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1
Q

Ant Pit/Hypothalamic Hormones-Receptors
GH and Prl activate?
TSH/FSH/LH/ACTH activate?

A

GH and Prl activate JAK-STAT

TSH/FSH/LH/ACTH activate GPCR

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2
Q

Explain regulation of pituitary and hypothalamic hormones
TRH, TSH, T3/4
GnRH, FSH/LH, E/P
CRH, ACTH, cortisol
GHRH, GH/IGF1, somatostatin
Thyrotrophin-RH, secretin, glucagon, VIP, GIP, Prl, and dopamine

A

TRH stim TSH which stim T3/4 which inhibits TRH and TSH
GnRH stim FSH/LH which stim E/P which inhibit GnRH and FSH/LH
CRH stim ACTH which stim cortisol which inhibits CRH and ACTH
GHRH stim GH and IGF1 which inhibit GHRH; SST inhibits GHRH
ThyrotrophicRH, secretin, glucagon, VIP, and GIP stim Prl which is inhibited by dopamine

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3
Q 
GH Drug- Somatropin
Kinetics? 
MOA?
Uses? (4)
AE? (Kids and adults)
CI?
A

Somatropin
Kinetics- somatropin is a rhGH, metabolized by liver, and induces p450
MOA- binds GH-R, activates JAK-STAT, leads to IGF1 mediated affects
Uses- GH deficiency (make short children nml size and reverse symptoms seen in adults like obesity and loss of m mass); short stature assoc w/ Prader Willi, Turners, or Noonan; wasting in AIDS pt; pt w/ short bowel syndrome
AE- kids- intracranial HTN, scoliosis, otitis media in Turners, hypothyroidism, gynecomastia, and pancreatitis
AE- adults- edema, myalgia, arthralgi, and carpal tunnel
CI- malignancy

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4
Q 
Mecasermin
Uses?
What is it made of?
How is it given?
AE? How to prevent
A

Mecasermin
Used in children w/ growth failure whohave severe IGF1 deficiency not responsive to exogenous GH
Complex made of rhIGF1 and rhIGFBP3 (inc half life of rhIGF1)
Give subQ
AE- hypoglycemia (eat 20 min before injection)

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5
Q

GH Antagnoists
What are the 2 classes
What is the use?

A

GH Antagonists
SST Analogs (reotides) and Pegvisomant
used for somatotroph adenomas

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6
Q

SST (somatostatin)Analogs
MOA
What are the 2 drugs and their uses
AE

A

SST Analogs
MOA- inhibit GH, glucagon, insulin, and gastrin
Octreotide- give subQ, use for acromegaly, carcinoid syndrome, gastrinomas, glucagonomas, VIPomas
Lanreotide- use for acromegaly
AE- GI, gallstones, b12 deficiency, and bradycardia

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7
Q

Peqvisomant
MOA
Uses

A

Peqvisomant
MOA- GH-R antagonist, binds GH-R but doesnt activate JAK-STAT
Uses- acromegaly

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8
Q

Dopamine Agonists (2)
MOA
Uses
AE (when do you discontinue)

A 
Dopamine Agonists
Bromocriptine and Cabergoline
MOA- D2R agonist
uses- hyperprolactinemia
AE- NV, HA, hypotension, fatigue
Discontinue if prego w/ microadenoma
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9
Q

Oxytocin uses?

A

Induce labor, limit post partum bleeding, and elicit milk ejection

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10
Q 
ADH Agonists (2)
Kinetics
MOA
Uses
AE (use caution with which one in pt with what condition?)
A

ADH Agonists
Vasopressin and Desmopressin
Kinetics- desmopressin has longer half life and minimal V1 activity
MOA- activate GPCR V1R and V2R; V1 vasoconstricts; V2 inc water reabsorption
Uses- Central DI (desmo) and hemophilia A or von willebrand disease (desmo)
AE- HA, NV, abdominal pain, hyponatremia, seizure; use vasopressin w caution in pt with CAD

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11
Q

ADH Antagonists
Kinetics
MOA
Uses

A

ADH Antagonists
Vaptans (T and C)
T vaptan is v2 selective; metabolized by cyp3A4
MOA- inc water excretion w/o changing electrolyte excretion
Uses- hyponatremia and CHF (T vaptan dec wt and dec dyspnea; C vaptan inc water excretion w/o affecting vascular resistance)

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12
Q

Explain effects of hyper/hypothyroidism on T3/4 clearnace and T3/4 half life

A

Hyperthyroid- inc clearance and dec half life

Hypothyroid- inc half life and dec clearance

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13
Q

What agents prevent the conversion of T4 into T3?

