Endocrine Drugs, Hormones and

Related Compounds

Overview
Endocrine System
composed of hormone-releasing
such
as the:hypothalamus
thymus
thyroid gland

pancreas
gonads

parathyroid

-ovaries

adrenal glands

-testes

pituitary gland

pineal gland

organs

Endocrine System
-is controlled by the hypothalamus and
the pituitary gland
-along with the Nervous System, it
coordinates and directs body function
-maintains homeostasis by releasing
chemicals called hormones

Endocrine vs Nervous
- the nervous system communicates
locally by electrical impulses and
neurotransmitters directed through
neurons to other neurons or to specific
target organs such as muscle or glands
- nerve impulses generally act within
milliseconds

Endocrine
- the endocrine system releases
hormones into the blood stream
- the hormones are then carried by the
blood stream into target cells throughout
the body
- hormones have broader range of
response times (they act from seconds
to days or longer)

Endocrine System
Processes controlled by the endocrine
System:
1.growth & development
2.reproduction
3.body defenses
water, electrolyte and nutrient
balance
regulation of cellular metabolism and
energy balance

Hormones

Hormones
- Greek word, to arouse
- chemical substances secreted by the
cells into the extracellular fluids that
stimulate or regulate the metabolic
activity of other cells in the body.
- Gen. MOA: binding of the hormone to
the target cell or organ elicits response.

Endocrine Drugs

Endocrine Drugs
- Hormones are pharmacologically
classified as drugs
- can be natural (from animals),
semi- synthetic or synthetic
compounds
- Indications:
replacement therapy
treatment for certain disorders
diagnostic purposes

Hypothalamic & Pituitary

Hormones

Hypothalamus
- master endocrine organ
- secretes releasing/inhibiting hormones

Pituitary Gland
- weighs 600 mg and rests in the sella
turcica under a layer of dura mater in
the brain
-composed of 2 lobes:
anterior lobe
posterior lobe

Hypothalamic & Pituitary Hormones

Hypothalamic Hormone
1.

Growth Hormone Releasing

Hormone (GHRH)
aka: Sermorelin
2.

Growth Hormone Inhibiting

Hormone (GHIH) aka:
Somatostatin

3. Corticotropin Releasing
Hormone (CRH)
4. Thyrotropin Releasing
Hormone (TRH)
5.

Gonadotropin Releasing
Hormone (GnRH) or Luteinizing
Hormone Releasing Hormone
(LHRH)

6.

Prolactin Releasing
Hormone (PRH)

7.

Prolactin Inhibiting
Hormone (PIH)

8.

Oxytocin

9.

Vasopressin

Pituitary Hormone Target Organ

Growth Hormone (GH) aka:
Somatotropin

Liver

Target Organ
Hormone
Somatomedins

Inhibits Growth Hormone

Adrenocorticotropic Hormone
(ACTH) aka: Corticotropin

Adrenal Cortex

Glucocorticoids
Mineralocorticoids
Adrenal Androgens

Thyroid Stimulating Hormone

(TSH) aka: Thyrotropin

Thyroid Gland

T3 (Triiodothyronine) T4
(Thyroxine)

Gonadotropins
a.Follicle Stimulating
Hormone (FSH)
b.Luteinizing Hormone
(LH)

Ovaries (Females)
Testes (Males)

Prolactin

Inhibits Prolactin

Stored in the Posterior Pituitary

Gland
Stored in the Posterior Pituitary
Gland

Breasts

Estrogen (by FSH)

Progesterone (by LH in
females) Testosterone (by
LH in males)

Growth Hormone

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)

Dwarfism

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)

Pituitary Gigantism

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

Thyrotropin Stimulating
Hormone

Thyrotropin Stimulating Hormone (TSH)

-aka: Thyrotropin
-released by the anterior pituitary in
response to TRH (aka: Protirelin)
produced by the hypothalamus
-stimulates the thyroid to produce T3 and
T4
-T3: triiodothyronine (most active)
-T4: thyroxine
(converted to T3 in the body)

Thyrotropin Stimulating Hormone (TSH)

-the thyroid hormones T3 and T4 are
essential for the normal growth and
maturation of the body
-Conditions:
hypothyroidism
hyperthyroidism

Hypothyroidism
- inability of the thyroid gland to supply
sufficient thyroid hormone to the body
- manifestations:
Cretinism
(infant-state)
Myxedema
(adult-state)

Cretinism
- infant-state hypothyroidism
- characterized by physical and mental
retardation

Myxedema
- adult-state hypothyroidism
- characterized by:

bradycardia
weakness and lethargy
dry skin and hair
coldness
goiter

Hyperthyroidism
- overabundance of thyroid hormone in
the body
- thyrotoxicosis
- Forms:
Graves Disease - most common
Plummers Disease - less common
- with cardiac abnormalities

Graves' Disease

Gonadotropins

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
3. Human Chorionic Gonadotropin

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 postmenopausal 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

Oxytocin

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:

Central DI - deficiency in
ADH

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