ADRENAL HORMONE THERAPY
MOA Uses
OVINE CRH
Corticorelin (like CRH stimulates
Corticorelin
ant. pituitary gland to make ACTH
ACTH DERIVATIVES
Cosyntropin
Like ACTH stimulate adrenal
Tetracosactide glands to produce cortisol
Athar
CORTICOSTEROIDS
Fludrocortisone: mineralocorticoid
Fludrocortisone
Hydrocortisone: glucocorticoid
Hydrocortisone
CYP11A1 (Desmolase) Inhibitor:
↓cholesterol → pregnenolone→
Aminoglutethimide all adrenal hormones
CYP11B1 (11 -hydroxylase) Inh:
↓Aldosterone & Cortisol
High dose:
CYP17 (17α-hydroxylase) inhib. →
↓Cortisol & ↓Androgens
Ketoconazole
Higher doses:
CYP11A inhibitor →
↓Steroidogeneses in all tissues
CYP11B1 (11 -hydroxylase) Inh:
Metyrapone ↓Aldosterone & Cortisol
↑Androgens & 11-deoxycortisol
Mitotane ? (Similar structure to DDT)
Aldosterone analog
Spironolactone
K+ sparing diuretic
Side Effects / CIs
Diagnosis: CRH stimulation test
→for pituitary function
Diagnosis: ACTH stimulation test (IV)
→diff. 1 . 2 ad e al i fficie c
→ should ↑cortisol in 3-60 min
Treatment: Myasthenia gravis
Addi di ea e - both
21-hydroxylase def. (CAH) both
Hypoaldosteronism - Fludrocortisone
Cushing s (CYP11A1)
Prostate & breast cancer (CYP11B1)
C hi g (most effective steroid
biosynthesis inhibitor)
Hypercorticism (adrenal neoplasms,
ACTH producing tumors)
Adjunct to pituitary radiation
C hi g di ea e
Adrenocortical carcinoma
(anti-neoplastic)
C Di ea e - 1 H e ald e
-Hypokalemic alkalosis + HTN
-Hypokalemia: weakness, paresthesia
-Alkalosis: Arrhythmias
Other / Drug Interactions
Prolonged use → HPA axis
suppression, HTN
↓Diuretic effects
Immunosuppression
Severe hypokalemia w/K+
Contraindications: Surgery,
depleting diuretics
1 ad e al i fficie c ,
heart failure
GI
Neurological
Maculopapular rash ↓Dexamethasone levels
Adrenal Insufficiency need
mineralo/glucocorticoid Rx
Hepatic dysfunction
Hirsutism
Hirsutism (↑androgens)
Not available in pharmacies
HTN (↑11-
(compassionate use)
deoxycorticosterone)
Hypocorticism
Spironolactone ↓effects
Nausea, dizziness, fainting
i m
Also Amiloride (K+ sparing) &
Ca2+ channel blockers (HTN)
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 REPRODUCTIVE HORMONE THERAPY
MOA Uses Side Effects Other
Diagnostic test (Gonadorelin HCl)
→pituitary function (LH, FSH release)
↓Androgen therapy efficacy
Females menopause Sx,
Infertility (Gonadorelin) promotes
GnRH ANALOGS depression, vaginal dryness, Nasal Decongestants
physiologic cycle
Gonadorelin Continuous stimulation of breast atrophy (Nafarelin acetate) = GnRH
GnRH-Dependent Precocious puberty
anterior pituitary → Males testicular atrophy, analogs that potential effects
Goserelin (<9 years old)
receptor downregulation → gynecomastia, ↓HCT
Leuprolide Hormone responsive tumors
decreased FSH & LH release Both - ↓libido, ↓bone density, Contraindications:
Triptorelin - Symptomatic Tx
dizziness/vertigo, insomnia, Pregnancy, breast feeding
↓Endometriosis, uterine leiomyomas,
headache Osteoporosis
acute intermittent porphyria
U D d agi al bleedi g
(Goserelin, leuprolide, triptorelin)
Pharmacologic castration (triptorelin)
GnRH ANTAGONISTS Infertility & ART inhibits premature
Nausea Contraindications (G & C):
Ganirelix Inhibits secretion of LH surge in women
Headaches Primary ovarian failure
Cetrorelix LH >> FSH Prostate cancer (Abarelix) prevents
Hypersensitivity (Abarelix) Pregnancy, breast feeding
Abarelix adverse consequences of tumor growth
Diagnosis: hCG pregnancy
hCG mimics LH action
GONADOTROPICS LH surge ovulation timing (36 hrs after)
urine of pregnant women, Females multiple
hCG Dxs of reproductive system
Menotropin equal pregnancies & ovarian
Menotropins LH & FSH urine of post- hyperstimulation syndrome
♀ Infertility/ART PCOD & anovulation
Follitropin-α menopausal ♀
♂ Infertility 2 LH/FSH deficie c
Follitropin- Follitropin recomb. FSH Males - gynecomastia
CRYPTORCHIDISM (hCG) stimulates
testicular descent
Tamoxifen Tamoxifen
ERα+ & ER/PR+ Breast Cancer Tamoxifen: Endometrial Ca Tamoxifen: Resistance usually
-ERα antagonist @ breast
develops after 5 yrs Rx
SERMs -ERα agonist @ uterus -Prophylaxis & Adjuvant Treatment
Tamoxifen Raloxifene Raloxifene
Osteoporosis & Invasive Breast Cancer Raloxifene: ↓Warfarin efficacy,
Raloxifene -ERα antagonist @ breast & Both: 2-3x ↑risk of DVT, PE
in post-menopausal women ↓Absorption w/ Ampicillin
uterus
-ER agonist @ bone Other Benefits: ↓LDL
Clomiphene Clomiphene:
Clomiphene
Infertility - ↓negative feedback by Multiple births
ANTI-ESTROGENS -Weak agonist @ ERs
endogenous estrogen → ↑FSH pulse Ovarian cysts
Clomiphene -Strong antagonist @ ERs
amplitude → multiple follicular dvpmt
Fulvestrant Fulvestrant
Fulvestrant
-Pure antagonist @ ERs
Tamoxifen-resistant ER+ Breast Ca.
