pharm_repro_ms2.txt

Card Set Information

Author:
soren101
ID:
139042
Filename:
pharm_repro_ms2.txt
Updated:
2012-03-03 21:04:45
Tags:
pharm repro ms2
Folders:

Description:
pharm just repro ms2
Show Answers:

Home > Flashcards > Print Preview

The flashcards below were created by user soren101 on FreezingBlue Flashcards. What would you like to do?


  1. 4 ESTROGENS
    • ESTRADIOL
    • CONJUGATED ESTROGENS
    • ETHINYL ESTRADIOL
    • DIETHYLSTILBESTROL (DES)
  2. ESTRADIOL MOA
    Natural steroidal estrogen

    ALL estrogens interact w/ intracellular receptors to alter gene tsc & thus protein synth
  3. CONJUGATED ESTROGENS MOA
    Composed of phytoestrogen

    Contains same 3 major & 6 minor estrogens as Premarin
  4. ETHINYL ESTRADIOL
    Synthetic steroidal estrogens

    Ethinyl group added to 17 position of steroid ring →rev 1st pass metab → incr:

    • --bioavailability
    • --potency
    • --t1/2
  5. DIETHYLSTILBESTROL (DES) MOA
    Synthetic non-steroidal estrogen

    • teratogenic (1st trimester)
    • --fetus: clear cell adenocarc of vagina in late teens-20s
    • --fetus: undesc testes, epidydymal cysts &
    • azoospermia
  6. PHARMACOLOGICAL EFFECTS OF ESTROGENS
    Nl sexual maturation of ♀

    Dev of 2o sex char

    Distrb fat to hips & breasts

    Accel growth phase & epiphyseal closure at puberty

    Maintenance of nL struct of skin, mucosa & blood vessels

    • Stim hepatic synth of:
    • --TBG, SHBG, transcortin, transferrin, renin substrate & fibrinogen →
    • --incr circ levels (thyroxine, estrogen, testosterone, Fe, Cu, etc.) but free conc ≤
    • nL

    Stim synth clotting factors 2, 7, 9, 10 → incr likelihood of thromboembolic disease

    • Antag PTH → decr rate of bone resorption by osteoclasts
    • --reason for postmenopausal bone loss

    Incr HDL & TG

    Decr LDL & total chol

    Facilitate mov of fluid from plasma to ECF → edema (Kidney has compensatory salt/H2O retention)
  7. PHARMACOKINETICS OF ESTROGENS
    Pharmacokinetics (of estrogens):

    1. Enterohepatic recirc → greater effect on liver than periphery

    2. Apply drugs topically (cream) for periph action to minimize hepatic effects
  8. THERAPEUTIC USES OF ESTROGENS
    Primary hypogonadism

    • Post-menopausal HRT
    • --> dec LDL & ­HDL & TGs
    • --> “Perfect” HRT:
    • ----Agonistic (+) at bone, skin & mucous membranes, CNS & plasma lipid profile.
    • ----Antagonistic or no effect at breast, uterus & liver

    • Contraception (***combo w/ progestin to prevent endometrial hyperplasia caused by
    • estrogen)

    “Morning after” contraception

    Dysmenorrhea

    Dysfunctional uterine bleeding

    OCP’s decr Sx of benign breast dz

    • Hirsuitism
    • --Combo w/ finasteride, flutamide & spironolactone may prevent
    • --Eflornithine applied topically → irrev inhb ornithine decarboxylase → prevent hair growth
  9. ADVERSE S/E OF ESTROGENS
    1. n/v

    2. Diarrhea

    3. Breast tenderness

    • 4. Endometrial hyperplasia
    • (post-meno dec via co-admin progestin)

    5. Salt & H2O retention

    6. HTN

    7. Gallbladder disease

    8. Chol jaundice (very rare)

    9. Thromboembolic disease

    10. Post-meno bleeding

    11. Headache

    • 12. Hyperpigmentation
    • (Chloasma or melasma)

    • DES:
    • teratogenic (1st trimester)
    • --♀ fetus: clear cell adenocarc of vagina in late teens-20s
    • --♂ fetus: undesc testes, epididymal cysts &
    • azoospermia
  10. CONTRAINDICATIONS FOR ESTROGEN USE
    • Relative:
    • 1. Fam hx of breast or uterine malign
    • 2. Severe varicose veins
    • 3. Hx of hepatic dz
    • 4. HTN

    • Absolute:
    • 1. Estgn-dep breast or uterine cancer
    • 2. UnDx abnl genital bleeding
    • 3. Hx of severe thromboembo dz
    • 4. Acute hepatic dz
  11. SERMS
    (selective estrogen receptor modulators)
    CLOMIPHENE

