Silodosin

Silodosin is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia. == Contraindications ==

Silodosin is contraindicated for people with kidney impairment or severe liver impairment. According to the US Food and Drug Administration (FDA), silodosin is contraindicated with paxlovid, a drug used in treating COVID-19. == Side effects ==

The most common adverse effect is loss of seminal emission. This seems to be caused by silodosin's high selectivity for α1A receptors. Intraoperative floppy iris syndrome occurs in some people taking alpha adrenoreceptor antagonists and may lead to complications during cataract surgery. Other common adverse effects (in more than 1% of patients) are dizziness, orthostatic hypotension, diarrhea, and clogged nose. Less common (0.1–1%) are tachycardia (fast heartbeat), dry mouth, nausea, skin reactions, and erectile dysfunction. Hypersensitivity reactions occur in fewer than 0.01% of patients. There have been reports about intraoperative floppy iris syndrome during cataract extractions. == Interactions ==

Combining silodosin with strong inhibitors of the liver enzyme CYP3A4, such as ketoconazole, significantly increases its concentrations in the blood plasma and its area under the curve (area under the curve (AUC)). Less potent CYP3A4 inhibitors such as diltiazem have a less pronounced effect on this parameters, which is not considered clinically significant. Inhibitors and inducers of the enzyme UGT2B7, alcohol dehydrogenases, and aldehyde dehydrogenases, as well as the transporter P-glycoprotein (P-gp), may also influence silodosin concentrations in the body. Digoxin, which is transported by P-gp, is not affected by silodosin; this means that silodosin does not significantly inhibit or induce P-gp. No relevant interactions with antihypertensive drugs or with PDE5 inhibitors have been found in studies; although combination with other α1-antagonists is not well studied. == Pharmacology ==

Mechanism of action Silodosin is an alpha adrenoreceptor antagonist. However, it also demonstrates significant β2‐adrenoceptor affinity (~30 nM). Silodosin has high affinity for the alpha1A-adrenergic receptor in the prostate, the bladder, and the prostatic urethra. By this mechanism, it relaxes the smooth muscles in these organs, easing urinary flow and other symptoms of benign prostatic hyperplasia. Pharmacokinetics The absolute bioavailability after oral intake is 32%. Food has little effect on the area under the curve. When in the bloodstream, 96,6% of the substance are bound to blood plasma proteins. Its main metabolite is silodosin glucuronide, which inhibits the α1A receptor with 1/8 of the affinity of the parent substance. 91% of the glucuronide are bound to plasma proteins. The enzyme mainly responsible for the formation of the glucuronide is UGT2B7. Other enzymes involved in the metabolism are alcohol dehydrogenases, aldehyde dehydrogenases and CYP3A4. File:Silodosin glucuronide.svg|Silodosin glucuronide File:Silodosin acid.svg|KMD-3293, the other main metabolite == History ==

Silodosin received its first marketing approval in Japan in May 2006, AbbVie absorbed Allergan in 2019. The FDA and Health Canada approved silodosin under the brand name Rapaflo in October 2008, and January 2011, respectively. == Society and culture ==

Brand names Brand names include Alphacept, Niksol, Rapilif, Sildoo, Silodal Silofast, Silorel, Silotime, Silotrif, Thrupas, and Flopadex, and Urorec. == Research ==

Alpha-1 adrenergic receptor antagonists are being investigated as a means to male birth control due to their ability to inhibit ejaculation but not orgasm. While silodosin was completely efficacious in preventing the release of semen in all subjects, 12 out of the 15 participants reported mild discomfort upon orgasm. The men also reported the psychosexual side effect of being strongly dissatisfied by their lack of ejaculation. == References ==