Reproductive Pharmacology PDF

Reproductive pharmacology Physiology of menstrual cycle:  Estrogen: Natrual estrogen: estradiol, estrone,estriol Semisynthetic estrogen: ethinyl estradiol,mestranol physiologic effects: 1- normal development of genital tract and breast 2-development of female secondry sex characters. 3- metabol...

Reproductive pharmacology Physiology of menstrual cycle:  Estrogen: Natrual estrogen: estradiol, estrone,estriol Semisynthetic estrogen: ethinyl estradiol,mestranol physiologic effects: 1- normal development of genital tract and breast 2-development of female secondry sex characters. 3- metabolic effect: increase bone mass and prevent bone resorption- Increase blood glucose and TGS Salt and water retention 4-increase blood coagulation  Therapeutic uses: 1- contraceptive pills 2-dysfunctional uterine bleeding 3-replacement therpy in ovarian  hypofunction 4-postmenopausal symptoms :atrophic  vaginitis, osteoporosis 5- cancer prostate  Progesterone and progestins: Natural : progesterone injection  Synthetic: medroxy progesterone acetate   therapeutic uses:  1- contraceptive pills 2-dysfunctional uterine bleeding  3-dysmenorrhea and endometriosis  4-threatened abortion Adverse effects: 1-breakthrough bleeding 2-increase risk of birth defects if given in early pregnancy 3-liver dysfunction  Androgens : Natural androgens :andeosterone and testosterone  synthetic androgens: methyltestosterone  Uses of androgens:  chronic debilitating diseases: renal 1-  failure,AIDs. 2- chronic anemia : sickle cell anemia , aplastic  anemia 3- use by athletes: to increase  muscle bulk and strength. Adverse effects:  1- reduction in spermatogenesis after stopping  2-methyltestosterone is hepatotoxic  contraindications:  1- prostatic tumors (benign and malignant)  2- liver diseases   Hormonal contraceptives: Types of hormonal contraceptives:  1- combined preprations( the most effective type):  contain both estrogen and progesterone given from the 5th day of menstruation for 21 days Single entity preprations:2-  1- progesterone alone(minipills): do not affect lactation  and do not carry risk of thrombosis but can cause uterine bleeding 2- estrogen alone : it is used within 72 hours after sexual  intercourse for 5 days 3-slow release progestins:medroxyprogesterone acetate  (depo-provera) given I.M every 3 months it is suitable for unreliable women 4-implantable progestin preparation   COC mechanism:  Combined oral pills: Commonly known -  Most effective and reversible method of -  fertility control -One tablet is taken every day for 21 days  followed by a 7days break to induce withdrawal bleeding Monophasic pills:  The pills contain constant dose of both  estrogen and progestin Multiphasic pills:  The pills contain constant dose of estrogen  with increasing doses of progestin to mimic the natural female cycle  Mechanism of action: Negative feedback inhibition of pituitary  gonadotropins(supressing FSH(estrogen), LH release(progesterone). -Estrogen and progestrone produce endrometrial  changes. Major Effect Is Anovulation and  Progestin Increase viscosity of cervical mucus impedes sperm penetration. Major effect is anovulation and impairment of sperm  transport and oocyte implantation.Major Effect Is  N.B Lactating women : progesterone only pills,  coc after 6 months Non- lactating women : coc after 3-6weeks  or after menstruation Amenorrhea : at any time after excluding  pregnancy + barrier method for 7 days 1st and second trimester abortion: during 7  days  Mini pills(progestin-only pills): Preparations:  1-Norethindrone-0.350mg  2- levonorgestral-0.075mg  3-norgestral- 0.030 mg  Indication:  1- age more than 40 years  2-lactating women  Mechanism of action: 1- cervical mucus thicking : effect starts in 2-4 hrs  and lastfor 20-24 hours 2-inhibit ovulation Schedule: 1st day of M.C and a backup method for 7 days- 6 weeks after delivery- no backupmethod- Missed tablet –backup method for 48 hrs Schedule: -1st day of M.C and a backup method for 7 days- -6 weeks after delivery- no backupmethod Missed tablet –backup method for 48 hrs advantages Can be used above 16 yrs of age , smokers 3-better in DM, CVS diseases ,SLE 2- obesity -disadvantages Irregular bleeding, Acne, mastalgia, amenorrhoea Contraindications: 1- pregnancy 2- breast cancer 3-unexplained vaginal bleeding Adverse effect of hormonal contraceptives: CVS:  The most serious side efects especially in women above  35 years and in women who are smokers: 1- hypertension and increase risk of myocardial  infarction. 2-thrombosis  3-increase TGs  CNS:  1- mood changes and depression  2-migraine headache  GIT:  1-Nausea and vomiting  2-cholecystitis and gall stones   Adverse effects: Endocrinal:  1-hyperglycemia and DM  2- weight gain and edema due to salt and water  retention 3-menstrual irregularities:  -spotting bleeding, amenorrhea, dysmenorrhea  4-Acne and hirsutism  Cancer: increase risk of breast cancer.  N.B: causes of failure of contraceptive pills:  1- if taken with enzyme inducers:e.g: rifampin,phenytoin  2-if taking broad spectrum antibiotics: tetracyclines  3-paraffin oil : decrease intestinal absorption of  contraceptive pills  Contraindications: 1-hypertetion or ischemic heart disease  2- history of embolism,thrombosis or cerebral  hemorrhage 3-history of breast cancer  4-migraine headache  5-diabetes mellitus  6-obese,smokers,women above 35  7-pregnancy  8-depression   Anti-estrogens: 1- clomiphene citrate:  Blocks estrogen receptors in hypothalamus and  pituitary, increase FSH and LH ,stimulate ovulation Adverse effect :ovarian enlargement.  2- selective estrogen receptor modulators(SERMs).  SERMs are ligands for the estrogen receptor that have  agonist activity in one tissue but may have antagonist activity or no activity in another tiusse. Examples: tamoxifen, raloxifene  Tamoxifen: an estrogen antagonist in the breast but  an agonist in the uterus and bone It is used in the treatment of advanced breast  cancer and prevention. Adverse effects: tamoxifen increase the risk of  endometrial cancer and thrombotic complications. Raloxifene:  It is an agonist in bone but has on effect on uterus or  breast It is used for the treatment and prevention of  postmenopausal osteoporosis. Adverse effects: hot flashes and thrombotic  Complications Antiandrogens: 5 a-reductase inhibitors : finasteride It inhibits 5 a-reductase enzyme responsible for conversion of testosterone into active form of dihydrotestosterone(DHT) It is used in treatment of benign prostatic hyperplasia,male baldness and treatment of hirsutism in female  2- testosterone receptor blockers: 1-cyproterone acetate : is a competitive bloker of  testosterone receptrs ,it is used in hirsutism in females. 2-flutamide: used in cancer prostate  Thank you 