B6 Endo/GU Pharmacology Final Exam with Correct Answers.

B6 Endo/GU Pharmacology Final Exam Definition & General Causes of Infertility - fail conceive after specif time w/ reg interc w/o contrac (ie. 12 mts if 35y/o & 6mts if 35 or PCOS) - 1/3 causes each fem orig, male orig, unk/combo of both partners - conceiv prob decr 3-5%/yr after 30-32, faster after 37-40y/o by dim oocyte qual+quant Pathophysiology, Sx, Labs, Causes, Solution for WHO Group I Infertility - - Pathophys = hypogonadotr hypogon by hypoth-pit fail - Sx/labs = amen, low FSH/LH, low estrad, +/- elev prolactin - Causes = eating disords, wt/exerc extremes, hyperprol - Soln = correct cause (ie. gain wt, thyr med, dopa ag); reg Gn & ind ovul Pathophysiology, Sx, Labs, Causes, Solution for WHO Group II Infertility - - Pathophys = normogonadotr anov by hypoth-pit-ovar fail **MOST COMMON** - Sx/labs = nl FSH, nl-elev LH, nl estrad, elev PRL, galactorr - Causes = PCOS, ovul-rel dysfunc, hyperPRL - Soln = meds ind ovul, Gn to reg ovul, decr PRL by Dopa ag Pathophysiology, Sx, Labs, Causes, Solution for WHO Group III Infertility - - Pathophys = hypergonadotr hypogon by ovar fail - Sx/labs = elev FSH, low estrad - Causes = adv age - Soln = oocyte don, IVF Other causes of Infertility - ut/outfl tract abnorms, tub dis by PID - Treat w/ meds/IVF Pathophysiology, Sx, Labs, Causes, Solution for Male Factor Infertility - - Pathophys = anat vars, chrom abnorms, erec/ejac dysf - Sx/labs = abnl FSH/LH, testost, semen analysis - Causes = inf, inj, tox expos, syst dis, sperm ABs, hypogon, testic dis, sperm transp defs - Soln = IVF, intraut insem, don sperm **MOST COMMON CAUSE is cryptorch** Overview of Repro Endocrinology - hypoth secr GnRH stim ant pit gonadotropins LH+FSH stim ovars+testes - -reg by inhibin (-FSH) & elev estrog/progest/testost (-GnRH+LH/FSH) - +reg by activin (+FSH) & estrog (+LH/FSH mid-cyc) Role of Gonadotropins in Menstrual Cycle - - Follic ph (prolif ph) = low estrog/inhib -- elev LH/FSH stim follic dev for dom foll form; high sust estrog, mid-cyc LH/FSH surge for ovul - Luteal ph (secr ph) = corp lut secr estrog+progest, endom prep for implant by progest incr blood supp spir arts **ovar dysf accounts for most infert cases** B6 Endo/GU Pharmacology Final Exam Gonadotropin Function in Women - - FSH = germ c mat by dir stim follic gr+mat, enh granul c LH responsiveness; steroidogen by follic ph estrog prod in foll - LH = steroidogen by ovar estrog & lut ph estrog+progest for follic w breakd for ovul & subseq resuming oocyte meiosis - hCG = LH analog for steroidogen, plac estrog+progest dur preg Gonadotropin Function in Men - - FSH = testost bind in Sertoli c mediating cell mat+spermatid diff (spermatogen) - LH = steroidogen by test Leydig c prod testost Role of Gonadotropins in Fertility & Pregnancy - - LH surge = impend ovul prediction det by ur ovul pred kits -- should engage in interc if LH elev - implant -- emb hCG prod working @ LH-R, meas in preg tests prev CL loss -- CL maint cont prod progest+estrad until placenta takes over Description & Treatment of PCOS - most comm anov infert cause w/ menstr irreg, infert, obes, hyperandrog, insul resis - Treat = wt red, low-d OCP/progestin decr LH+androg synth, Spirono for acne+hirsut b/c anti-androg, Clomiphene if desire preg, MEtformin if diab/metab synd feats or ocul issues, Aromatase inhibs off-lab for ovul Non-pharmacologic therapy for Infertility - - smok