1-Pituitary hormones(this).ppt

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Hypothalamic Pituitary Hormones

• Most body functions are controlled by two
  systems namely the nervous system the
  endocrine system.
• The endocrine system is composed of a number of
  glands that secrete chemicals called hormones
  directly in blood stream that affect body
  functions.ie they are ductless glands.
• The control of metabolism, growth reproduction
  is mediated through a combination of neural
  endocrine systems located in hypothalamus
  pituitary glands.

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The Endocrine Glands
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Control of petuitary hormones by Hypothalamus
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Hypothalamic Hormones

• Are called releasing factors or hormones.
• Regulate secretion of anterior pituitary
  hormones. Some are used for diagnosis or
  treatment of some diseases.They include
• 1-GH-releasing factor or hormone-also called
  somatorelin)
• Main function is to stimulate AP to release GH.
• An analogue called sermorelin is used as a
  diagnostic test for GH secretion
• 2-Somatostatin inhibits release of GH TSH from
  anterior pituitary insulin glucagon from
  pancreas, also deceases release of most GIT
  hormones acid.
• Octreotide is a long-acting analogue used to
  treat acromegally,carcinoid tumors tumors
  secreting

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• vasoactive intestinal peptide,glucagonomas
  various pituitary adenomas. Lanreotide is an
  other analogue that is used also for thyroid
  tumors.
• 3- Thyrotrohpin-releasing hormone(TRH-
  protirelin)
• Stimulates release of TSH from anterior piuitary.
  Protirelin is a synthetic analogue used for
  diagnosis of thyroid disorders.
• 4-Corticotropin-releasing factor (CRF) or hormone
• Releases ACTH ß endorphin from anterior
  pituitary.Acts synergistically with antidiuretic
  hormone (Vasopressin).
• Both its action and release are inhibited by
  glucocorticoids
• Synthetic preparations were used to test ability
  of pituitary to secrete ACTH and to assess
  whether ACTH deficiency is due to pituitary or
  hypothalamic defect.

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• 5-Gonadotropin releasing hormone(GnRH) and
  analogs
• Drugs available include gonadorelin (natural
  hormone).
• Long-acting analogs histrelin (Suprelin),
  leuprolide (Leupron), gosrelin (Zoladex),
  triptorelin(Trelstar), and nafarelin (Synarel).
• Gonadorelin is used for induction of ovulation in
  infertility
• Long acting analogs are used for treatment of
  endometriosis, prostate cancer, and central
  precocious puberty. Experimental use as male
  contraceptive.
• GnRH antagonists ganirelix (Antagon) and
  cetrorelix (Cetrotide)
• Used to inhibit premature LH surges prior to
  harvesting eggs for in vitro fertilization
• Also abarelix (Plenaxis) a GnRH receptor
  antagonist used to treat advanced prostate
  cancer. Danger of life-threatening allergic
  reactions in 4 of patients.

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The Pituitary Gland

• Consists of two lobes
• -The anterior lobe(adenohypophysis) secretes
  GH,TSH,ACTH, FSH,LH PRL
• -The posterior lobe(neurohypophysis)secretes
  oxytocin vasopressin.
• Drugs that mimic or block effects of pituitary or
  hypothalamus hormones are used in
• -Replacement therapy for hormonal deficiency.
• -As antagonists for diseases due to production
  of excess pituitary hormones.
• -As diagnostic tools for many endocrine
  diseases

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Pituitary Hormones
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Pituitary Control

• The pituitary is controlled by releasing factors
  (hormones) from hypothalamus, these are
• -growth hormone releasing hormone(GHRH)
• -corticotropin releasing hormone(CRH)
• -gonadotropin releasing hormone(GnRH)
• -thyrotropin releasing hormone(TRH)
• Also pituitary hormones their releasing factors
  from hypothalamus are subject to control by the
  hormones they regulate their secretion, namely
  T3,T4,cortisol sex hormones (estrogens
  progesterone).This is called negative feedback
  control.

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• The hypothalamus secretes two hormones that
  regulate release of GH, these are GHRH that
  stimulates GH production somatostatin(SST)
  which inhibits its production.
• GH and its peripheral mediator insulin-like
  growth factor -1(IGF-1) inhibit release of GH by
  a negative feedback mechanism also.
• Production of prolactin by AP is inhibited by
  dopamine dopamine analogs acting on D2
  receptors.
• No hypothalamic regulator for PRL production or
  release.

