H&P

HORMONES

Uses of
GnRH
agonists

Suppression therapy –
androgen or estrogen
production (flare first)
HYPOTHALAMIC HORMONES
2. GnRH Antagonists (ganirelix, cetorelix, abarelix,
degarelix)
a. Advantages over GnRH agonists given continuously: no
flare in hormone levels, more rapid onset of antagonist
effects
b. Uses: prostate cancer (alternative to GnRH agonists)
ANTERIOR PITUITARY HORMONES
Growth Hormone
1. Growth Hormone (GH) agonist, Somatropin
b. Therapeutic use: growth hormone deficiency;
diseases of growth failure such as Prader-Willi and Turner
syndrome; AIDS wasting or cachexia; idiopathic short stature

c. Alternative: Mecasermin – complex of IGF-1 and IGF

binding protein-3 for patients deficient in IGF-1 who don’t
respond to exogenous GH
ANTERIOR PITUITARY HORMONES
Growth Hormone
2. GH antagonists
a. Somatostatin analogs (octreotide, lanreotide): somatostatin
inhibits the release of GH, glucagon, insulin, and gastrin

b. Therapeutic use: 1) acromegaly or gigantism (GH-secreting

adenoma), 2) other hormone-secreting tumors such as
carcinoid syndrome, gastrinoma, glucagonoma, 3) bleeding
esophageal varices
ANTERIOR PITUITARY HORMONES
FSH and LH

1. Menotropins “Meno is mixed”

2. Urofollitropin “folli is FSH”

3. Lutropin, recombinant hCG “Lu is LH”

ANTERIOR PITUITARY HORMONES
Prolactin
Prolactin antagonists
a. Dopamine agonists: bromocriptine and cabergoline

b. Therapeutic use: hyperprolactinemia

Typical antipsychotics
POSTERIOR PITUITARY HORMONES
Vasopressin (ADH)
b. Therapeutic use of vasopressin agonists: desmopressin is
the drug of choice for central diabetes insipidus (V2); used in
primary nocturnal enuresis; hemophilia A or Von
Willibrand’s DZ
c. Therapeutic use of vasopressin antagonists: conivaptan
(V1, V2 blocker) and tolvaptan (V2 blocker) are used to treat
SIADH; the drugs are sometimes called aquaretics
(demeclocycline used more)
 Insulin Forms
Mealtime
Lispro, Aspart, Glulisine – No LAG with these, rapid onset
Regular

Basal
Glargine, Detemir - “large and determined to stay”
NPH
+ protamine
 Metformin
• “Euglycemic,”
• ↓ postprandial glucose levels, but does not cause hypoglycemia
or weight gain
• Mechanism:
• May involve ↑ tissue sensitivity to insulin and/or ↓ hepatic
gluconeogenesis
• Use:
• Monotherapy or combinations (synergistic with sulfonylureas)
• Side Effects:
• Lactic acidosis
• GI distress is common
 Sulfonylureas
• Glipizide
• Glyburide
Repaglinide:
works just like
SFUs
• Side Effects:
• Hypoglycemia
• Weight gain
 Thiazolidinediones:
Pioglitazone and Rosiglitazone
• Mechanisms: insulin sensitizers

• Bind to nuclear PPAR involved in transcription of insulin-

responsive genes sensitization of tissues to insulin, plus
hepatic gluconeogenesis and triglycerides and insulin receptor
numbers
• Side Effects:
• Less hypoglycemia than sulfonylureas
• Weight gain
Most common side effects
• Edema
 Alpha-glucosidase Inhibitors:
Acarbose, Miglitol
• Mechanisms:
• Block alpha glucosidase in the brush border of the small intestine
• Decrease post-prandial glucose

SGLT2 Inhibitors: Canagliflozin and

other “gliflozins”
• Mechanisms:
• Block sodium-glucose co-transporter 2 in the PCT to decrease
glucose reabsorption
 Actions of Drugs Affecting GLP-1

NOTE -
Pramlintide: synthetic version of amylin, slows the rate of food
absorption from intestine, decreases glucose production, and
decreases appetite. It is used in type 1 and 2 diabetes.
 Hypothyroidism
TYPE OF HYPOTHYROIDISM CAUSE

Primary Failure of the thyroid gland itself (iodine def. or Hashimoto’s)

