Hypothalamic and Pituitary Hormones Flashcards
dopamine aka
PROLACTIN-INHIBITING HORMONE
GHRH or GROWTH HORMONE RELEASING HORMONE aka
SOMATROPIN-RELEASING HORMONE
GROWTH HORMONE aka
SOMATROPIN
ACTH or adrenocorticotropic hormone aka
CORTICOPTROPIN
TSH aka
thyrotropin
two distinct components of the pituitary gland
adenohypophysis
neurohypohysis
connects hypothalamus and pituitary gland
hypothalamic or pituitary stalk
hormones that pass thru the pituitary portal stalk to stimulate the pituitary gland to release or inhibit hormone production
hypophysiotrophic hormones secreted by neurosecretory cells in the hypothalamus
hormones produced in the PPG will act
directly on target organs
PPG hormones secreted in response to stimulus
VASOPRESSIN/ ADH
OXYTOCIN
prolactin from APG acts
directly on mammary glands
hormone that acts both directly and indirectly
GROWTH HORMONE
hypothalamic and pituitary hormones are ALL
peptides
hormones of the posterior pituitary are stored in
granules
makes the hormone susceptible to destruction by proteolytic enzymes of the digestive tract
peptidyl nature
TRH may
increase levels of PROLACTIN causing galactorrhea
no pharmacologic preparation available
PROLACTIN
hormones used for diagnosing pituitary insufficiency
GHRH CRH TRH TSH ACTH
hormones released by the hypothalamus
TRH CRH GHRH GnRH Dopamine somatostatin
anterior pituitary gland hormones
TSH ACTH GH FSH, LH PRL GH
posterior pituitary gland relese the ff hormones
VASOPRESSIN / ADH
OXYTOCIN
steroid or steroid-like hormones are _____ in the circulation
protein bound
only the ____ form of steroid and steroid like hormones that is active and can enter the cell membrane
free
peptides cannot enter the cell membrane therefore they are
hypdrophilic
receptor for GH and PRL
Jak STAT
Januse kinase signal transducer and activator of transcription
receptor for GHRH, TSH, FSH, LH, ACTH, VASOPRESSIN
Gs
Gs function
stimulates adenylyl cyclase
receptor for SST and DOPAMINe
Gi
Gi function
inhibits adenylyl cyclase
GnRH, OXYTOCIN, VASOPRESSIN 1A & B receptor
Gq
Gq function
muscarinic receptor
2nd messenger for IP/DAG
SST or somatostatin aka
growth hormone-inhibiting hormone
SST is secreted by
the D cells of the stomach
the delta cells of the islets of Langerhan
somatostatin moa
inhibits secretion of GH, TSH, INSULIN, GLUCAGON, GASTRIN, and other GI hormones
use of somatostatin is limited due to
short duration of action
multiple effects esp in cho metabolism
rebound hypersecretion
SST analogs
OCTREOTIDE (Sandostatin)
LANTEOTIDE
receptors for OCTREOTIDE
SSt-2
selectivity of OCTREOTIDE to SST2 receptors have less
effect on insulin therefore less hyperglycemia
OCTREOTIDE preparation
50-200 mcg SC q8hr, once a month
indication for SST ANALOGS
acromegaly
GEP tumors such as carcinoid and gastrinoma
bleeding esophageal varices
SST analog dosage for acromegaly
initially 0.05 - 0.1 mg, SC q8-12 hr
max of 1.5 mg per day
gep tumor tx of sst analog dosage
initially 0.05 mgOD/BID
may gradually inc to 0.1-0.2mg TID
SST analog adverse effects
GIT 50%
Gallstones 20%
GH receptor antagonist
PEGVISOMANT
effect of PEGVISOMANT
blocks peripheral effects of GH ➡️ decrease IGF 1
PEGVISOMANT administration
daily via SC route
PEGVISOMANT Indication
px with acromegaly who do not respond to SST analogs
PEGVISOMANT AE
inc in tumor size- uncommon
changes in liver fxn tests
physiological fxn of GnRH
released in PULSATILE manner that controls the synthesis and release of FSH and LH
pharmacological fxn of GnRH
pulsatile: every 4hrs, stimulates GONADOTROPIN release
continuously: via injection, inhibits GONADOTROPIN RELEASE
cause of iNhibitory release of gonadotropin when released continuously
receptor desensitization
downregulation
changes in signaling pathways
GnRH analogs
LEUPROLIDE GOSERELIN NAFRELIN GONADORELIN HCL BUSERELIN
LEUPROLIDE preparation
7.5mg per month IM for prostatic cancer
q3months
1mg/day SC
GOSERELIN preparations
3.6 mg SC q28days
NAFARELIN preparation
nasal spray 200 mcg BID
not available!
