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Pharmacology of the Endocrine System. Topics. Pituitary and hypothalamic hormones Thyroid and antithyroid Drugs Adrenal Drugs Pancreatic Drugs Gonadal hormones and inhibitors. The Endocrine System. Controls many body functions

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topics
Topics

Pituitary and hypothalamic hormones

Thyroid and antithyroid Drugs

Adrenal Drugs

Pancreatic Drugs

Gonadal hormones and inhibitors

the endocrine system
The Endocrine System
  • Controls many body functions
    • exerts control by releasing special chemical substances into the blood called hormones
    • Hormones affect other endocrine glands or body systems
hormone
Hormone

A substance that is released in one tissue and travels through the circulation (usually) to the target tissue.

Hormones reach all parts of the body, but only target cells are equipped to respond

Hormones are secreted in small amounts and often in bursts (pulsatile secretion)

endocrine functions
Endocrine Functions
  • Maintain Internal Homeostasis
  • Support Cell Growth
  • Coordinate Development
  • Coordinate Reproduction , fertility, sexual function
  • Facilitate Responses to External Stimuli
4 classes of hormones
4 Classes of Hormones

Peptide/ Protein (Range from 3 amino acids to hundreds of amino acids in size. )

Steroid

Amine (Thyroid hormones and Catecholamines)

Eicosanoid (Fatty acid derivatives )

slide9
The hormones fall into two general classes based on their solubility in water.

The water soluble { amine (epinephrine) and peptide/protein hormones} are secreted by exocytosis, travel freely in the bloodstream, and bind to cell-surface receptors.

The lipid soluble hormones { thyroid hormone, steroid hormones and Vitamin D3}. diffuse across cell membranes, travel in the bloodstream bound to transport proteins, and diffuse through the membrane of target cells .

slide10
Fat-soluble

hormone

Water-

soluble

hormone

Transport

protein

Signal receptor

TARGET

CELL

Signal

receptor

NUCLEUS

(a)

(b)

location of receptors
Location of receptors

On cell surface

Peptides and proteins

In cytoplasm

Steroids

In nucleus

Thyroid hormones

mechanisms of endocrine disease
Mechanisms of endocrine disease

Endocrine disorders result from:

Hormone deficiency,

(HRT)

Hormone excess

(Specific antagonists or release inhibitors )

Hormone resistance

(sensitizers)

sources of hormones
Sources of hormones:

Natural

Human (GH; LH & FSH; hCG);

Animal (Insulin, T3 & T4)

Biosynthetic

Insulin (Porcine & Bovine)

Synthetic

Most hormones and their antagonists

DNA recombinant technology

slide15
Cerebrum

Thalamus

Pineal

gland

Hypothalamus

Cerebellum

Pituitary

gland

Spinal cord

Hypothalamus

Posterior

pituitary

Anterior

pituitary

hypothalamus and pituitary
Hypothalamus and Pituitary

The output of the hypothalamus-pituitary unit regulates the function of the thyroid, adrenal and reproductive glands and also controls somatic growth, lactation, milk secretion and water metabolism.

Hypothalamic Hs can have effect of stimulating or inhibiting the release of ant. Pit. Hs. Called RELEASING HORMONES “RH” or INHIBITING HORMONES “IH”respectively, reflecting their influence on ant. Pit. Hs.

the pituitary gland
The Pituitary Gland
  • The Pituitary Gland is divided into 2 areas, with separate types of hormone production.

The anterior pituitary makes and releases H under regulation of the hypothalamus

      • Growth Hormone (GH)
      • Thyroid-stimulating Hormone (TSH)
      • Adrenocorticotropin (ACTH)
      • Follicle-stimulating Hormone (FSH) ),
      • Leutinizing Hormone (LH),
      • Prolactin
    • The posterior pituitary stores and secretes H that are made in the hypothalamus: oxytocin and antidiuretic hormone (ADH)
hypothalamic hormones
Hypothalamic hormones:

1- Growth Hormone- Releasing Hormone(GHRH):

Together with somatostatin controls release of the GH from the ant. pit.

It is released from hypothalamus in a pulsatile fashion, with 5-9 major pulses detected per day.

• GHRH release is enhanced by α2-adrenergic agonists (e.g. clonidine) and opioids.

