Pituitary Flashcards
GH MOA
Physiologic effects are exerted either directly or mediated through somatomedins (Insulin-like growth factors-IGF-1 and IGF-2)
In acromegaly, IGF-1 levels are consistently high, reflecting elevated GH
Therapeutic uses of GH
Congenital/acquired GH deficiency (Dwarfism)
Prader-Willi syndrome
GH deficiency in adults
AIDS related muscle wasting and cachexia
Turner syndrome (to stimulate growth)
Idiopathic short stature (in children)
also approved for treatment of patients with short bowel syndrome (with glutamine)
used by athletes for a purported increase in muscle mass and athletic performance- one of the drugs banned by the Olympic Committee
FDA also approved in 1993 the use of recombinant bovine Growth Hormone (rbGH) in dairy cattle to increase milk production
GH ADR in children
Increased Intracranial tension Papilledema Headache Hypothyroidism*** Scoliosis DM
GH ADR in adults
Peripheral edema Arthralgia Myalgia Carpal tunnel syndrome DM
GH contraindication
Obese patients
Patients with closed epiphyses who do not have GH deficiency
Patients with a known malignancy
Mecasermin
recombinant human (rh) IGF-1
Mecasermin approved for the treatment of patients with?
GH deficiency with antibodies against GH
severe IGF-1 deficiency that is not responsive to GH
mutations in the GH receptor
primary IGF-1 deficiency
Most common ADR of mecasermin
hypoglycemia
take food 20 min before or after administration of the drug
Octerotide
a synthetic octapeptide analog of somatostatin
more potency and longer half-life than the natural compound (Somatostatin)
Octerotide used in?
treatment of acromegaly and gigantism caused by hormone-secreting tumors, pituitary tumors that secrete thyroid stimulating hormone (thyrotropinoma)
hypersecretory diarrheas associated with tumors producing the vasoactive intestinal peptide (VIPomas), Carcionoid syndrome
useful in acute variceal bleeding
Lanreotide
Long acting octreotide
ADR of somatostatin analogs
Gi problems
Gall stones
Vit B12 deficiency on long term use
Pegvisomant
GH receptor antagonist [recombinant polyethylene glycol (PEG) variant GH (mutant GH)]
acts as an antagonist at GH receptors
Pegvisomant used in?
treatment of acromegaly that is refractory to other modes of surgical, radiologic, or pharmacologic intervention
Gonadorelin
Short acting GnRH analog
Gonadorelin uses
“Pulsatile”manner to stimulate pituitary to secrete FSH and LH; (however, continuous administration inhibits FSH and LH release)
Diagnostic purpose (hypogonadism)
Female infertility: to induce ovulation and treat infertility in women with Hypothalamic amenorrhea
Male infertility
Goserelin, Nadarelin, Leuprolide, Histrelin, Triptorelin
Long acting Synthetic GnRH analogue
After initial stimulation, they will cause suppression of gonadotropin (FSH, LH) release.