    TAMOXIFEN

    RALOXIFEN

    • Acts as estrogen agonist (+) in some tissues
    • & estrogen antagonist (-) in other tissues
  12. CLOMIPHENE MOA AND PHARM EFFECTS
    SERM

    Orally active non-steroidal

    • 1. BLOCKS estgn rec in hypothal → interrupts nl feedback inhb of GnRH &
    • gonadotropin secretn

    2. Incr GnRH secrtn → incr FSH & LH

    • 3. Incr FSH & LHgametogenesis & estgn
    • --------------------------

    Induce ovulation in ♀ w/ amenorrhea or anovulatory cycles

    (-) CNS (nl sleep & temp regltn)

    (+) liver: protein synth



  13. TAMOXIFEN MOA AND PHARM EFFECTS
    SERM

    Orally active non-steroid comptv estgn receptor antag (-) w/ partial agon (+) in some pts

    1. Estgn receptor antag (-) in BREAST

    • 2. Agonist (+) in liver & uterus*** → S/E
    • --DVT or PE in high risk pts
    • --Prolonged tx: endometrial hyperplasia → endometrial cancer

    • Pre-meno ♀: Tamox antag (-)
    • estgn receptors in hypothal & pit
    • → incr GnRH → incr LH → incr estgn → (-) tamox effects.
    • ----Prev the incr estgn w/ GnRH analog

    Post-meno ♀: Same as pre-meno but ovaries quit making estgn → doesn’t matter

    -----------------------------------------------

    • (-) breast
    • (-) CNS (nl sleep & temp regltn)
    • (-) skin/mucous membr

    • (+) bone density
    • (+) plasma lipids
    • (+) liver: protein synth
    • (+) uterus: hyperplasia***
  14. RALOXIFENE MOA AND PHARM EFFECTS
    SERM

    Estrogen receptor AGONIST (+) on:

    • 1. Bone: decr bone resorption by osteoclasts
    • 2. Plasma lipid profile
    • 3. Hepatic protein syn

    • ANTAGONIST (-) on:
    • 1. Uterus***
    • 2. Breast
    • -------------------------------------

    • (-) breast
    • (-) CNS (nl sleep & temp reg)
    • (-) skin/mucous membr
    • (-) uterus: hyperplasia***

    • (+) bone density
    • (+) plasma lipids
    • (+) liver: protein synth
  15. CLOMIPHENE THERA AND ADVERSE S/E
    SERM

    Want to be pregnant!!!!

    Induce ovulation in ♀ w/ amenorrhea or anovulatory

    • Poss:
    • 1. Multiple births
    • 2. Stillbirths
    • 3. Ovarian enlargement
    • ------------------------------------

    ADVERSE

    • 1. Ovarian enlargement
    • 2. Temp scintillating scotomata
    • (blurred spots or flashes)
    • 3. Sx of menopause (hot flashes, etc.)

    • Contraindicated in pts w/ thromboembo
    • d/o b/c acts as an estrogen receptor (+) in liver → incr clot factor synth
  16. TAMOXIFEN THERA AND ADVERSE S/E
    SERM

    1. Tx E(+) breast cancer

    2. Breast cancer prophylaxis in high risk ♀

    • 3. Post-meno: same (+) agonistic
    • (good) effect on bone density & lipids as estrogen
    • ----------------------------------

    ADVERSE

    • 1. n/v
    • 2. Hot flashes
    • 3. Less freq vag bleeding & menstrual irreg
    • 4. Comp prevents metab of warfarin → incr PT
  17. RALOXIFENE THERA AND ADVERSE S/E
    1. Decr size of uterine leiomyomas in post-meno ♀

    2. Maint post-meno bone density

    3. Decr incid of vertb fractures by 30-40% (but effctv < HRT w/ conjugated estrogens)

    4. Decr breast cancer in high risk ♀

    • 5. Decr Tc & LDL. No incr HDL
    • (like HRT w/ estgn)
    • ------------------------------------

    • ADVERSE
    • 1. Hot flashes
    • 2. Flu-like sx
    • 3. Arthralgia
    • 4. Thromboembo (inc hep clot factor synth)
    • 5. p.o. → prev bene of topical estradiol in post-meno ♀ w/ atropic vaginitis
    • (dec estrogen → vaginal itching & dryness)
  18. AROMATASE INHIBITORS
    ANASTROZOLE

    LETROZOLE

    (Block synth of ALL estrogen in body)
  19. AROMATASE INHIBITORS MOA AND PHARM EFFECTS
    Prevents conversion of androgens to estrogens

    • LH → thecal cells make Androstenedione (ASDN) →
    • granulosa cells take up ASDN → testn → [aromatase (fat cells)] → estradiol

    • Aromatase (CYP450 enz) converts andgns → estgns (testn → estradiol & DHEA → estrone)
    • --------------------