• GHRH release is increasedby vigorous exercise.

slide21
Diagnostic Uses of GHRH (Sermorelin)

To test pituitary function in patients with GH deficiency.

GH deficiency could reflect either a hypothalamic or a pit. defect.

If the primary defect is hypothalamic, as is most common, GHRH will elicit an increase in GH release.

If the defect is at the level of the pituitary, there will be no increase in GH following GHRH administration.

Therapeutic Uses of GHRH to enhance GH secretion

Pulsatile subcutaneous delivery of GHRH, mimicking the normal endogenous patterns (e.g. ~ every 3 hours) has been used to stimulate GH release in patients with GH deficiency that is not of pituitary origin.

IV, SC, intranasal

2 somatostatin growth hormone releasing inhibiting hormone ghrih
2- Somatostatin (Growth hormone-releasing inhibiting hormone (GHRIH):
  • Inhibits GH release and TSH from the ant. pituitary .
  • Inhibits release of most GI hormones, reduces gastric acids and pancreatic secretion. (glucagon , insulin & gastrin),

Therapeutic Uses Somatostatin

Somatostatinis of no clinical value because of it's short half-life(<3 min)

Octreotide ,a synthetic somatostatin analogue with a longer duration of action

  • Lanreotide ismuch longer acting, and is administered only twice a month.
  • used to treat: Acromegaly, Gastrinoma ,Glucagonoma & Other Endocrine Tumors , and esophageal varices bleeding. (Inhibits Mesenteric vasodilatation induced by glucagon)

A/E: GI disturb. postprandial hyperglycemia.

Gall stones often form as a result of decreased biliary flow and gall bladder contraction.

3 thyrotropin releasing hormone trh
3- Thyrotropin-Releasing Hormone(TRH):

Stimulates release of thyrotropin (TSH) from the ant pit.

Is used in diagnostic testing of thyroid dysfunction

Protirelin: IV

4- Corticotropin Releasing Hormone(CRH)

It stimulates secretion of both ACTH & beta –endorphin (a closely related peptide ) from the ant. pituitary .

CRH can be used in the diagnoses of abnormalities of ACTH secretion .

5 gonadotropin releasing hormone gnrh
5- Gonadotropin-Releasing Hormone:(GnRH):

Stimulate the gonadotroph cell to produce and release LH and FSH,

Gonadorelin, Buserelin, Nafarelin

GnRH agonists, SC infusion in pulses mimic physiological GnRH, stimulates ovulation.

In contrast, steady dosing inhibits gonadotropin release by causing down –regulation (desensitization) of GnRH receptors in pituitary cells that normally release gonadotropins .

GnRH is used in the diagnosis & treatment (by pulsatile administration) of hypogonadal states in females & males .

Continuous GnRH agonists are used in sex H-dependent conditions: prostate & breast cancers, uterine fibroids, endometriosis or precocious puberty .

6 prolactin inhibiting hormone pih dopamine
6- Prolactin-Inhibiting Hormone (PIH,dopamine):

Dopamine is the physiologic inhibitor of prolactin release

Because of its peripheral effects & the need for parenteral administration, dopamine is not useful in the control of hyperprolactinemia, but bromocrptine & other orally active ergot –derivatives (eg. Cabergoline, pergoline) are effective in reducing prolactin secretion from the normal glands as well as from prolactinomas .

Also used in treatment of acromegaly

A/E: orthostatic hypotension, Psychiatric manifestations

growth hormone
Growth Hormone

Derived from the somatotroph cells

Its secretion is controlled by GHRH and somatostatin;

GH secretion is high in newborn, deceasing at 4 yr to an intermediate level, which is then maintained until puberty, when there is further decline.

Insulin-like growth factor 1 (IGF-1) released from the liver inhibits GH secretion by stimulating somatostatin secretion from the hypothalamus,

growth hormone activity
Growth Hormone Activity
  • Increases plasma free fatty acids (source of energy for muscle tissue)
  • Increases hepatic glucose output
  • Decreases insulin sensitivity in muscle
  • Is protein anabolic hormone
  • Growth Hormone Deficiency
  • Can have a genetic basis or can be acquired as a result of damage to the pituitary or hypothalamus by a tumor, infection, surgery, or radiation therapy.
  • In childhood: short stature and adiposity, hypoglycemia.
  • Adults : generalized obesity, reduced muscle mass.
growth hormone excess
GROWTH HORMONE EXCESS

Mainly benign pituitary tumor

In adults causes acromegaly,

If this occurred before the long bone epiphyses close, it leads to the rare condition, gigantism.

