repro II drug

Question 1

estrogen in sex hormone therapy

Answer 1

• three main estrogen: estradiol (E2) → most potent / estrone (E1) → mainly produced during menopause / estriol (E3) → mostly produced during preg
• estrogen devided 4 types: natural estrogen → IV only / ester and conjugated estrogen → for oral intake (ปรับเพื่อลด 1st pass ที่ตับ) / steroidal synthetic estrogen → ethinyl estradiol (EE) เป็น most potent OCP เลย!
• PK: E2 bind w SHBG, metabolized by liver, half life in minute, ขับออกทาง bile / EE bind w albumin, half life 13-27hrs
• estrogen receptor: ERα — female repro tract, mammary gland, hypothalamus, endothelial cell, vascular smm / ERβ — highest express at prostate ovaries BUT less express at lung brain bone
• metabolic effect of estrogen: bone ดี, HDL↑, coag factor 2 7 9 10 12 ↑, anti-thrombin III & protein C & protein S ↓
• therapeutic uses เชื่อมกับ effect ของมัน: contraception, postmenopausal hormonal replacement, dysfunctional uterine bleeding (DUB), dysmenorrhea, primary hypogonadism, turner’s syndrome / สมัยก่อนเคยใช้ tx prostate CA, acne, hirsutism, decrease lactation (กดการหลั่ง)
• ADR: n/v, headache, breast engorgement, thromboembolism, **gynecomastia, endometrial CA, breast CA
• contraindication: thromboembolic disorder, estrogen-dependent tumor, family history of breast CA, endometrial CA, undiagnosed genital bleeding, liver disease

Question 2

progestin in sex hormone therapy

Answer 2

• 1st gen estrane → androgenic จัดเต็ม ผญไม่โอเค (e.g. lynestrenol, norgestrel, norethindrone) / 2nd gen → have androgenic activity / 3rd gen → less androgenic (e.g. gestodene desogestrel norgestimate) / 4th gen → some anti-androgenic (e.g. drospirenone)
• ทวนเบสิก synthetic and secretion: secreted by ovary (corpus luteum), during second half of menstrual cycle, endocervical gland (viscid↑)
• PK (progestin): oral and IM, bind w SHBG+albumin, metabolized by liver & excrete in urine
• physio & pharmaco action: insulin↑, 19-nor comp → HDL↓, aldosterone fx ↓ at kidney but ↑ at adrenal cortex
• therapeutic uses: contraception, menopause (HT), dysmenorrhea, endometriosis (amenorrhea), uterine fibroid, delay menstruation (norethindrone) แบบเลื่อนสักวีค ถ้าจะเลื่อนนาน ๆ ใช้ OCP แทนเถ้อ, hirsutism, uterine bleeding from hormonal imbalance (DUB)
• ADR: breakthrough bleeding เกิดจากสัดส่วน proges:estro ที่สูง (ซึ่งทำให้ endometrium → atrophic and ulcerated → irregular bleeding), amenorrhea, androgenic action (high dose), increase BW, headache, decrease HDL

Question 3

anti-progestin in sex hormone therapy 🤘🏻🔥

Answer 3

1st gen - mifepristone

• luteolysis → hCG↓ / PGs in uterus↑ → contraction↑ [ซึ่งทั้งสองขาทำให้เกิด abortion]
• antiglucocorticoid activity
• uses: medical abortion in 1st tri ใช้คู่กับ PGs (medabon: mifepristone+misoprostol), post-coital contraception ยาคุมฉุกเฉินในตปท, induce labor (death in utero), endometriosis, breast CA, leiomyoma, meningioma, excess adrenal cortisol secretion
• ADR: n/v, diarrhea, heavy vaginal bleeding, abdominal pain uterine cramp

2nd gen - ulipristal

• weak glucocorticoid antagonist
• mechanism: inh ovulation by inh LH at hypothalamus and pitui, inh endometrial implantation of fertilized egg
• uses: benign tumor e.g. leiomyoma, postcoital contraception (take pill after SI<120hrs) ในตปท
• ADR: endometrial thickening, hot flush, headache

Question 4

hormonal contraception: COC

Answer 4

combined hormonal contraception ~ combinanation oral contraceptives //effective 99%

