HORMONES AND HORMONE ANTAGONISTS

HORMONES AND HORMONE ANTAGONISTS

THYROID HORMONES

Introduction

• Thyroxine (T4) and Triiodothyronine (T3) regulate metabolism.
• Hypothalamus → releases TRH → stimulates pituitary → releases TSH.
• TSH stimulates thyroid gland to release T3 and T4.

 

Synthesis & Storage

• Synthesized from: Iodine + Tyrosine.
• Process:
• Iodine is actively transported into thyroid follicular cells.
• Combines with tyrosine → forms T3 & T4.
• Stored in thyroid follicles.
• Released when stimulated by TSH.

 

Classification of Thyroid Drugs

1. Thyroid Hormone Replacements

• Used in hypothyroidism.
• Examples:

Levothyroxine (Synthroid)

• L-Thyroxine (Euthyrox)

2. Thyroid Hormone Analogs

• Mimic action of natural thyroid hormones.
• Examples:
• Liothyronine (Cytomel)
• Dextrothyroxine

 

LEVOTHYROXINE

Pharmacological Actions

1.    Metabolic Effects

• ↑ Metabolic rate
• ↑ Carbohydrate, fat & protein breakdown
• ↑ Energy production

2.    Cardiovascular System (CVS)

• ↑ Heart rate and cardiac output
• ↑ Cardiac contractility
• ↓ Serum cholesterol

3.    CNS Function

• Essential for infant brain development
• ↑ Cognition in adults with hypothyroidism

4.    Temperature Regulation

• Maintains normal body temperature

5.    Growth and Development

• Supports growth in children
• Aids bone maturation

 

Therapeutic Uses

1. Cretinism
2. Hypothyroidism
3. Myxedema
4. Goiter

 

ANTI-THYROID DRUGS

Purpose: Inhibit thyroid hormone synthesis/release → treat hyperthyroidism.

Classification

1.     Thionamides

• Examples: Methimazole, Propylthiouracil (PTU)

Mechanism of Action (MOA):

• Inhibit iodine incorporation into tyrosine.
• ↓ T3/T4 synthesis.

2.     Iodine-Containing Compounds

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

MOA:

• Saturate thyroid with iodine → inhibits iodine uptake.
• ↓ T3 & T4 synthesis and release.

 

PARATHORMONE (PTH)

• Secreted by: Parathyroid glands
• Function: Maintains blood calcium level
• Actions:

Ø  Stimulates osteoclasts → bone resorption (breakdown or removal of bone tissue) → ↑ blood calcium

Ø  Increases calcium reabsorption in kidneys

Ø  Promotes calcitriol formation → ↑ calcium absorption from intestines

 

TERIPARATIDE

Mechanism of Action (MOA):

• Stimulates osteoblasts → ↑ bone formation
• Acts as an anabolic agent

Adverse Effects:

• Hypercalcemia
• Nausea

Therapeutic Uses:

• Severe osteoporosis
• Prevent fractures in postmenopausal women

 

[Parathormone (PTH)

• When released continuously in the body, it increases bone resorption (breakdown) by stimulating osteoclasts → raises calcium in blood.

 

Teriparatide (PTH analog)

• It is a synthetic form of PTH, but given in low doses, intermittently (once daily injection).
• In this pattern, it stimulates osteoblasts more than osteoclasts → leads to bone formation, not breakdown.]

 

CALCITONIN

• Lowers blood calcium level

Mechanism:

• Inhibits bone resorption (osteoclasts)
• Increases calcium excretion via kidneys

Uses:

• Osteoporosis treatment
• Hypercalcemia management

 

SALMON CALCITONIN

• Source: Salmon fish

Mechanism:

• Inhibits osteoclasts → ↓ bone resorption → ↓ blood calcium

Uses:

• Postmenopausal osteoporosis
• Hypercalcemia (especially malignancy-related)

 

ESTROGEN

• Female sex hormone
• Mainly produced by ovaries; also by adrenal glands & fat tissue
• Regulates menstrual cycle & supports reproductive health

 

Receptors

• Acts on:

Ø  ERα

Ø  ERβ

 

Pathological Roles

Ø  Breast Cancer – Long exposure ↑ cell growth → cancer

Ø  Ovarian Cancer

Ø  Endometriosis –Abnormal endometrial tissue growth

Ø  PCOS – Hormonal imbalance with ↑ estrogen

Ø  Osteoporosis – ↓ Estrogen in menopause → bone loss

 

Classification of Estrogens

• Natural Estrogens
• Estradiol (E2) – main form
• Estrone (E1), Estriol (E3) – lesser amounts
• Synthetic Estrogens
• Man-made
• Examples: Ethinyl estradiol, Mestranol
• SERMs (Selective Estrogen Receptor Modulators)
• Act as agonist or antagonist
• Examples: Tamoxifen, Raloxifene, Bazedoxifene

 

Pharmacological Actions

Ø  Reproductive – Supports menstrual cycle & secondary sexual traits

Ø  Bone Health – Maintains bone density, prevents resorption

Ø  Cardiovascular – ↑ HDL, ↓ LDL, improves blood flow

Ø  Menopause Relief – Reduces hot flashes

Ø  HRT (Hormone Replacement Therapy) Role – Replaces lost hormones during menopause

 

Uses

• HRT – Treats menopausal symptoms
• Osteoporosis – Prevents/treats bone loss
• Contraceptives – Inhibits ovulation
• Hypogonadism – Treats hormone deficiency
• Breast Cancer Prevention – With SERMs in high-risk women

