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anterior pituitary hormones-analogues and their inhibitors.pptx
- 1. ANTERIOR PITUITARY HORMONES- Analoguesand their inhibitors THE MASTER ENDOCRINE GLAND -By Shivarudra
- 2. Points tobe covered ◦ Introduction-Pituitary gland • Growth hormone ◦ Growth hormone inhibitors • Prolactin ◦ Prolactin inhibitors • Gonadotropin • GnRH antagonist (gonadotropin releasing hormone inhibitors)
- 3. • Introduction- Pituitarygland oAnterior pituitary gland is also called as “MASTER ENDOCRINE GLAND” o It involves number of important regulatory hormone (peptide), which acts on extracellular receptors of target cells o The secretion of these hormones is controlled by hypothalamus via releasing & inhibiting hormone o Each hormone produced by the gland is produced by a separate group of cells i.e. Acidophilic or basophilic (according to their staining characteristics)
- 4. Anterior and posteriorpart of pituitary gland are also known as ???
- 6. • Growth hormone-Physiological role 1. Major Growth Functions o -GH promotes growth of almost all body tissues except the brain and eyes. o increases amino acid uptake and protein synthesis, helping in nitrogen retention and muscle development (positive nitrogen balance). o Enhances formation of body tissues and organ growth during childhood. 2. Metabolic Effects o GH breaks down fat stored in body provide energy by process of lipolysis o It promotes glycogen breakdown into glucose (glycogenolysis) in the liver by doing so GH raises blood glucose levels, acting opposite to insulin (hence called anti-insulin or diabetogenic effect. o It also reduces glucose utilization by muscles, conserving glucose for vital organs like the brain.
- 7. 3. Bone andSoft Tissue Growth:- • GH directly stimulates bone growth by increasing number and maturation of cartilage cells at the growth plates. • Promotes growth of soft tissues such as muscles and connective tissue Do you know the terms hyperplasia and hypertrophy?? 4. Indirect Effects (Somatomedins / IGFs) :- insulin like growth factors • IGF-1, mainly produced by the liver, acts like insulin and stimulates cell growth, protein synthesis, and bone elongation. • IGF-1 is responsible for most of the growth-promoting actions of GH. • Many of GH’s effects are mediated indirectly through somatomedins (IGF-1 and IGF-2).
- 8. • Regulation ofGH Secretion • The hypothalamus controls GH release by:GHRH (Growth Hormone Releasing Hormone) → stimulates GH secretion. • Somatostatin (Growth Hormone Inhibiting Hormone) → inhibits GH secretion. • Both are peptide hormones acting through G-protein coupled receptors. Clinical Note • Since GH increases blood glucose and opposes insulin, it can worsen diabetes or cause insulin resistance (diabetogenic effect)
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- 10. GIGANTISM in childhoodACROMEGALY in adults 7’ft 1 inch (216 cm) 63 cm Dwarfism Hypersecretion Deficiency
- 11. • Pharmacological usesof rhGH (recombinant human growth hormone) :- • Two forms of human GH produced by recombinant DNA technique= somatropin and somatrem • Uses:- • Pituitary Dwarfism: A condition in children caused by a deficiency of growth hormone, which can be treated with rhGH to accelerate growth and help them attain a near-normal height. • Turner Syndrome: A genetic condition in girls causing short stature (height), which can be largely corrected with rhGH treatment. • Chronic Renal Insufficiency: In children with this condition, rhGH can be used to treat suboptimal growth. • Adult GH Deficiency: Treatment with rhGH can increase lean body mass, decrease body fat, and improve energy and metabolism. • Other Uses: Somatropin is also used to improve mental and physical health in AIDS-related problems and for catabolic stress in patients with severe burns or chronic renal failure
- 12. • Adverse effects •Pain, swelling, and redness at the injection site. • Fluid retention (edema), which can cause swelling in the arms and legs. • Joint and muscle pain. • Headache. • Mildly high blood sugar levels.
