Endocrine Drugs, Hormones and

Related Compounds
Endocrine Drugs
Hypothalamic & Pituitary Hormones
Hypothalamic Hormone Pituitary Target Organ Target Organ
Hormone Hormone
1. Growth Hormone – Growth Hormone (GH) Liver Somatomedins
Releasing Hormone aka: Somatotropin
(GHRH)
aka: Sermorelin
2. Growth Hormone – Inhibits Growth Hormone
Inhibiting Hormone (GHIH)
aka: Somatostatin
3. Corticotropin – Releasing Adrenocorticotropic Adrenal Cortex Glucocorticoids
Hormone (CRH) Hormone (ACTH) Mineralocorticoids
aka: Corticotropin Adrenal Androgens
4. Thyrotropin – Releasing Thyroid – Stimulating Thyroid Gland T3 (Triiodothyronine)
Hormone (TRH) Hormone (TSH) T4 (Thyroxine)
aka: Thyrotropin
5. Gonadotropin – Releasing
Hormone (GnRH) or Gonadotropins Ovaries (Females) Estrogen (by FSH)
Luteinizing Hormone – a. Follicle Stimulating Testes (Males) Progesterone (by LH
Releasing Hormone Hormone (FSH) in females)
(LHRH) b. Luteinizing Hormone Testosterone (by LH
(LH) in males)
6. Prolactin – Releasing Prolactin Breasts
Hormone (PRH)

7. Prolactin – Inhibiting Inhibits Prolactin

Hormone (PIH)

8. Oxytocin Stored in the Posterior

Pituitary Gland
9. Vasopressin Stored in the Posterior
Pituitary Gland
OXYTOCIN
ADH
 ADH
Acts on 3 types of receptors
V1-R OXYTOCIN-R V2-R
V1-ALPHA

V1-BETA
 ADH
Uses of receptors
V1-R OXYTOCIN-R V2-R
ADH ANALOGUES
CRH
GnRH
PULSATILE

CONTINUOUS
GnRH analogues
Leuprolide
Nafarelin
Gonadorelin

USES:
GnRH ANTAGONIST
Cetrorelix
Ganirelix

USES:
PROLACTIN REGULATORY
FACTOR
TRH
ANTERIOR PITUITARY
GLAND
TSH
PROLACTIN
ACTH
MSH
Growth Hormone
GH
Growth Hormone (GH)
- aka: Somatotropin, Asellacrin
- a large polypeptide: about 191 amino
acids (MW: 21,500)
- released by the anterior pituitary in
response to GHRH (Sermorelin)
produced by the hypothalamus
- produced synthetically by recombinant
DNA technology
Growth Hormone (GH)
- animal source is ineffective in humans
- induces the release of somatomedins in
the liver
- promotion of cell proliferation and bone
growth at open epiphyses
- boosts cartilage synthesis
Growth Hormone (GH)
Indications:
- for long term treatment in growth
hormone deficiency in children
(Dwarfism)
- for non-GH deficient short children (can
grow up to 2 cm per year)
Somatrem
- a therapeutically equivalent drug of GH
- contains an extra terminal methionyl
group
Growth Hormone Inhibiting
Hormone
Growth Hormone Inhibiting
Hormone (GHIH)
- aka: Somatostatin
- inhibits Growth Hormone
- Indications:
Pituitary Gigantism (pre-pubertal)
Acromegaly (post-pubertal)
Acromegaly
macrognathia (large jaw)
wide-spaced teeth
macroglossia
thickened lips
broad nose
enlarged joints
cardiomegaly
organomegaly
Octreotide
- synthetic octapeptide analog of
somatostatin
- 45x more potent than GHIH
Gonadotropins
LH and FSH
Gonadotropins
- include:
Follicle-Stimulating Hormone (FSH)
Luteinizing Hormone (LH)
- released by the anterior pituitary gland in
response to GnRH / LHRH
- stimulates the gonads (ovaries & testes)
to produce sex hormones
- Females: FSH → estrogen
LH → progesterone
- Males: LH → testosterone
Gonadotropins
NOTE: Pituitary gonadotropins (FSH, LH)
are not available for therapeutic use,
however, there are non-pituitary
gonadotropins that have FSH-like or
LH-like activity and are the ones used
therapeutically
Non-Pituitary Gonadotropins
1. Menotropins
2. Urofollitropin/Follitropin alpha and beta
3. Human Chorionic
Gonadotropin/lutropin
Non-Pituitary Gonadotropins
- Indications:
women: to induce ovulation &
pregnancy
men: to induce spermatogenesis

