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93 Cards in this Set
- Front
- Back
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Describe difference etween anterior and posterior pituitary systems
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Anterior: vascular link to hypothalamus via hypothalamic pituitary portal system
posterior pituitary- hormones made in hypothalamu, transported to posterior pituitary, and released later via signal |
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Hormones made by AP and by PP
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AP: Prolactin (direct activity on tissue)
GH, TSH, ACTH, LH, FSH (work on endocrine organ) PP: ADH and Oxytocin |
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Growth Hormone Axis:
anterior pituitary hormone hypothalamic hormone target organ primary target organ hormone/mediator |
Hypothal: GH releasing hormone (+), somatostatin (-)
AP: Growth Hormone Target organ: Liver, muscle, bone, kidney, others Primary target hormone: Insulin like growth factor -1 (IGF-1) |
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Thyroid hormone axis:
anterior pituitary hormone hypothalamic hormone target organ primary target organ hormone/mediator |
Hypothal: Thyrotropin releasing hormone (TRH)
AP: Thyroid stimulating hormone (TSH) Target organ: thyroid Primary target hormone: thyroxine/triiodothyronine |
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adrenal axis:
anterior pituitary hormone hypothalamic hormone target organ primary target organ hormone/mediator |
hypothal: corticotropin releasing hormone (CRH) +
AP: adrenocorticotropin (ACTH) Target organ: adrenal cortex primary target organ hormone: glucocorticoids, mineralcorticoids, androgens |
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gonad endocrine axis:
anterior pituitary hormone hypothalamic hormone target organ primary target organ hormone/mediator |
Hypothal: gonadotropin releasing hormone (GnRH) +
AP: Follicle stimulating hormone (FSH), and luteinizing hormone (LH) Primary target: gonads end hormones: estrogen, protesterone, testosterone |
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breast endocrine axis:
anterior pituitary hormone hypothalamic hormone target organ primary target organ hormone/mediator |
hpotha: Dopamine (-)
AP: Prolactin Target tissue: Breast no secondary hormones!! |
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Type of receptors that endocrine axis function by? GH and prolactin specifically what kind?
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G protein coupled
GH and Prolactin: JAK/STAT |
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Major factors that inhibit and promote GHRH release?
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+: Sleep, hypoglycemia, stress
-: aging, disease, glucose |
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What does GH do to peripheral tissues?
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Adipose: decrease glucose uptake, increase lipolysis
Muscle: Increase glucose and aa uptake, increase protein synthesis Chondrocytes: Increase AA uptake, increase protein synth, increase DNA/RNA synth, Increase chondroitin sulfate, increase collagen, increase cell size/number Liver: release IGF-1 |
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What does IGF-1 do to peripheral tissues:
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Muscle: Same as GF
Chondrocytes: same as GF |
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Effects of GH in childhood
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-promote linear growth
-long bone growth -cartilage, muscle, organ system growth MAJOR DETERMINANT OF ADOLESCENT GROWTH SPURT |
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Major effects of GH on adults
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PRIMARILY METABOLIC
1. Increase protein synthesis and bone density 2. promote lipolysis and inhibit lipogenesis 3. promote gluconeogenesis/glucose release 4. oppose insulin-induced glucose uptake (adipose) 5. reduce insulin sensitivity |
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GH secretion:
-manner -when -regulated by what -pattern with aging |
pulsatile
during sleep regulated by GHRH and somatostatin interplay GH secretion decreases with age |
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Describe the MOA of GH
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bind receptor activates signaling cascade (via JAK tyrosine kinases and STATs)
Effects are primarily mediated by IGF-1, released from liver via GH stimulation |
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GH deficiency symptoms in children
major cause |
short stature ad adiposity
hypoglycemia **Usually due to deficiency in GHRH** |
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GH deficiency symptoms in adults
major cause |
-change in body composition (increased adiposity)
decreased skeletal muscle mass/strength decrease bone density CV changes (card muscle atrophy, atherogenic blood lipid profile) fatigue, weakness, depression, malaise **Usually pituitary problem, or continuation of childhood-onset disease from gHRH** |
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Major drugs used to effect the GH axis
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synthetic GHRH (Sermorelin)
Recombinant human growth hormone (Somatotropin, somatrem) Recombinant IGF1 (Mecasermin) |
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Pt has a defective hypothalamic release of GHRH, but normal pitutary functioning. Treat them with what?
