Review of Pharmacology - 9E (2015)

Review of Pharmacology
Actions
• Natural estrogens are ineffective orally due to extensive first pass metabolism.
Estrogens undergo enterohepatic circulation that is also responsible for hepatic adverse
effects (hepatic adenoma and thromboembolism).
• Growth and development of female reproductive system.
• Increased risk of breast, endometrial and cervical carcinoma.
• Feedback inhibition of gonadotropin (LH/FSH) secretion.
• Stimulation of CTZ to cause nausea and vomiting.
• Increased predisposition to deep vein thrombosis and pulmonary embolism due to
increased synthesis of factor VII, VIII, IX and X and decreased production of
antithrombin III by the liver. Favourable effect on lipid profile by decreasing LDL-C
and LP (a) and increasing HDL-C. Slight increase in triglycerides may also occur.
• Glucose intolerance and sodium and water retention.
• Maintain bone mass by decreasing the bone resorption.
• Increased risk of gall bladder stones and cholestatic jaundice.
• Can result in hepatic adenoma on prolonged use.
• Vasodilation by increasing the production of NO.
Endocrinology
Progesterone is added to hormone
replacement to decrease
the risk of endometrial carcinoma.
Indications
Deficiency of this hormone as seen in postmenopausal females may result in osteoporosis,
hot flushes, urogenital atrophy and increased risk of cardiovascular diseases. Major use
of estrogen is for hormone replacement therapy (HRT) in post menopausal females.
Progesterone is added to HRT to decrease the risk of endometrial carcinoma. Estrogens can
reverse all the features of its deficiency.
• Another important use of estrogens is as a component of oral contraceptives.
• These can be used in the treatment of dysfunctional uterine bleeding (DUB), if it is
due to estrogen withdrawal.
• Estrogens reduce testosterone production due to feed back inhibition of LH secretion.
This property has been utilized for the treatment of testosterone dependent tumors like
prostatic carcinoma. But now a days, GnRH agonists and antagonists are preferred for
this indication.
256
N
Ospemifene is a new SERM
indicated for dyspareunia due to
menopause
Adverse effects and interactions
• Treatment with estrogen can result in feminization, gynaecomastia and decreased libido
in males and nausea, migraine and increased risk of carcinomas (endometrial and breast) in
females.
• Diabetes, fluid retention, hepatic adenoma, cholelithiasis and predisposition to thromboembolism
can be seen in both the sexes.
• Increased incidence of vaginal and cervical adenocarcinoma was noted in the female
offsprings of mothers who have taken diethylstilbesterol (DES) during first trimester
of pregnancy. Intake of DES during pregnancy has also been associated with
development of hypospadias in new born babies.
• Antimicrobials like ampicillin and enzyme inducers like rifampicin decrease the effect
of estrogen; former by inhibiting enterohepatic cycling and latter by increasing the
metabolism of estrogen.
Selective Estrogen Receptor Modulators (SERMs)
These are the agents that act as estrogen agonists in some tissues and antagonists in other
tissues. Agonistic action is beneficial in tissues like bone (decreased resorption) and blood (better
lipid profile) whereas it is deleterious in endometrium, breast (increased risk of carcinoma) and liver
(predisposition to thromboembolism).
https://kat.cr/user/Blink99/