Comparative effect of alfuzosin and tamsulosin on the contractile response of isolated rabbit prostatic and iris dilator smooth muscles

Abstract

Tamsulosin was more effective than alfuzosin at blocking adrenergic contraction of the iris dilator muscle in pigmented rabbits. Both drugs were less potent in the iris than in the prostate, which suggests that an additional iris receptor could be involved. If valid in humans, our results suggest that attainable plasma concentrations of tamsulosin are able to antagonize iris dilator smooth muscle contraction, whereas those of alfuzosin are not. This could explain the higher frequency of intraoperative floppy-iris syndrome in patients treated with tamsulosin than with alfuzosin.

Risk factors for intraoperative floppy iris syndrome: a prospective study

“…This could be possibly explained based on a rabbit experimental model, postulating the existence of a hypothetical additional receptor besides the a1-receptor with relevance to iris dilator muscle, which may exhibit higher affinity for tamsulosin. 32 Another interesting finding of our study was the positive association between benzodiazepine use and IFIS, which confirmed the results of our previous retrospective study in a different population. 9 The mechanism by which benzodiazepines were associated with IFIS remains elusive, although we hypothesized that a biochemical link may exist.…”

Pharmacologic pupil dilation as a predictive test for the risk for intraoperative floppy-iris syndrome

“…1,13,21,22 However, when IFIS is anticipated and proper management strategies are used, the outcome is favorable and the complication rate is low for both skilled surgeons and residents. 3,22,25 The present study found no difference in pupil diameter under mesopic conditions between patients on tamsulosin, patients on another a 1 -ARA, or patients on no a 1 -ARA. This may be due to the complexity of the biology of the aging iris in which multiple factors affect pupil functionality and could overcome the a 1 -ARA effect.…”

“…Another study based on an animal model found that the plasma concentration of tamsulosin antagonized pupil dilation, whereas that of alfuzosin did not. 25 Chang et al 3 and Chang 30 found that IFIS was less common and less severe in patients taking nonselective a blockers, such as alfuzosin, doxazosin, and terazosin. It is not clear why nonselective a 1 -ARAs inhibit pharmacologic mydriasis in humans but are not strongly associated with IFIS.…”

Pathophysiology and Pre-Operative Evaluation of Patients at Risk for Intraoperative Floppy Iris Syndrome (IFIS)

“…In rabbits, tamsulosin was more effective than the non-specific 1 AR antagonist alfuzosin at blocking adrenergic-mediated iris dilator contraction (Palea et al, 2008). Interestingly, functional studies assessing the affinity of different ARs as measured by pKi (negative logarithm of the equilibrium dissociation constant) reflect higher affinity of silodosin for 1A AR compared to older agents; when compared to other currently available 1 AR antagonists, silodosin is 1400 times more specific in terms of 1A AR versus 1B AR binding than doxazosin and terazosin and 40 times greater compared to tamsulosin (Thiyagarajan, 2002).…”

“…It remains to be seen if silodosin has a greater likelihood to cause IFIS than the other available agents. In a rabbit study, Palea et al suggested an additional unrecognized receptor may be involved in contraction of the iris dilator muscle as 1 AR blockade with tamsulosin and alfuzosin was less prominent in the iris than the prostate (Palea et al, 2008). While 1A AR are commonly reported as the predominant subtype in the iris dilator muscle in animal studies (Suzuki et al, 2002;Yu & Koss, 2003), Flach pointed out that assuming 1A AR predominate in the human iris dilator muscle based off rabbit studies may be misleading (Flach, 2009).…”