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• Anterior pituitary hormones include
• -Growth hormone(GH, somatotropin)
• -Thyroid stimulating hormone(TSH,thyrotopin)
• -Follicle stimulating hormone(FSH)
• -Lutinizing hormone(LH)
• -Adrenocorticotrophic hormone(ACTH)
• -Prolactin (PRL)
• All anterior pituitary hormones,except prolactin,
  are trophic hormones i.e. they regulate
  production of other hormones produced by other
  endocrine glands promote growth of these glands.

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Mechanism of Action

• TSH,FSH,LH,and ACTH all act through G protein
  coupled receptors, while GH and PRL act through
  JAK/STAT superfamily receptors

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1- Growth Hormone(GH,Somatotropin)

• A single chain polypeptide hormone of 191 aa.
• Secretion is high in the new born,decreasing at
  4yrs to an intermediate level, maintained until
  after puberty, then further declines.Secretion is
  high during sleep.
• Secretion is inhibited by somatostatin IGF-1.
• Significant differences in amino acid sequence
  between humans other species prevent the use of
  non-human hormone.
• Actionsis required in children adolescents for
  attainment of normal adult size.
• Also has important effects on CHO lipid
  metabolism lean body mass( protein anabolism,
  lipolysis, glycogenolysis)
• Effects are mediated through IGF-1 (somatomedin-
  c)

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• Congenital or aquired deficiency in children
  leads to failure to attain normal adult
  size(dwarfism), disproportionate increased body
  fat decreased muscle mass.
• Increased release of GH before closure of
  epiphysis leads to gigantism.
• Deficiency leads to short stature, adposity,
  hypoglycemia due to unopposed action of insulin.

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Growth Hormone

• Physiological Actions
• Promotes growth of bone muscle
• Has anabolic effects in muscle catabolic
  effects in lipid cells, shifting the balance of
  body mass to an increase in muscle mass and
  reduction in lipids.
• Promotes use of lipids for energy production
  instead of CHO
• Reduces insulin sensitivity leading to
  hyperinsulinemia
• Effects mediated through IGF-1

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Growth Hormone

• Physiological actions
• Mechanism GH receptor stimulation activates an
  intracellular tyrosine kinase, JAK/STAT cytokine
  superfamily type recepors, resulting in
  phosphorylation of proteins and gene regulation.
• Growth-promoting effect is mediated through
  production of IGF-1 in liver,bone,muscle
  kidneys.
• Growthalmost all body tissues are stimulated to
  grow.
• Nitrogen metabolism increased nitrogen
  retention, amino acid transport into tissues, and
  incorporation into protein

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• Carbohydrate and lipid metabolism GH appears
  to promote use of lipids as energy source instead
  of carbohydrates.
• GH IGF-1 have opposite effects on insulin
  sensitivity.
• GH reduces insulin sensitivity leading to
  hyperinsulinemia
• IGF-1 lowers serum glucose and reduces
  circulating insulin through action on IGF-1
  receptors and insulin receptors.

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Growth Hormone

• Physiological actions (cont..)
• Conserves muscle at the expense of fat during
  stress
• Insulin-like growth factor-1 (IGF-1 IGF-2,
  somatomedins) are peptides produced by liver and
  other tissues in response to GH appear to
  mediate many GH effects.
• Some children with growth failure have severe
  IGF-1deficiency that is not responsive to
  exogenous GH may be due to mutation in GH
  receptor or development of antibodies to GH.
• rhIGF-1 (mecasermin, Increlix) is now available
  for treatment of growth failure in GH-resistant
  patients

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Growth Hormone

• Clinical applications one of the few pituitary
  hormones with long-term therapeutic utility.
  Recombinant human growth hormone (rhGH,
  somatropin) is used clinically. There are two
  forms, somatropin and somatrem.
• Hypopituitary dwarfism in children with
  insufficient GH secretion, GH will generally
  produce an increased growth rate over several
  years.
• Recently, FDA approved its use in children with
  idiopathic, non-GH-deficient short stature.

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Growth Hormone

• Clinical applications cont
• Treatment of AIDS associated wasting
• Treatment of adult onset growth hormone
  deficiency.
• Turners syndrome a genetic disease that occurs
  in girls, in combination with gonadotropins.
• Prader Willi syndrome a genetic disease due to
  GH deficiency, is associated with growth failure,
  obesity and carbohydrate intolerance.GH decreases
  body fat increases lean body mass,linear growth
  energy expenditure.
• Idiopathic short stature
• Anti-aging supplements OTC supplements which
  suggest they contain hGH. Contain amino acids
  that are supposed to release GH.

