone to serum
and increasing urinary excretion of calcium
Short-acting
Vitamin D
Fat soluble vitamin that functions as a
hormone
Functions in regulation of calcium levels
by increasing intestinal absorption of
calcium and mobilizing calcium from bone
Must be converted to intermediate
metabolite in liver then to calcitriol in
kidneys
Vitamin D
PTH and adequate hepatic and renal
function necessary to produce calcitriol the
active form of vitamin D (1,25
dihydroxyvitamin D)
Adrenal Hormones
Aldosterone is the primary and most
potent mineralocorticoid
Conserves sodium through its action on
cells in distal nephron
Regulated by the renin-angiotensin-
aldosterone system
Protein bound amounts of aldosterone
serve as depot or storage
Effects of Mineralocorticoids
Conserve sodium and water and
eliminating potassium
Secretion of aldosterone is largely
controlled by kidneys
Inadequate 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 Hormones
Generally must be given by injection or
intranasally as will be broken down by GI system
Are equivalent to gonadotropin releasing
hormones
Chronic administration inhibits gonadotropin
secretion
Gonadorelin (Factrel)used for diagnostic
testing of gonadotropic function
Goserelin (Zoladex)endometriosis, metastatic
breast and prostate cancer


Hypothalamic Hormones
Leuprolide (Lupron)used in advanced
prostatic cancer, central precocious
puberty, endometriosis, uterine fibroid
tumors
Adverse effects are those of estrogen or
testosterone deficiency; may cause
depression, bone pain and difficulty in
urinating
Hypothalamic and Pituitary Agents
Octreotide (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 Hormones
Corticotropin (Acthar Gel, or ACTH)diagnostic
test of adrenal function
Somatrem (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 Hormones
Menotropins (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 Hormones
Desmopressin (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 Hormones
Oxytocin (Pitocin)promotes uterine
contractility and is used to induce labor
and in the postpartum period to control
bleeding.
Drugs used for Calcium and Bone
Disorders
Bisphosphonatesalendronate
(Fosamax), risedronate (Actonel) and
zoledronate (Zometa)
Bind to bone and inhibit calcium resorption
Poorly absorbed from GI tract
Take on empty stomach, with water, 30
minutes before other intake
Drugs Used for Calcium and Bone
Disorders
Calcitonin-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
Disorders
Symptomatic hypcalcemia, calcium
gluconate may be given intravenously
Oral preparations (e.g. calcium citrate or
carbonate) available. For nutritional
deficiency of calcium and for osteopenia.
Drugs used for calcium and bone
disorders
Corticosteroids 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
disorders
Estrogens and Antiestrogens
Estrogens 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 calcium
Raloxifen (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 calcium
Teriparatide (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 calcium
Vitamin 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 calcium
Sodium chloride solution useful as inhibits
reabsorption of calcium in renal tubules
Bone and calcium
Neutro-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
hormones
Fludrocortisone (Florinef, Apothecon) only
mineralocorticoid described in text. Used
in conjunction with a glucocorticoid.
Pearls
Thiazide diuretics are contraindicated in
patients with hypercalcemia as they
decrease urinary excretion of calcium
Must consider albumin levels when looking
at calcium levels
For children on growth hormone, must
follow bone growth and epiphysial closure,
record ht. and wt. weekly
Pearls
Dietary calcium is superior to
supplemental
Menopausal women on HRT should have
1000mg of calcium daily, for those not
taking hormones, should have 1500mg per
day
Pearls
Vasopressinwatch for water intoxication,
chest pain, MI, hypertension, nausea and
diarrhea
Oxytocincan result in uterine rupture
Octreotide can cause arrhkythmias,
bradycardia, headache, hyperglycemia,
injection site pain and symptoms of
gallstones
Acute hypercalcemia
Medical emergency
For severe symptoms or level >12mg/dL,
rehydrate
IV saline
Lasix
Alendronate (Fosamax) or zolendronate
(Zometa)
Monitor serum calcium levels
Calcium channel blockers not so effective when
hypercalcemic
Thyroid and Antithyroid Drugs
Thyroid produces thyroxine,
triidothyronine, and calcitonin
Thyroxine is called T4 (has 4 atoms of
iodine)
Triidothyronine has 3 atoms of iodine so is
called T3
Thyroid
Required for normal growth and
development and are critical for brain and
skeletal development and maturation
Increase rate of cellular metabolism and
oxygen consumption
Increase heart rate, force of contraction
and cardiac output
Thyroid
Increase fat metabolism including
metabolism of cholesterol
Inhibition of pituitary secretion of TSH
Thyroid Disorders
Goiter 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 thyroid
To 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 result
Correction of goiter involves replacing
iodine;replacement of thyroid hormone;
may have some regression of goiter or
may need excision
Hypothyroidism
Occurs secondary to disease or
destruction of thyroid gland resulting in
insufficient production of thyroid hormones
Causes include: Hashimotos thyroiditis,
previous exposure to radiation, treatment
with amiodarone, lithium or iodine.
Hypothyroidism
Congenital (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 retardation
Hypothyroidismmay be subclinical but
may progress. May have mildly elevated
TSH with normal thyroxine levels.
Hypothyroidism
Signs and symptoms initially vague then
become 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
Hypothyroidism
Treatment is exogenous replacement of
thyroxine
Replacement indicated if TSH level is
higher than 10 microunits/L
Hypothyroidism
Myxedema coma is severe hypothyroidism
Characterized by hypothermia,
cardiovascular collapse, coma,
hyponatremia, hypoglycemia, and lactic
acidosis
Predisposing factors include: cold,
infection, CNS depressants.

Hypothyroidism
Treatment=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/L
In myxedema coma, tx will be with IV
levothyroxine.
Hyperthyroidism
Characterized 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.
Hyperthyroidism
Subclinical 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 replacement
Greatly increases the risk for atrial
fibrillation and for osteoporosis
Hyperthyroidism
Thyroid storm or thyrotoxic crisis is a
severe complication of hyperthyroidism
resulting in: severe tachycardia, fever,
dehydration, heart failure and coma.
Hyperthyroidism
Treatment 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 Hypothyroidism
Levothyroxine (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 Hyperthyroidism
Propylthiouracil (PTU) is the prototype of
the thioamide antithyroid drugs
Can be used alone or incombination with
thyroidectomy and in the treatment of
thyrotoxic crisis
Acts by inhibiting conversion of T4 to more
active T3. Does not affect thyroid stores.
Short acting requiring tid dosing.
Drugs used in hyperthyroidism
Methimazole (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 131
Radioactive 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 Drugs
Iodine preparations and thioamide
antithyroid drugs are contraindicated
during pregnancy as can lead to goitor and
hypothyroidism in the fetus or newborn