Pharm of Hypothalamic, Anterior, and Posterior Pituitary Hormones Flashcards Preview

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Flashcards in Pharm of Hypothalamic, Anterior, and Posterior Pituitary Hormones Deck (26)
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1

Hypothalamic vs Pituitary Agents

  • Hypothalamic:
    • Growth Hormone releasing hormone (GHRH)
    • Thyrotropic releasing hormone (TRH)
    • Corticotropin releasing hormone (CRH)
    • Gonadotropin releasing hormone (GnRH)
    • Dopamine (DA)
    • Somatostatin (SST)
  • Anterior Pituitary--> Endocrine glands/Liver/Bone/other-->target
    • Growth Hormone (GH)
    • Thyroid Stimulating Hormone (TSH)
    • Adrenocorticotropin (ACTH)
    • Luteinizing hormone (LH)
    • Follicle Stimulating hormone (FSH)
    • Prolactin (PRL)
  • Posterior Pituitary-->Target Tissues
    • Antidiuretic hormone (ADH)
    • Oxytocin

2

Drugs that mimic or block the effects of hypothalamic & Pituitary Hormones

  • Anterior Pituitary
    • Growth Hormone:
      • Agonist Action
        • Somatropin 
        • Mecasermin
      • Antagnoist Action
        • Octreotide
        • Pegvisomant
    • Gonadotropins:
      • Agonist Action
        • Mixed LH & FSH
          • Menotropins
        • LH
          • Lutropin
          • hCG
        • FSH
          • Follitropin
    • Prolactin
      • Antagonist Action
        • D2 dopamine agonists 
          • bromocriptine
  • Hypothalamus
    • GnRH
      • Agonist Action
        • Gonadorelin
      • Antagonist Action
        • GnRH receptor agonist-leuprolide
        • GnRH receptor antagonist-ganirelix
  • Posterior Pituitary:
    • Oxytocin
      • Agonist action
        • Oxytocin
      • Antagonist Action
        • Atosiban (not FDA approved)
    • Vasopressin:
      • Agonist Action
        • Desmopressin
      • Antagonist Action
        • Conivaptan

3

Growth Hormone Axis:

Stimulatory vs inhibitory inputs and hormones

  • Stimulatory inputs:
    • genetics
    • exercise
    • Increased:
      • grhelin
      • amino acids
    • Decreased
      • blood sugar
      • fatty acids
  • Stimulatory hormones:
    • Hypothalamus-GH releasing Hormone (GHRH)
    • Anterior Pituitary- Growth Hormone (GH)
    • Liver-Insulin-like growth factor 1 (IGF-1)
  • Inhibitory inputs: Negative feedback
    • Genetics
    • lethargy, stress, disease 
    • Decreased
      • ghrelin
      • amino acids
    • Increased
      • blood sugar
      • fatty acids
  • Inhibitory hormones:
    • hypothalamus-Somatostatin (SST)
      • direct downregulation

4

clinical presentation of low GH

  • affects growth and development of jaws and teeth
  • Children
    • short stature:
      • Delayed dental age
      • Delayed replacement of deciduous teeth by permanent teeth
      • Newly erupted permanent teeth often require ortho tx
    • low age-adjusted growth velocity
    • hypoglycemia due to unopposed action of insulin
      • IGF-1 expression and postnala growth are GH-dependent during 1st year
    • Subnormal serum GH after stimulation
  • Adults:
    • Decreased:
      • muscle mass
      • exercise capacity
      • bone density
    • Generalized obesity
    • weak/lack of energy
    • Dyslipidemia
    • Reduced cardiac output

5

Pharmacological management of low GH

  • Tesamorelin
  • Somatotropin
  • Mecarsermin
    • patients that do not respond to GH or somatotropin
      • mutations in receptor
      • antibodies against hormone
      • IGF-1 deficiency

6

Tesamorelin

  • Synthetic GHRH
  • Mechanism=GHRH agonist
  • used clinically to diagnose GH and GHRH sufficiency
  • not used in disorders of GHRH or GH/IGF-1 secretion
    • used to reduce excess abdomina fat in adult patients with HIV
  • No side effects
  • no contraindications

7

Somatotropin

  • Recombinant form of GH
  • Mechanism: GH agonist
  • Used in both adults and children
    • additional symptoms
  • Given to:
    • children
      • during active growth (before epiphyseal fusion)
    • older children
      • higher dosesae
      • may be extended past puberty and into adulthood
  • Side effects: 
    • Children: Well tolerated
      • can have rare but serious side effects:
        • pseudotumor cerebri
        • slipped capital femoral epiphysis
        • scoliosis progression
        • edema
        • hyperglycemia
    • Adults: Less tolerated

8

Mecasermin

  • recombinant IGF-1
  • mechanism: IGF-1 agonist
  • Used in children with growth failure and unresponsive to GH therapy
  • Side effect:
    • Hypoglycemia
      • high carb meal or snack 20 minutes before administration limits 

9

clinical presentation of High GH

  • Presentation: highly dependent on age
  • Excess growth hormone can affect jaws and teeth:
    • Gigantism- GH excess before fusion of growth plates
      • prognathic mandible
      • malocclusion
      • hypercementosis
    • Acromegaly- GH excess in adults
      • change in occlusion
      • prognathism
      • jaw thickening
  • Test=GH supression test (Not Tesamorelin)
    • blood levels measured before and after sugar consumed
    • glucose decreases levels of GH

