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STEP 8: EndoRepro PATHOMA FA > Pilch_HypothalamusPituitary > Flashcards

Pilch_HypothalamusPituitary Flashcards

1
Q

GH is CATABOLIC in which process(es) and ANABOLIC in which process(es)? Which hormone is GH the exact opposite of?

A

GH - Catabolic in LIPID, Anabolic in PROTEIN/MUSCLE

Opposes CORTISOL - Catabolic in PROTEIN/MUSCLE, Anabolic in LIPID

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2
Q

Which drug is the #1 used for GROWTH HORMONE DEFICIENCY?

A

rhGH (recombinant human growth hormone) - SOMATROPIN: recombinant form used bec natural form from cadavers was infected with prions

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3
Q

What is the administration method of SOMATROPIN?

A

SubQ 6-7x/wk

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4
Q

Somatropin’s #1 use is GH deficiency. Can it treat other conditions as well?

A

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

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5
Q

When a child has GH deficiency, what other conditions should he/she be checked for?

A

Deficiencies in OTHER Anterior pituitary hormones (e.g. CORTISOL/GONADAL) - Likely to have these other deficiencies as well

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6
Q

In terms of Glc control, what is the toxicity of SOMATROPIN (rhGH) and what is the toxicity of MECASERMIN (rhIGF-1)

A

SOMATROPIN (rhGH) - HYPERGLYCEMIA - due to TRANSIENT induction of insulin resistance
MECASERMIN (rhIGF-1) - HYPOGLYCEMIA - due to activation of insulin receptor -> Potentiation of INSULIN

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7
Q

Toxicity of SOMATROPIN is more severe in children or adults? What toxicity is seen?

A

ADULTS - PERIPHERAL EDEMA, MYALGIAS, ARTHRALGIAS (particularly of hands/wrist), carpal tunnel syndrome

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8
Q

Children with what type of growth failure will NOT respond to exogenous GH?

A

IGF-1 DEFICIENCY (All the exogenous GH won’t do anything for these pts because GH works through IGF-1)

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9
Q

What is the administration method of MECASERMIN?

A

SubQ, BID

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10
Q

Due to the adverse effect of HYPOGLYCEMIA when taking MECASERMIN, what is an important instruction of prescription?

A

Requires consumption of carbohydrate-containing meal/snack 20min BEFORE or AFTER drug administration

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11
Q

What is the Tx protocol of SMALL GH-secreting ADENOMAS?

A

GH antagonists - either SOMATOSTATIN analogs (OCTREOTRIDE, LANREOTIDE) or GH-R antagonist (PEGVISOMANT)

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12
Q

What is the Tx protocol of LARGER GH-SECRETING ADENOMAS?

A

SURGERY/RADIATION

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12
Q

Why are OCTREOTIDE and LANREOTIDE used instead of SOMATOSTATIN?

A

Analogs are used because SST gets cleared too quickly (short half-life)

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13
Q

OCTREOTIDE is the most widely used SST analog for acromegaly or gigantism (excess GH). Is it generally safe?

A

NO, lots of toxicity - BRADYCARDIA + CONDUCTION DISTURBANCES = 35%, Nausea/Vomiting/Gallstones/Cramps/Flatulence

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14
Q

What is the mechanism of PEGVISOMANT? Is this drug generally safe?

A

GH receptor antagonist - Used to treat gigantism (Before epiphyses plate closes) and acromegaly (after plate closure)
PILCH LIKES THIS, no cardiotoxicity or other toxicities

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15
Q

Name the 3 forms of purified FSH. Name if they are recombinant or natural.

A

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

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16
Q

Name the purified form of LH. Is it natural or synthetic (recombinant)? When is it used?

A

LUTROPIN-alpha: RECOMBINANT synthetic form
ONLY used in combination with FOLLITROPIN-alpha to stimulate follicular dvlm in women with PROFOUND LH DEFICIENCY (for ovulation)

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17
Q

Name 2 purified forms of hCG. Name if they are natural or synthetic (recombinant). Which has a greater consistency of biologic activity?