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- 14. • Somatostatin Also knownas growth hormone-inhibiting hormone (GHIH) or somatotropin release-inhibiting factor (SRIF), is a peptide hormone that acts as a powerful inhibitor in the body. It has two active forms, one with 14 amino acids and one with 28 amino acids. Inhibition Effects: Somatostatin inhibits the release of various hormones and secretions from different parts of the body: • Pituitary Gland: Inhibits the release of growth hormone (GH), prolactin, and thyroid-stimulating hormone (TSH). • Pancreas: Inhibits the secretion of insulin and glucagon, as well as bicarbonate and other digestive enzymes. • Gastrointestinal Tract: Suppresses the release of hormones like gastrin and secretin, reduces gastric emptying, and decreases blood flow in the intestine.
- 15. • Side Effects:- includegastrointestinal issues such as steatorrhea (fatty stools), diarrhea, dyspepsia, nausea, and vomiting. It can also cause fluctuations in blood glucose levels. • Medical uses for somatostatin include treating acute gastrointestinal hemorrhage, managing fistulas (abnormal connections) in the intestines, bile ducts, and pancreas, and as an adjunct treatment for diabetic ketoacidosis. Its use in conditions like acromegaly is limited due to its short duration of action, with a half-life of 1-3 minutes in the body.
- 16. • Octreotide Octreotide isa synthetic analog of somatostatin with a longer and more potent effect (40x). It has a much longer half-life (around 90-120 minutes) compared to natural somatostatin. • Uses: Octreotide is preferred over somatostatin for long-term treatment of certain conditions: • Acromegaly: It is used to treat this condition caused by excess growth hormone production. manage symptoms like severe watery diarrhea •Other uses: It is also used to prevent complications after pancreatic surgery and to treat bleeding from esophageal varices. • Side Effects: Common side effects Octreotide of octreotide are often gastrointestinal, including abdominal pain, diarrhea, constipation, nausea, and flatulence. It can also lead to the formation of gallstones and affect blood sugar and thyroid function.
- 17. • Prolactin ◦ Itis a 199 amino acid single chain peptide. ◦ It is secreted by the lactotroph cells in the anterior pituitary gland, and its release is controlled by the hypothalamus. ◦ Induces milk secretion after child birth that’s why it is called as Mammotropin or lactogenic hormone (GPAT oriented) ◦ Dopamine and dopamine agonist (DA) inhibits the secretion of Prolactin.
- 18. • Physiological functions:- • It causes growth & development of breast during pregnancy. • Promotes proliferation (multiplication or increasing the number) of acinar cells in breast & induces synthesis of milk proteins and lactose. • After parturition it induces milk secretion . • It suppresses hypothalamo-pituitary-gonadal axis by inhibiting GnRH release. • It is responsible for lactational amenorhoea (temporary absence of menstruation that occurs after childbirth)
- 19. • Prolactin abnormalities ◦Hyperprolactinaemia is responsible for Galactorrhoea (discharge of milky light color secretion), amenorhhea (absence of menstruation), infertility. ◦ Causes:- - disorders of hypothalmus removing the inhibitory control over pituitary - antidopaminergic or DA depleting drugs
- 20. • PROLACTIN INHIBITORS-BROMOCRIPTINE ◦ It is an synthetic ergot derivative 2-bromo-a-ergocryptine, a potent dopamine agonist. ◦ It has greater action on D2 receptors while at certain dopamine sites in the brain it acts as a partial agonist. ◦ It decrease prolactin release from pituitary by activating dopaminergic receptors on lactotroph cells. ◦ Increase GH release in normal individuals, but decrease the same from pituitary tumors that cause acromegaly. ◦ It can produce nausea and vomiting by stimulating dopaminergic receptors.
