Pilch_HypothalamusPituitary Flashcards
GH is CATABOLIC in which process(es) and ANABOLIC in which process(es)? Which hormone is GH the exact opposite of?
GH - Catabolic in LIPID, Anabolic in PROTEIN/MUSCLE
Opposes CORTISOL - Catabolic in PROTEIN/MUSCLE, Anabolic in LIPID
Which drug is the #1 used for GROWTH HORMONE DEFICIENCY?
rhGH (recombinant human growth hormone) - SOMATROPIN: recombinant form used bec natural form from cadavers was infected with prions
What is the administration method of SOMATROPIN?
SubQ 6-7x/wk
Somatropin’s #1 use is GH deficiency. Can it treat other conditions as well?
YES - Other conditions associated with short stature in pediatric pts NOT caused by GH Deficiency [e.g. PRADER-WILI, TURNER, NOONAN, IDIOPATHIC SHORT STATURE]
Not as robust of effects though
When a child has GH deficiency, what other conditions should he/she be checked for?
Deficiencies in OTHER Anterior pituitary hormones (e.g. CORTISOL/GONADAL) - Likely to have these other deficiencies as well
In terms of Glc control, what is the toxicity of SOMATROPIN (rhGH) and what is the toxicity of MECASERMIN (rhIGF-1)
SOMATROPIN (rhGH) - HYPERGLYCEMIA - due to TRANSIENT induction of insulin resistance
MECASERMIN (rhIGF-1) - HYPOGLYCEMIA - due to activation of insulin receptor -> Potentiation of INSULIN
Toxicity of SOMATROPIN is more severe in children or adults? What toxicity is seen?
ADULTS - PERIPHERAL EDEMA, MYALGIAS, ARTHRALGIAS (particularly of hands/wrist), carpal tunnel syndrome
Children with what type of growth failure will NOT respond to exogenous GH?
IGF-1 DEFICIENCY (All the exogenous GH won’t do anything for these pts because GH works through IGF-1)
What is the administration method of MECASERMIN?
SubQ, BID
Due to the adverse effect of HYPOGLYCEMIA when taking MECASERMIN, what is an important instruction of prescription?
Requires consumption of carbohydrate-containing meal/snack 20min BEFORE or AFTER drug administration
What is the Tx protocol of SMALL GH-secreting ADENOMAS?
GH antagonists - either SOMATOSTATIN analogs (OCTREOTRIDE, LANREOTIDE) or GH-R antagonist (PEGVISOMANT)
What is the Tx protocol of LARGER GH-SECRETING ADENOMAS?
SURGERY/RADIATION
Why are OCTREOTIDE and LANREOTIDE used instead of SOMATOSTATIN?
Analogs are used because SST gets cleared too quickly (short half-life)
OCTREOTIDE is the most widely used SST analog for acromegaly or gigantism (excess GH). Is it generally safe?
NO, lots of toxicity - BRADYCARDIA + CONDUCTION DISTURBANCES = 35%, Nausea/Vomiting/Gallstones/Cramps/Flatulence
What is the mechanism of PEGVISOMANT? Is this drug generally safe?
GH receptor antagonist - Used to treat gigantism (Before epiphyses plate closes) and acromegaly (after plate closure)
PILCH LIKES THIS, no cardiotoxicity or other toxicities
Name the 3 forms of purified FSH. Name if they are recombinant or natural.
UROFOLLITROPIN - NATURAL form extracted from urine of post-menopausal women
FOLLITROPIN alpha - Recombinant
FOLLITROPIN beta - Recombinant
*Recombinant forms have shorter half-lives and are more expensive
Name the purified form of LH. Is it natural or synthetic (recombinant)? When is it used?
LUTROPIN-alpha: RECOMBINANT synthetic form
ONLY used in combination with FOLLITROPIN-alpha to stimulate follicular dvlm in women with PROFOUND LH DEFICIENCY (for ovulation)
Name 2 purified forms of hCG. Name if they are natural or synthetic (recombinant). Which has a greater consistency of biologic activity?