uses (rare) of GnRH
pulsatile: pituitary stimulation in GnRH deficiency (male or female)
continuous: suppress gonadotropins
diagnostic
GnRH use for pituitary stimulation in GnRh deficiency addresses
male or female infertility or hypogonadism
suppression of gonadotropins through continous admin of gnRh is for
endometriosis central precocious puberty prostatic cancer and BPH uterine leiomyoma contraception ART
form of GnRH analog for GnRH deficiency
GONADORELIN INFUSION PUMP, IV or SC
short half life
cause of GnRH use in assistied reproductive technology
prevent premature ovulation caused by FSH and LH injection
GnRH is a diagnostic tool for
delayed puberty in hypogonadism
GnRH analogs AE
flare or worsening of symptoms
headache, abdominal discomfort, hot flushes
decreased bone density with prolonged use
flare occurs during
first 7-10 days of treatment
GnRH antagonist moa
suppress gonadotropin release
potent mast cell degranulators
GnRH antagonists
CETRORELIX
GANIRELIX
DEGARELIX
CENTRORELIX (Cetrotide) preparation
250 mcg SC OD
use of GnRH antagonists
female infertility, ART
advanced prostate cancer
specific GnRH antagonist drug for advanced prostate cancer
DEGARELIX
GnRH antagonist most common AE
nausea, headache
GnRH antagonist ae
nausea, headache
hot flushes, sweats, depression, decreased libido
NO FLARE SYMPTOOOOMS!
Dopamine action
reduces elevated PROLACTIN level caused by physiologic, pathogenic, iatrogenic conditions
PIH analogs are _____ agonists
D2
effect of PIH analogs on normal patients
increase GH release
PIH analogs effect on acromegaly patients
suppress GH release
PIH analogs are given
orally
only available PIH analog
BROMOCRIPTINE (parlodel)
PIH analogs
BROMOCRIPTINE
CABERGOLINE
PERGOLINE
QUINAGOLIDE
main use of PIH analogs
hyperprolactinemia in patients with prolactinoma or hypothyroidism
uses of PIH analogs
hyperprolactinemia
suppress physiologic lactation
Parkinson’s dse
acromegaly
BROMOCRIPTINE is not recommended for physiologic lactation because
risk of thromboembolism
AE of PIH analogs
nausea, vomiting headache, dizziness constipation fatigue cramps hair loss hallucination dyskinesia dry mouth
direct effects of SOMATOTROPIN
increased lipolysis➡️increased fat utilization➡️increased FFA in plasma
mixed effect on CHO metabolism
somatotropin directly decreases sugar levels by
increasing IGF ➡️increased INSULIN
indirect effects of SOMATOTROPIN
skeletal growth
increased cell proliferation
increased protein anabolism
increased formation of HYDROXYPROLINE from PROLINE boosts cartilage synthesis
approved uses of SOMATOTROPIN
GH deficient children and adults hypogonadism and growth failure in Turner's sx, Prader-Willi sx CRF in pedia patients SGA or small for gestational age NGHDSS
approved uses of SOMATOTROPIN in adults without GH deficiency
wasting in AIDS px
short bowel sx in patients on parenteral nutrition
unapproved uses of SOMATOTROPIN
increase muscle mass in adult athletes
anti-aging
AE of SOMATOTROPIN
Creutzfeldt-Jakob dse
children: hypothyroidism,scoliosis,increased intracranial pressure
adults: peripheral edema,myalgia,arthralgia, new onste of Type 2 DM
CI of GH
acute critical illness ➡️ increased mortalities
evidence of neoplasm
closed epiphyses
GH on drug interaction
increases CYP450 activity, enzyme inducer
rHGH drugs
SOMATROPIN
SOMATREM
HUMAN GROWTH HORMONE
SOMATROPIN preparation
0.025-0.07 mg/kg/week IM/SC x 4 years or until epiphyses have fused
inc dose for px with Turner’s sx and chronic renal insufficiency
highest level of GH are released in pulsatile manner during
SLEEP!
