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134 Cards in this Set
- Front
- Back
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All hypothalamic and pituitary hormones except _______ are PEPTIDES.
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Dopamine (prolactin-inhibiting hormone)
it is a catecholamine. |
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Which route of administration can NOT be used with peptides?
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Orally.
They must be administered SQ, IM, or IV because they are rapidly degraded within the GI tract. |
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What two hormones of the anterior pituitary are SINGLE TRANSMEMBRANE PEPTIDES and activate Tyrosine Kinase (JAK2) resulting in phosphorylation of proteins and influencing gene transcription?
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GH and Prolactin
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What mechanism do the receptors for GH and Polactin use?
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The single transmembrane peptides receptors activate intracellular tyrosine kinase (JAK2) which phosphorylates intracellular proteins, resulting in gene transcription
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With the exception of GH and Prolactin, what mechanism do ALL OTHER hypothalamic and pituitary hormone receptors use?
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ALL OTHER (except GH and Prolactin) hypothalamic and pituitary hormones are SEVEN TRANSMEMBRANE DOMAIN SERPENTINE PEPTIDES and activate G-PROTEINS (Gs) --> adenylyl cyclase, synthesis of cAMP, activation of PROTEIN KINASES and PHOSPHORYLATION of INTRACELLULAR PROTEINS.
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What hormones activate JAK2?
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Growth Hormone and Prolactin
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Which hormones activate G proteins?
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ALL peptide hormones of the hypothalamus except GH and Prolactin
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Steroids mostly produce genomic effects. Peptide hormones and some steroid produce NON-genomic effects. Which is faster?
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Non-genomic effects don't activate transcription so it is FASTER.
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What are the physiologic stimuli for the release of vasopressin?
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Hypotension and increased plasma tonicity.
NOT through regulation of the hypothalamus. |
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What pituitary hormones are not released due to hypothalamic releasing factors?
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oxytocin and vasopressin
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All hypothalamic and pituitary hormones except _______ are PEPTIDES.
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Dopamine (prolactin-inhibiting hormone)
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Which route of administration can NOT be used with peptides?
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Orally.
They must be administered SQ, IM, or IV because they are rapidly degraded within the GI tract. |
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What two hormones of the anterior pituitary are SINGLE TRANSMEMBRANE PEPTIDES and activate Tyrosine Kinase (JAK2) resulting in phosphorylation of proteins and influencing gene transcription?
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GH and Prolactin
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What mechanism do the receptors for GH and Polactin use?
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The single transmembrane peptides receptors activate intracellular tyrosine kinase (JAK2) which phosphorylates intracellular proteins, resulting in gene transcription
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With the exception of GH and Prolactin, what mechanism do ALL OTHER hypothalamic and pituitary hormone receptors use?
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ALL OTHER (except GH and Prolactin) hypothalamic and pituitary hormones are SEVEN TRANSMEMBRANE DOMAIN SERPENTINE PEPTIDES and activate G-PROTEINS (Gs) --> adenylyl cyclase, synthesis of cAMP, activation of PROTEIN KINASES and PHOSPHORYLATION of INTRACELLULAR PROTEINS.
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What hormones activate JAK2?
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Growth Hormone and Prolactin
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Which hormones activate G proteins?
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ALL peptide hormones of the hypothalamus except GH and Prolactin
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Steroids mostly produce genomic effects. Peptide hormones and some steroid produce NON-genomic effects. Which is faster?
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Non-genomic effects don't activate transcription so it is FASTER.
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What are the physiologic stimuli for the release of vasopressin?
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Hypotension and increased plasma tonicity.
NOT through regulation of the hypothalamus. |
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What pituitary hormones are not released due to hypothalamic releasing factors?
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oxytocin and vasopressin
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Which pituitary hormones work by increasing protein synthesis? (ANABOLIC)
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Growth hormone and Prolactin
Single Transmembrane Proteins --> JAK2 --> phsophorylation of intracellular proteins --> GENE REGULATION! |
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Which hypothalamic hormones activate Gi receptors, leading to a DECREASE in adenylyl cyclase and cAMP?
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Dopamine and Somatostatin
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What is the target organ for GH and what is produced in the target organ?
