Pharm 1 Pituitary Flashcards
Growth Hormone regulation
++ GRH
– Somatostatin (SRIF, somatotropin release-inhibiting factor)
Somatostatin functions (GI, brain)
- Suppress basically every GI hormone
- Inhibit GH, TSH secretion (not synthesis)
Somatostatin regulation
++ low pH
Posterior pituitary hormones
Vasopressin (ADH)
Growth hormone synonym
Somatotropin
Growth hormone replacement
Species specific (only human)
- Risk of CJD
- Use synthetic (recombinant rhGH)
Growth hormone feedback mechanism
Liver IGF-1 (insulin-like growth factor)
2 ways to induce SRIF
IGF-1
B-agonist
GH actions
- Synthesize chondroitin and collagen
- Grow bone and soft tissue
- Renal retain N, K, PO4
GH MOA (important)
Cytokine membrane receptors ->
a) IGF-1 (mitogen & antiapoptogen)
b) + triglyceride hydrolysis, insulin resistance, protein synthesis
IGF-1 v IGF-2
Adult vs infant
GH interaction with diabetes
Causes more problems in morning (GH secreted at night)
Most common pituitary tumor
Prolactinoma
Age associated GH pathology
Up to 1/3 of elderly
Gigantism
GH hypersecretion before fusion of epiphysis
Acromegaly enlargements
Head, face, hands, feet, thorax
Acromegaly clinical
- Carpal tunnel syndrome
- Hypogonadism
- Glucose intolerance and hyperinsulinemia
- Heat intolerance, sweating, fatigue, lethargy
rhGH therapeutic uses
- GH deficient patients
- Very short children with normal GH
- HIV related wasting or cachexia
Prader-Willi syndrome
Parental allele not expressed (chromosome 15 unbalanced)
-Retardation, obesity, hypogonadism, hypotonia
AngelMan’s syndrome
Maternal allele not expressed (15)
-Retardation, inappropriate laughter, ataxic gait, seizures
Prader-willi and AngelMan’s pathology
Disorder of genomic Imprinting (silencing of paternal/maternal alleles)
-rhGH-
administration
adverse effects
- Subcutaneous
- Carpal tunnel, arthralgia in adults
- few AE in children
- NO hyperglycemia
-rhIGH-1-
receptor
Tetrameric receptor autophosphorylation (like insulin)
-rhIGH-1-
indication
administration
contraindications
- Children who don’t respond to GH
- Subcutaneously before or after meal (prevent hypoglycemia)
- Neoplasia; closed Epiphyses
Somatostatin drug
Octreotide
Octreotide advantages over somatostatin
Increased half life (1.7 hours v 1-3 minutes)
Somatostatin production
- Hypothalamic anterior periventricular nucleus
- Pancreas Delta cells
Somatostatin (octreotide) MOA
Gi-protein -> decrease cAMP -> decrease GH, TSH secretion
Octreotide indications
- Acromegaly after surgery
- Carcinoid tumors
- VIPomas (pancreas)
VIPoma pathology
WDHA syndrome
- Watery Diarrhea (dehydration)
- Hypokalemia
- Achlorhydria
Octreotide AE
GI disturbances
Reduced bile, gallbladder contractility
-Pegvisomant-
indication
MOA
Cindication
- Acromegaly (most effective Tx)
- Prevent GH-R dimerization and signaling (rhGH analog)
- Liver dysfunciton
Measure effectiveness of acromegaly Tx
-Normalize IGF-1 levels
3 Tx for acromegaly
Somatostatin GH analog (receptor antagonist) Dopamine agonist (Bromocriptine)
Prolactinoma hypogonadism mechanism
hyperprolactinemia inhibits pulsatile GnRH secretion
Prolactinoma Tx
Cabergoline (more effective than bromo)
-Also helps GH hypersecretion
Drug for LH
hCG (human chorionic gonadotropin)