A
  1. NATURAL hCG - purified from human urine (where it gets extracteD)
  2. CHORIOGONADOTROPIN-alpha (rhCG)- Recombinant form of hCG **greater consistent biologic activity
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18
Q

Which is the only ENDOGENOUS anterior pituitary hormone that can be used as reliable,consistent pharmacotherapy?

A

UROFOLLITROPIN - Endogenous FSH

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19
Q

What is the #1 use of GONADTROPIN PHARMACOTHERAPY?

A

CONTROLLED OVARIAN HYPERSTIMULATION (COH) in assisted reproductive procedures (e.g. IVF)

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20
Q

Pt tries CLOMIPHENE, but it doesn’t work as well. Pt tries GONADOTROPIN therapy finally. What condition is this targeting?

A

ANOVULATORY WOMEN - To induce ovulation in infertile women

To stimulate spermatogenesis in men

21
Q

In women treated with hCG and GONADOTROPINS, what are the two most serious complications? Which one is more serious? Why?

A
  1. OVARIAN HYPERSTIMULATION SYNDROME **More serious - Ovarian enlargement -> Ascites, hydrothorax (serous fluid accumulates in pleural cavity=pleural effusion), hypovolemia -> SHOCK
  2. Multiple pregnancies
22
Q

What conditions are GnRH agonists used for?

A
  1. ENDOMETRIOSIS
  2. UTERINE LEIOMYOMATA (FIBROIDS)
  3. PROSTATE CANCER
  4. CENTRAL PRECOCIOUS PUBERTY
23
Q

Name the GnRH agonists, if they’re synthetic or recombinant.

A
  1. NATURAL GnrH (GONADRELIN)
  2. SYNTHETIC GnRH agonists (-Relins + Leuprolide): GOSERELIN, HISTRELIN, LEUPROLIDE, NAFARELIN, TRIPTORELIN - MORE POTENT/LONGER LASTING than gonadorelin
24
Q

What is the mechanism of GnRH agonists?

A

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

25
Q

Name the 3 GnRH agonists approved for ENDOMETRIOSIS. How do they work

A

‘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

26
Q

What are UTERINE FIBROIDS? What is the clinical triad of UTERINE FIBROIDS?

A

BENIGN, Estrogen-sensitive, Uterine fibrous growths IN UTERUS
Clinical Triad: MENORRHAGIA (hyperbleeding) + ANEMIA + PELVIC PAIN

27
Q

What is the Tx protocol of UTERINE FIBROIDS?

A

Same as Endometriosis (GOSERELIN/LEUPROLIDE/NAFARELIN) + Supplemental Fe for the anemia for 3-6mo
(Will reduce fibroid size)

28
Q

What is the main goal of therapy for PROSTATE CANCER?

A

REDUCE TESTOSTERONE LVLS

29
Q

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?

A

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)

30
Q

What is the unique GnRH agonist that can be used in combination pharm therapy for PROSTATE CANCER?

A

HISTRELIN

31
Q

What are the 2 indications of continuous GnRH agonist Tx for CENTRAL PRECOCIOUS PUBERTY?

A
  1. Child whose FINAL HEIGHT would be greatly compromised (evidenced by advanced bone age)
  2. Child who has EMOTIONAL DISTRESS due to pubertal secondary sexual characteristics/menses
32
Q

Which GnRH agonists are used for continuous Tx of CENTRAL PRECOCIOUS PUBERTY? What is the method of administration?

A

MONTHLY IM depot injection of

LEUPROLIDE + HISTRELIN

33
Q

When is the continuous Tx of LEUPROLIDE or HISTRELIN for pts with CENTRAL PRECOCIOUS PUBERTY generally continued until?

A

GIRLS - age 11

BOYS - age 12

34
Q

Which side effect is of MOST CONCERN for both women and men with GnRH agonist therapy (-RELINS + LEUPROLIDE)?

