Pharmacology Unit 4 - Endocrine Pt. 1 Flashcards
What hormones are released from the anterior pituitary gland?
- GH
- ACTH
- FSH
- TSH
- LH
- Prolactin
the __________________ receives signal/stimulation from hypothalamus to synthesize a hormone and release it
anterior pituitary (adenohyphysis)
what hormones are released from the posterior pituitary
Oxytocin & ADH (vasopressin)
T/F: hormones that are released from the posterior pituitary are also synthesized there
false; they are synthesized in the hypothalamus and then stored and released from the posterior pituitary
what inhibits growth hormone release from the anterior pituitary?
somatostatin
________________ is a medication that is analogous to growth hormone and is considered an agonist
somatotropin
Growth hormone stimulates ________________
Insulin Like Growth Factor
_______________ inhibits the release of prolactin
dopamine
pharmacology is applied to the pituitary hormones and glands in what 3 ways?
- replacement therapy for deficiency
- antagonists for excessive disease states
- Diagnostic tools
what medication is used in the treatment of IGF deficiency not responsive to Growth Hormone?
Mecasermin
anabolic effects of growth hormone occur in ___________________
muscle
catabolic effects of growth hormone occurs in ___________________
lipid cells
_____________________ is d/t a growth hormone deficiency in females
turners syndrome
__________________ is a genetic disease associated with growth failure, obesity, and carbohydrate intolerance
Prader willi syndrome
Growth Hormone increases _________________, thus higher doses of certain medications metabolized in this capacity may be required
CYP450
What is acromegaly
abnormal growth of cartilage and bone tissue after epiphyseal plate closure (30-50 years old)
what is gigantism
GH secretion (likely d/t adenoma) occuring in childhood before epiphyseal plate closure
how does octreotide affect insulin secretion?
reduces insulin secretion d/t somatostatin inhibiting GH
How do FSH, LH, and hCG signal transduce?
G-coupled protein receptors
what are the 3 classes of hormones?
- peptides
- amines
- steroids
which class of hormones are water soluble
peptides
which class of hormones are fat soluble
amines & steroids
name the hormones which are “amines”
- serotonin
- thyroid hormones
- catecholamines
name the hormones which are “steroids”
- glucocorticoids
- mineralcorticoids
- androgens
- estrogens and progestins
what amino acid are most “amine” hormones derived from?
tyrosine
most “amine” hormones are derived from the same amino acid; however, serotonin is an amine that is derived from __________________
tryptophan
which hormone class is synthesized and released on demand and is not stored in vesicles?
steroids
what are the 3 hormone signaling pathways?
- endocrine function
- paracrine function
- autocrine function
__________________ is a hormone signaling mechanism in which transmission of hormone signal goes through the blood stream to a distant target cell
Endocrine signaling (function)
________________ is a hormone signaling mechanism in which the hormone signal acts on neighboring cells of a different type
paracrine signaling (function)
__________________ is a hormone signaling mechanism in which the hormone secreted acts on the producer cell itself or on neighboring identical cells
autocrine
what is the target tissue of growth hormone
liver and most other tissues
what is the target tissue of ACTH
adrenal cortex
what is the target tissue of TSH
thyroid gland
what is the target tissue of FSH
ovaries
what is the target tissue of LH
ovaries and testes
what is the target tissue of prolactin
mammary glands
growth hormone stimulates the release of what in the liver
insulin like growth factors
ACTH will stimulate the adrenal cortex to release what
glucocorticoids, mineralcorticoids, and androgens
TSH will stimulate the thyroid to release what?
thyroxine (T3/T4)
the hypothalamus stimulates two hormones which regulate GH, ___________ which stimulates the production of GH, and _____________ which inhibits the production of GH
GHRH; somatostatin
growth promoting effects of GH are mediated principally through an increased production of ____________
IGF-1
GH stimulates what?
- IGF-1 production in bone, cartilage, muscle, kidney, and other tissues
- longitudinal bone growth
- anabolic effects in muscle
- catabolic effects in lipid cells
in turners syndrome treatment, in order to achieve maximal height _____________ must be started in conjunction with growth hormone to achieve maximum height
gonadal steroids (d/t absence of ovaries)
prader willi syndrome is a _____________________ genetic disease
autosomal dominant
T/F: the long term effects of growth hormone treatment in childhood is unknown
true
some adverse effects of somatropin?
- edema
- hyperglycemia
- pancreatitis
- gynecomastia
- increased CYP450 enzymes
contraindications of somatropin
- patients with known malignancy
- critically ill pts (increases mortality)
______________ is a GH hormone agonist that is a recombinant human IGF-1
mecasermin
primary adverse effect of mecasermin
hypoglycemia
what are GH antagonists used for
- to reverse the effects of GH secreting cells (somatotrophs) from the anterior pituitary.