ESTROGEN SYNTHESIS
INHITORS nd
Exemestane 2 Line or Adjuvant Rx for Do NOT protect bones like
Aromatase inhibitors
Tamoxifen-resistant ER+ Breast Cancer tamoxifen
Anastrozole
Letrozole

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 Drug-Int:
Uterine bleeding
↓Glucocorticoids, coagulant
st Abdominal pain/cramping
PR antagonist: Terminate pregnancy (1 trimester w/PG) effects
ANTI-PROGESTERONE Contraindications:
↓Implantation of embryo Post-coital contraception CYP3A4 inhibitor →
Mifepristone ↑Uterine contraction (↓implantation) morning-after pill
Vaginal bleeding, adrenal
↑Protease inhibitor, CCB &
dysfunction, asthma (anti-
carbamazepine effects
glucocorticoid effect)
O he CI :
OCPs Thrombosis (MI, stroke esp. Pregnancy,
Post-menopausal HRT st
in 1 year of therapy) Incomplete bone growth
-↑bone density, ↓LDL, ↑HDL, ↓S → CI = stroke, ♥ Dx, DVT
ESTROGENS Drug Interactions:
Primary hypogonadism
Estradiol Estradiol poor oral Endometrial/Breast Ca ↓Anti-coagulants,
↓Ovulation in dysmenorrhea, hirsutism
Ethinyl-estradiol
bioavailability (patch, IM
Infertility → CI = Breast/uterine Ca risk, hypoglycemics effects
Depo, topical, vaginal ring) d d agi al bleedi g ↓↑Benzodiazepine effects
Mestranol ↑TCA, -blocker,
(prodrug) Other Benefits (w/progestin):
↑Negative feedback on FSH HTN, Bloating (Fluid retention) corticosteroid effects
Premarin ↓Dysmenorrhea,
& prevents LH surge Bleeding CYP inducers/substrates:
↓Blood loss during menstruation,
∆Menstruation S . J h W , Tetracycline,
Regulate cycle in anovulatory women,
Ampicillin, HIV protease
↓Benign breast & ovarian cysts,
♂Gynecomastia, impotence inhibitors, Rifampin→ ↓OCP
50%↓ in ovarian & endometrial cancer
effect
Progesterone low oral Contraception Formulations
bioavailability (patch, oil- Monophasic =21 days fixed [estrogen] & fixed [progestin]
PROGESTINS containing gelatin capsules, → 7 days hormone-free pills
Progesterone vaginal gels, slow-release OCPs (gonanes > estranes)
-Alone or in combo with estrogen Biphasic = fixed [estrogen] & 2 different [progestin]
Medroxyprogesterone IUDs)
Emergency contraceptive (low for 7-10 days → high for 11-14 days)
Estranes: -75% effective if taken within 72 hrs Limits exposure to high [progestin]
Norethindrone Androgenic side effects:
-Does not harm established pregnancies
Gonanes: (estranes>gonanes) Triphasic = fixed [estrogen] & 3 different [progestin]
-High levels progestin → ↓implantation
Norgestrel -Levonorgestrel most common Better mimics hormonal changes in menstrual cycle
↑Negative feedback of Post-menopausal HRT
Nomegestrol GnRH Progestin Only = for smokers >35 & those at high risk of
Norgestimate -↓Estrogen-induced endometrial hyperplasia
↓Follicular dvpmt, ovulation -Medroxyprogesterone is DOC CV event or thrombosis (oral daily, subdermal implant 5
Desogestrel ↓Uterine receptiveness Uterine bleeding disorders yrs, IM injection 3 mos., slow-release IUD)