- Adverse effects:
ovarian enlargement
multiple births
gynecomastia in men
Menotropin
- aka:
Human Menopausal Gonadotropin
(hMG)
Pergonal®
- obtained from the urine of post-
menopausal women
- partially broken down into FSH and LH
in the body
Urofollitropin
- Metrodin®
- obtained from the urine of post-
menopausal women
- high in FSH-like activity
Human Chorionic Gonadotropin
- aka: hCG, Follutein®
- a placental hormone
- LH agonist effect
-obtained from the urine of pregnant
women
Hormones of the Posterior
Pituitary Gland
Hormones of the Posterior
Pituitary Gland
1. Oxytocin
2. Vasopressin
Oxytocin
- stimulates uterine contraction and plays an
important role in the induction of labor
- also promotes breast milk ejection
- Indications:
to induce contraction during labor
to control postpartum bleeding
- Contraindications:
abnormal fetal presentation
fetal distress
premature births
MOA
UTERINE STIMULANTS
UTERINE STIMULANTS
UTERINE STIMULANTS
UTERINE RELAXANTS
UTERINE RELAXANTS
UTERINE RELAXANTS
UTERINE RELAXANTS
Vasopressin
- aka: Antidiuretic Hormone (ADH)
- has both antidiuretic and vasopressor
activity
-acts by binding to its receptor in the
kidneys promoting the reabsorption of
water in the collecting tubules
-Indications:
Diabetes Insipidus
Postoperative Abdominal Distention
Diabetes Insipidus (DI)
- a disorder due to the deficiency or lack
of response to Antidiuretic Hormone
(ADH)
- 2 Types:
a. Central DI - deficiency in ADH
b. Nephrogenic DI - sufficient ADH
but body does not respond
to the hormone
Desmopressin
- modified analog of vasopressin
- more preferred for DI and nocturnal
enuresis because it is largely free of
pressor effects and is longer-acting
Steroid Hormones
Steroid Hormones
- contain the steroid nucleus, CPPP
cyclopentanoperhydrophenanthrene
Steroid Hormones
A. Gonadal / Sex Hormones
1. Estrogens
2. Progestins
3. Androgens
B. Hormones of the Adrenal Cortex
1. Adrenocoticosteroids
a. Glucocorticoids
b. Mineralocorticoids
2. Adrenal Androgens
Estrogens
Estrogens
- Effects:
1. normal female maturation and
development
2. inhibit bone resorption
3. increase HDL, decrease LDL
4. decrease platelet adhesiveness
Estrogens
- Indications:
contraception
postmenopausal hormone therapy
primary hypogonadism
osteoporosis
Natural Steroidal Estrogens
Estradiol - most potent estrogen
produced by women
Estrone, Estriol - have about one tenth
the potency of estradiol
Synthetic Steroidal Estrogens
Ethinyl estradiol
Mestranol
Quinestrol
Equilin
Synthetic Nonsteroidal Estrogens
Diethylstilbestrol - possible cause of a
rare, clear cell cervical or vaginal
adenocarcinoma among daughters of
women who took the drug during early
pregnancy
Synthetic Nonsteroidal

a. Methestrol h. Genistein
b. Dienestrol
c. Benzestrol
d. Hexistrol
e. Diethylstilbestrol
f. Chlorotrianisene
g. Methallenestril
Estrogen Antagonists /
Antiestrogens

Clomiphene - fertility drug; it induces

ovulation by negative feedback
mechanism

Tamoxifen & Toremifene - palliative

treatment of advanced breast cancer in
postmenopausal women
Estrogen Related Drugs
Aromatase Inhibitors
Selective Estrogen Receptor Modulators
Aromatase Inhibitors
- are potent and selective non-steroidal
inhibitors of aromatase, an enzyme
reponsible for the conversion of
androgens to estrogens
- used to treat advanced breast cancer
- Anastrozole, Letrozole
SERMs
- Selective Estrogen Receptor Modulators
- reduce bone resorption and decrease
bone turnover
- used for the prevention of osteoporosis
- Raloxifene
Progestins
Progestins
- Effects:
1. endometrial changes
2. alveolobular development of
secretory apparatus in breasts
3. hepatic glycogenesis &ketogenesis
4. increase lipoprotein lipase activity
and fat deposition
Progestins
- Indications:
contraception
for menstrual disorders
-dysfunctional uterine bleeding
-dysmenorrhea
endometriosis
 Natural Progestin
Progesterone
- endogenous progestin produced in
response to luteinizing hormone (LH)
- also synthesized by the adrenal cortex
- in females, it promotes the development
of a secretory endometrium that can
accommodate implantation of a newly
forming embryo
Synthetic Progestins
- more stable to first-pass metabolism,
allowing for lower doses when
administered orally
- medroxyprogesterone
hydroxyprogesterone
megestrol
norethindrone
norgestrel
Progestin Antagonist /
Antiprogestin