A

Iopanoic acid, ipodate, amiodarone, b-blockers, and corticosteroids

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14
Q

What agents dec T4 absorption?

A

Antacids, ferrous sulfate, cholestyramine, and colestipol

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15
Q

What agents induce cyp450 to inc metabolism of T4/3?

A

Rifampin

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16
Q

What are thyroid hormone drugs MOA?

A

T4/3 enter cell -> T4 converted to T3 -> T3 enters nucleus and binds TR -> complex binds RXR ->gene transcription -> effects after a lag period

17
Q

What is the 1st line choice for T4 replacement?

A

Levothyroxine

18
Q

Thioamides (2)
Kinetics (kinetics of each then explain their use during pregnancy)
MOA
AE (when do you discontinue)

A

Thioamides
Propylthiouracil and methimazole
Kinetics- PTU- radpily absorbed, fast acting, 1st pass effect, requires multi doses
Kinetics- methimazole- completely absorbed, take once a day
Kinetics- can cross placenta and accumulate in fetal thyroid; take PTU in 1st trimester; methimazole in 2nd and 3rd trimester
MOA- inhibit thyroid peroxidase and iodide organification; inhibit thyroid hormone synthesis/release; PTU blocks conversion of t4 to t3; DOES NOT block iodide uptake
AE- maculopapular rash, urticarial rash, vasculitis, LAD, hepatitis (PTU), and jaundice (methimazole); agranulocytosis-reverse by discontinuing

19
Q

Lugols Iodide Solution
MOA
Uses
AE

A

Lugols Iodide Solution
MOA- inhibit organification and hormone release; dec size and vascularity of thyroid
Uses- thyroid storm, preop reduction of hyperthryoid gland, and block uptake of radioactive isotopes
AE- acneiform rash, swollen salivary glands, ulcers, conjunctivitis, and metallic taste

20
Q

Radioactive Iodine
Uses and kinetics
CI

A

Radioactive Iodine
I131
Used for thyrotoxicosis; give PO, rapidly absorbed; destroys parenchyma
CI- prego or breast feeding

21
Q

B-Blockers for thyroid

Uses

A

B-blockers
Propranolol, metoprolol, atenolol
Uses- improve symptoms, reduce T3 (propranolol) by preventing conversion of T4 to T3

22
Q 
Explain the treatment of Hypothyroidism 
Drug of choice? How do you give it?
If drug induced?
Myxedema coma?
Myxedema and CAD?
Prego?
A

Mgmt of Hypothyroidism
Levothyroxine is 1st choice; give on empty stomach
Drug induced- remove drug or add levo
Myxedema coma- large loading dose of levo followed by IV dosing
Myxedema and CAD-use levo w/ caution to avoid arrhythmia or MI
Prego- maintain nml level for fetal brain development

23
Q 
Explain mgmt of Graves
When do you use drugs? What drug is preferred?
When do you perform thyroidectomy?
When do you use radioiodine?
What are the adjuvant therapies?
A

Graves Mgmt
Use methimaxole in young pt
Thyroidectomy in pt w/ large thyroid or multinodular goiter
Use radioiodine in pt over 21 unless pt has heart disease or if elderly w/ thyroid storm
Adjuvant therapy- beta blockers for cardiac effects

24
Q

Explain multidrug therapy of thyroid storm

A

B-blockers for arrhythmias
K iodine to prevent thyroid hormone synthesis
PTU or methimazole to prevent synthesis
Hydrocortisone to prevent shock and block conversion of t4 to t3
Plasmapheresis or dialysis to dec t4