Uses of long acting GnRH
Precocious puberty Breast Ca Prostate Ca Uterine leiomyomata (uterine fibroids) Endometriosis
AdR of GnRH analogue
gonadorelin: hypersensitivity, dermatitis and headache
In women, the analogs may cause:
hot flushes and sweating
diminished libido, depression and ovarian cysts
Ganirelix, Cetrorelix, Abarelix, Degarelix
competitive antagonists at GnRH receptors
inhibit the secretion of FSH and LH in a dose-dependent manner
do not cause surge of testosterone or estradiol upon initiation of therapy
approved for preventing the LH surge during controlled ovarian stimulation (for the purpose of assisted reproductive technologies such IVF)
given SC or IM
Menotropins
Gonadotropin prep:
(human menopausal gonadotropins, hMG) (LH + FSH)- obtained from the urine of menopausal women
.Largely being replaced by recombinant Gonadotropins
hCG
gonadotropin prep:
Human chorionic gonadotropin) - a placental hormone, has LH like activity
- also excreted in urine and acts as an LH agonist
Urofollitropin
FSH obtained from menopausal women and is devoid of LH activity
Follitropin
human FSH manufactured by recombinant DNA technology
Gonadotropin prep uses
Infertility
Assisted reproductive techniques (ART)
Menotropins are used in concert with hCG to stimulate ovulation in women with functioning ovaries
hCG can be used both in men and women to stimulate gonadal steroidogenesis in cases of LH insufficiency
Cryptorchidism*** (undescended testes) – hCG
hCG- can also be used to induce sexual maturation and spermatogenesis in men with secondary hypogonadism (requires months of treatment)
Gonadotropin prep ADR
Multiple Births
Ovarian enlargement
OHSS (ovarian hyper-stimulation syndrome) Hypovolemia Electrolyte imbalance Fluid accumulation (ascites) Acute respiratory distress syndrome Shock
Gynecomastia
Prolactin releasing factor
Antipyschotics (Chlorpromazine and halopreridol), antidepressants (Imipramine) increase prolactin secretion
Drugs that promote prolactin secretion are used to treat lactation failure
Prolactin inhibiting factor
Prolactin secretion can be inhibited by a number of dopamine agonists
Bromocriptine PIF
acts as an agonist at dopamine D2 receptors
Cabergoline PIF
potent D2 agonist - more effective in reducing hyperprolactinemia than bromocriptine
Pergolide PIF
nonselective agonist at both D1 and D2 receptors
PIF uses
- Hyperprolactinemia
inhibition of prolactin secretion in amenorrhea, galactorrhea, and prolactin-secreting tumors
also to correct female infertility secondary to hyperprolactinemia
- Parkinsonism
- Acromegaly
- dose required is higher than those used to treat hyperprolactinemia - To suppress physiologic lactation
- to prevent breast engorgement when breast feeding is not desired
Oxytocin theraputic uses
for induction and maintenance of labor
to control post-partum hemorrhage
Oxytocin ADR
Fetal distress, placental abruption and uterine rupture (due to excessive uterine contraction)
Fluid retention/water intoxication, leading to heart failure, hyponatremia, seizures and death (due to activation of vasopressin receptors in high concentration); fetal death
contraindicated in fetal distress, abnormal fetal presentation, prematurity and CPD (cephalo-pelvic disproportion)
Atosiban
Oxytocin antagonist, a nonapeptide
Tocolytic agent
Used in preterm labor (tocolysis)
Vasopressin receptors
V1a*** (vascular smooth muscle)
V1b (CNS and adrenal medulla) &
V2*** (renal tubules) : coupled to increased cAMP (increased water permeability and reasorption in the collecting tubules)
Extrarenal V2 receptors: mediate the release of coagulation factor VIII and Von willebrand factor
V1: coupled to increased inositide turnover and increased intracellular Ca2+
vasoconstriction
Drugs enhancing ADH secretion
NSAIDs
Carbamazepine
Vinca alkaloids
Drugs inhibiting ADH
Lithium
Demeclocycline
Therapeutic uses of vasopressin
Pituitary diabetes insipidus (neurogenic diabetes insipidus)
Desmopressin
long acting, vasopressin synthetic analog
more ADH action (V2 receptor) and much less vasoconstrictive (V1 receptor) effect (4000:1)
extrarenal V2 receptors mediate the release of coagulation factor – von Willebrand factor- hence useful in the treatment of coagulopathy in hemophilia A and von Willebrand’s disease
Nasal spray is available for
Neurogenic diabetes insipidus
Nocturnal Enuresis
ADR vasppressin
Water intoxication
Hyponatremia
Headache, tremor and bronchoconstriction
Caution must be used when treating patients with coronary artery disease, epilepsy and asthma
Conivaptan, Tolvaptan
ADH antagonists:
Conivaptan: approved for use in SIADH
Tolvaptan: has a 30-fold higher affinity for V2 than for V1 receptors.
Approved by FDA in 2009