Mifepristone
- aka: RU 486
- progestin antagonist with partial
agonist activity
- can cause abortion of the fetus due to
the interference with progesterone and
the decline in hCG
Oral & Implantable
Contraceptives
Major Classes
1. Combination Pills
2. Progestin Only Contraceptives
3. Postcoital Contraceptives
Combination Pills
- contain both estrogen and progestin
- provided as 21 day or 28 day-packs
- most common type of oral contraceptives
- estrogen: suppresses ovulation
ethinyl estradiol - most common
mestranol
Combination Pills
- progestin: prevents implantation in the
endometrium and makes the cervical
mucus impenetrable to the sperm
norethynodrel
norethindrone
norgestrel
Progestin Only Contraceptives
- less effective than combination pills
- dosage forms/ delivery systems:
a. “mini-pill” - low dose progestins
350 g norethindrone or
75 g norgestrel
b. progestin implants - subdermal implant
of 216 mg of norgestrel (Norplant®)
effective for 5 years
Progestin Only Contraceptives
c. intramuscular - given every 3 months
150 mg of medroxyprogesterone
acetate (Depo-Provera®)
Progestin Only Contraceptives

d. intrauterine device (IUD) - for yearly

insertion; Progestasert®
Postcoital Contraceptives
- called, “morning-after pills”
- high dose estrogen administered within
72 hours after coitus and continued 2x
for 5 days
- ethinyl estradiol
diethylstilbestrol
conjugated estrogens
estrone
Adrenal Cortex
3 Zones:
1. Zona glomerulosa
- produces mineralocorticoids
2. Zona fasciculata
- produces glucocorticoids
3. Zona reticularis
- produces adrenal androgens
Androgens
Androgens
- basic nucleus: androstane

Testosterone
Androgens

- group of steroids that have anabolic

and/or masculinizing effects in both
males and females
Endogenous Androgen
Testosterone/androstenedione
- primary natural endogenous androgen
- synthesized by Leydig cells in the testes
of males and in smaller amounts by the
cells in the ovary of females, and in the
adrenal gland
-produced in response to LH
Synthetic Androgens
Methyltestosterone
Fluoxymesterone
Danazol
Stanozolol
Nandrolone
oxandrolone
Therapeutic Uses
1. Androgenic Effects
- in hypogonadism in males
2. Anabolic Effects
- in senile osteoporosis, severe burns,
speedy recovery from surgery or from
chronic debilitating diseases
3. Endometriosis (Danazol)
Unapproved Use
Used to increase lean body mass, muscle
strength and aggressiveness in athletes
and body builders (Nandrolone &
Stanozolol)
Finasteride 5-alpha reductase inhibitor.
Useful in BPH.
Also promotes hair growth—male
pattern baldness.
Flutamide A nonsteroidal competitive inhibitor
of androgens at the testosterone
receptor.
Used in prostate CA
Ketoconazole, Inhibits steroid synthesis.
Spironolactone Useful in the treatment of polycystic
ovarian syndrome to prevent hirsutism.
Antiandrogens
- inhibit the action of androgens by
interfering with androgen synthesis or
by blocking their receptors
a. Finasteride - used in Benign Prostatic
Hypertrophy (BPH)
Antiandrogens
b. Flutamide - for prostatic carcinoma

c. Cyproterone acetate - for hirsutism in

females
Hormones of the Adrenal
Cortex
Hormones of the Adrenal Cortex
1. Adrenocorticosteroids
a. Mineralocorticoids
b. Glucocorticoids
2. Adrenal Androgens
Mineralocorticoids
- possess sodium-retaining and
potassium-secreting effects
- essential for fluid and electrolyte balance

