Side Effects of Self-Administration of Intracavernous Papaverine and Phentolamine for the Treatment of Impotence

Levine, Stephen B.; Althof, Stanley E.; Turner, Louisa A.; Risen, Candace B.; Bodner, Donald R.; Kursh, Elroy D.; Resnick, Martin I.

doi:10.1016/s0022-5347(17)40585-4

Cited by 146 publications

(47 citation statements)

References 13 publications

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“…The disadvantage of ICI is its invasiveness causing discomfort and anxiety in the patient, resulting in veno-occlusive dysfunction and the risk of inducing ®brosis and priapism. 3 With the advent of the effective oral erectogenic agent sildena®l, we investigated whether the traditional mode of pharmacological stimulation in PPDU (a low dose ICI with papaverinea phentolamine) could be replaced by a high dose of oral sildena®l. age was 50.4 y (range 28 ± 78).…”

Section: Introductionmentioning

confidence: 99%

The value of sildenafil as mode of stimulation in pharmaco-penile duplex ultrasonography

et al. 2001

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The purpose of this work was to assess whether a single intracavernous injection (ICI) of a low dose of the combination of papaverine ± phentolamine is replaceable by a high dose of the oral erectogenic agent sildena®l as mode of stimulation during pharmaco-penile duplex ultrasonography (PPDU). Eleven patients with complaints of erectile dysfunction were included in a crossover study. With an interval of two weeks the patients were exposed to ICI with papaverineaphentolamine (3.75 mga0.125 mg) and oral administration with sildena®l (100 mg) preceding PPDU. Five patients started with ICI. Six patients started with sildena®l. In the sildena®l stimulation mode, visual erotic stimulation (VES) was used to initiate erection. VES was applied by personal LCD monitor. Cut-off values to de®ne suf®cient arterial response were: peak¯ow velocity (PSV) b 25 cmas and acceleration time (AT)`72 ms. Cut-off value to de®ne suf®cient venoocclusion was a resistance index ! 1.00. Statistical analysis of PPDU parameters shows no signi®cant difference between the two modes of stimulation for arterial response (PSV, AT), whereas the resistance index, as a parameter of veno-occlusive response was signi®cantly higher in the sildena®l mode. This ®nding is con®rmed in the clinical translation of the results: two patients with an insuf®cient arterial response to ICI had a suf®cient arterial response to sildena®l and only one patient showed an insuf®cient arterial response following sildena®l, whereas the response following ICI was suf®cient. Analysis of veno-occlusive responses shows remarkable differences between both modes of stimulation. Whereas following the administration of sildena®l all veno-occlusive responses were classi®ed as suf®cient, seven patients showed an insuf®cient veno-occlusive response following ICI. As mode of stimulation in PPDU, high dose sildena®l yields signi®cantly less false positive diagnoses of`veno-occlusive dysfunction' than intracavernous injection of the combination papaverineaphentolamine. No difference was found in the quality of the arterial response. Based on this study we conclude that sildena®l may replace ICI as mode of stimulation during PPDU.

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Section: Introductionmentioning

confidence: 99%

The value of sildenafil as mode of stimulation in pharmaco-penile duplex ultrasonography

et al. 2001

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“…18 The recent introduction of oral sildena®l, a drug which facilitates the NOac-GMP relaxant mechanism in erectile tissue, has offered MED patients with a new therapeutic option. An alternative therapeutic strategy is to antagonize the a 1 -adrenoceptor contractile pathway.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of oral Ro70-0004/003, an α1A-adrenoceptor antagonist, in the treatment of male erectile dysfunction

Choppin¹,

Blue²,

Hegde

et al. 2001

Int J Impot Res

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a-Adrenoceptor antagonists have been used for the treatment of male erectile dysfunction (MED). Ro70-0004a003 (Ro70-0004) is a selective and orally active a 1A -adrenoceptor antagonist. The objective of this study was to: (1) pharmacologically elucidate the a 1 -adrenoceptor subtype mediating norepinephrine-induced contraction of human isolated corpus cavernosal tissue and (2) conduct a clinical proof-of-concept study with Ro70-0004 to test the hypothesis that selective a 1A -adrenoceptor blockade would improve erectile function in patients with MED. In vitro organ bath studies were conducted with strips of human isolated corpus cavernosal tissue obtained from patients undergoing penile prosthesis implantation. Prazosin, cyclazosin, RS-100329 and Ro70-0004a003 antagonized norepinephrine-induced contractile responses with af®nity estimates (pK B or pA 2 ) of 8.4, 7.3, 9.2 and 8.8, respectively, consistent with the singular involvement of a 1A -adrenoceptor subtype. A clinical study (single center, observer-blind, randomized, placebocontrolled, extended period Latin-Square crossover design) was conducted in 24 male patients (mean age 44 y) with MED of no established organic cause to evaluate the ef®cacy of a 5-mg oral dose of Ro70-0004. The primary ef®cacy endpoint was the duration of rigidity b60% at the base of the penis measured between 0.5 and 2.5 h post-dose. Rigidity was assessed by penile plethysmography using the RigiScan Plus 1 1 1 device during visual sexual stimulation. The safety and ef®cacy of Ro70-0004 was also assessed. A 50-mg dose of sildena®l was included as a positive control. For the primary ef®cacy endpoint, the mean duration of erection was 9.69 min following administration of placebo, 8.28 min following Ro70-0004, and 22.64 min following sildena®l. Only the difference between sildena®l and placebo reached statistical signi®cance (P`0.05). A similar pattern was observed when measuring a duration of rigidity b 80% at the base of the penis (secondary endpoint). Ro70-0004 was safe and generally well tolerated (only two out of 20 patients reported at least one adverse event). The highly selective a 1A -adrenoceptor antagonist, Ro70-0004, given at a single dose of 5 mg, did not improve erectile function when compared to placebo.