10

Pharmacological management of High GH

  • Pegvisomant
  • Octreotide or Lanreotide
  • Bromocriptine or cabergoline

11

Pegvisomant

  • mutant GH derivative
  • Mechanism=GH Antagonist
    • cross-link GH receptors
    • does not induce conformation change so no activation of receptor
      • prevents GH from activating GH signaling pathways
  • Does not reduce GH secretion
  • May elevate liver enzymes and induce lipodystrophy

12

Octreotide

  • or Lanreotide
  • Synthetic SST analogs
  • Mechanism: SST agonist
    • longer half lives than SST (SST=1-3 min)
  • Tx: Acromegaly and gigantism
    • reduce GH and IGF-1
  • Octreotide is the Most widely used SST analog
  • Side effects:
    • GI disturbances
    • Gallstones
    • abnormal cardiac conduciton

13

Bromocriptine

  • or cabergoline
  • Dopaine Agonist with high affinity for DA D2 receptors (prolactin)
    • but can reduce GH release at high doses in patients with acromegaly
  • mechanism: unclear 
  • only 70% of patients respond
    • can increase GH in patients without acromegaly
  • Only affects GH and prolactin

14

Dopamine pathway

  • Positive feedback control=Prolactin
  • Dopamine inhibits prolactin release from anterior pituitary

15

Clinial Presentation: Low Prolactin

  • Not a medical problem
  • Problem for women who want to breastfeed and cannot due to low prolactin
  • no approved treatments in US

16

Pharmacological management of low prolactin

  • Domperidone

17

Domperidone

  • Stimulate prolactin production
  • Not FDA approved due to cardiac concerns
  • Single patient expanded access for tx of severe GI motility disocers but not endocrine

18

Clinical Presentation of High prolactin

  • most common pituitary hormone hypersecretion in both sexes
  • Thyrotropin releasing hormone (TRH) can stimulate prolactin secretion
    • When High TRH due to primary hypothyroidism
    • Thyroid hormone levels may help diagnose underlying disorder
  • Male and Females patients may present with hypogonadism
    • Females
      • infertility
      • oligo or amenorrhea
        • galactorrhea
    • Males
      • loss of libido
      • ED
      • infertility
  • these Symptoms indicate the CROSS talk b/w receptors can lead to change in multiple systems
    • patient management=complex

19

Pharmacological management of High Prolactin

  • Bromocriptine and cabergoline
    • Mechanism: dopamine agonists
      • high affinity for dopamine D2 receptors
    • Standard first line treatment to suppress prolactin release in patients with hyperprolactinemia
  • Side effects:
    • Common:
      • Nausea
      • Headache
      • Light-head
      • orthostatic hypertension
      • fatigue
    • Sometimes:
      • psychiatric manifestations
      • eryhromelalgia
      • pulmonary infiltrates
      • cold-induced peripheral digital basospasms
  • Remember: GH suppressive @ high doses

20

Clinical Presentation of Oxytocin pathway

  • Oxytocin-->Mammary gland, uterine muscles
  • induces labor for conditions requiring expedited vaginal delivery 
    • uncontrolled maternal diabetes
    • intrauterine infection
    • worsening preeclampsia
  • Augment protracted labor
  • stop vaginal bleeding due to uterine atony

21

Oxytocin side effects

  • excess stimulation of uterine contractions which leads to 
    • fetal distress
    • placental abruption
    • uterine rupture
  • inadvrtent activation of vasopressing receptors leads to:
    • excessive fluid retention or water retention
      • leads to:
        • hyponatremia
        • heart failure
        • seizures 
        • death
  • SHOULD NOT BE USED in fetal distress or malpresentation, placental abruption, and other predispositions for uterine rupture

22

Pharmacological management of oxytocin pathway

  • Atosiban
    • Oxytocin antagonist
    • not FDA approved in US
      • approved for preterm labor outside US

23

Vasopressin/ADH pathway: Clinical presentation

  • Diabetes insipidus (polyuria and polydipsia)
  • esophageal variceal and/or colonic diverticular bleeding

24

Pharmacological management: Low Vasopressin

  • Vasopressin or desmopressin
  • Desmopressin
    • synthetic analgue
    • mechanism: Vasopressing agonists
    • can also treat:
      • diabetes insipidus from vasopressin deficiency
      • nocturnal ensuresis and coagulopathy in hemophilia A & Von willebrand
  • Desmopressin vs vasopressin
    • Fewer V1 side effects
    • longer acting
  • Vasopressin:
    • excessive vasoconstriction
  • Both associated with:
    • headache
    • nausea
    • agitation
    • allergic rxns
    • abdominal cramps

25

Clinical presentation of low vasopressin

  • Fluid retention from excess vasopressin 
  • associated with hyponatremia or acute heart failure

26

Pharmacological management of High vasopressin

  • Conivaptan
    • vasopressin antagonist
      • V1a and V2
  • Tolvaptan
    • vasopressing antagonist
      • Higher affinity for V2>V1
    • Side effects:
      • only give for 30 days=risk of hepatotoxicity and life-threatening liver failure