- endogenous: aldosterone
desoxycorticosterone

- synthetic: fludrocortisone
Glucocorticoids
- Endogenous: Cortisol
Cortisone
Corticosterone
Hydrocortisone
- essential for the metabolism of
carbohydrates, fats and proteins
- they enhance response of the vascular
and bronchial smooth muscles to
catecholamines
Glucocorticoids
Other Preparations:
Prednisone Betamethasone
Methylprednisolone Dexamethasone
Triamcinolone
- anti-inflammatory, anti-allergy and
immunosuppressant effects
- inhibit cell growth and division
- catabolic effects on protein and bones
Glucocorticoids
Therapeutic Uses:
Allergy
Inflammation of joints and bones
Skin diseases
Organ transplant immunosuppression
Pulmonary Diseases: Bronchial Asthma
COPD
Glucocorticoids
Adverse effects:
Cushing’s syndrome
Adrenal suppression
osteoporosis
PUD
impaired wound healing
increased susceptibility to infection
hyperglycemia/DM
cataract
Addison’s Disease
• hyposecretion of adrenocorticosteroids

• characterized by:
– anorexia
– dehydration
– weakness and lethargy
– hyperpigmentation (bronze-colored skin)
Cushing’s Syndrome
• hypersecretion of adrenocorticosteroids

• characterized by:
– moon face
– buffalo hump
– pendulous abdomen
– hypertension
 Thyroid Hormones and
Drugs for Thyroid Disorders
Thyroid Hormone Synthesis
1. Iodide uptake
2. Peroxidation of iodide to iodine
3. Organification of iodine
4. Coupling reaction: DIT + DIT → T4
MIT + DIT → T3
5. Proteolysis
6. Peripheral conversion of T4 to T3
SYNTHESIS
THYROID CONDITIONS
DRUGS FOR
HYPOTHYROIDISM
Thyroid Hormone Preparations
Preparation T4:T3 ratio
Thyroid, USP
Beef 4:1
Pork 2-3:1
Thyroglobulin 2:1
Levothyroxine Pure T4
Levothyronine Pure T3
Liotrix 4:1
DRUGS FOR
HYPERTHYROIDISM
Antithyroid Drugs
1. Thioamides
2. Inorganic Anions/Anionic Inhibitors
3. Iodides
4. Radiocontrast dyes
5. Beta-blocker
6. Dexamethasone
7. Radioactive Iodine
 ANTITHYROID
DRUG EXAMPLES MOA SE

THIOAMIDES

INORGANIC
ANIONS

IODIDES

RADIOCONTRAST
DYES

B-BLOCKERS

DEXAMETHASONE

RADIOACTIVE
IIODINE
 ANTITHYROID
DRUG EXAMPLES MOA SE

THIOAMIDES

INORGANIC
ANIONS

IODIDES

RADIOCONTRAST
DYES

B-BLOCKERS

DEXAMETHASONE

RADIOACTIVE
IIODINE
 ANTITHYROID
DRUG EXAMPLES MOA SE

THIOAMIDES

INORGANIC
ANIONS

IODIDES

RADIOCONTRAST
DYES

B-BLOCKERS

DEXAMETHASONE

RADIOACTIVE
IIODINE
Anti-diabetic Agents
Pancreas
- is a mixed gland
- Exocrine portion
-releases pancrealipase & chymotrypsin
- Endocrine portion
-1million islets of Langerhan
-have at least 4 hormone-producing
cells
Endocrine Pancreas
Cell Type % islet Hormone
A (alpha) 20 glucagon
proglucagon
B (beta) 75 insulin
pro-insulin
D (delta) 3-5 somatostatin
F (PP cell) <2 pancreatic
polypeptide (PP)
Insulin - Effects
1. It facilitates transport of glucose across
cell membrane
2. In the liver, it promotes glycogenesis
and gluconeogenesis
3. In the muscles, it increases amino acid
transport, protein synthesis and
glycogenesis
4. In adipose tissues, it increases
triglyceride storage
 Insulin
CARBOHYDRATES
 glucose release from liver
 glycogenolysis
 glycogen synthesis
 glycolysis
 ketogenesis
Insulin
LIPIDS
 adipose FFA release
 FFA synthesis

PROTEINS
aa transport to liver and muscle
 protein synthesis
Facilitate entry of glucose into cell
Insulin - Indications
• Diabetes Mellitus Type 1
• Diabetes Mellitus Type 2 that cannot be
controlled by diet, exercise and oral
hypoglycemic agents (OHAs)
• Ketoacidosis
• Diabetic coma
INSULIN PREPARATIONS
Insulin Preparations
Pharmakokinetic Species Type Activity in hours
Type Peak Duration
Ultra rapid-acting Human
Insulin Lispro (Modified) 0.25 – 0.50 3–4