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“…For these reasons, up to 50% of erectile dysfunction patients using intracavernous injection therapy eventually discontinue the treatment. 2,[4][5][6] Up to now, prostaglandin E 1 (PGE 1 ) has been known as one of the most potent compounds used as a single-dose pharmacotherapy for erectile dysfunction 7) generally administered by intracavernosal injection (e.g., Caverject ® , Pfizer). PGE 1 increases the intracellular concentration of 3Ј,5Ј-cyclic adenosine monophosphate (cAMP) by activation of specific membrane receptors that interact with stimulatory guanine nucleotide proteins to trigger adenylate cyclase and elevate intracellular cAMP concentration.…”

Section: )mentioning

confidence: 99%

Design and Evaluation of Prostaglandin E1 (PGE1) Intraurethral Liquid Formulation Employing Self-Microemulsifying Drug Delivery System (SMEDDS) for Erectile Dysfunction Treatment

Lee

Choi

2008

Biological & Pharmaceutical Bulletin

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Erectile dysfunction is a common disease that affects approximately 10% of adult men in the world.1) It impairs sexual performance, diminishes self-esteem and disrupts personal relationship.2) It becomes more frequent with age but it is not an inevitable consequence of normal aging. 3)Since 1983, several products for the treatment of erectile dysfunction such as injection formulations of phenoxybenzamin, papaverin hydrochloride, phentolamin mesylate and prostaglandin E 1 , intended to be injected into the corpus cavernosum were introduced. However, the intracorporeal injection of these products has occasionally been accompanied by the side effects such as pain, priapism, penile hematomas and fibrosis. For these reasons, up to 50% of erectile dysfunction patients using intracavernous injection therapy eventually discontinue the treatment. 2,[4][5][6] Up to now, prostaglandin E 1 (PGE 1 ) has been known as one of the most potent compounds used as a single-dose pharmacotherapy for erectile dysfunction 7) generally administered by intracavernosal injection (e.g., Caverject ® , Pfizer). PGE 1 increases the intracellular concentration of 3Ј,5Ј-cyclic adenosine monophosphate (cAMP) by activation of specific membrane receptors that interact with stimulatory guanine nucleotide proteins to trigger adenylate cyclase and elevate intracellular cAMP concentration.8) Increasing the intracellular cAMP concentration induces the relaxation of arterial and trabecular smooth muscle in the corpus cavernosum and thereby causes penile erection. 7)A non-invasive intraurethral PGE 1 suppository (MUSE ® , Vivus Inc.) has been introduced as a more convenient and safer formulation compared to the injection type of PGE 1 . 1)However, intraurethral suppository formulation may cause some discomforts including feeling of foreign body and pain mainly exhibited by bulky insertion device. 9,10) For this reason, we attempted to develop a novel liquid type intraurethral PGE 1 delivery formulation using a self-microemulsifying drug delivery system (i.e. SMEDDS). The liquid type intraurethral formulation has some pharmaceutical significances from the viewpoint of patients' compliance as follows; i) non-invasive drug delivery is possible, ii) administration is easier into the urethra than pellet type solid suppository products, and iii) less pain is expected.SMEDDS can be defined as an isotropic multi-component drug delivery system composed of surfactant, co-surfactant and oil, which in some cases transforms to viscous solution with contacting moisture and spontaneously forms microemulsion in the presence of excessive water.11-13) Traditionally, SMEDDS formulation has been used to increase dissolution rate or bioavailability of water insoluble drugs.14-16) The liquid type intraurethral formulation presented in this paper is practically a precursor mixture for forming a microemulsion. Thus, it is expected that the present SMEDDS formulation can be administered into the urethra by simple input procedure, reside in the urethra as a viscous liquid by taki...

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Side Effects of Self-Administration of Intracavernous Papaverine and Phentolamine for the Treatment of Impotence

Cited by 146 publications

References 13 publications

The value of sildenafil as mode of stimulation in pharmaco-penile duplex ultrasonography

The value of sildenafil as mode of stimulation in pharmaco-penile duplex ultrasonography

Evaluation of oral Ro70-0004/003, an α1A-adrenoceptor antagonist, in the treatment of male erectile dysfunction

Design and Evaluation of Prostaglandin E1 (PGE1) Intraurethral Liquid Formulation Employing Self-Microemulsifying Drug Delivery System (SMEDDS) for Erectile Dysfunction Treatment

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