Growth hormone-Releasing Hormone

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					Growth hormone-Releasing Hormone              Somatostatin
            (GHRH)                 (Growth Hormone-Inhibiting Hormone)

           octreotide               Gonadotropin-Releasing Hormone

    Gonadorelin hydrochloride                GnRH analogs
-hypothalamic agent
1. aka somatotropin release-inhibiting hormone, a two         -hypothalamic agent
      chain peptide; one is 14aa and the other is 28aa        1. stimulates synthesis and release of growth
2. inhibits GH release in normal individuals, thus opposes        hormone from the anterior pituitary
      the effects of GHRH
3. widely distributed throughout the entire body, including
                                                              2. 44aa peptide produced in the arcuate
      pancreas and GI tract, thyroid, skin, heart and eye         nucleus of the hypothalamus
      *so it has multiple actions                             3. released in a pulsatile manner
      a. inhibits release of                                  4. bears distinct structural homologies to
         1. thyroid-stimulating hormone
         2. glucagons and insulin
                                                                  certain gastrointestinal peptide hormones
         3. luteinizing hormone                                   ex/ gastrin, gastric inhibitory peptide,
      b. suppresses the release of gastrointestinal                  secretin, vasoactive intestinal polypeptide
         hormones (gastrin, secretin, motilin, vasoactive     5. not currently available therapeutically
         intestinal peptide, gastric inhibitory polypeptide
                                                                   *removed from the U.S. market in 2002 by
      c. lowers the rate of gastric emptying and reduces
         smooth muscle contractions and decreases blood                Serono
         flow within the intestines
-synthetic drug: octreotide

                                                              1. synthetic somatostatin, administered SC or IV
-hypothalamic agent                                           2. inhibits the release of GH from the anterior pituitary
1. aka luteinizing hormone-releasing hormone                  3. 45X more potent than the natural hormone
2. pulsatile GnRH secretion stimulates the                    4. trtmt of
                                                                a. acromegaly
    gonadotroph cells in the anterior pituitary
                                                                    -GH levels and IGF-1 to within normal limits in 50%
    to pdc and release luteinizing hormone                               pts
    (LH) and follicle stimulating hormone                       b. hormone-secreting tumors
    (FSH)                                                           -diarrhea and flushing episodes assoc with carcinoid
3. sustained non-pulsatile admin inhibits the                       -diarrhea assoc with vasoactive intestinal peptide-
    release of FSH and LH by the pituitary in                            secreting tumors
    both males and females                                    5. adverse reactions
                                                                a. biliary tract abnormalities (63%)
                                                                    -inhibits gallbladder contractility and decreases bile
                                                                         secretions in normal volunteers
                                                                    -gallstones, sludge without stones, biliary duct dilation
                                                                b. sinus bradycardia (25%)
                                                                c. nausea and vomiting
                                                                d. ab cramps
                                                                e. flatulence

1. synthesized by selective substitution of aas               1. synthetic GnRH
     in the GnRH peptide                                      2. diagnostic use only
2. trtmt of                                                   3. portable pump system allows for pulsatile
     a. endometriosis and uterine fibroids                        delivery every 90min
     b. breast cancer                                             -trtmt of male and female infertility
     c. prostate cancer                                       4. SE
     d. central precocious puberty                                -flushing
     e. off-label                                                 -tachycardia
          -female and male infertility                            -injection site probs
          -dysfunctional uterine bleeding                         -nausea
                                                                  -possibility of a LH surge during trtmt
leuprolide       nafarlin

goserelin    GnRH antagonists

ganirelix        cetrorelix
                                                       -GnRH analog
-GnRH analog                                           1. uses
1. uses                                                    a. endometriosis
    a. endometriosis                                       b. uterine fibroids
    b. central precocious puberty                          c. palliative prostate cancer
    c. uterine fibroids                                    d. central precocious puberty
2. pharmacodynamics                                    2. pharmacodynamics
    a. comes as a nasal spray                               a. acts as a potent inhibitor of Gonadotropin
                                                              secretion when given continuously
3. SE (uncommon and transient)                         3. SE
    -acne (10%)                                            -malaise
    -breast enlargement (8%)                               -fatigue
    -vaginal bleeding (8%)                                 -dizziness
    -depression (6%)                                       -hot flashes
    -possibility of a LH surge during trtmt                -colitis
                                                           -possibility of a LH surge during trtmt