Rapid acting
Insulin injection, USP Human, Pork 0.50 – 3 5–7
(Regular, Crystalline)
Intermediate acting
NPH Insulin Human, Pork 8 – 12 18 – 24
(Isophane)
Lente Insulin Human, Pork 8 – 12 18 – 24
(Insulin zinc susp)
Long acting
Ultralente Insulin Human 8 – 16 18 – 28
(Insulin zinc susp
extended)
Ultra long acting
Insulin glargine Human No peak > 24
(Modified)
RAPID 1.

2.

3.
SHORT 1.

INTERMEDIATE 1.

LONG 1.

2.

3.
Oral Hypoglycemic Drugs
AMYLIN ANALOGUE
Insulin Secretagogues
• Sulfonylureas
• Meglitinides
Sulfonylureas
MOA:
- stimulate pancreatic release of insulin
- inhibit pancreatic release of glucagons
- increase insulin receptor binding
- decrease hepatic extraction of insulin
Sulfonylureas
Ist Generation
Chlorpropamide Acetohexamide
Tolbutamide Tolazamide

2nd Generation
Glibenclamide Glipizide
Gliclazide
Glimepiride
Sulfonylureas
Side-effects:
hypoglycemia
blood dyscrasias
disulfiram-like reactions with 1st Gen
and glipizide
weight gain
Meglitinides
- MOA: increase pancreatic insulin
secretion
- short duration of action: 1 to 3 hours
- examples: Repaglinide
Nateglinide
- S/E:
hypoglycemia
weight gain
Biguanides
MOA:
Liver: Decrease the amount of glucose made
by the liver
Muscles and Fat Tissue: Increase insulin
sensitivity of muscles and adipose tissue
Biguanides
- reduce blood glucose level even in the
absence of beta cell function
- DOC among OBESE patients
- not associated with hypoglycemia
- ex. Metformin (most proven)
Phenformin ( no longer available)
- S/E: lactic acidosis, megaloblastic
anemia
Alpha-glucosidase inhibitors
- MOA: competitive inhibition of intestinal
alpha-glucosidase enzyme, preventing
digestion of dextrins and disaccharides
into absorbable monosaccharides
- examples: Acarbose
Voglibose
Miglitol
- S/E: flatulence, potential hepatotoxicity
of acarbose
Thiazolidinedione derivatives
- MOA: insulin sensitizers - increase
skeletal muscle sensitivity to insulin;
they also decrease hepatic
gluconeogenesis
- examples: Rosiglitazone
Pioglitazone
- S/E: Hepatic failure (reason for the
withdrawal of Troglitazone), edema and
mild anemia
 BILE ACIDE SEQUESTRANTS
COLESEVELAM HYDROCHLORIDE
Increase GLP-1 secretion
What are incretins?
• Two hormones:
- Gastric inhibitory polypeptide (GIP).
- Glucagon-like peptide-1 (GLP-1).
 GLUCAGON-LIKE POLYPEPTIDE-1
(GLP-1) RECEPTOR AGONISTS
Multiple Actions
1. Potentiates glucose-mediated insulin secretion
increase beta cell mass
• decreased beta cell apoptosis
• increase beta cell formation
2. Suppress postprandial glucagon release
3. Central loss of appetite
GLUCAGON-LIKE POLYPEPTIDE-1
(GLP-1) RECEPTOR AGONISTS
◼2 synthetic analogs: help restore GLP-1
activity
◼EXENATIDE
◼LIRAGLUTIDE
Incretin mimetics
Exenatide
The first incretin-related therapy
available for patients with type 2
diabetes.

Resistant to DPP-IV inactivation.

Serious S/E: necrotizing & hemorrhagic
pancreatitis
 Liraglutide
◼Long-acting synthetic GLP-1 ANALOG
◼ONCE-DAILY dosing
◼Increase insulin & decrease glucagon
release
 Dipeptidyl Peptidase-IV (DPP-4)
Antagonists /Inhibitors

SITAGLIPTIN
SAXAGLIPTIN
LINAGLIPTIN
Sodium Glucose Transport
(SGLT2) Inhibitors
Sergliflozin
Remogliflozin
Dapagliflozin