- Tx GH non-cancerous adenomas that cause acromegaly and/or gigantism
what are the three growth hormone antagonist tx options (in order for how they should be implemented)
- Endoscopic transphenoidal surgery
- medical therapy if surgery unsuccessful
- radiation
what are the drugs used as growth hormone antagonists
- somatostatin analogues: Octreotide and Lanreotide
- dopamine receptor agonists
- GH receptor antagonists (Pegvisomat)
what is the most widely used Somatostain analogue
octreotide
which drug is 2x more potent than somatostatin at decreasing insulin secretion from pancreatic beta cells?
octreotide
adverse effects of octreotide
- GI effects
- biliary sludge –> gall stones
- bradycardia
- conduction defects
- B12 deficiency
_________________ is used in the tx of acromegaly. It decreases GH levels and normalizes IGF-1 concentrations
Lanreotide
fx of LH/FSH (gonadotropins)
- stimulate spermatogensis in men
- induce ovarian follicle development in women
what is the most common clinical use of LH/FSH
controlled ovarian stimulation for in-vitro fertilization
________________ is a placental glycoprotein nearly identical to LH, and actions are mediated through LH receptors
hCG
what is the primary treatment for male and female infertility
gonadotropins and hCG
_______________ GnRH secretion is required to stimulate the gondatroph cell to produce and release LH and FSH
pulsatile
what happens if you have continous nonpulsatile administration of GnRH or GnRH analogs?
inhibits the release of FSH and LH by the pituitary in males and females –> desensitization and down regulation –>shut down of AP –> hypogonadism
What is the most widely used GnRH agonist
Gonadorelin
Gonadorelin is a synthetic ____________, that causes the release of ________&___________
GnRH; LH; FSH
continuous administration of gonadorelin (or longer acting analogus) produces a biphasic response which are:
- flare
- inhibitory action of the continuous presence of GnRH
how long is a GnRH agonist (like gonadorelin) expected to produce the “flare” response
7-10 days
what happens in the first part of the biphasic response, “Flare”, with GnRH agonists (like gonadorelin)
produces increased concentration of gonadal hormones
when would you use a GnRH analogue to stimulate the production of gondatrophins
- female infertility
- male infertility
- diagnosis of LH responsiveness (delayed puberty)
when would you use GnRH antagonists to suppress gonadotropic release/production?
- endometriosis
- prostate cancer
- central precocious (early) puberty (female 8; male 9)
- breast and ovarian cancer
GnRH receptor antagonists end in _____________
”- relix”
GnRH receptor antagonist meds produce a _____________________ of the secretion of FSH and LH
dose dependent inhibition
advantages of GnRH receptor antagonists over Agonists
- immediate antagonist effect results in shorter use time
- less suppressive effect on ovarian response to gonadotropin (decrease total duration and dose)
- reduces the concentrations of gondatropin and androgens more rapidly that GnRH agonists
- no testosterone surge
what is the principle hormone responsible for lactation
prolactin
hyperprolactinemia can result from ________________
prolactin secreting adenomas
what is the effect of hyperprolactinemia in males
loss of libido and infertility
what is the effect of hyperprolactinemia in females
amenorrhea and Galactorrhea
____________________ are medications that act in the pituitary to inhibit prolactin release
dopamine agonists
what are your dopamine agonists
- bromocriptine
- cabergoline
- quinagolide
what is the half life of bromocriptine
7 hours
what is the half life of cabergoline
65 hours
what is the half life for quinagolide
20 hours
high doses of ergot derivative dopamine agonists (bromocriptine, cabergoline, and Quinagolide) can cause ____________________; which means the anesthesia provider should move __________________
cold-induced peripheral digital vasospasm; pulse ox to ear or nose
where is vasopressin (ADH) and oxytocin synthesized
in the neuronal cell bodies of the hypothalamus
what are the 2 primary reasons oxytocin is used?