elevated GH levels in patients with acromegly are reflected by
increase in IGf-1
FSH stimulates
gametogenesis, folliculare development
spermatogenesis
stimulated by FSH to provide nutrients to spermatogenic epithelium
Sertoli cells
FSH effect in women
responsible for early development and growth of ovarian follicles
LH regulates
gonadal steroid hormone production or steroidogenesis
LH in men
stimulates growth of Leydig cells which produce androgens causing ext sexual maturation
LH in women
responsible for final maturation of the ovarian follicles and estrogen secretion
for ovulation, the initial formation of corpus luteum, and secretion of progesterone
hCG function
stimulates ovaria corpeus luteum to produce progesterone and maintiain placenta
hCG is a substitute for
LH
hCG is derived from
syncytiotrophoblast of placenta
1st line of drug for women suffering anovulation
CLOMIFENE
gonadotropic hormone preparation for female infertility derived from urine of postmenopausal women
hMG or uFSH
75 iu IM OD, 7-12 days ➡️CG 5000-10000 IU im
oligospermia is treated with this gonadotropic hormone preparation
hCG+hMG x 4-6 months
give both LH and FSH for sperm maturation
pregnancy diagnosis
hCG levels
ovulation diagnosis
LH level
ART day 1-11
hMG or uFSH with or without LH
stimulate follicular enlargement
ART day 7-11 n
give GnRH antagonist (CETRORELIX) to suppress premature ovulatio
ART day 12
give hCG
to mimic LH surge
ART after 34-46 hours - day 13?
egg retrieval or insemination either by ISCI or IVF
give PROGESTERONE to prime the uterus before implanting
gonadotropic hormones AE
multiple pregnancies 15-20%
multiple pregnancies as AE of gonadotropic tx result to
increased risk of premature delivery, gestational diabetes, preeclampsia, CS
ovarian hyperstimulation results to
ascites, hydrothorax, hypovolemic shock, thromboembolism, death
purified extract of FSH and LH
MENOTROPIN
Menotropin is derived from
urine of postmenopausal women
primarily FSH preparation with LH removed
UROFOLLITROPIN or uFSH
stimulates estrogen secretion more efficiently
has short half life
rFSH
rFSH available as pen that can be injected
FOLLITROPIN alpha- Gonal-f
LH substitute that induces ovulation
hCG
may only be used with rFSH follitropin alpha for stimulation of follicular development in infertile women with LH deficiency
rLH/ LUTROPIN
LUTROPIN is NOT used
to induce ovulation
to stimulate endogenous LH surge for follicular development and ovulation
not regulated by releasing hormones
posterior pituitary hormones
posterior pituitary hormone structure
nonapeptide with a circular structure due to disulfide bridges
effects of OXYTOCIN
milk ejection
induce uterine contraction
weak antidiuretc and pressor effects
onset of OXYTOCIN
fast
preparation for induction or augmentation
IV
prep for postpartum hemorrhage
IV, IM
half life of oxytocin
short, 3 mins
assess term or post-term pregnancy for fetal well being
oxytocin challenge test or contraction stress test
oxytocin AE
uterine overstimulation
hypertension
water retention
afibrogenemia
oxytocin CI
fetal distress
prematurity
abnormal fetal presentation
cephalopelvic disproportion
preparation of oxytocin
5 iu per mL , IV or IM
IV oxytocin
induction of labor
IM oxytocin
postpartum hemorrhages
induced by high plasma tonicity and low BP
vasopressin or ADH
v1 is found in
vascular smooth muscles ➡️ vasoconstriction
Gq receptor
V2 is found in
renal tubular cells
endothelium
v2 receptor activation
stimulate and inc cAMP➡️inc PKA➡️inc synthesis of aquaporin channel 2➡️inc water resorption
extrarenal v2 receptors regulate
release of factor 8 and vWF
uses of vasopressin
central diabetes insipidus
nocturnal enuresis
haemophilia A and vWF dse
variceal bleeding
central diabetes insipidus tx
0.1-0.2 mg TID DESMOPRESSIN
nocturnal enuresis tx
0.2mg at HS
AE of ADH
GIT disturbances nausea and vomiting hyponatremia vasoconstriction- angina or MI headache
parenteral ADH for pressor effect like septic shock
VASOPRESSIN
nasal spray, oral, parenteral preparation of ADH commonly used with more v2 effect
DESMOPRESSIN