- 21. ◦ PHARMACOKINETICS ◦ Only1/3 part is absorbed of an oral dose. ◦ Bioavailability is further lowered by high first pass metabolism in liver. ◦ Metabolites excreted in bile. ◦ Plasma t1/2 is 3-6 hours. ◦ USES:- ◦ Always started at low dose (1.25 mg BD) and then gradually increased till response occurs. ◦ To treat hyperprolactinemia. ◦ Treat acromegaly due to small pituitary tumours. ◦ Treat parkinsonism, similar to levodopa
- 22. ◦ SIDE EFFECTS ◦Side effects are frequent and dose related. ◦ Early side effects are; nausea, vomiting, constipation, nasal blockage. Postural hypotension ◦ Late side effects are; behavioural alteration, mental confusion, hallucination, psychosis.
- 23. • Cabergoline • Anewer D2 agonist: It is more potent and selective for the D2 receptors in the pituitary gland than bromocriptine. • Long-acting: With a long half-life, it can be administered only twice a week, which improves patient compliance. • Better tolerated: Compared to bromocriptine, cabergoline has a lower incidence of side effects like nausea and vomiting. Some patients who did not tolerate or respond to bromocriptine have been successfully switched to cabergoline. • First-choice drug: Due to its high efficacy and better tolerability, it is considered the first- choice drug for treating hyperprolactinemia.
- 24. • Gonadotropins (Gns)/Gonadotropin Releasing Hormone ◦ The anterior pituitary secretes two Gonadotropins viz. FSH and LH. ◦ Stimulates the gonads and promote gametogenesis and secretion of gonadal hormones. • FSH ◦ In female :induces follicular growth, development of ovum and secretion of estrogen. ◦ In male- spermatogenesis • LH: ◦ In female Ripening of graffian follicles, triggers ovulation, rupture of follicles ◦ and sustaining of corpus leuteum. ◦ In male stimulates testosterone secretion
- 25. • Superactive/long actingGnRH agonists ◦ GnRH analogs used clinically are triptorelin and nafarelin - Superactive GnRH 15-50 times more potent than natural GnRH - longer acting (2-6 hours) - high affinity to receptors ◦ (GnRH) Synthetic GnRH - causes release of FSH and LH, Short plasma half life: 4-8 minutes (rapid enzymatic degradation) ◦ Non Pulsatile (continuous) exposure to GnRH releases FSH/LH - Desensitization of pituitary gonadotrophs - loss of Gn release
- 26. • Adverse effects:- -ovarian bleeding - polycystic ovary -pain in lower abdomen • Therapeutic uses :- ◦ Amenorrhea and infertility in low Gns patients (decreased secretion from pituitary) to induce ovulation ◦ Controlled ovarian hyperstimulation- suppression of endogenous FSH/LH - by super active GnRH/GnRH antagonist ◦ Hypogonadism in males: oligospermia (low sperm count), male sterility ◦ Cryptorchism: undescended testes (condition where one or both testicles fail to descend into the scrotum from the abdomen)
- 27. ◦ Nafarelin ◦ Longacting GnRH agonist and 150 times more potent than GnRH -plasma half life 2-3 hrs ◦ Uses: ◦ Assisted reproduction: when menstrual bleeding occurs, for suppression of endogenous LH surge- matured oocyte can be harvested ◦ For the treatment Uterine fibroid-benign growths in the uterus that can cause heavy bleeding or pain. By reducing FSH and LH, estrogen production drops, which can shrink fibroids and reduce symptoms. ◦ Endometriosisuterine- tissue grows outside the uterus, causing pain and bleeding. Suppressing FSH and LH lowers estrogen levels, which reduces growth of endometrial tissue Precocious puberty- arrest of breast and genital development. • Triptorelin:- ◦ long acting(once a month) : for regular release daily SC injection (female infertility)
- 28. • GnRH antagonists ◦Inhibits Gn without initial stimulation ◦ Older ones - reactions due to histamine release ◦ Newer - Ganirelix, cetorelix ◦ Used in in vitro fertilization for suppression of LH surge ◦ Advantages: ◦ Quick - competitive antagonist ◦ Lower risk of ovarian hyperstimulation ◦ Complete suppression