- stimulate uterine contractions
- milk letdown
post-C section, the anesthesia provider should immediately start what drug to reduce the risk of post-partum hemorrhage
pitocin (oxytocin)
what drug is an oxytocin antagonist, and is approved outside the US for preterm labor tx
atosiban
Vasopressin acts on which G-coupled protein receptor
V1
Desmopressin Acetate acts on which G protein coupled receptor
V2
V1 receptors
- on vascular smooth muscle cells
- causes vasoconstriction (via Gq)
V2 receptors
- on renal tubule cells
- reduces diuresis through increasing water resorption in CD (via Gs)
- Extrarenal V2 regulate the release of cogaulation factors VIII, and vWF
what are your Vasopressin (ADH) antagonist drugs
“-vaptan”
- Conivaptan
- Tolvaptan
______________ is a vasopressin (ADH) antagonist that has a high affinity for both V1 and V2 receptors
Conivaptan
_______________ is a vasopressin (ADH) antagonist that has a 30-fold higher affinity for V2 than V1
Tolvaptan
Conivaptan and Tolvaptan are both FDA approved for IV administration in the tx of ______________
hyponatremia
what are the 3 zones of the adrenal cortex
- zona glomerulosa
- zona fasiculata
- zona reticularis
what is secreted from the zona glomerulosa
aldosterone (mineralcorticoids)
what is secreted from the zona fasciculata
cortisol (glucocorticoids)
what is secreted from the zona reticularis
androgens
decrease in adrenocortical hormone = _________________, and an increase in adrenocortical hormone = _________________
addisons; Cushings
what are the 3 major hormones secreted from the adrenal gland
- mineralcorticoids (aldo)
- glucocorticoids (cortisol)
- androgens
all adrenal hormones are made from the precursor __________________
cholesterol
what is the fx of glucocorticoids (cortisol)
important effects on metabolism, CV function, growth, and immune function
what is the primary fx of mineralcorticoids (aldo)
salt and water retaining activity
the peak of cortisol secretion ins in the ___________
morning; fall throughout the day
when are patient most sensitive to dosing of exogenous steroids?
at night, due to the decline of endogenous steroids in the eventing
cortisol is 90% bound to ______________, and 5% bound to ____________
corticosteroid binding protein (CBG); albumin
5% of endogenous cortisol is bound to ______________; however, the synthetic cortisol is signifcantly more bound to this protein
albumin
_______________ is an exogenonous cortisol agonist that is used to prevent inflammation, high risk PONV, and peds undergoing tonsillectomy/adenoidectomy
dexamethasone (decadron)
dexmethasone (decadron) is primarily bound to what protein
albumin
what are the physiologic effects (pharmacodynamics) of cortisol
- metabolic
- catabolic and anabolic
- anti-inflammatory
- immunosuppressive
chronic corticosteroid therapy can lead to:
- insomnia, euphoria, depression, and increased ICP
- suppression of ACTH, GH, TSH, and LH (d/t desensitization)
- PUD
- fat redistribution to viscera, face, nape of of neck and supraclavicular
- antagonize the effects of vitamin D on calcium absorption
- increases RBCs and plts
how does cortisol decrease inflammation
- catabolizes proteins that cause inflammation
- anti-anabolic of things that cause inflammation
- profound effects on the concentration, distribution, and fx of peripheral leukocytes
- suppressive effects on inflammatory cytokines, chemokines, and other inflammatory mediators
describe the immunosuppressive effect of a single dose of short acting glucocorticoids (cortisol)
- increase neutrophil concentration
- decrease lymphocytes, monocytes, eosinophils, and basophils
the peak effect of single dose short acting glucocorticoid is ________, and then it decreases starting at _____
6hrs; 24 hrs
what is a “large dose” glucocorticoid
20 mg/d of prednisone
immunosuppresive effect of large dose glucocorticoids ?
decreases antibody production, which decreases phagocytosis ability, decreases TNF-alpha, decreases interleukins, metalloproteins, and plasminogen factor
immunosuppressive effects of cortisol
- inhibits phospholipase A2
- decreases COX2 –> decreased prostaglandins
- vasoconstriction (transdermal)
what is the net effect of cortisol?
to maintain adequate glucose supply to the brain
cortisol deficiency has really important implications on ____________________
fetal lung development
_________________ is adjunct in the creation of surfactant
cortisol
which drug should you give for fetal lung development?
betamethasone
what is the prodrug of synthetic corticosteroids?
prednisone
prednisone is rapidly converted to _________________ (active product) in the body
prednisolone
which are your short-to-medium acting glucocorticoids
- hydrocortisone
- prednisone
- methylprednisolone
what are your long acting glucocorticoids
- betamethasone
- dexmethasone
which are your synthetic corticosteroids that are mineralcorticoids
fludrocortisone
which synthetic corticosteroid has the highest anti-inflammatory properties
- betamethasone (25-40)
- Dexmethasone (30)
which synthetic corticosteroid is the best for increasing salt retention
fludrocortisone
if a patient comes in for surgery on chronic steroids, you supplement intraoperatively with ______________, and give ___________ the amount of what they normally take the day of surgery
hydrocortisone; 2x