Drug for LH & FSH
hMG; menotropin (human menopausal gonadotropin)
Drug for FSH
rFSH (recombinant FSH)
uFSH (Urofollitropin; menotropin with LH removed)
FSH action (female, male)
- Stimulate ovarian follicle development
- Stimulate androgen-binding globulin (maintain T levels in testes)
LH action (female, male)
- Stimulate production of estrogen and progesterone
- induce ovulation
- Stimulate production of testosterone
Ovarian stimulation routine
FSH for 6-12 days followed by LH for 1 day
OHSS - Ovarian hyperstimulation syndrome
Increase in vascular permeability -> rapid fluid accumulation in peritoneum, thorax, pericardium
-Clomiphene-
indication
MOA
Estrogen receptor competitive inhibitor
- infertility (non hormonal)
- Decrease estrogen negative feedback -> increase pulsatile LH, FSH
Clomiphene similar drug
Tamoxifen
-Leuprolide Acetate-
MOA
indication
Synthetic GnRH -> downregulate GnRH-R -> suppress LH/FSH release
- Precocious puberty, ovarian cyst, prostate cancer
- suppress endogenous LH surges during menotropin Tx
-Leuprolide Acetate-
t1/2
AE
- 3 hours (normal GnRH is 5 minutes)
- Early menopause - hypogonadism, osteoporosis, hyperglycemia
-Ganirelix Acetate-
indication
GnRH-R antagonist (analog)
-inhibit premature LH surges during controlled ovulation
Posterior pituitary
Nerve endings from
- Supraoptic hypothalamus (oxytocin)
- Paraventricular hypothalamus (vasopressin)
Vasopressin synonyms
AVP (arginine vasopressin)
ADH
AVP inhibitor
Ethanol
Phenytoin
AVP stimulator
Nicotine
Epinephrine
Angiotensin II
AVP MOA
V1a - contract vascular and GI smooth muscle
V1b - ACTH secretion by a.pituitary
V2 -> cAMP -> collecting duct aquaporins
AVP dosing
V2 effects at much lower concentrations than V1
(V1 probably for extreme hypovolemia & hypotension)
-both circulate plasma unbound
-Desmopressin-
indication
Synthetic AVP
- Tx Diabetes Insipidus (central, not nephrogenic)
- differentiate btwn central and nephrogenic DI
-Desmopressin-
t1/2
administration
- 12-24 hours (AVP is 15 minutes)
- Oral or subcutaneous
-Desmopressin-
AE
Primarily due to V1 effects
- Vessel constriction
- GI stimulation
- Uterine contraction (oxytocin cross-rxn)
Uses for Vasopressin (not desmopressin)
- Post-operative Ileus, dispel abd. gas before imaging
- Emergency Tx of hemorrhagic varices/gastritis
SIADH Tx (non drug)
- Water restriction
- IV hypertonic saline
- Loop diuretics
-Demeclocycline-
Antibiotic
- Reduces renal AVP sensitivity (Tx SIADH)
- SE nephrotoxicity
SIADH Tx (drug)
- Conivaptan (V-R antagonist)
- Tolvaptan (V2-R selective antagonist)
Oxytocin main stimulation
- Parturition (distention), suckling
- Plasma hypertonicity, hemorrhage
Oxytocin inhibition
Opioids
Pain
Heat
Oxytocin action
- Uterine contraction
- Mammary myoepithelial contraction
Oxytocin MOA
G-protein (phospholipase C)
-Oxytocin-
indication
- Induction of term labor
- Control of postpartum bleeding
- Increasing milk ejection
-Oxytocin-
AE
-Uterine rupture, infant trauma (monitor closely)
Other uterine stimulators
- Methylergonovine (2nd line for bleeding; CI in HTN)
- Dinoprostone (PGE - for abortion)
- Carboprost (PGF - for bleeding and abortion)
-Terbutaline-
B2-agonist (asthma)
-used to delay pre-term labor