- NATURAL hCG - purified from human urine (where it gets extracteD)
- CHORIOGONADOTROPIN-alpha (rhCG)- Recombinant form of hCG **greater consistent biologic activity
Which is the only ENDOGENOUS anterior pituitary hormone that can be used as reliable,consistent pharmacotherapy?
UROFOLLITROPIN - Endogenous FSH
What is the #1 use of GONADTROPIN PHARMACOTHERAPY?
CONTROLLED OVARIAN HYPERSTIMULATION (COH) in assisted reproductive procedures (e.g. IVF)
Pt tries CLOMIPHENE, but it doesn’t work as well. Pt tries GONADOTROPIN therapy finally. What condition is this targeting?
ANOVULATORY WOMEN - To induce ovulation in infertile women
To stimulate spermatogenesis in men
In women treated with hCG and GONADOTROPINS, what are the two most serious complications? Which one is more serious? Why?
- OVARIAN HYPERSTIMULATION SYNDROME **More serious - Ovarian enlargement -> Ascites, hydrothorax (serous fluid accumulates in pleural cavity=pleural effusion), hypovolemia -> SHOCK
- Multiple pregnancies
What conditions are GnRH agonists used for?
- ENDOMETRIOSIS
- UTERINE LEIOMYOMATA (FIBROIDS)
- PROSTATE CANCER
- CENTRAL PRECOCIOUS PUBERTY
Name the GnRH agonists, if they’re synthetic or recombinant.
- NATURAL GnrH (GONADRELIN)
- SYNTHETIC GnRH agonists (-Relins + Leuprolide): GOSERELIN, HISTRELIN, LEUPROLIDE, NAFARELIN, TRIPTORELIN - MORE POTENT/LONGER LASTING than gonadorelin
What is the mechanism of GnRH agonists?
SUSTAINED, NON-PULSATILE GnRH or GnRH agonists INHIBIT AP release of FSH/LH bec PULSATILE GnRH is required for the stimulation of production and release of FSH/LH
Name the 3 GnRH agonists approved for ENDOMETRIOSIS. How do they work
‘GLN’
GOSERELIN, LEUPROLIE, NAFARELIN.
Inhibit the prdn/release of FSH/LH -> REDUCE Estrogen/Progesterone levels responsible for the pain/bleeding of endometrial tissue that implanted OUTSIDE the uterus
What are UTERINE FIBROIDS? What is the clinical triad of UTERINE FIBROIDS?
BENIGN, Estrogen-sensitive, Uterine fibrous growths IN UTERUS
Clinical Triad: MENORRHAGIA (hyperbleeding) + ANEMIA + PELVIC PAIN
What is the Tx protocol of UTERINE FIBROIDS?
Same as Endometriosis (GOSERELIN/LEUPROLIDE/NAFARELIN) + Supplemental Fe for the anemia for 3-6mo
(Will reduce fibroid size)
What is the main goal of therapy for PROSTATE CANCER?
REDUCE TESTOSTERONE LVLS
What is the FIRST LINE pharmacological therapy of prostate cancer? What is the standard protocol for COMBINED pharm therapy? What drug is given in Sx ADVANCED PROSTATE CANCER?
FIRST-LINE = Anti-Androgens by ANDROGEN-Receptor antagonists [BF - BICALUTAMIDE/FLUTAMIDE]
COMBINED = BF + GnRH agonists [Goserelin/Leuprolide/Nafarelin + HISTRELIN] since DECREASED LH = DECREASED testosterone
Sx ADVANCED Prostate cancer - GnRH receptor ANTAGONIST (DEGARELIX)
What is the unique GnRH agonist that can be used in combination pharm therapy for PROSTATE CANCER?
HISTRELIN
What are the 2 indications of continuous GnRH agonist Tx for CENTRAL PRECOCIOUS PUBERTY?
- Child whose FINAL HEIGHT would be greatly compromised (evidenced by advanced bone age)
- Child who has EMOTIONAL DISTRESS due to pubertal secondary sexual characteristics/menses
Which GnRH agonists are used for continuous Tx of CENTRAL PRECOCIOUS PUBERTY? What is the method of administration?
