1 / 65

PREPARED BY : NISHIDA M

CELLULAR AND MOLECULAR MECHANISM OF GROWTH HORMONE , THYROID HORMONE , PROLACTIN , CORTICOSTEROIDS AND DRUGS AFFECTING CALCIUM BALANCE. PREPARED BY : NISHIDA M. ENDOCRINE SYSTEM.

azure
Download Presentation

PREPARED BY : NISHIDA M

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. CELLULAR AND MOLECULAR MECHANISM OF GROWTH HORMONE , THYROID HORMONE , PROLACTIN , CORTICOSTEROIDS AND DRUGS AFFECTING CALCIUM BALANCE PREPARED BY : NISHIDA M

  2. ENDOCRINE SYSTEM Endocrine glands consist of group of secretory cells surrounded by a extensive network of capillaries that facilitates diffusion of hormone. Endocrine glands: Secrete their hormones directly into the bloodstream for distribution throughout the body—ductless.

  3. The word ‘hormone’ is derived from a Greek word Hormaowhich means ‘to impel ’ .Hormones are defined as chemical substances secreted by endocrine glands directly in to the circulation, and which act on distinct target organs or tissues to control or modulate physiological function and maintain homeostasis. HORMONES

  4. THE MAJOR ENDOCRINE GLANDS

  5. Hypothalamus and Pituitary Gland • The hypothalamus maintains homeostasis through the autonomic system. • Controls heartbeat, body temperature, water balance. • Controls glandular secretions of the pituitary gland.

  6. PITUITARY GLAND • Pituitary gland: The pituitary gland lies in the hypophysealfossa of sphenoid bone bolow the hypothalamus.A small gland connected to the hypothalamus by a stalk-like structure. Contains two portions- posterior pituitary and anterior pituitary. • 1. Posterior Pituitary Antidiuretic hormone (ADH) oxytocin.

  7. 2. Anterior Pituitary • The hypothalamus controls the anterior pituitary by producing hypothalamic-releasing hormones and hypothalamic-inhibiting hormones. • Three of the six hormones produced by the anterior pituitary have an effect on other glands. • a. Thyroid-stimulating hormone (TSH) stimulates the thyroid to produce thyroid hormones. • b. Adrenocorticotropic hormone (ACTH) stimulates the adrenal cortex to produce cortisol. • c. Gonadotropic hormones (FSH and LH) stimulate the testes in males and the ovaries in females to produce gametes and the sex hormones.

  8. The other three hormones produced by the anterior pituitary do not affect other endocrine glands. • Prolactin (PRL) is produced in quantity only after childbirth. Causes the mammary glands in the breasts to develop and produce milk. • Melanocyte-stimulating hormone (MSH) causes skin-color changes. concentration of this hormone in humans is very low. • Growth Hormone (GH) promotes skeletal and muscular growth. Quantity produced is greatest during childhood and adolescence. This affects height of an individual.

  9. GROWTH HORMONE • Growth hormone is a single unbranched poly peptide chain containig 191 amino acid with MW 21500. • Derived from the somatotroph cells and synthesized by the acidophils of anterior lobe and stored in large amount in the anterior pitutary . • Also called somatotrophin or somatotrophic hormone.

  10. Action of growth hormone and regulation of its secretion

  11. Stimuli that increases growth hormone secretion; Hypoglyceamia, Exercise,i.v. infusion of arginine,Stress,fasting,trauma,fears,deep sleep. • Stimuli that decrease growth hormone secreation; Increase in plasma free fatty acid level, High dose of glucocorticoids , REM sleep , giucose

  12. Growth hormone abnormalities Juvenile hypopituitarism leads to pituitary dwarfism. • Adult hypo pituitarism leads to sheehan’s syndrome • Hyper secretion of GH leads to acromegaly and gigantism

  13. GH GH GH PEGVISOMANT J A K 2 J A K 2 No GH signaling STAT 5 IRS -1 SHC PI3K MAPK Gene expression IGF-1 Glucose transport

  14. Physiological actions • Control balanced growth. • Stimulate production of hepatic somatomedins. • Stimulate protein synthesis in skeletal muscle and regulate bone growth. • Increased insulin secretion in response to hyperglyceamia. • Induce lipolysis.