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Growth Hormone

• Problems associated with therapy
  possibility of intracranial hypertension and
  visual changes exist, so fundoscopic exams
  needed.
• Also possibility of type 2 diabetes and
  respiratory difficulties in patients with obesity
  or sleep apnea due to Prader-Willi syndrome.
• Possible contamination of human-derived GH with
  Creutzfeldt-Jakob virus,thus recombinant form,
  somatropin is preffered.

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Growth Hormone

• Acromegaly hypersecretion of GH in adults after
  closure of epiphysis, may result in acromegaly.
• Octreotide (Sandostatin) or other somatostatin
  analogs are most commonly used to decrease GH
  secretion in these patients.
• Dopamine agonists such as bromocryptine will
  inhibit GH secretion from some GH secreting
  tumors.
• Pegvisomant (Somavert), a GH receptor
  antagonist, is now available to treat acromegaly
  in patients who have not responded to other
  treatment. Pegvisomant prevents GH stimulation
  of IGF-1 production.25/10/2016

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2-Gonadotropins(LH FSH)Human Chorionic
Gonadotropin(hCG)

• Luteinizing hormone (LH,interstitial cell
  stimulating hormone)
• Chemistrya glycoprotein hormone with 2 peptide
  chains produced by the anterior pituitary
  gonadotrophs under stimulation of GnRH from
  hypothalamus.
• Mechanisms Physiological actions in women
• Mechanism FSH LH act by stimulating Gs protein
  coupled receptors.
• In ovary FSH promotes ovarian follicle
  development.
• Both FSH and LH are needed for ovarian
  steroidogenesis

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• In womenthe main function of FSH is to direct
  ovarian folicle development.
• Both FSH LH are needed for ovarian
  steroidogenesis.
• In ovary LH stimulates androgen production by the
  theca cells in the follicular stage of menstrual
  cycle, whereas FSH stimulates the conversion by
  granulosa cells of androgens to estrogens.
• In the luteal phase production of both estrogen
  progesterone is first under control of LH and
  then if pregnancy occurs under control of human
  chorionic gonadotropin(hCG),a placental protein
  identical to LH and acts on LH receptors.
• FSH,LH hCG are used in infertility to stimulate
  spermatogenesis in men ovulation in women.

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• Follicle stimulating hormone (FSH)
• Chemistry a glycoprotein with 2 peptide chains.
• Agents available are recombinant human FSH,
  follitropin (Gonal-F and Follistim), and urinary
  human FSH, urofollitropin obtained from urine of
  postmenopausal women.
• Physiological actions of FSH
• Mechanism acts through Gs coupled receptors.
• FSHLH regulate gonadal function
• In ovaryit promotes follicular development to
  produce oocyte.
• FSH,LH hCG are given s/c,im,t1/21040 hrs

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• In Testis FSH stimulates spermatogenesis,
  whereas LH stimulates testosterone synthesis by
  Leydig cells.
• FSHLH are required for steroidogenesis in
  ovaries.
• In women FSH stimulates conversion of androgens
  to estrogens in granulosa cells
• FSH enhance Sertoli cells in testes to produce
  androgen-binding proteins that maintain high
  concentration of androgens in the vicinity of
  developing sperms.
• FSH also stimulates conversion by Sertoli cells
  of testosterone to estrogen.
• Clinical useto enhance ovulation
  spermatogenesis

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• Menotropinsare FSH and LH -like products
  isolated from urine of postmenopausal women. Also
  called human menopausal gonadotropins (hMG)
• FSH three forms of purified FSH are available
• -Urofollitropin(uFSH) isolated from urine of post
  menopausal women
• -Follitropin alfa and follitropin beta are
  recombinant forms of FSH(rFSH).They have shorter
  duration of action than human form but may be
  more efficient

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• Luteinizing hormone
• -Lutropin alfa is a recombinant form of human
  LH.Is given s/c with t1/2 of 10hrs
• Used in combination with follitropin alfa for
  stimulation of follicular development in
  infertile women with profound LH deficiency
• Human chorionic gonadotropin(hCG) is produced by
  placenta and excreted in urine
• -Choriogonadotropin alfa(rhCG) is a
  recombinant form
• Pharmacodynamics the gonadotropins and hCG act
  through Gs protein coupled receptors