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The target organ is the LIVER and it produces SOMATOMEDINS (IGF)
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What is the mechanism of action of Somatostatin?
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Somatostatin activates Gi receptors and decreases cAMP which INHIBITS GROWTH HORMONE!
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What is the mechanism of action of Corticotropin releasing hormone?
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Activates Gs and increases ACTH production in the Adrenal Cortex --> Glucocorticoids, mineralocorticoids, and androgens
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What is the mechanism of action of Dopamine?
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Dopamine activate Gi and INHIBITS Prolactin production.
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What are the releasing/stimulatory hypothalamic hormones?
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Somatorelin (GHRH)
Thyrotropin-Releasing Hormone (TRH) Corticorelin (Corticotropin-Releasing Hormone -CRH) Gonadotropin-Releasing Hormone (Gonadorelin) |
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What is the clinical use of TESAMORELIN (Egrifta)?
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Treatment of excess abdominal fat in HIV-infected patients with LIPODYSTROPHY (increase of abdominal fat)
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What drug is used to treat excess abdominal fat (lipodystrophy) in patients with HIV/AIDS?
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Tesamorelin (Egrifta)
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Tesamorlin (egrifta) is a synthetic analog of which hypothalamic hormone?
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Growth Hormone Releasing Hormone (Somatorelin) (GHRH)
--> stimulates release of GH from anterior pituitary. |
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What is the clinical use of Thyrotropin Releasing Hormone (TRH) ?
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NONE!
- results were unreliable. |
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Corticorelin (ACTHrel) stimulates the secretion of what from the anterior pituitary?
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ACTH and B-Endorphins
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What is the clinical use of Corticorelin (Acthrel) ?
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It is used for DIFFERENTIAL DIAGNOSIS between Cushing's Disease and Cushing's Syndrome.
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If Corticorelin (Acthrel) is injected in a patient with Cushing's Disease, will you see an increase or decrease of ACTH and Cortisol?
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Corticorelin (Acthrel) will cause an INCREASE of ACTH and cortisol in a patients with Cushing's DISEASE.
Because |
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Corticorelin (Acthrel) was injected in a patient with Cushing's. ACTH and Cortisol levels did not change. Does the patient have Cushing's disease or Syndrome?
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Cushing's SYNDROME.
- because adrenal and ectopic tumors do not respond to Corticorelin. |
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Why are adverse side effects seen with Corticorelin (Acthrel) minimal and transient?
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Because the drug is only given ONCE for differential diagnosis of Cushing's and it has a short 1/2 life of 9 minutes.
Causes transient flushing, mild dyspnea and hypotension. |
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What is the effect of continuous dosing of Gonadorelin (Factrel)
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Initially will increase LH and FSH production but continuous dosing will lead to INHIBITION of LH and FHS resulting in a "pharmacological castration"
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What is the effect of pulsatile dosing of Gonadorelin (Factrel)
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Pulsatile dosing will stimulate gonadotropin (LH and FSH) release from the anterior pituitary.
i.e: once every 90 minutes. |
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What is the clinical use of Gonadorelin (Factrel)
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Gonadorelin (Factrel) is used for differential diagnosis of hypogonadal states.
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A patient is injected with Gonadorelin (Factrel) and there is increase of LH/FSH. Does the patient have secondary hypogonadism or delayed puberty?
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Secondary hypogonadism
(hypogonadotropic hypogonadism) |
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A patient is injected with Gonadorelin (Factrel) and there is NO increase in LH/FSH. Does the patient have secondary hypogonadism or delayed puberty?
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Patient has delayed puberty .
(NOT secondary hypogonadism AKA hypogonadotropic hypogonasim ) |
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Why are Gonadorelin ANALOGS used for continuous administration?
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Gonadorelin analogs (Leuprolide, Nafarelin, Goserelin, Triptorelin) are used for continuos administration because they are longer lasting, more potent, and have higher affinity for the receptors.
*note: Gonadorelin (Factrel) is only given in pulsatile doses for differential diagnosis of hypogonadal states. |
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Leuprolide, Nafarelin, Histrelin, Goserelin, and Triptorelin are analogs of what hypothalamic hormone ?