  15. Preparation and dosage • Currently available hGH is produced by recombinant DNA technology. • Somatremis available as protorpin and stomatonorm. • somatropin(non-methionylhGH) is available as humatrope, genotropin,norditropin DOSE: 20-40mcg/kg/day,IM or SC daily in children with GHD adult: 3-4mcg/kg/day,daily USES: GH deficiency with short stature in children. Turner syndrome chronic renal failure with short stature

  16. GH INHIBITORS Somatostatin It is a peptide containing 14 amino acids,inhibit the secretion of GH,prolactin by pituitary ,TSH , insulin and glucagon by pancreas and almost of all GI secretion. Adverse effect steatorrhoea,diarrhoea,hypoclorhydria, dyspepsia, nausea Dose;250ug slow i.v over 3 min followed by 3mg i.v. infusion over 12hr

  17. Octreotide • synthetic and long acting analogue of somatostatin , but only weak inhibitor of insulin secretion. • Preffered over somatostatin for acromegaly and secretorydiarrhoea associated with carcinoid, AIDS,and cancer therapy. • Adverse effect; abdominal pain,nausea, steatorrhoea and gall stones,diarrhoea. • Dose;injectedi.v.(100ug followed by 25-50ug/hr)

  18. LANTREOTIDE : Long acting analogue of octeotride. PEGVISOMANT: a genetically altered GH antagonist. They block the binding of GH to its tissue receptor. Used for acromegaly.

  19. PROLACTIN • Also called lactogenic or mammotrophic or galactopoetic hormone • It is synthesized in the pituitary acidophils cells. • It is a single peptide chain containing 199 amino acids,MW 23000, half life;20 min. • Normal serum level in adults; female: 8ng/ml male : 5ng/ml

  20. PRF TRH DOPAMINE Dopamine antagonist (-) (-) + (+) (+) Sucking reflex (+) REGULATION OF SECREATIONS

  21. Physiological function • primary function is lactation • Prolactin in a complex interaction with estrogen , progestrone and several other hormone cause growth and development of breast during pregnancy • They stimulate RNA synthesis for milk production protein and promote lactose genesis. • It exerts an anti-gonadotropic effect inducing inhibition of ovulation and,hence, natural contraception.

  22. PROLACTIN INHIBITORS • Bromocriptine synythetic ergot derivative of 2-bromo-α-ergocryptine. Greater action on D2 receptor ACTIONS • Decreases release from pituitary by activating dopaminergic receptor . • Increase GH release in normal individual, but decreases the same from pituitary tumors that cause acromegaly. • Hypotension. • Has levodopa like action. • Produce nausea and vomiting by stimulating dopaminergic receptor on the CNS • Decrease GI motility

  23. SIDE EFFECTS • EARLY : nausea, vomiting, constipation , nasal blockage, postural hypotension . • late : behaviouralalteration,mental confusion, hallucination ,psychosis ,abnormal movement. • PHARMACOKINETICS • Only 1/3 of an oral dose is absorbed. • Bioavailability is lowered by first pass metabolism. • Excreted through bile. • Plasma t1/2 3-6 hrs.

  24. USES HYPER PROLACTINEMIA ACROMEGALY PARKINSONISM HEPATIC COMA

  25. CARBERGOLINE • Newer D2 agonist, More D2 selective • Long acting (t1/2 60 days) • Incidence of nausea, vomiting is lower • Used for hyper prolactinemia , and acromegaly . • Dose start with 0.25 mg twice weakly PERGOLIDE Least expensive dopamine receptor agonist can be given once a day Starting at 0.025mg and increased to a maximum daily dose of 0.5mg QUINAGOLIDE Non ergot D2 dopamine agonist with half life 22 hr. daily dose 0.1 – 0.5mg/day

  26. Thyroid gland HORMONES OF THYROID GLANDS • TETRAIODOTHYRONINE • TRIIODO THYRONINE • CALCITONIN

  27. synthesis ,storage and release of thyroid hormone • Iodide uptake • synthesis of thyroglobulin • Oxidation and iodination • Coupling • Storage and release • Peripheral conversion of T4 and T3

  28. ACTION OF THYROID HORMONE • Growth and development • Metabolic effect • Carcinogenesis • CVS • Nervous system • Skeletal muscle • GIT • Kidney • Haemopoiesis • Reproduction

  29. PREPARATION OF THYROID HORMONES Thyroxine Liothyronine sodium Liotrix

  30. USES • CRETINISM • ADULT HYPOTHYROIDISM • MYXOEDEMA COMA • NON TOXIC GOITER • THYROID NODULE • PAPILLARY CARCINOMA OF THYROID

  31. THYROID INHIBITORS CLASSIFICATION • Inhibit hormone synthesis(anti thyroid drugs) propylthiouracil,methimazole,carbimazol • Inhibit iodide trapping(ionic inhibitors) thiocyanates,perchlorate,nitrates. • Inhibit hormone release iodine,iodides of Na and K , organic iodide • Destroy thyroid tissue radio active iodine.

