bennett pituitary

give the rundown of pituary path

1. hypothalamys

2. antierior pituitary

3. target organ

run down of growth hormone path specfiically

1. hypothalamus: GHRH stimulations grwoth hormone, somatostatin inhibits GH

2. anterior pitary: release grwoth hormone

3. target organ: liver, muscle, bone, kidney

where most pit hormoes released from

anterior

• posterior is the back lol per bennett

what 2 homrones that are released by posterior

• oxytocin

• ADH

what is the one hormoone that does NOT have negative feedback loo[

oxytocin

thyroid pathway

1. hypothalamus: thyroid release hormone

2. anterior pitary: thy stimulating hormone

3. target organ thyroid produces t3/t4

what is the reproductive/gonad path

1. hypothalamus: GnRH

2. anterior pitary: FSH+ LH

3. target organ: Gonads which release estrogen, progesterone, testosterone

adrenal pathway

hypothalamus: CRH (Corticotropin-Releasing Hormone)

anterior pitary: ACTH (Adrenocorticotropic Hormone)

target organ: adrenal cortex (on top of the kidneys) which releases glucocorticoid production, especially cortisol

prolactin pathway

hypothalamus: dopamine

anterior pitary: INHIBITION of prolactin

target organ: breast tissue (this is why antipsych can cause hyperprolactinemia)

what are general drugs used for acromegaly

Acromegaly : Growth hormone antagonist, Somatostatin analog, Dopamine agonist

what IS acromegaly ? how present

too much growth hormone

• think anterior pit tumor

• enlargement of hands, feet, facial features, overgowth of skin (thicker and oily), deeper voice from vocal cord enlargemnet

• can cuase HTn, enlarged heart, t2dm

what is common source for all the sex hormones

cholesterol

what besides GH is increased in acromegaly

IGF-1 (insulin like growth factor)

what is the GH antagonist and what used for

Pegvisomant (Somavert®)

• acromega

Pegvisomant (Somavert®) adr (for acromeg)

hepatotox, increased LFT, n/d, pain at injection site

Pegvisomant (Somavert®) MOA for acromeg

Binds to GH receptors in liver and inhibits IGF.

• doesn’t stop PRODUCTION by stops effect on certain tissues

what are the Somatostatin analogues (SSA) and what used to treat

• acromeg

• Octreotide, Lanreotide, Paltusotine (Palsonify)— the po if can’t have surgery on tumor

Somatostatin analogues (SSA) — Octreotide, Lanreotide, Paltusotine MOA

• RECALL somatostatin is a natural inhibitor of GH so it acts like a super potent somatostatin

• stops GH from pit

• also therefore results in decreased IGF-1

Somatostatin analogues (SSA) — Octreotide, Lanreotide, Paltusotine ADRs

diarrhea/abdominal discomfort, can cause hypo OR hyperglycemia, nausea, flatulence, gallstones, bradycardia, deficient in vitamin B12, chest pain, hyperglycemia in type II DM, severe hypoglycemia in type I DM, malaise, fever

Somatostatin analogues (SSA) — Octreotide, Lanreotide, Paltusotine what needs to be adjusted

renal AND hepatic in dysfunctions

Dopamine agonsits what used for and what are the drugs for it

• for acromeg

• bromocriptine, cabergoline

what hormone is always antag to others

somatostatin

• ex to insulin, also GH

how dopamine ags work for acromegaly

suppress Gh secretion, AND suppress IGF-1 release

• but by extension also decreases prolactin increase

which DA ag is longer acting

cabergoline (vs bromocrip)

which DA ag is more potent and better tolerated (newer)

cabergoline

what does TOO much DA do ? what drugs this include

cause psychosis

• DA antags are antipsychs like haldol

what does TOO LITTLE DA do

parkinsons , too much prolactin, acromegayl

• give DA ags

what are the ADRs of DA ags for acromegaly

naus, HA, orthostatic hypotension, fatigue, abdominal pain

waht is cheapest drug for acro? most expens?