Secondary Pituitary failure causing decreased TSH production

Tertiary Hypothalamic failure causing decreased TRH production

Congenital Hypothyroidism at birth (most common preventable cause of

Hashimoto’s dz = mental retardation worldwide; results in cretinism if not treated
antibodies against with thyroid hormone replacement therapy)
thyroid peroxidase
Patient Symptoms and Signs: fatigue, lethargy, cold intolerance, mental
slowness, depression, dry skin, constipation, mild weight gain, fluid
retention, muscle aches, goiter (only with primary), bradycardia, cool and dry
skin, nonpitting edema, facial puffiness
 Treatment of Hypothyroidism
1. Levothyroxine (T4)
a. Is the DOC for hypothyroidism (effective and low cost)
2. Liothyronine (T3) – treating Myxedema Coma (High cost)
3. Liotrix - a mixture of T4: T3 in a 4:1 ratio; expensive and
no clinical advantage over T4 alone
4. Dessicated thyroid – is a naturally occurring preparation
from pig, beef, or sheep thyroid gland available in ~4:1 ratios
of T4: T3; antigenic, inexpensive
 Hyperthyroidism
oxidation organification coupling
PTU,
Methimazole
Grave’s disease
block #2
characterized by
increased thyroid
hormone
production,
diffuse goiter, and
IgG antibodies I131 taken up Iodide blocks
and destroys release of3TT4
that bind to and thyroid (DOC)
activate the TSH
receptor.

PTU, Propranolol
COMMONLY USED CORTICOSTEROIDS
Activity (potency relative to hydrocortisone)
Drug Anti-Inflammatory Salt-Retaining Duration
Hydrocortisone (cortisol) 1.0 1.0 Short
Cortisone 0.8 0.8 Short
Prednisone 4.0 0.3 Intermediate
(prednisolone, methylprednisolone)

Triamcinolone 5.0 0.0 Intermediate

Betamethasone 30.0 0.0 Long
Dexamethasone 30.0 0.0 Long
Fludrocortisone 10.0 250.0
CLINICAL USES OF ADRENAL CORTICOIDS
1. Chronic Adrenal Insufficiency (Addison’s Disease)
2. Acute Adrenal Insufficiency
Treatment: 20-30 mg of hydrocortisone daily (chronic) or
100 mg/day (acute); supplementation with fludrocortisone
is necessary at the lower doses
1. Congenital Adrenal Hyperplasia
Most commonly caused by a defect in 21β-hydroxylase
Causes decreased cortisol and aldosterone production
and a compensatory increase in ACTH
Treat with hydrocortisone +/- fludrocortisone
CLINICAL USES OF ADRENAL CORTICOIDS
4. Cushing’s Syndrome
• Treatment: surgical removal of the tumor producing
ACTH or cortisol, irradiation of the pituitary tumor,
hydrocortisone up to 300 mg/day on the day of surgery
and reduced over to time to maintenance levels
5. Aldosteronism
• Primary aldosteronism (renin independent)
• hypertension, weakness because-renal loss of potassium
leads to hypokalemia, alkalosis, and Na in serum
• Treatment: Remove of the tumor or spironolactone
 Treat primary aldosteronism
X – by spironolactone, eplerenone

V2 X – by demeclocycline, “vaptans”
(Treat SIADH)
 Inhibitor of Glucocorticoids and Mineralocorticoids

Causing Syndrome

Cimetidine
 ANTIANDROGENS
1. GnRH antagonists (ganirelix and other “relix”)
a. Suppresses production of LH to decrease testosterone
production
b. Used in prostate cancer

2. Ketoconazole
a. Blocks 17α-hydroxylase to prevent testosterone
production
b. Rapid reduction of testosterone in prostate cancer
 ANTIANDROGENS
3. Androgen receptor blockers (flutamide)
a. Together with continuous GnRH agonists (leuprolide) for prostate
cancer; to avoid tumor flare with GnRH drugs alone - for metastasis
PC
b. Combination blocks production and action of testosterone
4. 5-α Reductase Inhibitors (finasteride)
a. MOA: block the conversion of testosterone to DHT
b. Use: BPH; male pattern baldness
 ERECTILE DYSFUNCTION
1. PDE 5 Inhibitors (sildenafil, vardenafil, tadalafil)
a. MOA: block the metabolism of cGMP by inhibiting PDE5;
increased cGMP activates PKG which activates a phosphatase
causing dephosphorylation of the myosin light chain
b. side effects: headache and facial flushing (vasodilator effect);
blurred vision or loss of blue-green color discrimination (PDE 6
inhibitory effect; pilots beware); tadalafil (36 hr, (“the
weekender”) has the greatest inhibitory effect on PDE 11 –
lower back and limb pain in 7-30% of patients
c. Drug interactions: PDE 5 inhibitors and nitrates
(Nitroglycerin) – due to increased production of NO and
drop in BP
 ESTROGENS
Clinical Note: menopausal symptoms such as hot flushes
often is short term, while prevention of osteoporosis is long-
term.
Never use unopposed estrogens in
women with an intact uterus
Toxicity
a. in hypogonadal girls, the dosage must be adjusted
carefully to prevent premature closure of the epiphyses
of the long bones and short stature
b. when used as HRT, estrogen increases the risk of
endometrial cancer; this effect is prevented by
combining the estrogen with a progestin
 ESTROGEN ANTAGONISTS
1. Selective estrogen receptor modulators (SERMS):
tamoxifen, raloxifene
a. MOA: act as partial agonists at estrogen receptors
b. clinical use: estrogen receptor (+) breast cancer;
raloxifene for osteoporosis;
c. side effects: tamoxifen has an increased risk of
endometrial cancer
Drug Bone Breast Endometrium
Tamoxifen Agonist Antagonist Agonist