25
``` Menopause Menopause transition? Post menopause? symptoms? Comorbidities? Treatment? ```
Menopause transition- variations in cycle w/ skipped cycles Post menopause- 12 months complete amenorrhea Symptoms- hot flash, night sweats, sexual dysfunction, dec QoL Comorbidities- osteoporosis and fractures and CV events Treatment- estrogen w/ or w/o progestin (women w/ intact uterus REQUIRE E and P)
26
Menopause Hormone Therapy (MHT) What are the estrogenic forms? (4) What are the progestinic forms? (3) MOA?
MTH Estrogenic Forms Estradiol, conjugated estrogen CE (many estrogen derivatives), esterified estrogen EE (Na esterone sulfate and Na equilin sulfate), estropipate (crystalline estrogen solubilized with sulfate and stabalized w/ piperazine) Progestinic forms Medroxyprogesterone MPA (MPA alone or w/ CE), methyltestosterone (alone or with EE), and progesterone MOA- mimics effects of endogenous hormone by binding target R
27
Estrogen only MHT effects
Endometrial prolif Dec LDL, antithrombin 3, and osteoclast activity Inc HDL, TAGS, clotting factors, platelet aggregation, Na retention, and TBG
28
What are the goals of the Womens Health Initiative study with regards to MHT?
The goals were to examine MHTs effects on heart disease, osteoporosis, and risk of cancers
29
What were the findings of the Womens Health Initiative study with regards to E/P therapy and E therapy alone; harms and benefits? What did they find with regards to age and therapy?
Estrogen and Progesterone Harms- breast cancer, CAD, dementia, gall bladder disease, stroke, thromboembolism, and incontinence Benefits- dec DM, fractures, and colorectal cancer Estrogen Alone Harms- dementia, gallbladder disease, stroke, thromboembolism, and incontinence Benefits- dec breast cancer, fractures ,and DM Benefits better in 50 > 60 > 70 yo
30
What were the summary findings and recommendations from the Womens Health Initiative with regards to MHT? - what does it effectively treat - what should it not be used to treat - benefits vs risks for bone and colon cancer
MHT effectively treats vasomotor symptoms and vaginal change MHT should not be used to treat CAD or dementia Benefits of bone and colon cancer are outweighed by other risks
31
List the 5 MHT Agreements - acceptable to treat? - what is preferred treatment for vaginal symptoms only - what treatment is preferred in women with uterus to prevent cancer - MHT inc risk of what? - MHT inc risk of what where the risk dec if MHT is stopped
MHT is acceptable to treat mod-severe menopause symptoms for women under 60 or w/in 10 years of menopause Low dose topical estrogen is preferred treatment for women w/ vaginal symptoms alone Women with uterus need combo E and P therapy to prevent uterine cancer MHT inc risk of blood clots and stroke MHT inc risk of breast cancer, risk dec if MHT is stopped
32
What are SERMs? What do they do? What are the drug examples?
SERMs Selective Estrogen R Modulators Have pro-estrogenic actions in select tissues and anti-estrogenic actions in others Drugs- ospemifene, clomiphene, and “fenes”
33
What are TSECs? What are they made of? What is the drug example?
TSECs Tissue selective estrogen complexes Combo SERM and estrogen compound Drug- Bazedoxifene (use in combo w/ CE)
34
``` Ospemifene Uses MOA SE CI ```
Ospemifene Use to treat dyspareunia caused by vulvovaginal atrophy assoc w/ menopause MOA- agonist at vaginal ER; antagonist in breast; inc superficial cell growth and vaginal secretions, dec pH and pain during sex SE- hot flash, night sweats, inc risk of stroke and thromboembolism, endometrial thickening and hyperplasia CI- unexplained vaginal bleeding, CV disease, or estrogen assoc neoplasia
35
Clomiphene Use MOA SE
Clomiphene Anti-estrogen SERM used to treat infertility in anovulatory women MOA- induce ovulation by blocking actions of estrogen on GnRH, FSH, and LH; inc gonadotropin rlease and occyte follicle development SE- multi-births, ovarian cysts, hot flash, blurred vision, and luteal phase dysfunction (dec progresterone)
36
``` Bazedoxifene Use MOA SE CI ```
Bazedoxifene used in women with intact uterus to treat vasomotor symptoms assoc w/ menopause and prevent osteoporosis MOA- antagonists in endometrium and breast tissue; agonist in bone; does not cause endometrial prolife; destroys HER2 cells SE- hot flash, night sweats, and estrogen assoc effects (used in combo with CE) CI- same CI as with estrogens

Endo II Pharm (3 decks)

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