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Figure 56-4. The hypothalamic-pituitary-gonadol
axis A single hypothalamic releasing factor,
gonadotropin-releasing hormone (GnRH), controls
the synthesis and release of both gonadotropins
(LH and FSH) in males and females. Gonadal
steroid hormones (androgens, estrogens, and
progesterone) cause feedback inhibition at the
level of the pituitary and the hypothalamus. The
pre-ovulatory surge of estrogen also can exert a
stimulatory effect at the level of the pituitary
and the hypothalamus. Inhibin, a polypeptide
hormone produced by the gonads, specifically
inhibits FSH production by the pituitary.
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• Luteinizing hormone
• Clinical application
• Infertility menotropins (a mixture of urinary
  LH and FSH) and chorionic gonadotropin have been
  used to induce ovulation. Recombinant human LH
  lutropin alpha (Luveris) is now available.
• Hyperstimulation of ovary may occur
• May also increase fertility in men
• Kits available to predict time of ovulation by
  measuring urinary LH

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Clinical use of GonadotropinshCG

• Ovulation induction
• - To induce ovulation in women with
  unovulatory cycles for many reasons,who failed to
  respond to other treatments such as clomiphene
• -For controlled ovarian over stimulation in
  assisted reproductive technology procedures
• Male infertility
• Most signs and symptoms of hypogonadism in
  males(eg delayed puberty,retension of prepubertal
  secondary sex characteristics after puberty) can
  be treated by exogenous androgens ,but
  infertility rquires the use of LH and FSH

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Toxicity and contraindications

• In women
• -Ovarian hyperstimulation syndrome,characteriz
  ed by ovarian enlargement, ascites, hydrothorax,
  and hypovolemia that may result in
  shock,hemoproteinemia, fever and arterial
  thromboembolism.
• -Headache depression,edema,precocious puberty
  and production of antibodies against hCG(rare).
• In men the risk of gynecomastia

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Gonadotropin-releasing hormone(GnRH) and its
analogs

• Is a peptide hormone secreted by hypothalamus
• It acts on G protein coupled receptors on
  gonadotrophs in anterior pituitary to stimulate
  secretion of LH and FSH
• Pulsatile iv or s/c (frequency every 1-4hrs) of
  GnRH secretion is required for release of LHFSH
• Sustained nonpulsatile administration of GnRH or
  its analogs(as depot formulations) inhibits
  release of LHFSH resulting in hypogonadism
• GnRH analogs are used to produce gonadal
  supression in men with advanced prostate cancer

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Preparations

• Gonadorelin is an acetate form of a synthetic
  human GnRH
• Goserelin,histrelin,leuprolide,nafarelin and
  triptorelin are synthetic analogs of GnRH
• Gonadorelin is administered iv or s/c, GnRH
  analogs are administered s/s, im,
  intranasal(nafarelin)or as s/c implants
• T1/2 for GnRH is 4 minutes and for synthetic
  analogs is 3hrs

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Pharmacodynamics

• Pulsatile release of GnRH stimulates LH FSH
  release during fetal and neonatal period
• From age 2years until the onset of puberty GnRH
  secretion falls off and the pituitary
  simultaneously exhibits very low sensitivity to
  GnRH
• Just before puberty an increase in frequency and
  amplitude ofGnRH release occurs and the
  sensitivity of pituitary to GnRH increases due to
  released of steroidal hormones
• By the end of puberty the sysyetm is well
  established so that menstrual cycles proceed at
  constant intervals

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Clinical pharmacology of GnRH

• Assessment of delayed puberty for (a)
  constitutional delay or (b)hypogonadotropic
  hypogonadism
• LH response distinguishes between causes
• Following s/c GnRH bolus
• -peak LH responses more than 15.6mU/ml
  indicates normal(ie puberty will occur soon)
• -peak LH impaired suggests hypogonadotropic
  hypogonadism)

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• GnRH agonists are used for stimulation of
  gonadotropins production or their suppression
• A stimulation by pulsatile administration
• -Female and male infertility to stimulate
  pituitary function.
• Inhibition management of prostate
  cancer,endometriosis,uterine fibroids,polycystic
  ovary syndrome and precocious puberty
• By continuous administration of GnRH or its
  analogs