    • ANASTROZOLE
    • LETROZOLE
  20. AROMATASE INHIBITOR THERA AND ADVERSE S/E
    Tx breast cancer in post-meno ♀:

    • 1. Estro receptor (+) cancer
    • 2. Advanced or metastatic breast cancer
    • 3. NOT responded to tamoxifen
    • 4. Been on tamoxifen for 5 years
    • ----------------------------

    ADVERSE:

    • 1. MENOPAUSAL Sx
    • 2. MSK PROBS
  21. LIST OF PROGESTINS
    PROGESTERONE

    NORETHINDRONE

    NORGESTIMATE

    NORELGESTROMIN

    DROSPIRENONE

    MEDROXYPROGESTERONE
  22. PROGESTERONE MOA
    PROGESTIN

    ANTI-MINERALOCORTICOID

    ANTI-ANDROGENIC
  23. NORETHINDRONE MOA
    PROGESTIN

    FAMILY OF DERIVATIVES OF 19-MORTESTOSTERONE

    SOME ANDROGENIC EFFECTS

    LACK ANTI-MINERALOCORTICOID ACTIVITY
  24. NORGESTIMATE & NORELGESTOMIN MOA
    PROGESTINS

    • Norelgestromin = 17-deacylated norgestimate
    • = actv metabolite of norgestimate

    • 1. Does NOT stim androgen receptors
    • → NOT (-) antagonize estrogen effect on plasma HDL conc
    • ---- NO stim of sebum prodn → good skin (No acne)

    2. Combo w/ ethinyl estradiol (OCP) → 3x incr serum conc of SHBG → 50% decr in serum free testosterone conc
  25. DROSPIRENONE MOA
    PROGESTINS

    Spironolactone derivative

    1. Stim (+) progesterone rec

    2. Blocks (-) androgen & mineralocorticoid rec

    3. Block mineralocorticoid rec → CV benefits
  26. MEDROXYPROGESTERONE MOA
    PROGESTIN

    I.M. DEPO PROVERA

    COMPLETE AMENORRHEA --> CONTRACEPTION LASTING 3 MONTHS
  27. THERAPEUTIC USES OF PROGESTINS
    Uses of OCPs

    1. Contraception: combo w/ ethinyl estradiol

    • 2. Acne
    • --Estgn inhb hypothal & pit → decr LH → decr testn
    • prodn by ovaries

    --Incr hepatic synth of SHBG → decr free testn conc

    --Decr free testn → decr sebum prodn in skin

    • 3. HRT for post-meno (esp drospirenone***)
    • --Constant estgn w/ cyclic or intermittent progestin
    • --Const estgn & progestin
    • --Ethinyl estradiol + drospirenone: Drospirenone has
    • anti-androgenic and anti-mineralocorticoid effects
  28. PROGESTIN ADVERSE EFFECTS
    • NORETHINDRONE
    • --LOW ANDROGENIC ACT --> INC SEVUM PROD --> ACNE
    • --Tx w SPIRONOLACTONE

    • MEDROXYPROGESTERONE
    • --NO RISK OF THROMBOEMBOLIC Dz BUT UNPREDICTABLE MENSTRUAL BLEEDING
  29. LIST OF PROGESTIN ANTAGONISTS
    MIFEPROSTONE (RU-486)

    ULIPRISTAL
  30. MIFEPRISTONE MOA AND THERAPEUTIC USES
    PROGESTIN ANTAG

    GLUCOCORTICOID REC ANTAG

    OUTPATIENT ABORTION OF FETUS < 49 DAYS

    • INTERRUPTS PREG
    • --2 DAYS LATER GIVE SYNTH PG DINOPROSTONE --> CONTRACTS UTERINE SMOOTH MUSC
    • ---------------------------------------

    THERA

    1. Prevent implantation of fertilized egg

    2. Alleviate sx of endometriosis

    3. Tx non-resectable meningiomas

    4. Tx uterine leiomyomas

    5. Tx Cushing’s syndrome (b/c also glucocorticoid receptor antag)
  31. ALENDRONATE & IBANDRONATE
    BISPHOSPHONATES

    INH BONE REABS BY STIM OSTEOBLASTS

    • BINDS TO REMODELING BONE SURFACES
    • --> INH OSTEOCLASTS

    • PREVENT POST-MENO BONE LOSS
    • -------------------------------------

    ADVERSE

    • Esophagitis:
    • --Pts should take drug w/ 8 oz of H2O & remain upright for 30 min.

    • --If drink too much or lie down (before 1st
    • meal of the day) → level of drug reaches LES → damage

    Osteonecrosis of the jaw (mostly w/i.v.)

What would you like to do?

Home > Flashcards > Print Preview