Raloxifene Agonist Antagonist Antagonist

 competitive selective
ER+ or tamoxifen
resistance breast

antagonist at progesterone
progesteron receptor
modulator
cancer

e receptors
increase the (SPRM), partial
amplitude of Use before PG agonist
Advance breast
cancer FSH and LH
Abortifacient Emerg. Contr.
blocks Use: infertility
receptor but (levonorgestrel
to stimulate
also alters for also)
degradation
ovulation
 HORMONAL CONTRACEPTIVES
Three types of oral contraceptives for women are available
in the United States:
1) combination estrogen-progestin tablets that are taken
in constant dosage throughout the menstrual cycle
(monophasic preparations);
2) combination preparations (biphasic and triphasic) in
which the progestin or estrogen dosage, or both,
changes during the month (to more closely mimic
hormonal changes in a menstrual cycle): and
3) progestin-only preparations.
 HORMONAL CONTRACEPTIVES
1. Estrogen (ethinyl estradiol)
2. Progestins
a. norethindrone, norgestrel, levonorgestrel (testosterone
derivatives), norgestimate, desogestrel, drospirenone
b. norelgestromin (transdermal patch), etonogestrel (vaginal
ring)
 HORMONAL CONTRACEPTIVES
3. Progestin-only Preparations
a. Medroxyprogesterone (Depo-Provera) – IM injection
lasts 3 months
b. Etonogestrel (Implanon) – 4 cm long implant lasts 3
years (under skin of upper arm)
c. Norethindrone (Micronor) - oral
 Side Effects of COCs
1. Cardiovascular
a. Nonsmokers without other risk factors (HTN, diabetes)
= low risk
b. WHO precautions state that COC are
contraindicated in women >35 who smoke ≥ 15
cigarettes/day (use progestin only preparations)
c. Thromboembolism

2. Androgenic activity
hirsutism and acne from norethindrone mainly (testosterone
derivative)
TREATMENT OF DISORDERS OF MINERAL
HOMEOSTASIS AND BONE METABOLISM
1. Treatment of Hypocalcemia

• Ca++ salts such as CaCl2, Calcium gluceptate, and

Calcium gluconate are used for hypocalcemic tetany
and laryngospasm
• Calcium gluconate is the treatment of choice for
severe hypocalcemic tetany; given IV (never IM)
TREATMENT OF DISORDERS OF MINERAL
HOMEOSTASIS AND BONE METABOLISM
2. Treatment of Hypercalcemia
a. oftentimes patients with hypercalcemia are severely
dehydrated so large volumes of isotonic saline must
be used
b. bisphosphonates
c. calcitonin (Miacalcin): acts specifically on osteoclasts
to inhibit bone resorption
d. corticosteroids: in sarcoidosis, lymphoma -
hypervitaminosis D
3. Indications to use Vitamin D

a. prophylaxis and cure of nutritional rickets – due to

inadequate sunlight or dietary deficiency; give 3,000-
4,000 units/day (normal is 400 units/day)
b. treatment of metabolic rickets and osteomalacia
c. treatment of hypoparathyroidism – dihydrotachysterol
(DHT) is used; other vitamin D preps also effective;
DHT has faster onset and shorter duration of action
Active, doesn’t need
liver or kidneys
25-OH from liver
1-OH from kidneys
DRUGS USED IN OSTEOPOROSIS
1. Bisphosphonates (alendronate, risedronate, zoledronate,
pamidronate, tiludronate, ibandronate)
a. MOA: inhibit osteoclast activity
b. therapeutic use: considered the DOC in the
management of osteoporosis; Paget disease;
hypercalcemia
c. adverse effects: esophageal irritation, esophagitis,
heartburn. osteonecrosis of the jaw is the most
serious side effect
2. Teriparitide
a. MOA: synthetic PTH fragment that can increase
new bone formation (it is the only currently available
drug that can do this)
3. SERMs (raloxifene)
4. Denosumab* – RANKL inhibitor (NFκ – B pathway)
inhibits osteoclast activity
5. Calcium
6. Vitamin D
7. Calcitonin – available as a nasal spray