HORMONES AND HORMONE ANTAGONISTS

HORMONE AND HORMONE ANTAGONISTS

PREPARED BY MR. ABHIJIT DAS

THYROID HORMONES

INTRODUCTION

Thyroid hormones, primarily thyroxine (T4) and triiodothyronine (T3), are essential for regulating metabolism. The hypothalamus releases thyrotropin-releasing hormone (TRH), which stimulates the pituitary gland to release thyroid-stimulating hormone (TSH). TSH then prompts the thyroid gland to produce and release T3 and T4, which exert their metabolic effects throughout the body.

SYNTHESIS AND STORAGE

Thyroid hormones (T3 and T4) are synthesized in the thyroid gland from iodine and the amino acid tyrosine. Iodine is actively transported into the thyroid follicular cells, where it's combined with tyrosine to form T3 and T4. These hormones are then stored in the thyroid follicles until they're released in response to signals from the pituitary gland to regulate metabolism and other bodily functions.

CLASSIFICATION

1.    Thyroid Hormone Replacements:

·        Examples:

·        Levothyroxine (Synthroid)

·        L-Thyroxine (Euthyrox)

2.    Thyroid Hormone Analogs:

·        Examples:

·        Liothyronine (Cytomel)

·        Dextrothyroxine

 

LEVOTHYROXINE:

PHARMACOLOGICAL ACTIONS

Metabolic Effects:

  • Increases metabolic rate.
  • Enhances the breakdown of carbohydrates, fats, and proteins.
  • Promotes energy production.

Cardiovascular System (CVS):

  • Increases heart rate and cardiac output.
  • Enhances cardiac contractility.
  • Lowers serum cholesterol levels.

Brain Function:

  • Supports normal brain development in infants.
  • Improves cognitive function in adults with hypothyroidism.

Temperature Regulation:

  • Helps maintain body temperature within the normal range.
  • Prevents sensitivity to cold in hypothyroid individuals.

Growth and Development:

  • Essential for proper growth and development in children.
  • Promotes bone growth and maturation of the skeleton.

THERAPEUTICAL USES

1.    Cretinism

2.    Hypothyroidism

3.    Myxedema

4.    Goiter

ANTI THYROID DRUGS

Anti-thyroid drugs are medications that inhibit the production or release of thyroid hormones and are primarily used to treat hyperthyroidism.

CLASSIFICATION

1.    Thionamides:

·        Examples: Methimazole (Tapazole), Propylthiouracil (PTU)

2.    Iodine-Containing Compounds:

·        Examples: Potassium Iodide (SSKI), Radioactive Iodine (I-131)

THIONAMIDES

MOA

The mechanism of action of thionamides is to inhibit the incorporation of iodine into tyrosine residues and the subsequent coupling of these iodinated tyrosine residues, which are essential steps in the synthesis of thyroid hormones (T3 and T4).

IODINE CONTAINING COMPOUNDS

MOA

Iodine-containing compounds, such as potassium iodide and radioactive iodine (I-131), work by saturating the thyroid gland with iodine. This high iodine level reduces the thyroid's ability to take up and concentrate iodine, ultimately lowering the production and release of thyroid hormones, helping to treat hyperthyroidism.

 

PARATHORMONE

Parathormone (PTH) is a hormone produced by the parathyroid glands that plays a crucial role in bllod calcium regulation. It stimulates osteoclasts to break down bone, releasing calcium into the bloodstream. PTH also enhances the reabsorption of calcium in the kidneys and promotes the release of calcitriol, the active form of vitamin D, which further increases calcium absorption from the intestines. These actions collectively help maintain calcium homeostasis in the body.

TERIPARATIDE

MOA

Teriparatide stimulates bone formation by increasing osteoblast activity, promoting new bone growth, and improving bone density. It acts as an anabolic agent in the treatment of severe osteoporosis.


ADVERSE EFFECTS OF TERIPARATIDE:

1.    Hypercalcemia

2.    Nausea

THERAPEUTIC USES OF TERIPARATIDE:

1.    Treatment of severe osteoporosis.

2.    Prevention of fractures in postmenopausal women at high risk of fractures.

 

CALCITONIN

Calcitonin is a hormone that lowers blood calcium levels by inhibiting calcium release from bone and increasing calcium excretion by the kidneys. It is primarily used in the management of hypercalcemia and for the treatment of osteoporosis.

SALMON CALCITONIN

Salmon Calcitonin is derived from the salmon fish and used to treat osteoporosis and hypercalcemia.

MOA
Salmon calcitonin works by inhibiting bone resorption (the breakdown of bone) and reducing calcium levels in the blood by directly inhibiting osteoclast activity, leading to decreased bone loss.

THERAPEUTICAL USES

1.    Treatment of postmenopausal osteoporosis.

2.    Management of hypercalcemia, especially in cases related to malignancies.


ESTROGEN

Estrogen is a female sex hormone produced primarily in the ovaries, but also in smaller amounts in the adrenal glands and fat tissues. It plays a key role in regulating the menstrual cycle, promoting the development of secondary sexual characteristics in females, and supporting reproductive health.

The basic pharmacology of estrogen involves its interaction with estrogen receptors in target tissues, which can be classified into two main types: ERα and ERβ. Estrogen receptor activation influences gene expression and cellular responses.

PATHOLOGICAL ROLE OF ESTROGEN

1.    Breast Cancer: Prolonged exposure to high levels of estrogen can increase the risk of breast cancer. Estrogen promotes cell proliferation, and when this occurs in breast tissue, it can lead to the development of malignant tumors.