Treatment of excess GH disorders:

- Synthetic Somatostatin(Octreotide)

- DA agonists(Bromocriptine)

- Surgical removal / Radiotherapy of the tumor

- GH Antagonists(Pegvisomant)

clinical uses of gh somatotropin
Clinical uses of GHSomatotropin
  • GH deficiency in children & adults.
  • Children with short stature that is due to factors other than GH deficiency:
  • Idiopathic short stature, Turner syndrome, Chronic renal failure

A/E:

Hypothyroidism, Pancreatitis, Gynecomastia, Possibilities of abuse have also arisen, e.g. creation of “super” sports people.

thyroid stimulating hormone tsh
Thyroid-stimulating Hormone (TSH)
  • Also called thyrotrophin
  • Stimulates secretion of thyroid hormone & growth of thyroid gland.

Diagnostic Uses of TSH

  • In patients who have been treated surgically for thyroid carcinoma, to test for recurrence
adrenocorticotropin acth
Adrenocorticotropin (ACTH)

Stimulates cortisol secretion by the adrenal cortex & promotes growth of adrenal cortex

Diagnostic use: as a test of the capacity of the adrenal cortex to produce cortisol;

follicle stimulating hormone fsh
Follicle –stimulating hormone (FSH)
  • Females:stimulates growth & development of ovarian follicles, promotes secretion of estrogen by ovaries.
  • Males: required for sperm production

3 preparations are available for clinical use:

  • Urofollitropin ,purified from of the urine of post menopausal women,
  • 2 recombinant forms, follitropin alpha & follitropin beta.
  • These products are used in combination with other drugs to treat infertility in women & men.
leutinizing hormone lh
Leutinizing hormone (LH)
  • Females: responsible for ovulation, formation of corpus luteum in the ovary, and regulation of ovarian secretion of female sex hormones.
  • Males: stimulates cell in the testes to secrete testosterone
  • Lutropin alfa,approved for use in combination with follitropin alfa for stimulation of follicular development in infertile women with profound LH deficiency.
prolactin
Prolactin
  • Secreted by lactotroph cells of the ant. Pit., which increase in number during pregnancy.
  • Its secretion is stimulated by estrogen
  • Females: stimulates breast development and milk production.
  • Males: involved in testicular function
  • No preparation of prolactin is available for use in prolactin-deficient patients.
  • For patients with symptomatic hyperprolactinemia, inhibition of prolactin secretion can be achieved with dopamine agonists, which act in the pituitary to inhibit prolactin release.
oxytocin
Oxytocin
  • It is synthesized in the hypothalamus & transported to the post. Pit.
  • It is an effective stimulant of uterine contractions & is used intravenously to induce or reinforce labor .
  • Induces the release of milk
  • Suckling sends a message to the hypothalamus via the nervous system to release oxytocin, which further stimulates the milk glands
slide40
Clinical uses of oxyticin

IV, IM

  • Induction of labor
  • Control of postpartum bleeding

A/E :

fetal distress, placental abruption, or uterine rupture

excessive fluid retention

vasopressin antidiuretic hormone adh
Vasopressin (antidiuretic hormone ADH)
  • It is synthesized in the hypothalamus & transported to the post. Pit.
  • The function of ADH is to increase water conservation by the kidney.
  • If there is a high level of ADH secretion, the kidneys reabsorb water.
  • If there is a low level of ADH secretion, the kidneys release water in dilute urine.

ADH release increases if blood pressure falls or blood becomes too salty.

ADH causes peripheral blood vessel constriction to help elevate blood pressure .

clinical uses
Clinical uses
  • Diabetes insipidus,
  • Nocturnal enuresis (by decreasing nocturnal urine production)

A/E: hyponatremia and seizures

Synthetic ADH drugs

    • Vasopressin: IV, IM
    • Desmopressin: IV, IM. PO, intranasal
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