Levonorgestrel ↑Cervical mucus Premature labor (↓uterine contraction)
Gestogene ↓Peristalsis (tubes) ↑Appetite in AIDS/Cancer Extended Regime = 91 day estrogen/progestin & placebo pill
Drospirenone ↓Uterine contraction Period every 3 mos w/ risk of breakthrough bleeding
↓Endometrial proliferation
by estrogen

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 REPRODUCTIVE HORMONE THERAPY
MOA Uses Side Effects Other
TESTOSTERONE
Testosterone (patch) Male hypogonadism ↓Spermatogenesis (negative feedback)
17α alkylated androgens Andropause Acne - women
Testosterone low oral Virilization, hirsutism children, women
Methyltestosterone (oral) ↓impotence, ↑muscle mass/strength
bioavailability (transdermal ↑BPH & prostate cancer older men
17α hydroxyl group esters ↑cognition, sense of well-being
patches) Hepatotoxicity (for 17α alkylated androgens)
Testosto. propionate (IM) Prostate Cancer
Testost. enanthate (IM) Male pattern Baldness ↑LDLs
Testo. undecanoate (oral)
ANDROGEN ANTAGONISTS Metastatic Prostate Cancer Hepatotoxicity Contraindication:
Inhibit Androgen R → (Flutamide >> Bicalutamide) Women of childbearing age
Flutamide (in combo w/GnRH analogs)
↓nuclear gene expression (male fetus → female dvpmt)
Bicalutamide ♀Excessive hirsutism
Finasteride 5α-reductase inhibitor BPH & male pattern baldness Fi e a ide
LACTOTROPIC HORMONE THERAPIES
Hyperprolactinemia
D2 agonists → Nausea, headaches ↑Anti-HTN effects
DOPAMINE AGONISTS ♀ = galactorrhea, amenorrhea, infertility
↓PRL secretion → shrink PRL Orthostatic HTN ↓D2 antagonists effects (anti-
Bromocriptine Drug → restores ovulation
tumors & restore ovulation in (presynaptic inhibition) psychotic, phenothiazine)
♂ =↓libido, impotence, infertility
Pergolide adenomas
Cabergoline Parkinson s (Pergolide) Longest half-life & least side Contraindication: Pregnancy
↓GH secretion effects = Cabergoline
GH Excess Gigantism, Acromegaly (except Bromocriptine)
SOMATOTROIC HORMONES
GHRH DERIVATIVE ↑GH secretion Children with tertiary hypothalamic GH
(Pulsatile secretion)
Sermorelin deficiency
Growth: Pediatric patients
GH deficiency (Dwarfism)
Prader-Willi, Turner Syndromes
↑Growth (muscle, bone, organs) Small for age before age 2
RECOMBINANT GH ↑IGF-1 release GH deficiency in adults Hyperglycemia
Given in the evening to
Somatotropin Anabolic, +Nitrogen balance ↑Lean mass, metabolic state & sense of -Careful with diabetics
mimic GH peak at night
Somatrem Anti-Insulin (↑glucose) well being Increased ICP
AIDs muscle wasting
↑Lean mass, weight, physical endurance
Short Bowel Syndrome
Improves GI Fxn in nutritional support
RECOMBINANT IGF Complex of IGF-1 & IGF binding Kids: Type 2 Diabetes, Scoliosis
Laron Dwarfism GH receptor mutation
Mecasermin protein Adults: edema, carpal tunnel, arthralgia, myalgia
SOMATOSTATIN Octreotide LAR IM
ANALOGS Octreotide Somatostatin ↓Cyclosporine bioavailability injection every 28 days (vs.