Are they administered in pulsatile doses or continuously? |
Analogs of Gonadorelin and are administered continuously.
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What drug is given internasally for endometriosis?
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Nafarelin (Synarel)
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What drugs can be given intramuscularly for the palliative treatment of pain associated with prostate cancer?
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Leuprolide (Lupron DEPOT) or Triptorelin (Trelstar DEPOT)
*Depot means Intermuscular injection |
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What category of drugs can be given to manage patients with prostate cancer, breast cancer, uterine fibroids, endometriosis, precocious puberty, and hirsutism?
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GnRH analogs such as:
Leuprolide Nafarelin Histrelin Goserelin Triptorelin |
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Which drug is given internasally for treatment of precocious puberty?
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Nafarelin (Synarel)
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What category of drugs can be given to suppress gonadotropin release in females undergoing controlled ovarian hyperstilumation and in assisted reproduction (tx of infertility) ?
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GnRH analogs such as:
Leuprolide Nafarelin Histrelin Goserelin Triptorelin |
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What is the physiologic effect of Luoprolide, Nafarelin, Histerelin, Goserelin, and Triptorelin?
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They initially cause an increase in LH/FSH but through continuous use will INHIBIT LH/FSH secretion resulting in a "pharmacologic castration"
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What category of drugs cause adverse effects similar to postmenopause?
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GnRH analogs such as:
Leuprolide Nafarelin Histrelin Goserelin Triptorelin Adverse effects are: Sweats, hotflashes, headaches, depression, decreased libido, vaginal dryness |
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Which hypothalamic hormone analog can cause OSTEOPOROSIS as an adverse effect?
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GnRH analogs such as:
Leuprolide Nafarelin Histrelin Goserelin Triptorelin - Also cause postmenopausal syndrome. |
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What is the difference in clinical use between GnRH analogs and GnRH antagonists?
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GnRH antagonists have immediate actions because they do not cause an initial stimulation of hormone release like analogs.
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What category of drugs are Cetrorelix (Cetrotide), Ganirelix, Degarelix (Firmagon) ?
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They are GnRH ANTAGONISTS used to cause immediate effects in decrease of LH and FSH.
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What drug can be used to decrease testosterone in advanced prostate cancer?
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Degarelix (Firmagon)
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What drugs can used in the treatment of infertility to inhibit premature LH surge in females undergoing contolled ovarian hyperstimulation?
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Cetrorelix (Cetrotide) and Ganirelix
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Somatostatin inhibits release of what?
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Inhibits release of GH from the anterior pituitary AND thyrotropin, insulin, glucagon, and gastrin.
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Why is Somatostatin clinically worthless?
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Somatostatin is clinically worthless because it has a half life of 1-3 mins. However, if it lasted longer it could be used for Acromegaly.
Analogs (OCTREOTIDE and :ANTREOTIDE) are used instead. |
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T/F: Somatostatin causes hyperglycemia through the inhibition of insulin.
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FALSE.
Somatostatin is more potent at inhibiting GH than at inhibiting Insulin. Therefor, it can be given in low enough doses where it does not affect insulin. |
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What drug is used in acute management of bleeding due to esophageal varices?
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Octreotide (Sandostatin, Sandostatin LAR Depot)
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What drugs can be used in the management of ACROMEGALY, Carcinoid tumors, VIPomas and other endocrine tumors?
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Somatostatin Analogs such as:
Octreotide (Sandostatin, Sandostatin LAR Depot) Lanreotide (Somatuline Depot) |
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What drugs can be used to manage the diarrhea associated with Carcinoid tumors?
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Somatostatin Analogs:
Octreotide (Sandostatin, Sandostatin LAR Depot) or Lanreotide (Somatulin Depot) |
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What is the ONLY Depot injection that is NOT administered IM (administered deep SQ) ?
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Lanreotide (Somatuline Depot)
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What is the main adverse effect of somatostatin anaglogs such as Octreotide and Lanreotide?
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Biliary disorders (biosludge and gall stones)
also, nausea, vomiting, flatulence, and abdominal craoms. |
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T:F Dopamine is used in the treatment of hyperprolactinemia?