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synthetic GHRH (Sermorelin)
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When would you use recombinant human growth hormone?
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most cases of GH deficiency
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What is somatotropin?
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synthetic growth hormone
191 aa peptide, identicay to native hGH |
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What is Somatrem?
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192 aa peptide consisting of 191aa + extra methionine on N terminus
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Indications for use of recombinant GH
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1. documented growth failure in peds pts due to GH deficiency, CRF, prader willi, turner syndrome
2. small for gestational age condition, and fail to catch up by 2yo 3. idiopathic short stature (non GH deficient) >2.25SD below mean height 4. GH deficiency in adults 5. Wasting in pts with AIDs 6. short bowel syndrome in pts with specialized nutritional support |
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Peds conditions where it is indicated to use recombinant GH
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GH deficiency
chronic renal failure prader-willi turner syndrome |
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Major controversies for use of recombinant GH
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anti aging uses
use by athletes to cheat |
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What does recombinant GH improve in children?
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increase linear growth, weight gain to low normal
increases muscle mass, organ size, and RBCs |
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What does recombinant GH improve in adults?
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increased bone mineral density
normal body composition (dec central adiposity) increase muscl emass/strength improves lipid profile/card function improves psych sx/ wellbeing |
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Side effects of recombinant GH
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leukemia (rapid growth of melanocytic lesions)
hypothyroidism insulin resistance arthralgia increased cytop450 activity |
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Contraindications for recombinant GH
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pts with closed epiphyses
active underling intracranial lesion active malignancy proliferative diabetic retinopathy |
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What are some considerations prior to use of recombinant GH?
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-caution in pts with DM and children whose GH deficiency is from intracranial lesion
-glucocorticoids inhibit growth promoting effects of the drug |
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What is Mecasermin?
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recombinant IGF1
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Pt has a severe IGF1 defiency due to mutations in GH receptor (Laron dwarfism). What drug should you use?
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Mecasermin (recombinant IGF-1)
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Pt has neutralizing antibodies against GH. what drug should you use?
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mecasermin (recombinant IGF-1)
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What causes GH excess?
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benign tumor of AP
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Symptoms of GH excess in children
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gigantism
-prior to closure of epiphyses, because excess IGF1 causes excessive longtiudinal bone growth |
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Symptoms of GH excess in adults
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acromegaly
after epiphyses close (excess IGF dosen't do long bone growth then) = promotes growth of deep organs and cartilaginous tissue. |
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Major symptoms of acromegaly
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-thickening of bones (face,hands)
-large facial structure, macroglossia, and hepatomegaly -increased soft tissue growth -enlarged, arthritic joints -ha, sleep apnea, excessive sweating -increased risk of CV disease, GI cancer (colon), and reproductive disorders |
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What are treatment options for growth hormone excess
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larger pituitary adenoma? - transsphenoidal surgery to remove
smaller adenomas- 1. somatostatin analogue 2. gh receptor antagonist 3. dopamine receptor agonist (bromocriptine) |
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What is Octreotide? used for what
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somatostatin analogue- inhibits GH secretion
long lasting, and 45x more potent vs somatostatin use in GH excess |
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What is Pegvisomant? used for what
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GH receptor antagonist (recombinant 191 aas)
-multiple polyethylene glycol (PEG) residues = longer half life used in GH excess |
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Drug indications for Octreotide?
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control pituitary adenoma growth in acromegalic pts
carcinoid crisis- flushing, diarrhea, sx from carcinoid syndrome secretory diarrhea from vasoactive intestinal peptide- secreting tumors (VIP) |
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Side effects of octreotide
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n/v
abd pain GI discomfort cardiac effects (sinus brady, conduction disturbance) hypoglycemia gallstone formation |
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Contraindications for octreotide?