receptor → ↓TSH & GH Nausea, cramps, diarrhea SubQ 3x/day with octreotide)
Octreotide
secretion Hypothyroidism Lanreotide IM every 1-2
Lanreotide GH Excess Gigantism, Acromegaly wks or SubQ every 28 days
Loss of IGF-1 feedback at
Competitive inhibitor of GH Contraindications
GH ANTAGONISTS hypothalamus & pituitary →
receptor → Breast feeding
Pegvisomant may cause ↑GH & excessive
↓GH effects & ↓IGF-1 release ↑Liver enzymes (AST, ALT)
tumor growth
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 POSTERIOR PITUITARY HORMONES
ADH ANALOG Central (Pituitary) Diabetes Insipidus Other Rx for Central DI:
↑Water conservation in the CT→
Desmopressin (NOT Nephrogenic) Chlorpropamide→ helps ↑ADH effects
↑Urine osmolality
Platelet aggregation (↑vWF, FVIII) Carbamazepine & Clofibrate → also used to ↓polyuria
NEPHROGENIC DI Rx Amiloride → blocks Li uptake
Amiloride Nephrogenic Diabetes Insipidus
Thiazides → can ↑PCT
Lithium caused (1/3) → Amiloride
Thiazide diuretics reabsorption of Na/H2O
Non-Lithium caused → Thiazides
Indomethacin Indomethacin → ↓PG → ↓GFR
SIADH
ADH ANTAGONIST -CNS Dx, Pulmonary Dx, Malignancy Demeclocycline (member of tetracyclines) → NDI,
Demeclocycline→ ↓ADH effects
Demeclocycline -Drugs (vincristine, chlorpropamide, photosensitivity, abnormalities bone/teeth
Tolvaptan → V2R antagonist
cyclophosphamide) Li → irreversible damage with chronic use (short-term only)
Tolvaptan Lithium → mild ↓ADH effects
Relative Hypervolemic States Tolvaptan → monitor Na2+ levels (hypernatremia)
Lithium w/Hyponatremia
- CHF, Cirrhosis, Nephrotic syndrome
Side Effects:
ADH-like effects → ↑BP → ↓HR (monitor fetus)
GCPR in myometrium → Uterine contraction
Hypersensitive uterine rxn → cervical laceration, postpartum
Oxytocin ↑Intracellular Ca2+ → Induce labor
hemorrhage, pelvic hematoma, uterine rupture
↑Prostaglandins → Control uterine hemorrhage
Drug Interactions:↑Vasopressor, ↓General anesthetic effect
↑Gap junctions Milk let-down
Contraindications: immature fetal lungs, fetal stress,
abnormal fetal position
TOCOLYTICS Atosiban = oxytocin R
Atosiban antagonist (competitive inhibitor) Atosiban less side effects that Ritodrine
Suppress Pre-Term Labor
Ritodrine Ritodrine = agonist
Terbutaline also used (another β agonist) -First Aid
Nifedipine Nifedipine = Ca channel blocker

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 THYROID HORMONES
Moa Uses Side Effects / Interactions Other
RECOMBINANT TSH
Like TSH stimulates thyroid gland Diagnostic test: Hypothalamic-
Thyrogen
to uptake iodine & produce T3/T4 pituitary-thyroid gland dysfunction
Thyrotropin
Excessive Doses →
Tachycardia, Arrhythmias
Hypothyroidism: ↓BMP, ↓cold Heat intolerance, sweating
Tremors Oral Admin:
THYROID HORMONES tolerance, bradycardia, ptosis, 2+
Ca & Fe supplements
Levothyroxine (T4) lethargy, ↓mentation, myxedema Drug interactions: BLOCK absorption
Mimic T3, T4 -Ha him h idi i
Liothyronine (T3) Estrogen→↑TBG→↓free T4/T3
Liotrix (T3+T4) -Endemic goiter (↓iodine) Barbiturates→↑metabolism Efficacy measured w/ serum
-Radioiodine Tx for Hyperthyroidism T3/T4→↑effects of TSH levels
-Congenital (Cretinism, ↓growth) anticoagulants, TCAs,
vasopressors, agonists
(sympathomimetics)
Low dose → ↑T3,T4
High dose → ↓T3,T4 Low dose → Endemic Goiter
131
(inhibits TPO→ ↓I2 organification ) (hypothyroidism due to I- deficiency) I takes long period
Iodine (Wolff-Chaikoff effect) High dose → G a e di ea e before gaining hyperthyroid
131 131
Iodine (oral) → partial Iodine → Failure of prolonged anti- control
destruction of thyroid gland thyroid Rx or thyroidectomy
(selectively hyperactive cells)
Inhibits ATP-dependent
Thiocyanate (SNC-) High doses → fatal aplastic Perchlorate 10x more potent
Na/I Symporter on basolateral Low doses → G a e
Perchlorate (ClO4-) follicular cells → ↓Iodine uptake
anemia than thiocyanate
Hyperthyroidism: ↑BMR, ↓heat Side Effects: Rashes, Joint Contraindication:
Methimazole
Inhibits TPO → ↓T3/T4 synthesis tolerance/sweating, tachycardia, pain, Agranulocytosis Pregnancy
(MMI) tremors, goiter Breast feeding
Propylthiouracil Inhibits TPO → ↓T3/T4 synthesis -G a e di ea e ( /e h halm ) Drug-Interactions: ↑Warfarin, 75% Plasma protein bound:
(PTU) Inhibits 5 Deiodinase → ↓T4→T3 -Toxic uni/multinodular goiter Digoxin & -blocker effects Short T ½ - 75 min
-Toxic thyroid adenoma
Sodium ipodate Inhibit 5 Deiodinase (1 & 2) → Thyrotoxicosis/Thyroid Storm → PTU +
Iopanoic acid ↓T4 conversion to T3 antipyretic + -blocker (↓HR)

22