• mechanism to inh preg: progesterone → pulse frequency of GnRH↓ → FSH LH↓ → estradiol↓ → no estrogen positive feedback → no LH surge → no ovulation / estrogen → negative feedback on ant pitui → slow FSH secretion
• ควรกินก่อนวันที่ 5 ของ menstrual cycle, take once daily at the same time (usually before bed time to maintain hormonal level)
• clinical uses: oral contraceptive, OB-GYN problem (e.g. severe dysmenorrhea, delay menstruation, DUB, endometriosis, lactation weaning from estrogenic effect)
• contraindication ตัวเหลือง ทุเม่อ สูบบุหรี่: breast CA, endometrial CA, cvs disease, jaundice w prior hormonal contraceptive use, liver tumor, severe HT, thrombotic disorder, prolonged immobilization, female smoker>35yo (>15มวนต่อวัน)
• serious ADR: pulmonary embolism, arterial and venous thromboembolism, HT, hepatic neoplasm, gallbladder disease
• มีแทรกเสริม vaginal ring ด้วยนิดนึง mechanism & ADR เหมือน OCP เลยย

Question 5

hormonal contraception: progestin-only, IUD

Answer 5

progestin-only contraception

• low dosage progestogen aka minipills (e.g. lynestrenol, desogestrel): mechanism → endometrial change, viscous cervical mucus / less effective than COC (70%) / uses → who cant tolerate estrogen ADR, smoke DM cvs or cerebrovascular disease, breast feeding เพราะ estrogen ลดน้ำนมแต่ progestin ไม่ / ADR → irregular period, amenorrhea
• post-coital contraception (e.g. levonorgestrel): high dose progestin, take immediately after SI or not>72hrs / mechanism → increase tubal peristalsis, endometrial change not appropriate for implant / less effective than COC / ADR → vaginal bleeding
• injectible contraception: DMPA - depot medroxyprogesterone acetate (via IM), ฉีด every 3mo / mechanism → inh ovulation / uses → breast feeding, dont want to take COC / contrain → hormone-dependent CA, migraine, liver problem, thrombosis / ADR จำ → intermenstrual bleeding, amenorrhea, delayed return of fertility เลิกใช้ก้ต้องรอเมนกลับมา, increase BW, headache, depression
• Implants (levonogestrel, etonogestrel): ADR → vaginal bleeding / ที่เหลือมันก้คล้ายกันหมด ขอยาดไม่พิมฮะ

intrauterine device (IUD)

• highly effective, can be used in lactating woman
• ADR: local → pelvic pain, dysmenorrhea, hypermenorrhea, leucorrhea / hormonal type ass w ectopic pregnancy คือไรไม่รู้ ㅋㅋ
• ผญที่ไม่ควรใช้ IUD: prostitute or multiple partner, คนที่ไม่เคยท้อง

Question 6

androgen in sex hormone therapy & danazol

Answer 6

androgen

• therapeutic uses: hypogonadism in male, impotence, anabolic agent (increase protein synthesis), drug abuse in sport…, growth stimulator, anemia, osteoporosis อันนี้ไม่มี indication นะ, aging (still on study)
• ADR: virillizing effect in female (e.g. hirsutism acne or abnormal menorrhea), feminizing effect in male (e.g. gynecomastia) จาก negative feedback, toxic effect (edema, increase BW, cholestatic jaundice), hormone replacement therapy may cause BPH or prostate CA :(, oligospermia, priapism ~ persistant erection, premature epiphysis closure
• contrain: pregnancy, prostate CA, breast CA

danazol

• inh FSH → no ovulation, endometrial atrophy
• therapeutic uses: endometriosis, fibrocystic breast disease, hematologic disorder (hemophillia)
• ADR: hot flush, sweating, masculinization, hirsutism, hoarseness, clitoral hypertrophy, edema, increase BW, abnormal liver enz

Question 7

pharmaco of prostate CA

Answer 7

inh androgen synthesis

• GnRH ago (leuprolide): continuous (depot formulation) / uses → prostate CA, endometriosis / ADR → DVT, pitui apoplexy, hot flush, gynecomastia, osteoporosis
• GnRH anta (degarelix): uses → metas prostate CA, assisted reproduction / avoiding initial surge of testosterone from GnRH
  agonist ข้อดีที่ต่างจาก ago / ADR → hot flush, weight gain, abnormal hepatic enz
• inh enz of testosterone production (abiraterone acetate): inh CYP17A1 / ADR → HT, hypoka, fluid retention, adrenal insuff, hepatotoxicity