 

 

VITAMIN D

Forms

• D2 (Ergocalciferol) – plant sources
• D3 (Cholecalciferol) – skin (sunlight), animal sources
• Active form: Calcitriol

 

Physiological Role

• Calcium Absorption – Increases calcium absorption from intestines
• Bone Health – Helps in bone mineralization
• Parathyroid Regulation – Suppresses PTH overactivity
• Immunity Support
• Muscle Function – Supports muscle strength and coordination

 

Pathological Role

Deficiency:

• Rickets (Children) – Soft, deformed bones
• Osteomalacia (Adults) – Bone pain, muscle weakness
• Hypocalcemia – Low calcium levels
• Immune Weakness – ↑ infections

Excess (Hypervitaminosis D):

• Hypercalcemia – Nausea, vomiting, kidney stones

 

Clinical Uses

• Treatment of Rickets & Osteomalacia
• Osteoporosis – Combined with calcium
• Vitamin D Deficiency – General supplementation

 

OXYTOCIN

Physiological Role of Oxytocin

Oxytocin is a hormone produced by the hypothalamus and released by the posterior pituitary.

Ø  Uterine Contraction:

o   Stimulates uterine smooth muscle contraction during parturition.

Ø  Milk Ejection:

o   Causes contraction of myoepithelial cells in the breast, leading to milk ejection during breastfeeding.

Ø  Social and Emotional Roles:

o   Influences bonding, affection, and maternal behavior.

Pathological Roles

• Deficiency is rare, but may cause:
• Poor milk ejection in breastfeeding mothers.
• Delayed parturition.
• Excess (usually due to overadministration during labor):
• Can cause uterine hyperstimulation.

Drugs: Oxytocin (Synthetic)

• Name: Oxytocin (synthetic form)
• Route: IV or IM
• Half-life: ~5 minutes
• Mechanism of Action: Binds to oxytocin receptors on uterine muscle → increases intracellular calcium → muscle contraction.

 

Clinical Uses of Oxytocin

Ø  Induction of Labor

Ø  Postpartum Hemorrhage (PPH): Used to contract uterus and reduce bleeding after delivery.

 

Adverse Effects

·       Uterine rupture

·       Hypotension

 

CORTICOSTEROIDS

Physiological Role of corticosteroids

Glucocorticoids (Cortisol):

• Maintain blood glucose during stress by promoting gluconeogenesis.
• Inhibits white blood cells (especially T-cells, macrophages).

·        Suppresses cytokine production, which are signals used by immune cells.

Mineralocorticoids (Aldosterone):

• Maintain water and mineral balance.
• Reabsorb Na⁺.
• Increases blood pressure.

 

Pathological conditions

Ø  Deficiency of Corticosteroids

• Addison’s Disease: adrenal insufficiency (↓ cortisol & aldosterone).
• Symptoms: fatigue, low BP, weight loss.

Ø  Excess of Corticosteroids

• Cushing’s Syndrome: excess cortisol (due to adrenal tumor or prolonged steroid use).
• Symptoms: moon face, obesity, hypertension, diabetes.

 

DRUGS (Synthetic Corticosteroids)

A. Glucocorticoids:

• Short-acting: Hydrocortisone
• Intermediate-acting: Prednisolone, Methylprednisolone
• Long-acting: Dexamethasone, Betamethasone

B. Mineralocorticoids:

• Fludrocortisone – strong mineralocorticoid with mild glucocorticoid effect

 

Clinical Uses of Corticosteroids

Glucocorticoids:

Ø  Inflammatory & Autoimmune Diseases:

o   Asthma, rheumatoid arthritis, lupus (AID).

Ø  Allergic Conditions:

o   Anaphylaxis.

Ø  Immunosuppression:

o   Post organ transplant to prevent rejection.

 

INSULIN

Physiological Role of Insulin

Insulin is a hormone secreted by beta cells of the pancreas (Islets of Langerhans).

Ø  Lowers blood glucose by promoting:

o   Glucose uptake into muscles and fat.

o   Glycogenesis (storage of glucose in liver and muscle).

Ø  Inhibits gluconeogenesis and glycogenolysis.

 

Pathological Conditions Related to Insulin

Insulin Deficiency / Resistance → Diabetes Mellitus

• Type 1 Diabetes (T1DM):
• No insulin production.
• Type 2 Diabetes (T2DM):
• Insulin resistance with relative insulin deficiency.

 

Clinical Uses of Insulin

Diabetes Mellitus:

• Type 1 DM: Lifelong insulin therapy.
• Type 2 DM: When oral drugs fail or in emergencies.

 

PROGESTERONE

Physiological Role of Progesterone

Secreted by corpus luteum (a temporary gland formed in the ovary after ovulation), placenta, and adrenal glands.

Ø  Prepares and maintains endometrium for implantation.

Ø  Maintains pregnancy.

Ø  Promotes breast development for lactation.

 

Pathological Conditions

Ø  Progesterone deficiency → infertility, menstrual irregularities, miscarriage.

Ø  Excess → may cause mood swings, bloating.

 

Drugs

• Natural: Micronized progesterone
• Synthetic: Medroxyprogesterone, Norethisterone, Levonorgestrel, Drospirenone

 

Clinical Uses

Ø  Hormonal contraception (alone or combined with estrogen)

Ø  Menstrual disorders (heavy bleeding)

 

NOTE

Micronized Progesterone

Micronized means the progesterone has been ground into very tiny (micro-sized) particles to improve its absorption in the body, especially when taken orally.