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Toxicity of GnRH

• For diagnosis,occasional headache, flushing,
• GnRH analogsinitial bone pain,exacerbation in
  prostate cancer and hot flushes(both sexes)
• Increased risk of osteoporosis in women if
  treatment is more than 6 months

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Human chorionic gonadotropin

• Human Chorionic Gonadotropin (hCG) not a
  pituitary hormone but is similar to pituitary
  gonadotropins
• Chemistry glycoprotein with 2 polypeptide
  chains a ß chains. Produced by placenta
  excreted in urine.
• a- chain closely resembles FSH, LH, TSH a-chain
• ß- chain closely resembles LH ß-chain
• Similar to LH structuraly
• Used to treat women and men with LH deficiency
• Recombinant human HCG, choriogonadotropin alfa
  (Ovidrel) is used clinically.
• Physiological actions
• stimulate and sustain function of ovarian
  corpus luteum to produce progesterone
• -placenta maintenance

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• Pharmacokinetics
• -im,administration, well absorbed,
  t1/28hrs(compared with LH t1/230 minutes)
• Pharmacodynamics
• -hCG stimulates gonadal steroidal hormone
  production
• Cells affected
• -Female interstitial corpusluteum cellsto
  produce progeterone
• -Male Leydig cells to produce testosterone
• -hCG administration stimulates midcycle LH
  surge which promotes ovulation in
  hypogonadotropic states

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• Clinical use of human chorionic gonadotropin
  (hCG)
• Diagnostic use
• Prepubertal boys with undescended gonadshCG
  distinguishes between retained testes(cryptorchid)
  and retracted testes (pseudocryptorchid)
• -If transient testicular descent occurs eith
  hCG administration?permenant pubertal descent
• -If transient testicular descent does not
  occur with hCG adminstration orchiopexy will be
  required to insure spermatogenesis

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• Conistitutional puberty delay vs hypogonadotropic
  hypogonadism distinuished using repetitive hCG
  administration
• -With hCG administration serum testosterone
  and estradiol levels increase in conistitutional
  puberty delay but not in hypogonadotropic
  hypogonadism states
• Presence of hCG inurine confirms diagnosis of
  pregnancy

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• Therapeutic use of hCG
• hCGhMG produce ovulation in women with
  hypogonadotropic hypogonadism or as part of
  invitro fertilization approach
• hCG testicular testosterone stimulation in men
  with hypogonadotropic hypogonadism(increased
  intratesticular testosterone)promotes
  spermatogenesis menotropins oftenalso required
  for fertility
• Toxicity of hCG
• Headache,edema,gynecomastia,precocious puberty ,
  hCG antibodies production(rare).
• Contraindications
• Presence of androgen-dependent neoplasia
• Presence of precocious puberty 25/11/2014

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3-Thyrotropin (TSH)

• Chemistry glycoprotein with 2 polypeptide
  chains produced by anterior pituitary .
  Thyrotropin alpha is a recombinant TSH used
  clinically.
• Physiological actions Receptor stimulation
  activates Gs protein coupled receptors which
  increases function of thyroid gland
• Increases uptake of iodine by thyroid gland,
  synthesis and release of T3 and T4,
  growth(enlargement) of gland.
• Pharmacokinetics administered im,or s/c
• T1/2 1hr, renal degradation
• Pharmacodynamics
• TSH activates thyroid cells cAMP
  iodine uptake T3T4 production

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Control of thyroid function
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Thyrotropin (TSH)cont.

• Clinical application
• Increases uptake of radioactive iodine.
• Used as a diagnostic tool for serum
  thyroglobulin testing or whole body scanning in
  the follow-up of patients with thyroid cancer.

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4-Corticotropin(Adrenal cortex trophic hormone,
ACTH)

• Chemistry natural hormone is a single chain
  polypeptide of 39 amino acids secreted by
  anterior pituitary.Stimulates cortisol synthesis
  release.
• A synthetic form (cosynotropin-tetracosactide)
  containing amino acids 1-24 is used to assess
  adrenal cortical status.
• Physiological actions stimulates adrenal cortex
  to synthesize secrete cortisol,
  corticosterone, aldosterone (slightly). Prevents
  atrophy of adrenal cortex due to its trophic
  effects on adrenal cells.
• Mechanism receptor interaction results in
  activation of adenylate cyclase synthesis of
  cAMP. cAMP activates enzymes involved in steroid
  synthesis.