A

Reduced BONE DENSITY (due to decreased Estrogen) -> OSTEOPOROSIS

36
Q

Name the 3 GnRH RECEPTOR ANTAGONISTS. Do they have better or worse efficacy than GnRH agonists?

A

-RELIX(es): GCD - GANIRELIX, CETRORELIX, DEGARELIX

Inhibits FSH and LH secretion with BETTER efficacy than GnRH agonists (more dose-dependent and complete)

37
Q

What type of side effects are generally seen with GnRH AGONIST + GnRH RECEPTOR ANTAGONIST therapy?

A

MENOPAUSAL Sx - hot flashes, edema, headaches, night sweats, decreased libido, depression, vaginal dryness

38
Q

Name the 2 DOPAMINE AGONISTS.

A

BROMOCRIPTINE

CABERGOLINE

39
Q

What is the #1 usage of DA agonists?

A

HYPERPROLACTINEMIA (due to Prolactin-secreting adenomas)

40
Q

How does HYPERPROLACTINEMIA affect women? How does it affect men?

A

WOMEN: Amenorrhea (less bleeding) + Galactorrhea (excess milk prdn)
MEN: Decreased libido + Infertility

41
Q

Are BROMOCRIPTINE and CABERGOLINE efficacious for hyper Prolactin-secreting microadenomas? For macroadenomas?

A

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)

42
Q

Are BROMOCRIPTINE/CABERGOLINE well-tolerated in terms of side effects? Which one is better tolerated?

A

NO, lots of toxicity - nausea, headache/light-headedness, orthostatic hypotension/fatigue
CABERGOLINE is better tolerated (Due to LESS NAUSEA)

43
Q

What is the #1 reason for BROMOCRIPTINE/CABERGOLINE discontinuation in pts with hyperprolactinemia? How can the side effect be relieved?

A

NAUSEA

Generally can be relieved by VAGINAL administration

44
Q

Even though CABERGOLINE is more well-tolerated in terms of nausea, which pt population is it absolutely CONTRAINDICATED in?

A

Pre-existing VALVULAR Disease (Cabergoline is associated with CARDIAC VALVULOPATHY)

45
Q

Name the synthetic OXYTOCIN drug.

A

PITOCIN

46
Q

What are the 2 usages of PITOCIN (synthetic oxytocin)?

A
  1. INDUCING LABOR in women requiring early vaginal delivery

2. CONTROLLING UTERINE HEMORRHAGE - Since Oxytocin increases frequency + force of uterine contractions**

47
Q

What conditions may lead to early vaginal delivery and thus mandate PITOCIN (synthetic oxytocin) therapy?

A

UNCONTROLLED MATERNAL DIABETES
WORSENING PRE-ECLAMPSIA
INTRAUTERINE INFECTION

48
Q

What are two physiological processes that may occur resulting in the potentially severe toxic complications of PITOCIN (synthetic oxytocin)?

A
  1. EXCESSIVE UTERINE CONTRACTION (Too much oxytocin)
    - > Fetal distress, placental abruption, uterine rupture
  2. INADVERTENT ADH-R ACTIVATION (Activation of a diff posterior pituitary receptor) -> Hypervolemic Dilutional Hyponatremia + Heart Failure + Seizures
49
Q

What are the CONTRAINDICATIONS of synthetic oxytocin therapy?

A

FETAL DISTRESS/Abnormal fetal presentation
CEPHALOPELVIC DISPROPORTION
Other predispositions of UTERINE RUPTURE

50
Q

Which conditions are GnRH ANTAGONISTS used for? Which specific ones are used?

A
  1. CONTROLLED OVARIAN HYPERSTIMULATION in assisted reproductive procedures - Lower OHS risk than GnRH agonists = GC (GANIRELIX, CETRORELIX)
  2. Sx ADVANCED PROSTATE CANCER - DEGARELIX

STEP 8: EndoRepro PATHOMA FA (7 decks)

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