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FALSE.
Dopamine is not practical for the management of hyperprolactinemia because of unwanted peripheral side effects and parenteral administration. note: Instead use D2 agonists like Babergoline and Bromocriptine |
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What is the physiology/mechanism of action of Bromocriptine and Cabergoline?
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Bromocriptine and Cabergoline are orally active dopamine (D2) agonists. They DECREASE prolactin secretion from normal glands and pituitary tumors.
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What drugs are clinically used to manage hyperprolactinemia?
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Bromocriptine and Cabergoline
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What drugs are clinically used to manage galactorrhea, amenorrhea, hypogonadism, infertility and breast tenderness?
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Bromocriptine and Cabergoline
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What drugs are clinically used to manage prolactin secreting adenoma (prolactinomas) ?
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Bromocriptine and Cabergoline
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What is the mode of administration of Bromocriptine and Cabergoline?
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ORAL administration
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What is a contraindication for Bromocriptine?
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Bromocriptine is contraindicated in people with a history of psychosis because it causes psychiatric disturbances.
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Orthostatic hypotension and Ergotism (severe vasospasms that lead to tissue necrosis) are side effects of what drugs?
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Bromocriptine and Cabergoline
(naturally occurring alkaloids) |
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What type of drugs can cause hyperprolactinemia?
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Dopamine angtagonists such as antipsychotics that deplete dopamine storage (Phenothiazine and haloperidol). Also, Reserpine which decreased dopamine.
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What is the physiological action of GH ?
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Growth hormone increases protein synthesis through stimulation of synthesis and release of SOMATOMEDINS (IGF-1 and IGF-2) --> cell proliferation, bone growth, and cartilage synthesis.
-Anabolic hormone, not metabolic steroid! |
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What drug can be used to manage patients with Turner Syndrome. Prader-Willi Syndrome, Chronic Renal Insufficieny, Cachexia, and Short Bowel Syndrome?
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SomatoTROPIN.
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What is the mechanism of action of Somatotropin?
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Initially produces "insulin-like effects" by enhancing tissue uptake of glucose and amino acids and decreasing lipolysis. Followed by peripheral insulin antagonistic effects that cause deceased glucose uptake and increased lipolysis.
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What are the adverse side effects of Somatotropin?
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myalgias (muscle pain), pancreatitis, intercranial hypertension, scoliosis, edema.
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What is the contraindication for Somatotropin?
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Children with closed epiphysis.
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If Somatotropin doesn't do anything in a patient with growth failure, what is the problem?
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Deficiency in Somatomedins (IGF-1 and IGF-2), GH gene deletion, or GH receptor mutation.
note: Mecasermin is used. |
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What is the clinical use of Pegvisomat (somavert)
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Management of Acromegaly
* Octreotide and Lanreotide are also used to treat acromegaly (somatostatin analogs) |
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If a patient has IFG-1 deficiency or GH receptor mutation, what drug should you give them?
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Mecasermin (Increlex) or Mecasermin (IPLEX) because Somatotropin won't do anything.
Mecasermin and Mecasermin fabate are rh-IGF-1 (Iplex also has binding protein) |
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If a patient has a GH gene deletion, what drug should they be given?
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Mecasermin or Mecasermin fabate.
* They should NOT be given Somatotropin because the body will create antibodies against it. |
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In a patient with IGF-1 deficiency and IGF-1 binding protein deficiency, what drug should be given?
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Mecasermin fabate (IPLEX)
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Why is Mecasermin Fabate (IPLEX) better than Mecasermin for reducing hypoglycemin side effects?
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Because Mecasermin fabate (Iplex) has binding proteins which means less of the drug is free.
other side effects" elevated hepatic enzymes, inter cranial pressure. |
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What is the difference betwee thyrotropin and thyrotropin alpha?
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1/2 life.
thyrotropin has a 1/2 life of 1 hr thyrotropin alpha has a half life of 22 hrs |
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What is the mechanism of action of Thyrotropin?
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Increases iodide uptake and increases synthesis and release of thyroid hormones (T3 and T4)
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What is the clinical use of thyrotropin?
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Differential diagnosis between primary and secondary HYPOthyroidism.