2.    Ovarian Cancer: Prolonged exposure to estrogen may be associated with an increased risk of ovarian cancer.

3.    Endometriosis: Estrogen is thought to contribute to the growth of endometrial tissue outside the uterus, leading to endometriosis, a painful condition.

4.    Polycystic Ovary Syndrome (PCOS): PCOS is characterized by hormonal imbalances, including elevated estrogen levels, which can lead to irregular menstrual cycles, ovarian cysts, and other symptoms.

5.    Osteoporosis: A decrease in estrogen levels during menopause can lead to bone loss, increasing the risk of osteoporosis and fractures.

CLASSIFICATION
Estrogens can be classified into several categories based on their origin and properties:

1.    Natural Estrogens:

·        Natural estrogens are endogenous hormones produced by the ovaries in females. The primary natural estrogen in the human body is estradiol (E2).

·        Estrone (E1) and estriol (E3) are also natural estrogens produced in smaller amounts.

2.    Synthetic Estrogens:

·        Synthetic estrogens are artificially created compounds that mimic the actions of natural estrogens. They are often used in medications and hormone replacement therapy.

·        Common synthetic estrogens include ethinyl estradiol, mestranol etc.

3.    Selective Estrogen Receptor Modulators (SERMs):

·        SERMs are a class of drugs that interact with estrogen receptors, acting as estrogen agonists in some tissues and estrogen antagonists in others.

·        Examples of SERMs include tamoxifen (used in breast cancer treatment and prevention), raloxifene (used in osteoporosis treatment and prevention), and bazedoxifene (used for menopausal symptom relief).

PHARMACOLOGICAL ACTIONS

1.    Reproductive Effects:

·        Estrogen promotes the development and maintenance of female secondary sexual characteristics, including breast development and the distribution of body fat.

·        It plays a central role in the regulation of the menstrual cycle and is necessary for normal ovulation and the preparation of the uterine lining for potential pregnancy.

2.    Bone Health:

·        Estrogen helps maintain bone density by inhibiting bone resorption (breakdown) and stimulating bone formation. It is essential for preventing osteoporosis.

3.    Cardiovascular Effects:

·        Estrogen has a favorable impact on the cardiovascular system. It can improve lipid profiles by increasing high-density lipoprotein (HDL or "good" cholesterol) levels and decreasing low-density lipoprotein (LDL or "bad" cholesterol) levels.

·        It may also have vasodilatory effects, helping to relax blood vessels and improve blood flow.

4.    Cognitive and Mood Effects:

·        Estrogen may have neuroprotective effects and can influence cognitive function and mood. Some research suggests that estrogen may help with memory and mood regulation, particularly in the context of menopause.

5.    Hot Flash Relief: Estrogen replacement therapy is effective in reducing hot flashes and other vasomotor symptoms associated with menopause.

6.    Hormone Replacement Therapy (HRT):

·        Estrogen is a key component of HRT, which is prescribed to relieve menopausal symptoms and manage certain health conditions associated with hormone deficiencies.

CLINICAL USES

1.    Hormone Replacement Therapy (HRT): Estrogen is used to alleviate menopausal symptoms, such as hot flashes, vaginal dryness, and mood disturbances, in postmenopausal women.

2.    Osteoporosis Prevention and Treatment: Estrogen can help maintain bone density and reduce the risk of osteoporosis, particularly in postmenopausal women.

3.    Contraception: Estrogen is a component of combined oral contraceptives, helping to prevent pregnancy by inhibiting ovulation and altering cervical mucus.

4.    Treatment of Hypogonadism: Estrogen therapy may be used to address hormone deficiencies in individuals with conditions like Turner syndrome or primary ovarian insufficiency.

5.    Breast Cancer Prevention: In some cases, estrogen receptor modulators like tamoxifen may be used to reduce the risk of breast cancer in high-risk individuals.


PROGESTERON

Progesterone is a naturally occurring hormone in the body. As a drug, it's used to regulate the menstrual cycle, support pregnancy, and in hormone replacement therapy to manage menopausal symptoms.

CLASSIFICATION

1.    Natural Progestin:

·        Example: Progesterone

2.    Synthetic Progestin:

·        Example: Medroxyprogesterone acetate (Provera)

3.    Third-Generation Progestin:

·        Example: Desogestrel (found in some birth control pills like "Desogen" or "Ortho-Cept")

PHARMACOLOGICAL ACTIONS

1.    Uterus: It makes the uterine lining thinner, which can prevent pregnancy.

2.    Cervix: It thickens cervical mucus, making it harder for sperm to reach the egg.

3.    Vagina: Progestin can sometimes cause vaginal dryness or irritation.

4.    Mammary Gland: It can stimulate breast tissue, leading to changes like tenderness or growth.

5.    Body Temperature: Progestin may slightly increase body temperature.

CLINICAL USES

1.    Birth control: It's used in birth control pills and hormonal methods to prevent pregnancy.

2.    Hormone replacement therapy (HRT): Progestin is part of HRT to manage menopausal symptoms.

3.    Treating menstrual disorders: It can help regulate irregular periods or reduce heavy bleeding.

4.    Support during pregnancy: It's sometimes prescribed to prevent miscarriages or preterm labor.

5.    Treating certain cancers: Progestin can be part of cancer treatment plans, such as for uterine cancer.


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