Tamsulosin

Tamsulosin

Russ Tolliver

Tamsulosin, or tamsulosin hydrochloride, is a synthetic compound that was approved for use in 2007 for the treatment of obstruction of the bladder outlet, a known symptom of benign prostatic hypertrophy or enlargement of the prostate gland.¹ When the prostate gland enlarges, it applies pressure on the outlet of the bladder oftentimes blocking urine flow.² Tamsulosin hydrochloride was developed using a target-based approach. Alpha-adrenoreceptors (1A,1B, & 1D) discovered in the prostate and around the bladder were found to control smooth muscle function in this area. The drug was discovered/designed to inhibit the alpha1A-adrenoreceptor. Inhibition of this receptor caused the surrounding muscle to relax, decreasing the pressure on the bladder outlet, resulting in an increased rate of flow of urine.

Tamsulosin inhibits the function of the alpha1A-adrenoreceptor (α_1A) by acting as a blocking agent at the bonding site on the receptor shown in Figure 1 (the red triangle). Therapeutically, tamsulosin is effective in treating symptoms of benign prostatic hypertrophy. Benign prostatic hypertrophy is usually experienced by older men. The most common adverse reactions to the drug according to the clinical studies include dizziness/vertigo, abnormal ejaculation, nausea, and headaches. In very rare instances, the drug has been associated with increased levels of aminotransferase, causing injury to the liver; however, the link between tamsulosin and this adverse reaction is not known.⁵ Older drugs such as doxazosin treated benign prostatic hypertrophy through relaxing blood vessels. This type of treatment had several adverse reactions relating to low blood pressure. In targeting the adrenoreceptors/muscles around the area instead of the blood vessels, these adverse reactions are no longer an issue with tamsulosin.⁶ I believe the most compelling aspect of development for future modification is targeting the other variants of the alpha1-adrenoreceptor, specifically α_1B and α_1D. This modification could improve efficacy.

References

1. "Tamsulosin." U.S. National Library of Medicine. Accessed September 24, 2018.               https://livertox.nlm.nih.gov/Tamsulosin.htm.

2. "Benign Prostatic Hyperplasia (BPH)." Mayo Clinic. July 07, 2018. Accessed September 24, 2018.               https://www.mayoclinic.org/diseases-conditions/benign-prostatic-hyperplasia/symptoms-              causes/syc-20370087

3. "Dutasteride and Tamsulosin Hydrochloride Capsules." Drug Information. Accessed September 24,         2018. http://www.druginformation.com/RxDrugs/D/Dutasteride and Tamsulosin Hydrochloride                 Capsules.html.

4. "The Physiology and Function of the Alpha-Adrenorecptor." Medscape. Accessed September 24,               2018. http://www.medscape.org/viewarticle/440787_4.

5. "Flomax® (tamsulosin Hydrochloride) Capsules, 0.4 Mg." Flomax® (tamsulosin Hydrochloride)                                   Capsules, 0.4 Mg. October 25, 2005. Accessed September 24, 2018. http://s3-us-west-       2.amazonaws.com/drugbank/fda_labels/DB00706.pdf?1265922798.

6. Monson, Kristi. "Doxazosin Warnings and Precautions." EMedTV: Health Information Brought To Life.     Accessed September 24, 2018. http://blood-pressure.emedtv.com/doxazosin/doxazosin-       warnings-and-precautions.html.