Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To date, there is no FDA-approved therapy for premature ejaculation (PE). Recently, phosphodiesterase 5 inhibitors (PDE5-Is) have been demonstrated to have encouraging results in the treatment of PE by a few studies. The aim of this review was to assess the updated manuscripts and thereafter present the practical recommendations and possible mechanisms concerning PDE5-Is for treating PE. Using MEDLINE, we searched and assessed the peer manuscripts published from 1 January 1996 to 1 September 2005 about PDE5-Is for treating PE. The results show that the number of patients in all the reports is very few and most of the studies do not employ double-blinded and placebo-controlled tests, though they are prospective and randomized. Therefore, the results and conclusions might be biased. PDE5-Is are suggested to be used in PE with old age or associated with erectile dysfunction (ED), or to be employed alone or in combination with selective-serotonin reuptake inhibitors (SSRIs) when SSRIs fail to treat PE; behavioural therapy is proposed to be used for preventing the recurrence of PE following withdrawal of PDE5-Is. In addition, for the PE patient with a definite aetiological cause, the aetiology should be cured first, if PE still exists, followed by PDE-Is prescription. Possible mechanisms that are involved include relaxing the smooth muscles of vas deferens, seminal vesicle, prostate and urethra; decreasing the central sympathetic output; inducing peripheral analgesia; prolonging the duration of erection; and increasing confidence, the perception of ejaculatory control, overall sexual satisfaction, and decreasing the post-orgasmic refractory time to achieve a second erection after ejaculation. Well-designed multicentre studies are urgently warranted to further elucidate the efficacies and safety as well as mechanisms of PDE5-Is in the treatment of PE.
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PMID:Phosphodiesterase 5 inhibitors in the treatment of premature ejaculation. 1657 7

This review examines the role of nitric oxide (NO) as a neurotransmitter involved in the central and peripheral control of ejaculation, the methods of phosphodiesterase type 5 inhibitor (PDE5I) drug treatment studies for premature ejaculation (PE), the adherence of methods to the contemporary consensus of ideal PE drug trial design, the impact of methods on treatment outcomes and the role of PDE5Is in the treatment of PE. NO/cGMP transduction is involved in both the central and peripheral control of emission, but evidence for a direct central or peripheral effect of PDE5Is on ejaculation is speculative. Thirteen of the 14 studies reviewed failed to fulfil the evidence-based medicine criteria for ideal PE drug trial design. Limitations of the studies include inadequately defined study populations, the lack of a double-blind placebo-controlled study design, and the absence of consistent objective physiological measures or sensitive, validated outcome assessment instruments as study endpoints. The broad range of intravaginal ejaculatory latency time (IELT) fold-increases reported with PDE5Is, on-demand selective serotonin re-uptake inhibitor (SSRI) drugs, and combined PDE5I/on-demand SSRIs is testament to the unreliability of data and conclusions from methodologically flawed studies. The one study that fulfilled the evidence-based medicine criteria of an ideal clinical trial design reported that treatment with sildenafil failed to significantly increase baseline IELT, supporting our conclusion that there is no convincing evidence to support any role for PDE5Is in the treatment of men with lifelong PE and normal erectile function. However, there is limited evidence to support a potential role for PDE5Is alone or combined with daily or on-demand SSRIs in the treatment of acquired PE in men with comorbid erectile dysfunction. Further controlled studies adhering to the contemporary consensus of ideal clinical trial design are required to clarify the role of PDE5Is in this subgroup of men with acquired PE.
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PMID:Efficacy of type-5 phosphodiesterase inhibitors in the drug treatment of premature ejaculation: a systematic review. 1687 63

This review discusses treatment options for men with premature ejaculation (PE), a common sexual dysfunction characterized by short ejaculatory latency, decreased sexual satisfaction, and distress. For a number of reasons, including embarrassment and the belief that PE is a normal part of aging, has no effective treatment, or will resolve itself, few men with PE seek treatment. Although several treatment options exist (eg, behavioral, cognitive, and sex therapy methods; desensitizing drugs; off-label use of antidepressants and/or phosphodiesterase type 5 inhibitors or alpha-blockers), the majority of men with PE generally are not satisfied with their results. New pharmacologic drugs, specifically for the treatment of PE, are undergoing evaluation in clinical trials. As an example, recent clinical research studies have revealed on-demand administration of one such drug, dapoxetine, which achieved significant improvements in ejaculatory latency, control over ejaculation, and satisfaction with sexual intercourse. In addition, partners of men who received dapoxetine likewise reported improved satisfaction with sexual intercourse. Future studies may reveal that integration of pharmacologic drugs with psychologic and/or behavioral therapy techniques may be the optimal approach to the management of PE. PE is a treatable condition, and new drugs in development may provide benefits over those available.
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PMID:Treatment of premature ejaculation: new drugs and treatment strategies. 1705 44