cess - wt modul BMI30 (ideal 18-30) - red excess caffeine - EtOH cess - folic ac suppl decr NTD w/ 400mcg/d, 5mg/d for high risk NTD incl obes, DM, epilep, hemat disords, prev NTD kids - approp coitus freq Q1-2d around expec ovul Description of Ovulation Induction (OI) for Infertility Management - used in anov pts to achieve preg w/ interc/IUI (just trying to control time of ovul) - most for PCOS, hyperPLN, hypogonatr hypogon (uncomm) Description of Controlled Ovarian Stimulation (COS) for Infertility Management - pts already having ovul cyc w/ unexpl infert, struc abnorms+dis - ova coll+fert ex vivo then reimplant (IVF) Pharmacological Management of Infertility - incl ovul induction & controlled ovar stim **mult pregs can occur** Drug Classes & Examples for Infertility Treatment - - SERMs = Clomiphene - Arom inhibs = Letrozole, Anastrozole - Gonadotropins = FSH, hMG (hum menop gonadotr), hCG - Dopa ags = Bromocriptine, Cabergoline - GnRH ags = Leuprolide, Goserelin - GnRH antags = Cetrorelix, Ganirelix B6 Endo/GU Pharmacology Final Exam - Progesterone Procedures for Treatment of Infertility - - Intraut insem (IUI) = prep sperm insert into ut just before antic ovul time often w/ Clomiphene and/or gonadotr for ovul ind - IVF & emb tx = ova coll, fert ex vivo, reins into ut; used w/ contr ovul stim (ie. gonadotr, GnRH ag/antag) Drug Classes used for Ovulation Induction (OI) - - Clomiphene - Aromatase Inhibitors - Gonadotropins - Dopamine agonists MOA, Indications, AEs, CIs of Clomiphene Citrate (clomid) for OI - - MOA = PO SERMlike action, part ag @ ER inhib estrog -FB -- hypoestrog state perceived by bod for incr GnRH rel incr FSH/LH+ovul ind; NO progest (ie. preg-prom), androg, anti-androg effs - most widely used agent for WHO GrII infert (normogonadotr anov) - Indics = infert by PCOS, anov, unexpl infert concom w/ IUI - AEs = common flush, VM sx, vis disturb; serious vis loss, **ovar hyperstim/HT (OHSS), mult pregs** - CIs = abnl ut bl, endom carc, liv dis, ovar cysts, preg, uncontr thyr/adr dysf Clinical Notes for Clomiphene Citrate - - beg menstr cyc D3-5 x5d, max 6cyc use w/ ovul most @6-12d after ther so time sex interc/IUI accordingly - simple, effic, cost-effec, safe w/ 75% women ovul & 30-40% bec preg - DOES NOT corr underl PCOS abnorms (ie. hyperinsul, hyperandrog) MOA, Indications, AEs, DIs, CIs of Anastrozole for OI - - MOA = arom inhib block aromatase conv androg to estrog -- +LH/FSH for ovul ind (real hypoestrog state) - Indics = FDA approv for breast ca, under investig for fail conceive w/ clomiphene by menstr cyc D3-7 admin x5d - AEs = common ed, hot flash by vasodil, rash (menop sx); serious **decr BMD** - DIs = Tamoxif red anastroz levels - CIs = preg, caution in IHD hx MOA, Indications, AEs, DIs, CIs, Notes of Letrozole for OI - - MOA = arom inhib - Indics = FDA approv for br ca & OI in endometriosis+PCOS - AEs = common ed, hot sw, appet loss, **decr BMD/fx** - DIs = 5-FU, Cilostazol, clarithro, tamox, propranolol; CYP3A4 subs, 2A6 inhib, 2C19 inhib -- use anastroz instead in these pts - CIs = hypersens, preg - Notes = more live births than Clomiph & no incr risk Examples, MOA, Indications, AEs, CIs, Notes of Gonadotropins for OI - incl hCG (LH analog to mimic LH surge), hMG (1:1 FSH:LH), FSH - MOA = nl ovar foll dev+mat in women, gon ster prod in wom+men, spermatog in men by cont elev levels desensit ant pit GnRH rel & pulsat expos to physio levels stim GnRH