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Chemistry of ACTH

• A single peptide chain of 39 aa
• aa from 1 24 is required for full biological
  activity
• aa from 25 39 is for species specificity
• Synthetic human ACTHis called cosynotropin or
  tetracosactide
• Aminoacid terminal 1-13 is identical to
  melanocyte- stimulating hormone(a-MSH)
• With excess ACTH pituitary secretion,
  hyperpigmentation
• due to excess a-MSH occurs

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Pharmacodynamics

• ACTH stimulates adrenal cortex to produce
  glucocorticoids,mineralocorticoids and androgens
• ACTH stimulates cholesterol esters activity
  (chlesterol pregnenolone steprate
  limiting- step in steroid hormone production
• ACTH promotes adrenal hypertrophy and hyperplasia
  
• ACTH may cause increased skin hyperpimentation

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• Clinical use of ACTH
• treatment of adrenal insufficiency
• Cosynotropin may be used to rule out adrenal
  insuficiency
• Following cosynotropin plasma cortisol should
  exceed 18µg/dl
• -subnormal response means primary or secondary
  adrenocortical insuficiency
• -primary adrenocortical insuficiencyincreased
  endogenous ACTH
• -secondary adrenocortical insuficiencydecreased
  ACTH levels
• Treatment of infantile spasms (epilepsy)

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• Differentiation of late-onset congenital
  hyperplasia from a state of ovarian hyper-
  androgenesim
• 21-hydroxylase deficiency,ACTH stimulation leads
  to increase in plasma 17- hydroxyprogesterone
  (substrate for the deficient enzyme).
• Hydroxylase deficiency ACTH stimulation leads to
  increased 11-deoxycortisol
• 3-ß-hydroxy-5- steroid dehydrogenase
  deficiency.ACTH stimulation leads to increased 17
  hydroxypregnenolone
• Therapeutics corticotropin no advantage over
  direct glucocorticid administration

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• Melanocyte-stimulating hormone(MSH)
• a,ß, and ? MSH are peptide hormones structurally
  related to ACTH and are derived from the same
  precursor.
• They are called melanocortins because they
  stimulate production of melanin by specialized
  skin cells called melanocytes
• They play an important part in determining hair
  and skin colour and reaction to UV light

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5-Prolactin(PRL)

• Chemistry single chain polypeptide hormone
  produced by anterior pituitary mamotroph
  cells,resembles GH structurally.
• Physiological actions
• Lactation causes growth and development of
  breasts, and increased synthesis of
  milk.Lactation requires appropriate secreting
  levels of progestins,estrogen,corticosteroids
  insulin.
• Decreases release or effectiveness of
  gonadotropins.
• PRL deficiency may be associated with pituitary
  states, resulting in lactation failure and luteal
  phase defect.

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Regulation of Prolactin secretion

• Its secretion is under tonic inhibitory control
  by the hypothalamus,the inhibitory mediator being
  dopamine
• The main stimulus fro release is suckling.
• Main function in women is to control milk
  production.
• At delivery,when oestrogen levels fall,prolactin
  levels rise and lactation is initiated.
• Hypersecretion may occur due to hypothalamic
  destruction that reduces release of dopamine.
• Hyperprolactinemia may cause galactorrhea,
  amenorrhea and infertility.
• Bromocriptine, pergolide (Permax), cabergoline
  (Dostinex) are dopamine agonists that are useful
  in suppressing PRL secreting tumors.

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• Bromocriptine and other Dopamine agonists
• Bromocriptine and cabergoline are ergot alkaloids
  with high affinity for dopamine D2 receptors.
• Quinagolide,a nonergot compd has similar
  properties.
• Dopamine agonists suppress prolactin release in
  patients with hyperprolactinemia shrinks
  pituitary(PRL secreting tumors).
• Bromocriptine also increases GH release in normal
  subjects, but decreases it in pts with acromegaly
  (paradoxical response).
• Cabergoline and bromocriptine are also used in
  parkinsonism.
• Newer nonergot D2 agonists used in parkinsonism
  include pramipexole and ropinirole

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• Clinical uses
• Hyperprolactinemia in PRL secreting adenomas
• To supress physiological lactation after abortion
• Treatmen of acromegaly alone or in combination
  with other agents
• Treatment of parkinsons disease as first-line
  drugs