ALSOOOOOO
- androgen-receptor anta (flutamide, bicalutamide)
- estrogen therapy
- steroid (prednisone)

Question 8

oxytocin

Answer 8

• drug: carbetocin (use for uterine atony, postpartum hemorrhage)
• stimulate cervix vagina breast & contract myoepith cause milk ejection
• use: induction labor, postpartum bleeding (ถ้ามี contraindication ในการใช้ methergin or sulprostone)
• ADR: uterine rupture and fetal ischemia (if use in high dose), n/v, high BP, water intoxication
• contraindication: cephalo-pelvic disproportion (CPD), fetal distress, uterine inertia มดลูกไม่ contract, breech or face or transverse presentation, previous uterine operation ถ้าเคยคลอดลูกด้วยการผ่า ท้องถัดมาต้องผ่าหมด, ถ้าจะผ่าคลอดก็ห้ามให้

Question 9

prostaglandin (PGE2)

Answer 9

• drug: dinoprostone, sulprostone, misoprostol
• use: cervical ripening (ทำให้ปากมดลูกนิ่ม เด็กพร้อมออก), abortion, postpartum hemorrhage
• clinical toxicity: stimulatory action → smm of GI tract, n/v, diarrhea / transient pyrexia / vasodi (if large dose)

Question 10

ergot alkaloid

Answer 10

• drug: ergonovine (ergometrine), methylergometrine, bromocriptine, ergotamine, dihydroergotamine
• claviceps purpurea
• action: sustain uterine contract
• use: postpartum hemorrhage
• ADR: n/v, high BP, decrease pain threshold

Question 11

สรุปอาการ แล้วมาแมตช์ยาที่ใช้ได้จ้า เลค 7

Answer 11

• postpartum bleeding: oxytocin, methylergonovine (methergin), prostaglandin (PGE2), misoprostol (PGE1)
• therapeutic abortion ∼ medical abortion: medabon is mifepristone+misoprostol (PGE1)

Question 12

tocolytic agent: beta-2 ago, calcium ch blocker, magnesium sulfate, PGS inh, oxytocin anta

Answer 12

1. beta-2 ago
   
   • drug: terbutaline, salbutamol, mirabegron
   • ADR: tachycardia, increase renin and hydration which can lead to pulmonary edema and myocardial failure
2. calcium channel blocker
   
   • drug: nifedipine
   • action: inh uterine contract → relax
   • use: premature labor
   • ADR: flushing, n/v, tachycardia, low BP
3. magnesium sulfate
   
   • action: inh uterine contract
   • use: eclampsia, severe preclampsia
4. prostaglandin synthetase inh
   
   • drug: indomethacin
   • action: inh COX lead to decrease PGS synthesis, inh uterine contract
   • ADR: closure of ductus arteriosus lead to pulmonary HT, oligohydramnios
5. oxytocin anta
   
   • drug: atosiban
   • action: block action of oxytocin at cellular level
   • use: preterm contraction
   • low ADR

Question 13

pregnant HT: antihypertensive drug, anticonvulsant

Answer 13

1. antihypertensive drug
   
   • hydralazine: action → vasodi / ADR → headache, nv
   • methyldopa: action → centrally acting α-adrenergic ago
2. anticonvulsant
   
   • magnesium sulfate: monitor urine, deep tendon reflex, respiratory rate

Question 14

clomiphene citrate

Answer 14

• antiestrogen use in induction of ovulation in intact HPA axis w adequate estrogen production
• bind to ER and inh negative feedback of estrogen at hypothalamus and pitui
• increase FSH LH, increase ovulation, increase spermatogenesis
• use: infertility
• ADR: hot flush, blurred vision, ovarian hyperstimulation syndrome (OHSS), multifetal gestation (แฝดด)

Question 15

gonadotropin

Answer 15

• FSH: use for ovarian stimulation, IVF (in vitro fertilization)
• hCG: use for infertility, cryptorchidism
• use: hypogonadotropic hypogonadism, PCOS who not response to clomiphene, conjunct w IVF
• ADR: multiple birth

Question 16

ovarian hyperstimulation syndrome (OHSS) ก้คือเปน ADR ที่มีต้อกของตัวเอง

Answer 16

• s&s: abdominal pain and/or distention, nv, diarrhea, dyspnea, oliguria, marked ovarian enlargement on u/s
• serious ADR: hypovolemia, e’lyte abnormality, acute respiraotry distress, thromboembolism event, hepatic dysfx
• prevention: w held FSH for 1-2 days if serum E2 reach top level

Question 17

GnRH ago ∼ buserelin —??