MONTHLY IM depot injection of
LEUPROLIDE + HISTRELIN
When is the continuous Tx of LEUPROLIDE or HISTRELIN for pts with CENTRAL PRECOCIOUS PUBERTY generally continued until?
GIRLS - age 11
BOYS - age 12
Which side effect is of MOST CONCERN for both women and men with GnRH agonist therapy (-RELINS + LEUPROLIDE)?
Reduced BONE DENSITY (due to decreased Estrogen) -> OSTEOPOROSIS
Name the 3 GnRH RECEPTOR ANTAGONISTS. Do they have better or worse efficacy than GnRH agonists?
-RELIX(es): GCD - GANIRELIX, CETRORELIX, DEGARELIX
Inhibits FSH and LH secretion with BETTER efficacy than GnRH agonists (more dose-dependent and complete)
What type of side effects are generally seen with GnRH AGONIST + GnRH RECEPTOR ANTAGONIST therapy?
MENOPAUSAL Sx - hot flashes, edema, headaches, night sweats, decreased libido, depression, vaginal dryness
Name the 2 DOPAMINE AGONISTS.
BROMOCRIPTINE
CABERGOLINE
What is the #1 usage of DA agonists?
HYPERPROLACTINEMIA (due to Prolactin-secreting adenomas)
How does HYPERPROLACTINEMIA affect women? How does it affect men?
WOMEN: Amenorrhea (less bleeding) + Galactorrhea (excess milk prdn)
MEN: Decreased libido + Infertility
Are BROMOCRIPTINE and CABERGOLINE efficacious for hyper Prolactin-secreting microadenomas? For macroadenomas?
YES, efficacious for both reducing the size of MICROADENOMAS and MACROADENOMAS (unlike small vs large GH-secreting adenomas where pharamacotherapy is ineffective in larger GH-secreting adenomas)
Are BROMOCRIPTINE/CABERGOLINE well-tolerated in terms of side effects? Which one is better tolerated?
NO, lots of toxicity - nausea, headache/light-headedness, orthostatic hypotension/fatigue
CABERGOLINE is better tolerated (Due to LESS NAUSEA)
What is the #1 reason for BROMOCRIPTINE/CABERGOLINE discontinuation in pts with hyperprolactinemia? How can the side effect be relieved?
NAUSEA
Generally can be relieved by VAGINAL administration
Even though CABERGOLINE is more well-tolerated in terms of nausea, which pt population is it absolutely CONTRAINDICATED in?
Pre-existing VALVULAR Disease (Cabergoline is associated with CARDIAC VALVULOPATHY)
Name the synthetic OXYTOCIN drug.
PITOCIN
What are the 2 usages of PITOCIN (synthetic oxytocin)?
- INDUCING LABOR in women requiring early vaginal delivery
2. CONTROLLING UTERINE HEMORRHAGE - Since Oxytocin increases frequency + force of uterine contractions**
What conditions may lead to early vaginal delivery and thus mandate PITOCIN (synthetic oxytocin) therapy?
UNCONTROLLED MATERNAL DIABETES
WORSENING PRE-ECLAMPSIA
INTRAUTERINE INFECTION
What are two physiological processes that may occur resulting in the potentially severe toxic complications of PITOCIN (synthetic oxytocin)?
- EXCESSIVE UTERINE CONTRACTION (Too much oxytocin)
- > Fetal distress, placental abruption, uterine rupture - INADVERTENT ADH-R ACTIVATION (Activation of a diff posterior pituitary receptor) -> Hypervolemic Dilutional Hyponatremia + Heart Failure + Seizures
What are the CONTRAINDICATIONS of synthetic oxytocin therapy?
FETAL DISTRESS/Abnormal fetal presentation
CEPHALOPELVIC DISPROPORTION
Other predispositions of UTERINE RUPTURE
Which conditions are GnRH ANTAGONISTS used for? Which specific ones are used?
- CONTROLLED OVARIAN HYPERSTIMULATION in assisted reproductive procedures - Lower OHS risk than GnRH agonists = GC (GANIRELIX, CETRORELIX)
- Sx ADVANCED PROSTATE CANCER - DEGARELIX