PDE5 Inhibitors Failures in Erectile Dysfunction – What are the Causes?

Fedorova, Anna; Vykhodtcev, Sergei; Lukyanov, A.L. Lukyanov (

doi:10.1016/j.jsxm.2017.04.471

Cited by 1 publication

(4 citation statements)

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“…Although the great success in the management of ED using PDE5Is, failure of PDE5Is therapy was reported to range between 30% and 35% in diabetic ED. 2 Chen et al 30 found that 52% out of 238 men complaining of ED, suffers from IR which was the most prevalent independent factor associated with ED. IR upregulates ET-1, where the latter acts on ETAR receptors causing vasoconstriction and penile flaccidity.…”

Section: Discussionmentioning

confidence: 99%

“…The pathophysiology of diabetic ED is complex, including abnormal neuro-endocrinal signaling and endothelial vascular dysfunction. 1,2 Although phosphodiesterase type 5 inhibitors (PDE5Is) are among the first line therapies of ED, failure of PDE5I was reported in about 51.1% of treated patients. 2 Insulin resistance (IR) is one of the features of type 2, non-insulin dependent DM (T2DM).…”

Section: Introductionmentioning

confidence: 99%

“…1,2 Although phosphodiesterase type 5 inhibitors (PDE5Is) are among the first line therapies of ED, failure of PDE5I was reported in about 51.1% of treated patients. 2 Insulin resistance (IR) is one of the features of type 2, non-insulin dependent DM (T2DM). High insulin levels observed in T2DM patients with IR, were found to increase the circulating Endothelin (ET-1) plasma levels through stimulating the transcription of ET-1gene (edn1).…”

Section: Introductionmentioning

confidence: 99%

“…1,2 Although phosphodiesterase type 5 inhibitors (PDE5Is) are among the first line therapies of ED, failure of PDE5I was reported in about 51.1% of treated patients. 2…”

Section: Introductionmentioning

confidence: 99%

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The potential effect of ambrisentan as monotherapy and combined with tadalafil on diabetic erectile dysfunction in rats

Azmy Nabeh,

Ahmed El-Batrawy,

Anwar Khorshid

et al. 2023

Urologia

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Introduction: This study investigated the role of ambrisentan; the selective endothelin type-A receptor (ETAR) blocker on experimental diabetic erectile dysfunction in rats. Materials and methods: Eighty-four adult male Sprague Albino rats were divided randomly into 7 groups. Three control groups received 1 mL saline, 0.2 mg/kg/d ambrisentan and 1.5 mg/kg/d tadalafil, respectively orally for 4 weeks. The remaining four groups were fed high fat diet for 14 days. Diabetes was induced by a single intra-peritoneal injection of 40 mg/kg streptozotocin. After 72 h, diabetes was confirmed by plasma glucose level ⩾250 mg/dL. Diabetic rats were divided randomly into four groups, numbered from 4 to 7. The fourth group was the diabetic-control group, while the fifth and sixth groups received ambrisentan and tadalafil respectively. The seventh group received a combination of both drugs. Treatment continued for 4 weeks then, copulatory, intracavernous pressure measurement, and laboratory tests were conducted. Results: In diabetic rats, ambrisentan and tadalafil improved fasting glucose, insulin, insulin resistance, testosterone, nitric oxide, and rho kinase (ROCK) values compared to diabetic group with the maximum improvement achieved in ambrisentan/tadalafil group ( p < 0.05). Ambrisentan also enhanced ICP and improved latency to erection and number of mounts with a tolerable SBP. Yet, ambrisentan/tadalafil combined therapy resulted in deterioration in SBP with consecutive worsening in ICP and mating indices. Conclusion: Ambrisentan showed significant therapeutic potential to prevent and improve diabetic ED in rats comparable to tadalafil.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…1,2 Although phosphodiesterase type 5 inhibitors (PDE5Is) are among the first line therapies of ED, failure of PDE5I was reported in about 51.1% of treated patients. 2…”

Section: Introductionmentioning

confidence: 99%

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