Answer 17

use for ovulation induction แหละ แต่มันไม่มีหน้าของตัวเองอะ..

Question 18

endometriosis druggggg

Answer 18

1. OCP: suppress GnRH axis / ADR → pseudopregnancy มมเมน
2. progestin: drug → MPA, dienorgest / ADR → breakthrough bleeding
3. GnRH analog: drug → leuprorelin, goserelin / action → suppress GnRH axis / ADR → longterm ระวัง osteoporosis jaa
4. androgen: drug → danazole / ปจบไม่ฮิตละ ADR เย้อ

Question 19

syphilis ABX

Answer 19

• causative: treponema pallidum
• drug of choice: penicillin, ceftri, doxy, azithro
• each phase
  
  • primary, secondary, early latent: benzathine pen G [single dose]
  • latent>1yr or unknown: benzathine pen G [weekly x 3 dose]
  • neurosyphilis: aqueous crystalline pen G / or use w procaine
• alternative for penicillin allergy
  
  • primary, secondary, early latent: doxy, ceftri
  • latent>1yr or unknown: doxy
  • neurosyphilis: ceftri
  • preg w syphilis: penicillin desensitization protocol, ceftri, erythromycin
• jarisch-herxheimer (JH) reaction → give NSAID

Question 20

genital herpes ABX

Answer 20

causative: HSV-1 HSV-2

drug: acyclovir, famciclovir, valacyclovir //no topical naka

Question 21

chancroid ABX

Answer 21

causative: Haemophilus ducreyi

drug: azithro, ceftri, cipro, erythro

Question 22

lymphogranuloma venereum (LGV) ABX

Answer 22

• causative: chlamydia trachomatis
• recommend drug: doxy
• alternative drug: azithro, erythro

Question 23

gonococcal urethritis (GC) ABX

Answer 23

• causative: N. gonorrhea
• drug of choice
  
  • ceftri / +add-on doxy, azithro (if chlamydial hasnt excluded)
  • cefixime ให้คู่นอนไปกิน
• disseminated gonococcal infection (DGI)
  
  • drug: ceftri for 7 days / can be switch to oral (cefixime) ให้ครบคอร์ส

Question 24

nongonococcal urethritis (NGU) ABX

Answer 24

• causative: chlamydia trachomatis ย้อมไม่ติด
• recommend drug: doxy
• alternative drug (เกิด treatment failure ได้): azithro, levoflox

Question 25

bacterial vaginosis (BV) ABX

Answer 25

causative: anaerobic bac (3 ตัวนั่น) recommend: metronidazole, clinda //ตปทนิยมใช้ทา แต่ถ้าคนไข้อยากกินแทนก้ได้ ๆ

Question 26

trichomoniasis ABX

Answer 26

causative: trichomonas vaginalis recommend: metronidazole

Question 27

vulvovaginal candidiasis (not STI) ABX

Answer 27

causative: candida albicans recommend: clotrimazole

Question 28

post-exposure prophylaxis for bac STI prevention (doxy PEP)

Answer 28

“**200 mg of doxycycline** within **72 hours** after **condomless** sex” for ป้องกัน: gonorrhea, chlamydia, syphilis //เพราะ doxy เป็น drug of choice ของไอพวกนี้

Question 29

basic menopause

Answer 29

- symptom - early: vasomotor → hot flush, night sweat / psycho → dizzy, palpitation, irritability, headache, insomnia, depression - moderate: urinary, sexual problem - long-term: CVS disease, osteoporosis - peak bone mass: พีคช่วงอายุ 20-30 ละค่อย ๆ ลด — ของผช gradual แต่ของผญลดฮวบมันเลยรู้สึกได้ - estrogen benefit - bone มีผลดีต่อกระดูก :)) เพราะไป suppress osteoclast ทำให้ bone resorption ↓ - circulating lipid เพิ่มไขมันดี ! HDL-c → cardiovascular mortality ↓ - may reduce AD, being antioxidant