Primary hypothyroidism (due to defected gland) --> no increase in thyroid hormone Secondary hypothyroidism (deficiency in hormone)--> increase production of thyroid hormone |
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If a patient has an INCREASE in production of thyroid hormone after Thyrotropin administration, so they have primary or secondary hypothyroidism?
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Secondary.
Primary hypothyroidism would not cause an increase because gland is defective |
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What is the clinical use of thyrotropin alpha (Thyrogen) ?
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Diagnostic tool for determining recurrence of thyroid carcinoma.
- After thyroid surgery, Thyrogen is used to increase I131 uptake and scan the body for any remaning thyroid cancer cells. |
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What are contraindications of thyrotropin?
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Patients with heart disease and adrenocortical insufficiency
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What is the clinical use of Cosyntropin (Cortrosyn)?
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Differential Diagnosis of secondary vs primary Addison's disease.
Primary Addison's --> no effect Secondary Addison's (pituitary hypofunction) --> increases release of corticosteroids |
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What are side effects seen with Corticotropin?
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Metabolic effects characteristic of Cushing's syndrome, peptic Ulcers, psychosis, impaired wound healing.
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What is the physiologic function of FSH in females?
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-Promote gametogenesis and follicular maturation.
-Promote biosynthesis of estrogens from androgens in granulosa cells. |
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What is the physiologic function of FSH in males?
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Stimulate spermatogenesis
Promote protein synthesis within testicular sertoli cells. (increase testosterone) Can also be used for cryptochidism. |
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What drugs are FSH analogs used with hCG for treatment of infertility?
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Urofollitropin (Bravelle)
Follitropin (Gonal-F) Follitropin alpha (Follistim AQ) |
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What are side effects in females and males of treatment with Urofollitropin (Bravelle), Follitropin (Gonal-F) or Follitropin alpha (Follistim AQ)
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Females: Ovarian enlargement and multiple births
Males: Gynacomastia |
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What is the physiological effect in males and females of LH ?
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LH is a major stimulant of gonadal steroid synthesis.
Females: regulates follicular development, induces ovulation, and promotes biosynthesis of progesterone and androgens in corpus luteum during luteal phase (corpus luteum formation) Males: promotes biosynthesis of testosterone within testicular Leydig cells. |
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What LH agonist is a glycoprotein produced by the placenta ?
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hCG (Pregnyl, Novarel)
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What is hCG (Pregnyl, Novarel) and hCG alfa clinically used for?
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-Tx of hypogonadism (with FSH/hMG) - triggers ovulation in females and testosterone production in males
- Tx of infertility (with FSH/hMG) in both males and females -Tx of Cryptochidism in males. |
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What LH analog can be used in males to treat cryptochidism?
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hCG (pregnyl or Novarel)
hCG (Ovidrel) *NOT LEUTROPIN ALFA (Luveris) because this is used only in women. |
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hCG (Pregnyl, Novarel), hCG alfa, and Leutropin afla (Luveris) are contraindicated in what pts?
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Patients with androgen dependent neoplasms and precocious puberty.
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What are side effects of hCG (Pregnyl, Novarel), hCG alfa, and Leutropin afla (Luveris) ?
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Progesterone associated side effects - ovarian enlargement, depression, edema, headache, precocious puberty.
In males - gynecomastia. |
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What drugs can be used in place of FSH with hCG for treatment of infertility in males and females with hypogonadotropic hypogonadism?
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Menotropins ( Repronex, Menopur)
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Menotropins ( Repronex, Menopur) have what physiologic effects ?
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"FSH-like effects"
Females: follicular growth and maturation Males: stimulates spermatogenesis |
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For treatment if infertility, what categories of drug must be used in combination?
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FSH/LH or Menotropin/LH
SO... one of these... LH: hCG hCG alfa Leutropin alfa (females only) And one of either of these... FSH: Urofillotropin Follitropin alfa Follitropin beta Menotropins: Repomex Menopur *Note: GnRH analogs can also be used to tx infertility |
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What drug is used solely for treatment of infertility in females due to hypogonadotropic hypogonadism (in combo with follitropin alfa)
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Leutropin alfa (Luveris)
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T/F Bromocriptine is used to treat all types of infertility.
