Our Express Video of the Week covers selective estrogen receptor modulators from the Pharmacology section of the Reporoductive chapter in First Aid for the USMLE Step 1.
Let’s say you have a patient with newly diagnosed breast cancer one of the first clues to developing a therapeutic strategy is to find out what kind of receptors are present as they may present as a target for certain medications in this lecture we will be learning what are the main drugs in the selective estrogen receptor modifier class understand the mechanism
Of action indicate the clinical uses and explain what kind of side effect profile we should be anticipating selective estrogen receptor modulators also known as serms are drugs that have different effects on estrogen receptors depending on where they are located basically they can be agonist or antagonist depending on where they bind here’s a little general farm
Review what type of drug is not able to be overcome by increasing the amount of partial agonists that’s right it’s a non-competitive antagonist clomiphene works by inhibiting estrogen receptors in the hypothalamus it does this with a combination of both competitive and non-competitive means normally estrogen binds with the estrogen receptors on the hypothalamus
And negatively inhibits gnrh release which reduces fsh and lh secretion from the anterior pituitary so clomiphene works by inhibiting the estrogen receptors and prevents this negative feedback thereby increasing lh and fsh this stimulates ovulation making clomiphene a good first line treatment for which condition that’s right for infertility testable side effects
Include hot flashes ovarian enlargement multiple simultaneous pregnancies and vision problems the reason behind the multiple gestation is that clomiphene causes an uncontrolled ovulation where both ovaries might release multiple eggs each unaware of what’s happening on the other side another serum that is highly board testable is tamoxifen it competitively binds to
The estrogen receptors as an antagonist in breast tissue as well as a partial agonist in uterine and bone tissue it is used to treat and prevent recurrent estrogen receptor or progesterone receptor positive breast cancer in pre and post-menopausal women on the other hand it is a partial agonist on the endometrium and it is linked to what cancer well that would be
Endometrial cancer so it is kind of a double-edged sword and must be used with caution also patients who smoke are at a higher risk of experiencing thromboembolic events and since we already know that tamoxifen works as a receptor agonist in bone try to recall from the musculoskeletal chapter what you learned about the effects of estrogen on the bone that’s right
It helps prevent bone loss riloxafin is a serm that is also an antagonist at the breast also has increased risk of thromboembolic events in smokers but what makes it unique is that it has estrogen agonist properties on bone without the effects on the endometrium it reduces resorption making an effective treatment for osteoporosis like tamoxifen it is an antagonist
On breast tissue so it also is used for invasive breast cancer but only in postmenopausal women unlike tamoxifen raloxophene is an antagonist on the endometrial tissue and therefore does not promote endometrial cancer the bottom line is that whilst tamoxifen and raloxophene are both agonists at the bone only tamoxifen is a partial agonist at the endometrium so
Only tamoxifen is associated with increased risk of endometrial cancer that is raloxifene is not associated with endometrial cancer so you can relax with reloxifene on the other hand tamoxifen would be safe to use in patients with a history of a hysterectomy since they no longer have an endometrium flash quiz what is the primary use of the serm tamoxifen and
The answer is to treat estrogen receptor positive breast cancer do make sure you know its side effects though especially the fact that it can ironically cause endometrial cancer as well all right let’s go over a test yourself question we have a 37 year old female who comes to the office with her husband with a two-year history of difficulty conceiving they have
Considered several options and would like to attempt pharmacological therapy the doctor suggests a medicine that works by inhibiting the negative feedback at the hypothalamus to stimulate ovulation the physician should inform the patient on which possible adverse reactions the answer is d hot flashes the excessive lh and fsh can lead to adverse reactions such
As hot flashes ovarian enlargement multiple simultaneous pregnancies and visual disturbances so wrapping up the serms lecture we learned that there are three main drugs in this class clomiphene tamoxifen and raloxifene each has its own unique binding capability clomiphene is used mainly for infertility treatment tamoxifen for estrogen receptor positive breast
Cancer and reloxifene for osteoporosis they all increase the risk of hot flashes and venothrombotic events but each has its own unique risk profile thanks for watching and be sure to click thumbs up if you enjoyed this video
Transcribed from video
USMLE-Rx Express Video of the Week: Selective Estrogen Receptor Modulators By USMLE-Rx