  32. ANTI THYROID DRUGS • Mechanism of action: they bind to thyroid peroxidase , and prevent oxidationof iodide residue, there by; 1. inhibit iodination of tyrosin residue in thyroglobulin 2.inhibit coupling of iodotyrosine residue to form T3 and T4 Adverse effect: hypo thyroidism, loss or graying of hair , GI intolerance , skin rashes, loss of taste , fever.

  33. IONIC INHIBITORS • MOA : certain monovalentcations inhibit iodide trapping by the thyroid because of similar hydrated ionic size. • USES :pre operative preparation of thyroidectomy. Thyroid storm , prophylaxis of endemic goiter , antiseptic . • ADVERSE EFFECTS : swelling of lips, angioedema of larynx ,fever , joint pain ,thrombocytopenia ,burning sensation in mouth

  34. PHARMACOINETICS • USES : • GRAVE’S DISEASE • NODULAR TOXIC GOITER • PRIOR TO SURGERY FOR HYPER THYROIDISM

  35. ADRENAL GLANDS There are two adrenal glands. Situated on the upper pole of each kidney . Each adrenal gland consists of an inner portion called the adrenal medulla and an outer portion called the adrenal cortex. The adrenal medulla is under nervous control. Portions of the adrenal cortex are under the control of ACTH.

  36. CORTICO STEROIDS • ADRENAL CORTEX ZONA GLOMERULOSA - GLUCOCRTICOIDS ZONA FASCICULATA - MINERALO CORTICOIDS ZONA RETICULARIS - SEX HORMONES ADRENAL MEDULLA EPINEPHRINE NOREPINEPHRINE CORTISOL CORTICO STERONE CORTISONE ALDOSTERONE ANDROGENS

  37. CHOLESTROL MINERALOCORTICOIDS PREGNENOLONE 17-HYDROXY-PREGNENOLONE DEHYDROEPIANDROSTERONE PROGESTRONE ANDROGENS 11- DESOXY CORTICOSTERONE 17-HYDROXY PROGESTRONE ANDROSTENEDIONE CORTICOSTERONE 11- DESOXY HYDROCORTISONE TESTOSTERONE GLUCO+MINERALO ALDOSTERONE HYDROCORTISONE

  38. mineralocorticoids • Aldosterone:regulate homeostasis of two mineral ions,Na ,& K. • Water electrolyte balance. • ACTION They bind to mineralocorticoid receptor DNA transcription of specific protein increase in number of Na+/K+ ATPase.this action is expressed by gene mediated transcription of m RNA direct synthesis of protein.

  39. GLUCOCORTICOID ACTIONS • Carbohydrate and protein metabolism • Fat metabolism • Calcium metabolism • Water excretion • CVS • Skeletal muscles • CNS • Stomach • Lymphoid tissue and blood cells • Inflammatory responses • Immunological and allergic responses

  40. HYDROCORTISONE[CORTISOL] • Rapidly act but short duration of action. • Significant mineralocorticoid activity. • Replacement therapy-20mg morning +10mg afternoon orally. • Shock, status asthmaticus, acute adrenal insufficiency-100mg+100mg 8 hourly i.v.inf • Topically and as suspension for enema in ulcerative colitis.

  41. PREDNISOLONE • 4 times more potent than hydrocortisone. • Less pituitary-adrenal suppression. • Used for allergic, inflammatory, auto immune diseases • Dose-5-60mg\day oral,10-40mg i.m.

  42. METHYLPREDNISOLONE • Minimal suppression of pituitary-adrenal axis • Slightly more potent and more selective than prednisolone. • Used as retention enema in ulcerative colitis. • Dose 4-32mg/day oral

  43. TRIAMCINOLONE • Slightly more potent than prednisolone. • Highly selective glucocorticoid. • Dose-4-32mg/day oral,5-40mg i.m.

  44. DEXAMETHASONE • Very potent and selective. • Marked pituitary-adrenal suppression. • Used for inflammatory and allergic conditions. • 0.5-5mg/day i.v. inf or i.m. inj. BETAMETHASONE Dose o.5 – 5 mg /day oral,4-20 i.m ,i,.v

More Related