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• Adverse effects of bromocriptine
• GITanorexia,nausea,vomiting(reduced by taking
  medication with food)
• -Conistipation,dyspepsia due to reflux
  oesophagitis
• -Peptic ulceration with bleeding
• CVs effects
• -Postural hypotesion
• -Digital spasm on long-term therapy
• -Cardiac arrhythemias may require stopping
  therapy
• Dyskinesia similar to leavodopa
• Mental disordershallucinations,confusion,dellusio
  ns
• Miscellaneous adverse effectsheadache,nasal
  congestion,pulmonary infiltrates,erythromelalgia,
  increased arousal

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Posterior petuitary Hormones
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• Posterior Pituitary Hormones
• They are synthesized in hypothalamus and
  transported via their axons to petuitary
• Oxytocin a nonapeptide hormone secreted by
  posterior pituitary.
• Physiological levels are required for milk
  ejection in lactating women
• Pharmacologic doses induce uterine contractions
  maintain labor.
• Pharmacokinetics
• -IV dose for labor induction
• -IM for control of postpartum bleeding
• -Nasal spray for postpartum lactation
  induction
• -Not bound to plasma proteins
• -Elimination renal and hepatic,t1/25
  minutes.

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• Pharmacodynamics
• Acts through G protein coupled receptors
• Influences ionic currents in myometrial smooth
  muscle which leads to uterine contraction.Also
  promotes release of PGs and leukotriens that
  increase uterine contraction
• Uterine sensitivity to oxytocin increase in
  pregnancy
• Inhibition of oxytocin-induced uterine
  contraction can be achieved by magnesium
  sulphate,ß-adrenergic agonists or inhalational
  anesthetics
• Oxytocin also promotes contraction of
  myoepithelial cell surrounding mammary alveolia
  which leads to milk ejection .Thus normal
  lactation requires oxytocin

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• Clinical uses of oxytocin
• -Labor induction
• -Promotion of dysfunctional labor
• -Control of post partum bleeding
• -To enhance impaired milk ejection(nasal
  route)
• Toxicity
• -Hypertensive reactions
• -Uterine rupture
• -Water intoxication
• -Fetal death
• -Afibrinogenemia
• Contraindications
• -Fetal dystress syndrome
• -Abnormal fetal presentation
• -Factors predisposing to uterine rupure

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• Oxytocin Antagonist
• Atosiban is an oxytocin receptor antagonist used
  to prevent preterm labor ( tocolysis).It is as
  effective as ß2-adrenergic agonists.
• Is administered IV

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• Vasopressin
• Is a nonapeptide hormone released by posterior
  piuitary in response to
• -Rising plasma tonicity,or
• -Decreased blood pressure
• Has antidiuretic and vasopressor properties
• Vasopressin deficiency causes diabetic insipidus
• Route of administration iv,im,intranasal
• T1/220 minutes
• Renal and hepatic catabolism
• Minimal amounts excreted unchanged in urine

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• Pharmacodynamics
• Receptor types
• -V1in vascular smooth muscle mediate
  vasoconistriction
• -V2in renal tubules,produce antidiuretic
  effect by increasing water permeability and
  increasing collecting tubules water reabsorption.
• -Extrarenal V2 receptors..promote coagulation
  factor VIII and von Willebrand factor release
• Desmopressin acetate a long-acting synthetic
  analog of vasopressin derivative with limited V1
  receptor activity
• Has significant antidiuretic/vasopressin ratio
  compared to vasopressin(40001)

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• Clinical uses of vasopressin
• Vasopressin and desmopressin are used alternately
  in treatment of diabetes insipidus
• Nocturnal enuresis(desmopressin at bed time) to
  reduce night urine production
• IV vasopressinmay be effective in managing
  esophageal variceal bleeding and colonic
  diverticular bleeding
• Toxicity
• Vasopressin (not desmopressin)causes
  vasoconistriction issues in patients with
  coronary vascular disease
• Unusual side effects includeaggitation,allergic
  reactions,abdominal cramping, headache nausea

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• Vasopressin Antagonists
• Conivaptan and tolvaptan are a group of
  nonpeptide vassopressin receptor antagonists that
  are investigated for pts with hyponatremia or
  acute heart failure that are usually associated
  with elevated concentrations of vasopressin.
• Conivaptan has high affinity for both V1a and V2
  receptors.
• Tolvaptan has higher affinity to V2 than V1
  receptors
• Both agents relieved symptoms and reduced signs
  of hyponatremia and heart failure

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• Thank You For Attention