                                                       -GnRH analog
1. reversibly binds to pituitary GnRH receps without   1. uses
      activating them, thus blocks the secretion and       a. endometriosis
      release of LH and (at high doses) FSH                b. breast cancer
      -produces an immediate suppression of LH             c. uterine bleeding
2. trtmt of                                                d. prostate cancer
      a. in vitro fertilization                        2. pharmacodynamics
         -produce less ovarian hyperstimulation than       a. avail as implantable cylinders
           do GnRH analogs and decrease the risk of    3. SE
           an LH surge                                     -irreg heartbeat
      b. endometriosis and uterine fibroids                -joint pain
3. adverse reactions                                       -changes skin color of face
      -mild nausea, HA                                     -irreg breathing, shortness of breath
      -vaginal bleeding                                    -skin rashes
      -injection site irritation                           -tightness in chest
                                                           -HA, nausea, vomiting
                                                          -possibility of a LH surge during trtmt

-GnRH antagonist                                       -GnRH antagonist
1. trtmt of                                            1. trtmt of
     a. in vitro fertilization                              a. in vitro fertilization
     -produce less ovarian hyperstimulation                 -produce less ovarian hyperstimulation
          than do GnRH analogs and decrease                      than do GnRH analogs and decrease
          the risk of an LH surge                                the risk of an LH surge
     b. endometriosis and uterine fibroids                  b. endometriosis and uterine fibroids
2. adverse reactions                                   2. adverse reactions
     -mild nausea, HA                                       -mild nausea, HA
     -vaginal bleeding                                      -vaginal bleeding
     -injection site irritation                        -injection site irritation
Corticotropin-Releasing Hormone   Thyrotropin-Releasing Hormone
              (CRH)                           (TRH)

       Growth Hormone                   Growth Hormone
            (GH)                             (GH)

             uses                    SE and contraindications

          Somatropin                        Somatrem
                                               -hypothalamic agent
-hypothalamic agent                            1. secreted in response to stress
1. protirelin                                  2. stimulate corticotropic cells of the anterior
2. diagnostic only (and rarely used)               lobe of the pituitary to produce
                                                   adrenocorticotropic hormone (ACTH)
                                               3. only used diagnostically to distinguish
                                                   Cushing’s disease from ectopic ACTH

                                                -anterior pituitary agent
                                                1. produces growth at open epiphyses via stimulation of
                                                insulin-like growth factor-1
1. SE                                           2. causes lipolysis in adipose tissue and growth of skeletal
-intracranial hypertension (rare)               muscle
                                                3. trtmt of
-vision changes, HA, nausea, vomiting
-pancreatitis, gynecomastia, nevus growth         A. certain conditions that cause failure to grow
-injection site pain                                  a. kidney disease, Prader-Willi syndrome, Turner’s
                                                      b. Laron syndrome-primary GH insensitivity
                                                         *have normal levels of GH, lack the receps
2. contraindications                                        necessary for normal body growth
-children with closed epiphysis                   B. GH deficiency (dwarfism)
-evidence of active malignancies                      a. genetic deficiency in approx 1:4000 live births
-monitor DM pts closelyinsulin will need to             *infant usually presents with hypoglycemic seizures
                                                      b. acquired due to pituitary and hypothalamic damage
be adjusted                                    -adults
                                               A. GH deficiency generalized obesity, reduces muscle
                                                  mass, asthenia and reduced cardiac output
                                               B. acquired immunodeficiency syndrome help patient
                                                  gain weight
                                               4. widely abused drug

