Ethinyloestradiol is rapidly and well absorbed from the gastrointestinal tract. The presence of an ethinyl group at the 17-position greatly reduces hepatic first-pass metabolism compared with oestradiol, enabling the compound to be much more active by mouth, but there is some initial conjugation by the gut wall, and the systemic bioavailability is only about 40%. Ethinyloestradiol is highly protein bound, but unlike naturally occurring oestrogens, which are mainly bound to sex-hormone binding globulin, it is principally bound to albumin. It is metabolised in the liver, and excreted in urine and faeces. Metabolites undergo enterohepatic recycling.
ORAL CONTRACEPTION, ENDOMETRIOSIS, DYSFUNCTIONAL UTERINE BLEEDING, DYSMENORRHOEA AND MENSTRUAL IRREGULARITIES: Usually 0.05mg along with a progestin daily. In combination with a progestin 0.05-0.1mg for variable periods. 0.05mg daily from 5th day of cycle for 21 days. discontinue for 7 days.
HRT: 0.05mg daily for 3 weeks with the 4th weeks off.
FEMALE HYPOGONADISM: 0.05mg 1-3 thimes daily for 2 weeks followed by progesterone for 2 weeks followed by progesterone for another 2 weeks. Repeat courses for 3-6 months. INOPERABLE BREAST CANCER IN SELECTED POSTMENOPAUSAL WOMEN: 0.1mg t.i.d INOPERABLE PROSTATIC CANCER 1.5-2.0mg daily.
Oestradiol is the major oestrogen in the premnopausal women. But it is not very effective when given orally. Addition of a 17-alpha-ethinyl group enhances oral activity. Ethinyl oestradiol has similar actions as oestradiol. It promotes growth of endometruim, thickening, stratification and cornification of the vagina, inhibits anterior pituitary by negative feed back effect and causes capillary dilation, fluid retention and protein anabolism. Ethinyl oestradiol is part of several oral contraceptive formulations along with a progestin.
ACE Inhibitors Antagonises hypotensive effect Anti-coagulants: Efficacy of anticoagulants reduced
TCAs: Pharmacological effects of TCAs altered, increased incidence of toxicity.
Antifungals: Griseofulvin accelerates metabolism of ehtinyloestradiol, reduced contraceptive effect.
Barbiturates, Rifampicin: Efficacy of ethinyloestradiol reduced; failure of contraception.
Beta blockers: Hypotensive action antagonised
Corticosteroids: Clearance reduced and elimination half-life o corticosteroids increased.
Cyclosporine: Increased plasma cyclosporine concentration.
Dantrolene: Hepatotoxicity, especially in women > 3 yrs of age.
Lab Test: With high doses of ethinlyloestradiol: Increased Sulfobromophthalein retention. Increased Prothrombin and cactors VII, IX, & X; decreased antithrombin III; increased norepinephirine: induced platelet aggregability. Increased thyroid binding globulin (TBG) leading to increased ciculating total thyroid hormone, as measured by PBI, T4 by column or T4 by radioimmuno assay. Free T3 resin uptake decreased, reflecting elevated TBG: Free T4 concentration unaltered. Impaired glucose tolerance, decreased pregnanediol excretion, reduced serum folate concentration, increased serum trighlyceride and phospholi pid concentration.
Effect & Precautions
Nausea, epigastric distress, prutus, skinrash, gynaecomastia, feminization in males, thromboembolism
Breast Feeding: Use only if clearly indicated.
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