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hypersensitivity to medication
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Major considerations for Octreotide:
-other syndromes -decreases what drug -drug that has additive effects with |
control gI bleeding too
decreases cyclosporin level octreotide + bromocriptine = increase available bromocriptine |
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MOA of pegvisomant
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competitive antagonist of GH activity
can bind transmembrane GH receptor but CANNOT activate subsequent signaling decreases serum IGF1 levels |
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Indications for use of pegvisomant
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used for treatment of acromegaly, refractory to other modes of intervention (surgery, radiation, pharm intervention)
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Side effects of pegvisomant?
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increased pituitary adenoma size
elevated serum aminotransferase levels (ALT/AST) |
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CI to pegvisomant?
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hypersensitivity to this medication
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considerations prior to use of pegvisomant:
-what precautions should be taken? |
yearly MRI to exclude enlarging adenoma
LFTs performed periodically |
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What is the function of LH and FSH in women during the follicular and luteal phases of menstruation
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Follicular:
LH stimulates androgen production (thecal cells) FSH stimulates androgen to estrogen conversion (Granulosa) Luteal phase: estrogen and progesterone are controlled by LH pregnancy- estrogen and progesterone controlled by hCG |
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What is the function of FSH and LH in men?
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FSH - regulates spermatogenesis.
FSH- Produces androgen binding protein in Sertoli cells (helps maintain high testicular testosterone) LH stimulates production of testosterone by Leydig cells. |
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Which drugs stimulate the hpg axis?
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gonadotropins (human menopausal gonadotropins, urofollitropin, hcg, follitropin)
Gonadotropin releasing hormone (GnRH) and analogue (Gonadorelin) = short pulsatile half life |
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What drugs inhibit HPG axis?
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synthetic analogs of GnRH (longer half lifes)
GnRH receptor antagonists |
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What are Ganirelix, Cetrorelix, Abarelix?
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GnRH receptor antagonists
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What are Goserelin, Histrelin, leuprolide, nafarelin, and triptorelin
-the relins? |
synthetic analogues of GnRH with long half lives
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How are menotropins obtained?
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urine of menopausal women (contain FSH and LH)
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What is hcG?
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placental hormone
LH agonist |
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What is urofollitropin?
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purified FSH isolated from urine of postmenopausal women
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what is follitropin?
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recombinant human FSH
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Drug indications for gonadotropins
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-ovulation induction in hypogonadotropic hypogonadism (women), PCOS, obesity
-controlled ovarian hyperstimulation in reproductive tech (IVF) -infertility in male hypogonadotropic hypogonadism |
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Side effects of gonadotropins
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-ovarian hyperstimulation syndrome (ovarian enlargement, ascities, hydrothorax, hypovolemia, possible shock)
-multiple pregnancies -increased risk gynecomastia (men) -ovarian cancer -ovarian cysts/hypertrophy |
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Contraindications for gonadotropins
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-endocrine disorder other than anovulation (thyroid/adrenal)
primary gonadal failure (ovaries/testes need to be functioning to work) pituitary tumors/sex hormone dependent tumors ovarian cysts/enlargement pregnancy |
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How do GnRH agonists work?
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pulsatile gnRH secretion or short half life GnRH analogue (gonadorelin)
stimulate gonadotroph cells to produce and release Lh and FSH MIMICKS PHYSIO |
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When would you use GnRH agonists (pulsatile)?
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stimulate ovulation
treat infertility in men diagnosis of hypogonadism |
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What dype of GnRH agonists are used to inhibit gonadal axis?
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Sustained release GnRH agonsts
"relins" and leuprolide long half life ~3 hrs |
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MOA of extended release GnRH agonists?
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Sustained nonpulsatile administration for long half life = desensitize GnRH receptors
inhibits the release of FSH and LH in women and men |
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Describe biphasic reaction to extended treatment of non-pulsatile GnRH agonists
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1. Transient 7-10 day increase in gonadal hormone levels (flare) = agonist effect
2. long lasting suppression of gonadotropins/gonadal hormones (inhibitory action) |
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Indications for GnRH agonists (non-pulsatile)
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keep LH surge low in controlled ovarian hyperstimulation (during IVF)
endometriosis uterine fibroids adjunctive in prostate/breast cancer central precocious puberty amenorrhea/infertility in women with PCOS |
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Side effects of GnRH agonists (non-pulsatile)
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hot flashes, sweats,
ha osteoporosis urogenital atrophy temporary worsening of precocious puberty in initial weeks of tx |
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Contraindications for GnRH agonists (non-pulsatile)
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hypersensitivity to GnRH and GnRH analogs
pregnancy breast feeding |
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Considerations before using non-pulsatile GnRH agonists
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depot formulations to supress gonadotropins and consequent decrease of gonadal steroids
initial increase in testosterone and estrogen levels |
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What do The "lix" drugs do?