-recombinant human growth hormone (rhGH)       -recombinant human growth hormone (rhGH)
-just like the real stuff                      -just like the real stuff
                                               -long acting injectable suspension
                                               -appear to be equipotent
Growth hormone recep antagonist   pegvisomant

  Follicle stimulating hormone     menotropin

         urofollitropin           follitropin beta
                                                 1. competitively binds to growth hormone
                                                  receps, thus blocking GH-stimulated hepatic
                                                  pdn of IGF-1, the main mediator of the
                                                  somatotrophic actions of GH
                                                 2. pegvisomant
                                                 3. trtmt of acromegaly
-growth hormone recap antagonist                 4. SE
                                                   a. allergic rxns: hives, shortness of breath,
                                                     swelling of face, lips or tongue
                                                   b. liver probs
                                                      -yellowing of skin, ab pain, vomiting, dark
                                                   c. discomfort at injection site, nausea,
                                                     diarrhea, dizziness or midl water retention
                                                     and weight gain

                                                 -anterior pituitary agent
                                                 1. stimulates gametogenesis and follicular develop in
                                                    a. acts on the immature follicular cells and induces
                                                      develop of the mature follicle and oocyte
-human menopausal gonadotropins (hMG)               b. stimulates androgen conversion into estrogen
-FSH and LH purified from urine of post-         2. stimulates spermatogenesis in men
menopausal females                                  a. acts on the Seroli cells to stimulate production of
-avail since 1960’s                                   androgen-binding protein
                                                 3. trtmt of
                                                    -pituitary and hypothalamic hypogonadism with
                                                    - anovulatory females
                                                    -ab pain, vaginal bleeding, ovarian cysts, breast
                                                    -injection site pain, rashes, fluid retention, HA,
                                                    -risk of multiple births

-recombinant technology                          -FSH purified
1. batch to batch consistency, and highly pure   -derived from urine of post-menopausal
2. cost 3X as much as hMG                        females
    Luteinizing hormone       Human chorionic Gonadotropin

Adrenocorticotropin hormone    Thyroid stimulating hormone
   (corticotropin, ACTH)

         prolactin                    bromocriptine
1. IM injections
2. diagnostic use
3. trtmt of infertility                          -anterior pituitary agent
4. SE                                            -no therapeutic availability

-anterior pituitary agent                        -anterior pituitary agent
-diagnostic use only                             -diagnostic use only

-dopamine agonist
-oral medication
1. decrease prolactin secretion thru dopamine-   -anterior pituitary agent
  mimic action                                   1. resp for lactation
2. trtmt of..                                    2. hypothalamic dopamine inhibits the
  -prolactin secreting adenomas                  secretion and release of prolactin
     (hyperprolactinemia)                        3. recombinant agents are not avail
  -acromegaly                                    4. dopamine agonist
  -parkinson’s and restless leg syndrome          -decrease prolactin secretion thru dopamine-
3.SE                                                 mimic action
  -nausea and vomiting
  -psychotic rxns
quinagolide     oxytocin

vasopressin   desmopressin
                                             -dopamine agonist
                                             -oral medication
                                             1. decrease prolactin secretion thru
-posterior pituitary agent                     dopamine-mimic action
-IV or nasal spray                           2. trtmt of..
-induce labor                                 -prolactin secreting adenomas
                                              -Parkinson’s and restless leg syndrome
                                              -nausea and vomiting
                                              -psychotic rxns

                                             -posterior pituitary agent
                                             -aka anti-diuretic hormone (ADH)
                                             1. MOA
                                              *stimulates the insertion of water channels or
1. synthetic vasopressin                         aquaporins into the membranes of the
2. injection, nasal spray, tablets               kidney tubules
3. 4,000X as potent as natural vasopressin        increases water permeability
                                                  decreases urine output
                                                  increases blood volume
                                             2. trtmt for diabetes insipidus
                                             3. SE
                                              -HA, nausea, ab cramps