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HYPOTHALAMIC & PITUITARY HORMONES

HYPOTHALAMIC & PITUITARY HORMONES. Pharmacological applications in : Replacement therapy for hormone deficiency status As drug therapy As diagnostic tools for performing stimulation tests. Hypothalamic and Pituitary Hormones. Anterior pituitary hormones include - Growth Hormone (GH)

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HYPOTHALAMIC & PITUITARY HORMONES

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  1. HYPOTHALAMIC & PITUITARY HORMONES

  2. Pharmacological applications in : • Replacement therapy for hormone deficiency status • As drug therapy • As diagnostic tools for performing stimulation tests Hypothalamic and Pituitary Hormones

  3. Anterior pituitary hormones include - Growth Hormone (GH) - Thyrotropin (TSH) - Follicular stimulating hormone (FSH) - Leutinizing Hormone (LH) - Prolactin - Adenocorticotropin (ACTH) Hypothalamic and Pituitary Hormones

  4. Hypothalamic releasing hormone - Growth hormone releasing hormone (GHRH) - Gonadotropin releasing hormone (GnRH) - Thyrotropin releasing hormone (TRH) - Corticotropin releasing hormone (CRH) - Somatostatin (GHIH) - Dopamine Hypothalamic and Pituitary Hormones

  5. GROWTH HORMONE Growth Hormone preparations: Somatropin Somatrem • Administered in a dose of 40 mg/kg per day. S.C in the evening t½ - 20 min.

  6. Toxicity & Contraindication - GH obtained from human cadaver – CREUTZFELDT JAKOB DISEASE - Children: intracranial hypertension, vision changes, headache, nausea and vomiting. - Adults: Peripheral edema, carpal tunnel syndrome, arthralgia and myalgia. GROWTH HORMONE

  7. GHRH • Sermorelin acelate: Synthetic form of human GHRH - Well tolerated and less expensive

  8. Toxicity of GHRH GHRH(IV) – flushing, injection site pain, erythema, nausea, headache, metallic last, pallor, chest tightness. GHRH(SC) – pain, swelling, erythema, headache, dysphagia, dizziness, hyperactivity, somnolence, urticaria

  9. Somatostatin (GHIH) • 14 amino acid peptide found in hypothalamus and CNS, also in pancreas and GIT. • Inhibits growth hormone release, shown to inhibit release of glucagon, insulin and gastrin • Exogenously administered SST has limited therapeutic usefulness - shorter duration of action and its multiple effects on many secretary system. • SST analogues – Octreotide, lantreotide, vapreotide

  10. OCTREOTIDE • Synthetic derivation of SST. • 45 times more potent than SST in inhibiting growth hormone release lent only --- as potent in reducing insulin secretion – hyperglycemia rarely occurs. • Greater potency – lower clearance and longer half life t½ - 80 min. • 100 µg , s. c three times daily.

  11. Uses • Acromegaly, carcinoid syndrome, gastrinoma, watery diarrhoea • Acute control of bleeding from esophagial varices Adverse effects • Diarrhoea, nausea, sbdominal pain, flatulance, steatorrhea with bulky bowel movements, gall stones,sinus bradycardia, conduction disturbances, vit B 12 deficiency OCTEOTIDE

  12. PEGVISOMANT(Growth hormone receptor antagonist) • Useful in treatment of acromegaly • PEG derivative of mutant growth hormone , increased affinity for one site of GH receptor but a reduced affinity at its second binding site- allows dimerization but blocks conformational changes • Administered by s.c

  13. GONADOTROPIN RELEASING HORMONE (GnRH) GnRH-Gonadorelin GnRH analogues- Leuprolide, Nafarelin, goserelin Administered IV, SC, IM or via nasal spray • Half life (IV)- 4 min ,other routes-3 hours • GnRH binds to receptors on pituitory gonadotrophs • Pulsatile IV administration of GnRH stimulates FSH & LH secretion • GnRH administered continuously inhibit gonadotropin release

  14. Therapeutic uses • GnRH stimulate pituitory function- treat infertility caused by hypothalamic hypogonadotropic hypogonadism • GnRH analogues induce hypogonadism when given continuously – prostate cancer, uterine fibroid, endometriosis, PCOS GONADOTROPIN RELEASING HORMONE (GnRH)

  15. Toxicity • Gonadorelin- headache, light headache, nausea,flushing, local swelling, dermatitis, hypersensitivity reactions • GnRH analogs- hot flushes, sweating, headache, depression, osteoporosis C/I – pregnancy and breast feeding GONADOTROPIN RELEASING HORMONE (GnRH)

  16. CETRORELIX(GnRHANTAGONISTS) • Synthetic decapeptide • Reversibly binds to pituitory GnRh receptors without activating them , inhibits secretion of FSH & LH • Uses In vitro fertilization Endometriosis Uterine fibroids

  17. Gonadotropins • Preparations: Menotropin Urofollitropin Follitropin • Uses Amenorhoea & infertility Hypogonadotropic hypogonadism Cryptorchism to aid in vitro fertilization

  18. GONADOTROPINS • Adverse effects Ovarian hyperstimulation, polycystic ovary, pain in lower abdomen, ovarian bleeding, allergic reactions, edema, headache, mood changes

  19. PROLACTIN • Principle hormone responsible fr lactation • Dopamine agonists inhibits prolactin • Bromocriptine, cabergalide, pergolide, quinagolide – lower circulatory prolactin levels and shrink pituitory prolactin secreting tumors

  20. Uses • Prolactin secreting adenomas • Amenorrhoea, Galactorhea • Acromegaly • Parkinson’s disease Toxicity • Nausea, headche, light headness,orthostatic hypertension, fatigue, behavioral alterations, mental confusion, hallucination,psychosis

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