• cheap: DA ags (caber)

  • ex: somatstatin analgoues (octeotide)

which acromeg drug class has cyp3a4 inx

somatostat— octreotide, lanreotide

how DA ags effect GH production in pts that do not have acromeg? what about when ahve acromeg

• not effected: DA ag increases GH production

• effected: decreases GH production

what can cause short stature

GH def; GH insuf, or idiopathic

what drug used to manage smptoms associated with short stature

Somatropin

what IS Somatropin

recombinant human GH

• used to treat symptoms with short stature to increase IGF-1 and increase bone and tissue growth

Somatropin adrs

WeLL TOLER

• BUT intracranial HTN

• vision, HA, nausea, edema. Hypothyroidism,

  pancreatitis, gynecomastia, myalgia, fluid imbalance, pain at injection,

• ok in preg

Somatropin ddi

glucocort can decrease GH effects

• could induce insulin resistance in Dm, otherwise cause hyperglycemia

why would use Somatropin (increases GH)

• slower growth in children

• help in muscle wasting in adutls

Somatropin DDI

glucocorticoids

• Growth hormone can induce insulin resistance in DM or cause hyperglycemia

Somatropin MOA for short-stature

• binds to grwoth hormone receptors

• stimulates IGF-1 production in the liver to get insulin-like growht factor 1 made

• IGF-1 promotes bone grwoth and msucle synthesis— increased lean body mass

• increases fat break down

what are the short to medium acting glucocorticoids

Hydrocortisone

-Cortisone

-Prednisone

-Prednisolone

-Methylprednisolone

intermediate acting glucocorticoids

Triamcinolone

- Fluprednisolone

long-acting glucocorticoids

Betamethasone

-Dexamethasone

what med is NOT a glucocort— its a MINERALCORT

Fludrocortisone

Fludrocortisone t1/2

3.5

• shorter than even teh short acting ones

hydrocort equiv oral dose

20

cortisone equiv oral dose

25

pred equiv oral dose

5

prednisolone equiv oral dose

5

methylpred equiv oral dose

4

traimnicinolone (intermed acting gluco) equiv oral dose

4

betamethasone equiv oral dose

0.6

dexamethasone equiv oral dose

0.75

how long is cortisol (hydrocortisone like) in the body naturally

t1/2 is 60-90 min

does IM or oral corticosteriods last longer

longer with IM

why do somatostatin analogues cause hypo/hyper glycemia

negative feedback to glucagon and insulin

glucocort DDIs

cyp3a4 substatres (inhibitors icnrease concentration), avoid with alcohol

which glucocort most bioavial? order of most avail to least

Triamcinolone Flunisolide Beclomethasone Budesonide Fluticasone

is prednisone or prednisolone the prodrug

prednisone is the prodrug

how long use glucocort before you start to get systemic adrs

two weeks or more!

what are the systemic effects of glucocort

1. adrenal suppression

2. hyperglycemia

3. HTn adn hypokalemia (retain Na and h2O at expense of K)

4. increased risk of infection (decreased lymphocytes)

5. osteoporosis

6. catabolic effect— increase protein breakdown in msucle, fat, skin — thinning of skin, myopathies

7. behavorial changes — depression, psychosis, insomnia

8. peptic ulcers

9. wt gain

10. glauocoma, cataracters— increased HTN in eye

11. iatrogenic cushing syndrome (drug-casued excess of SNS stim)

12. retard growth (suppresses osteoblasts)

what is cushing’s syndrome

too much cortisol

three reasons for cushing’s syndrome

1. exogenous (from drugs— iatrogenic)

2. independent from adrenocorticotropic hormone

3. endogenous— ACTH-dependent — pituitary adenoma, ectopic acth-secreting adenoma

manifestations of cushings

acne

 Buffalo hump

 Central obesity

 Cutaneous striae

 Glucose intolerance

 Hirsutism

 Hypertension

 Menstrual irregularities

 Moon face

 Myopathy/muscular weakness

 Osteoporosis

 Psychiatric changes

 Virilization

list alllll the drugs for cushings

1. metyrapone

2. ketoconazole

3. osildorostat

4. mifepristone

5. cyproheptadine

6. mitotane

metyrapone ind

cushings , can be used to test ACTH production?

