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Title: 1-Pituitary hormones(this).ppt

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.

The Endocrine Glands
Control of petuitary hormones by Hypothalamus
(No Transcript)
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
  • 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

  • vasoactive intestinal peptide,glucagonomas
    various pituitary adenomas. Lanreotide is an
    other analogue that is used also for thyroid
  • 3- Thyrotrohpin-releasing hormone(TRH-
  • 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
  • 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.

  • 5-Gonadotropin releasing hormone(GnRH) and
  • Drugs available include gonadorelin (natural
  • Long-acting analogs histrelin (Suprelin),
    leuprolide (Leupron), gosrelin (Zoladex),
    triptorelin(Trelstar), and nafarelin (Synarel).
  • Gonadorelin is used for induction of ovulation in
  • Long acting analogs are used for treatment of
    endometriosis, prostate cancer, and central
    precocious puberty. Experimental use as male
  • 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.

The Pituitary Gland
  • Consists of two lobes
  • -The anterior lobe(adenohypophysis) secretes
  • -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

Pituitary Hormones
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

  • 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
  • No hypothalamic regulator for PRL production or

  • 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.

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

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-

  • 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.

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
  • Effects mediated through IGF-1

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
  • Growthalmost all body tissues are stimulated to
  • Nitrogen metabolism increased nitrogen
    retention, amino acid transport into tissues, and
    incorporation into protein

  • 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
  • GH reduces insulin sensitivity leading to
  • IGF-1 lowers serum glucose and reduces
    circulating insulin through action on IGF-1
    receptors and insulin receptors.

Growth Hormone
  • Physiological actions (cont..)
  • Conserves muscle at the expense of fat during
  • 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

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
  • Recently, FDA approved its use in children with
    idiopathic, non-GH-deficient short stature.

Growth Hormone
  • Clinical applications cont
  • Treatment of AIDS associated wasting
  • Treatment of adult onset growth hormone
  • 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.

Growth Hormone
  • Problems associated with therapy
    possibility of intracranial hypertension and
    visual changes exist, so fundoscopic exams
  • 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.

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
  • 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

2-Gonadotropins(LH FSH)Human Chorionic
  • 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
  • Mechanisms Physiological actions in women
  • Mechanism FSH LH act by stimulating Gs protein
    coupled receptors.
  • In ovary FSH promotes ovarian follicle
  • Both FSH and LH are needed for ovarian

  • In womenthe main function of FSH is to direct
    ovarian folicle development.
  • Both FSH LH are needed for ovarian
  • 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.

  • 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

  • In Testis FSH stimulates spermatogenesis,
    whereas LH stimulates testosterone synthesis by
    Leydig cells.
  • FSHLH are required for steroidogenesis in
  • 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

  • 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

  • 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

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.
  • 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

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

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
  • -Headache depression,edema,precocious puberty
    and production of antibodies against hCG(rare).
  • In men the risk of gynecomastia

Gonadotropin-releasing hormone(GnRH) and its
  • 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

  • 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

  • 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
  • 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

Clinical pharmacology of GnRH
  • Assessment of delayed puberty for (a)
    constitutional delay or (b)hypogonadotropic
  • 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

  • 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

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

Human chorionic gonadotropin
  • Human Chorionic Gonadotropin (hCG) not a
    pituitary hormone but is similar to pituitary
  • 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

  • Pharmacokinetics
  • -im,administration, well absorbed,
    t1/28hrs(compared with LH t1/230 minutes)
  • Pharmacodynamics
  • -hCG stimulates gonadal steroidal hormone
  • 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

  • Clinical use of human chorionic gonadotropin
  • 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

  • Conistitutional puberty delay vs hypogonadotropic
    hypogonadism distinuished using repetitive hCG
  • -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

  • 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

3-Thyrotropin (TSH)
  • Chemistry glycoprotein with 2 polypeptide
    chains produced by anterior pituitary .
    Thyrotropin alpha is a recombinant TSH used
  • 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

Control of thyroid function
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.

4-Corticotropin(Adrenal cortex trophic hormone,
  • Chemistry natural hormone is a single chain
    polypeptide of 39 amino acids secreted by
    anterior pituitary.Stimulates cortisol synthesis
  • 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

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

  • 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

  • Clinical use of ACTH
  • treatment of adrenal insufficiency
  • Cosynotropin may be used to rule out adrenal
  • 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)

  • Differentiation of late-onset congenital
    hyperplasia from a state of ovarian hyper-
  • 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
  • Therapeutics corticotropin no advantage over
    direct glucocorticid administration

  • Melanocyte-stimulating hormone(MSH)
  • a,ß, and ? MSH are peptide hormones structurally
    related to ACTH and are derived from the same
  • 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

  • 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
  • Decreases release or effectiveness of
  • PRL deficiency may be associated with pituitary
    states, resulting in lactation failure and luteal
    phase defect.

Regulation of Prolactin secretion
  • Its secretion is under tonic inhibitory control
    by the hypothalamus,the inhibitory mediator being
  • The main stimulus fro release is suckling.
  • Main function in women is to control milk
  • 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.

  • Bromocriptine and other Dopamine agonists
  • Bromocriptine and cabergoline are ergot alkaloids
    with high affinity for dopamine D2 receptors.
  • Quinagolide,a nonergot compd has similar
  • 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
  • Newer nonergot D2 agonists used in parkinsonism
    include pramipexole and ropinirole

  • 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

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

Posterior petuitary Hormones
  • 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
  • -Not bound to plasma proteins
  • -Elimination renal and hepatic,t1/25

  • 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
  • Inhibition of oxytocin-induced uterine
    contraction can be achieved by magnesium
    sulphate,ß-adrenergic agonists or inhalational
  • Oxytocin also promotes contraction of
    myoepithelial cell surrounding mammary alveolia
    which leads to milk ejection .Thus normal
    lactation requires oxytocin

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

  • 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

  • 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

  • Pharmacodynamics
  • Receptor types
  • -V1in vascular smooth muscle mediate
  • -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)

  • 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

  • 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
  • Tolvaptan has higher affinity to V2 than V1
  • Both agents relieved symptoms and reduced signs
    of hyponatremia and heart failure

  • Thank You For Attention
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