benefits? |
inhibit gonadal axis- GnRH receptor antagonists
immediate effect= duration of administration during IVF is shorter |
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MOA of "lix" drugs
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competitive antagonists of GnRH receptors
inhibit secretion of FSH and LH in dose dependent manner no 'flare' effect (vs GnRH agonists) |
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Indication for GnRH antagonists (Ganirelix and Cetrorelix)
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keeps LH surge low (in controlled ovarian hyperstimulation during IVF) = improves implantation and pregnancy rates
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Indication for GnRH antagonists (abarelix)
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metastatic prostate cancer in pts with lots of mets or tumor encroaching spinal cord
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Side effects of 'lix' drugs
specific to abarelix? ganirelix? cetrorelix? |
nausea
ha ovarian hyperstimulation syndrome QT interval prolongation (abarelix) ectopic preg, thrombotic, spontaneous abortion (ganirelix) anaphylaxis (cetrorelix) |
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Contraindications to GnRH antagonists?
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pregnancy, lactation, ovarian cysts, or enlargement (not due to PCOS)
primary ovarian failure thyroid or adrenal dysfunction vaginal bleeding (unknown etiology) |
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Describe timetable of drugs used inIVF
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1. GnRH agonists during follicular phase (or GnRH antagonist at end)
2. Gonadotropin after onset of menses 3. Hcg at begining of luteal phase (extract oocyte and fertilize after) 4. progesterone after embryo transfer |
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Prolactin regulation
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Inhibitd: Dopamine (hypothalamus)
**Dopamine is increased by thyrotropin releasing hormone/TRH** No negative feedback Promote: Estrogen during pregnancy. Suckling very powerful prolactin release. |
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physio actions fo prolactin
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regulates mammary gland development
milk protein biosynth milk secretion Increased Prolactin = inhibit GnRH release (and HPG axis/estrogen synthesis) Ovulation is suppressed during lactation |
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Symptoms of hyperprolactinemia
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amenorrhea and galactorrhea, infertility (women)
loss of libidio, infertility (men) large tumor = visual changes (bitemporal hemianopsia) |
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Causes of hyperprolactinemia
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prolactin secreting adenoma- common
hypothalamic destruction -rare |
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Drugs used for hyerprolactinemia
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dopamine receptor agonists (bromocriptine)
also cabergoline and pergolide |
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How can you treat prolactin deficiency?
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no treatments known yet
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Major receptors affected by bromocriptine (and cabergoline, pergolide)
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High affinity for dopamine D2 receptors (agonists)
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MOA of bromocroptine and other dopamine agonists
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inhibit pituitary prolactin release
GH release is reduced in pts with acromegaly (but less effectively) |
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Drug indications for bromocriptine
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1. amenorrhea, galactorrhea, and infertility (hyperprolactinemia), permenstrual syndrome
2. acromegaly - need high doses. effective only if tumor secretes BOTH PROLACTIN AND GH. 3. parkinson's disease 4. hyperprolactinemia (cabergoline) |
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Side effects of dopamine agonists
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nausea
headache fatigue orthostatic hypoten |
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which dopamine agonist ccan cause seizure, or acute MI
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bromocriptine
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Which dopamine agonist can cause arrhythmia, MI, or heart failure
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pergolide
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which dopamine agonist can cause pulmonary fibrosis or pleural effusion
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cabergoline
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Contraindications to dopamine agonists
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hypersensitivity to ergots
pts on antihypertensives toxemia of pregnancy or preeclampsia (bromocriptine) |
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Considerations prior to dopamine agonist use:
-how to reduce nausea side effect -drug interactions |
Cabergoline = less nausea (vs others)
Intravag administration = reduce nausea (local irritation though) Interactions- 1. alcohol interolerance 2. coadmin with antihyperensives = potentiate hypotension 3. CNS depressants = additive effects |