Question 30

menopausal hormone therapy (MHT) 5 ตัวเบา ๆ ซึ่งเบาจริง จะเอาไรมาออกนิ

Answer 30

1. estrogen งงมาก คอนเท้นครือ? - natural estrogen: estrone, estradiol, estriol (cream, vaginal tab) - route: local (less ADR), transdermal patch or gel, vaginal cream, vaginal tablet 2. progesterone - MPA (synthetic progesterone) should be avoid (increase risk of CA breast) - route: เด่น ๆ ก็ oral, patch 💡 duration of tx depend on severity: **vasomotor** 3mo-2yrs, **vaginal atrophy**>4-6wk, **premature menopause** treat until average menopausal age, **NOT** start MHT for prevent osteoporosis after 60yo (เพราะเลย window of opportunity ไปแล้ว) 3. androgen: combine w estrogen, in case of sexual desire (ไม่ได้ใช้บ่อย), bone remodeling ↑ 4. raloxifene (SERM): estrogenic effect at bone CVS, antiestrogenic at uterus breast / ADR hot flush, leg cramp 5. tibolone: เป็น estrogenic+progestogenic+weak androgenic, for tx menopause (sexual desire) p.s. MHT ADR — endometrial cancer, breast cancer โปรดใช้อย่างมีสติ

Question 31

osteoporesis

Answer 31

"prevention: give calcium+vitD **during window of opportunity** till early menopause" 1. calcium - recommend dietary intake: adult 1000mg/day, เริ่มแก่ 1200mg/day - food: diary product, soy milk, tofu, fish w bone, green vegetable, blacksesame - calcium store: 99% in skeleton รู้อยู่ละ - therapeutic use: hypocalcemic state, prevent osteoporosis - prep: calcium carbonate (take w meal), calcium acetate 2. vitD - action, hypovitaminosis, hypervitaminosis - therapeutic use: nutritional or metabolic rickets, hypoPTH, prevent osteoporosis - recommend dietary intake: adult 600IU/day, เริ่มแก่ 800IU/day - prep: ergocalciferol (vitD2 ซึ่งเป็น inactive form) 3. anti-resorptive - bisphosphonate: induce osteoclast apoptosis, stabilize hydroxyapatite structure อาจทำให้กระดูกเปราะเลยต้องมี drug holiday / **1st line** for postmenopausal osteoporosis, also tx paget, hypercalcemia of malig (พวก MM), steroid-induce osteoporosis / **ADR** → esophagus ulcer, osteonecrosis of jaw, ไม่ควรใช้ long-term (>5yrs) - denosumab: RANKL anta / 2nd line for postmenopausal osteoporosis, also tx Iatrogenic hypogonadism in male / contraindication in hypocalcemia / ADR → osteonecrosis of jaw (in cancer pt), pancreatitis, hypoCa, hypoPO4 - calcitonin ฟังขำ ๆ: for tx paget disease, hypercalcemia, postmenopausal osteoporosis (not common use that much ปะ) 4. anabolic dual effect - PTH (teriparatide): increase bone formation by osteoblast / for tx severe osteoporosis in postmenopause แบบที่กระดูกหักละอะ ขั้นนั้น / ADR → hyperCa, ไม่ควรใช้ติดต่อกันเกิน 2 ปีเพราะจะ lead to bone loss - romosozumab: Ab sclerostin inh, tx high risk fracture postmenopausal osteoporosis / ADR → MI, stroke, or even death from CVS disease

Question 32

andropause

Answer 32

- CC: erectile dysfx (from TT ↓) พวกอาการอื่นเดาได้ เคยเรียนแล้ว - PADAM (partial androgen def in aging male) ↔ andropause ↔ LOH (late-onset hypogonadism) - testosterone replacement therapy: increase prostate CA risk, prostate hyperplasia, prostate specific antigen (PSA) ↑ - drug: sildenafil เน้นตัวเดียว, vardenafil, tadalafil - sildenafil (PDE5 inh) //fil ความต้องการ - mechanism: ลดการสลายของ cGMP ทำให้ cGMP ↑ → vasodi - CYP3A4: increase toxicity of macrolide, imidazole, statin, antiretroviral drug / ห้ามใช้คู่กับ nitrate เพราะจะเกิด severe hypotension ถึงตายได้เลย - ADR: headache, flushing, rhinitis, dyspepsia