metyrapone MOA

nhibit the last step of cholesterol synthesis→ cortisol synthesis via

11β hydroxylase (Steroidogenesis inhibitor

• and recallllll cholesterol is precursoor to progesterone which is precursor to glucocort

• note that androgens also being made from cholesterol so one can increase/decrease at expense of the other

metyrapone adrs

nausea, sedation, hypertension, hirsutism, acne (increase androgen), salt

and water retention

metyrapone who probs should not use and why (for cushings)

women bc increases androgens

what are Ketoconazole/Levoketoconazole used for

cushings!

Levoketoconazole/keto moa

antifungal to inhibit steriod-synthesis enzymes (17α-hydroxylase, 11β-hydroxylase, cholesterol side-chain cleavage enzyme)

• potent at high doses but not specific — also decreases androgens?

Levoketoconazole/keto which is being used OFF LABEL for cushings

keto

Levoketoconazole/keto ADRs (cushing treatment)

• gynecomastia— increase in estrogen

• decrease in testosterone and libido

• increase in hepatic enzymes

• naus/vom

Levoketoconazole/keto ddi

“lots” so helpful lol

Levoketoconazole/keto BBW

heptox, qt prolong

Levoketoconazole/keto for cushings counseling

take with food

Osilodrostat (Isturisa ®) ind

cushings!

• esp for ppl who can’t have surgery on the gland or still have cushings after surgery

Osilodrostat (Isturisa ®) MOA

inhibotrs 11-beta-hydroxylase that is used in cortisol biosynth

Osilodrostat (Isturisa ®) adr

adrenal INSUF, fatigue, nause, HA, edema

Osilodrostat (Isturisa ®) for cushings monitor

qt prolong

Osilodrostat (Isturisa ®) ddi

substrates of cyp 3a4, 2b6, 2d6; inhibitors 1a2, 2c19, 2d6, 3a4

Osilodrostat (Isturisa ®) for cushings— caution

hep dose adjustment, with other narrow therapeutic index drugs (theophylline, tizanidine)

Mifepristone (Korlym, Mifeprex ®) what used for IN THIS COURSE? what else?

• cushing!

• also for emergency contracep, terminate early preg, treat endometriosis

. Mifepristone (Korlym, Mifeprex ®) adr

abdorminal and uterine cramping, nausea, hypokalemia

cyproheptadine what used for

cushings

cyproheptadine class/moa

5-ht antagonist

• decreases release of acth

cyproheptadine adrs

sedation, hyperphagia (hunger) anti-ach

cyproheptadine advantages

can be used for cusingsin preg, more tolerable tah other agents

mitotane ind

cushings

mitotane moa

• toxic destruction of the adrenal cells; supposed to only destory adrenal gland though

mitotane for cushings bw

acute adrenal insuf during times of increased need of corticosteriods

mitotane preg category?

causing fetal adrenal insuf

mitotane adrs

lethargy, rash, CNS depression, naus/vom

waht is the adrenolytic agent ? what islong term ad eff

mitotane— atrophy of adrenal cortex

what are teh steriodogenesis inhibitors

metyrapone

ketoconaozle

Osilodrostat

what cushings drug is used to test acth production adn whow

metyrapone

• blocks cortisol’s negative feedback into ACTH , so in normal pitiutary it would cause ACTH to increase (so if it doesn’t you have a problem)

what is medroxyprogesterone acetate affect on cushings/cortisol

can potentialyl increase cushing risk bc it can act like glucocorticoid, so suppresses acth

can topical glucocorts cause cushing? (ie hydrocort cream?)

if using a lot over large area for long time

what supplement can increase risk of cushing

magnolia bark

what is addison’s disease

PRIMARY adrenal insufc

• the adrenal gland is not making enough cortisol or aldosteorne

some potential reasons for addisons

acquired autoimmune

infectious— TB. HIV, AIDS

drug-induced

durgs that inhibit cortisol syntehsis

drugs taht increase cortisol metabolism