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FALSE.
Bromocriptine is used to treat infertility only associated with hyperprolactinemia, not hypogonadism. |
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What drug is used to treat prolactin deficiency ?
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none.
No current therapy for prolactin deficiency. |
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What is the order of treatment for Acromegaly?
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Pituitary radiation --> Bromocriptine (Dopamine agonist) --> Pegvisomat ( GH antagonost) --> Octreotide or Lancreotide (Somatostatin Analogs).
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What Dopamine agonist can be used to treat Parkinsons?
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Bromocriptine
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What is the only peptide that can be given orally?
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Desmopressin is the only peptide that can be given orally because it has a D-Arginine. It is not inactivated by gastric acid
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Activation of renal V2 receptors by Vasopressin leads to what physiologic activity?
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increased water permeability in renal collecting tubules (antidiuretic)
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Activation of extrarenal V2 receptors by Vasopressin leads to what physiologic activity?
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Release of Von Willebrand factor and coagulation factor VIII.
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Activation of V1 receptors on vascular smooth muscle by Vasopressin leads to what physiologic activity?
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vasoconstriction
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Deficiency of Vasopressin results in what disease?
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Diebetis Insipidus
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What is the clinical use of Vasopressin (Pitressin) ?
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Tx of central diabetis insipidus and to control bleeding from esophageal varices and colonic diverticula.
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What drug is used to treat esophageal varies and acromegaly?
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Octreotide or Lantreotide
(also for VIPomas and carcidoid tumors) |
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Release of Vasopressin is stimulated through what physiologic stimuli?
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increased plasma tonicity and decreased blood pressure
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What are adverse side effects of Vasopressin?
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Hyponatremia, water intoxication, vasoconstriction, bronchoconstriction, tremor, increased intestinal activity, facial pallor
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What are contraindications when giving Vasopressin?
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Pts. with coronary artery disease, asthma, and epilepsy.
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What vasopressin antagonist is specific for V2 receptors?
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Tolvaptan (Samsca)
note: Conivaptan (Vaprisol) is an antagonists for both V1 and V2 |
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What drug is used to treat hyponatremic states (SIADH) AND heart failure?
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Tolvaptan (Samsca)
- Not Conivaptan (Vaprisol) because it is nonselective and it causes vasodilation through V1. |
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What are side effects of Tolvaptan and Conivaptan?
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Hypernatremia, dehydration, thirst, infusion site reaction (Conivaptan)
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What is the difference in administration of Conivaptan vs. Tolvaptan?
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Tolvaptan in administered ORALLY
Conivaptan is administered IV |
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What drug is a selective V2 receptor agonist?
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Desmopressin
-minimal V1 activity to so hypertension |
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What drug is used to treat Von Willebrand's disease and coagulopathy associated with hemophilia A ?
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Desmopressin
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What V2 selective agonist is used to treat pituitary diebetis insipidus and nocturnal enuresis?
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Desmopressin
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Why is Desmopressin preferred over Vasopressin in treatment of diabetis insipidus?
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Because it is selective for V2 so it doesn't cause hypertension AND it can be given orally or internasally.
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What is the physiologic effect of oxytocin?
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-Milk ejection
-Stimulation of uterine contraction (initiation of labor) |
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What is the mechanism of action of oxytocin?
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enhances sodium permeability in myometrial smooth muscle cells --> induces continuous uterine contractions and contraction of s.m in myoepith. cells of mammary glands.
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What drug can be used as a nasal spray to stimulate milk let down and relief of postpartum breast engorgement in lactating females?
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oxytocin
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What drug is given IV to induce or reinforce labor?
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oxytocin
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What drug is given IV or IM to control postpartum bleeding?
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oxytocin
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What drug is given IV to induce a therapeutic abortion AFTER THE FIRST TRIMESTER?
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oxytocin
- after the first trimester, the oxytocin receptors increase. |
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What are the adverse effects of oxytocin?
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hypertensive crisis (because it is similar in structure to vasopressin), water retention, uterine rupture, and fetal death
CI: premature births and abnormal fetal presentation. |