In recent years, the frequency of antidepressant drug-induced sexual dysfunction has increased, along with the use of new drugs for the treatment of erectile dysfunction and premature ejaculation. It has thus become common for pharmacists to counsel patients about sexual issues. Pharmacists must not only become knowledgeable about these drugs and their indications, but they must also become skilled and comfortable with counseling patients and answering questions from both patients and other health care providers. In addition to therapeutic information, pharmacists' discussions with patients should take into account factors that contribute to treatment nonadherence and treatment failure. Patient education is essential to ensure optimum outcomes for pharmacologic treatments for both erectile dysfunction and premature ejaculation. Improper use of phosphodiesterase-5 inhibitor drugs for erectile dysfunction accounts for most nonresponsiveness and discontinuation of treatment. Drug-induced sexual dysfunction is common with some psychotropic drugs. Up to 50% of men will experience delayed ejaculation, and at least 30% of men and women will experience anorgasmia from antidepressant drugs with serotonin agonist activity. Trazodone is the drug most commonly associated with the rare but very serious adverse effect of priapism. The pharmacist who is both competent and comfortable discussing sexual function and dysfunction with patients can make positive contributions to their therapeutic outcomes as well as their quality of life.
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PMID:Counseling patients about sexual issues. 1706 6

Premature ejaculation (PE) is a frequent male sexual complaint that is mediated mainly by disturbances of serotonergic neurotransmission and certain serotonin (5-HT) receptors and, to a lesser extent, oxytocinergic neurotransmission in the CNS. The current Diagnostic Manual of Mental Disorders (fourth edition, revised text) [DSM-IV-TR] definition of PE has a low positive predictive value and is inadequate for clinical, epidemiological and drug treatment research. Categorisation of PE into four well defined syndromes has recently been proposed for the pending DSM (fifth edition) definition of PE. Over the last decade, an increasing number of studies of drug treatment of PE have been published. A meta-analysis of those studies, conducted in accordance with current standards of evidence-based medicine, demonstrated similar efficacies for daily treatment with the serotonergic antidepressants paroxetine hemihydrate, clomipramine, sertraline and fluoxetine, with paroxetine (hydrochloride) hemihydrate exerting the strongest effect on ejaculation. On the basis of fundamental insights into serotonergic neurotransmission, it has been suggested that on-demand selective serotonin reuptake inhibitor (SSRI) treatment will not lead to similarly impressive delays in ejaculation as has been observed with daily SSRI treatment. Indeed, some on-demand studies with SSRIs and studies with the new SSRI dapoxetine have shown a weak ejaculation-delaying effect after 1-2 hours of drug intake. Apart from daily treatment with SSRIs, PE can be delayed by on-demand use of topical anaesthetics and tramadol. Treatment with phosphodiesterase type 5 inhibitors should not be prescribed to men with PE with normal erectile function, but may be used if PE is accompanied by erectile difficulties. There is no scientific support for treatment of PE with intracavernous injection of vasoactive drugs. Animal studies have shown that strong immediate ejaculation delay may be induced by administration of a combination of an SSRI with a serotonin 5-HT(1A) receptor antagonist. The combination of an SSRI and any other compound that immediately and potently raises serotonin neurotransmission and/or use of oxytocin receptor antagonists may form the basis for the development of new on-demand and/or daily drugs for the treatment of PE.
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PMID:Premature ejaculation: definition and drug treatment. 1766 30

Premature ejaculation (PE) is one of the most common male sexual dysfunctions. Successful treatment of PE has been hampered by the existence of a variety of definitions and diagnostic criteria and the lack of large, long-term studies of treatment efficacy. Numerous, diverse treatment approaches with varying degrees of efficacy have been used; these include behavioral, cognitive, and sex therapy techniques, and pharmacologic management with anti-depressants, phosphodiesterase-5 inhibitors, and topical anesthetics. The approach most likely to provide success is a combination of cognitive and sex therapy with a pharmacologic agent of proven efficacy that has an easy-to-follow dosing regimen.
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PMID:Premature ejaculation: the scope of the problem. 1736 15

Premature ejaculation (PE) is one of the most common sexual dysfunctions in men, with prevalence rates ranging from 21% to 31%. Because many physicians do not inquire about sexual dysfunction and patients are reluctant to offer it as a medical complaint, PE is underreported in clinical practice. A sexual history is therefore necessary to uncover the diagnosis. PE can have a significant impact on the quality of life of the patient and his sexual partner, and may lead to psychological distress and loss of self-esteem. It appears that PE has no single etiology, and treatments have been based on both its neurophysiologic and behavioral components. Although no therapies are currently approved for PE by the US Food and Drug Administration, medications that have shown some success include selective serotonin reuptake inhibitors, tricyclic antidepressants, phosphodiesterase type 5 inhibitors, and topical anesthetics. Behavioral techniques have been the mainstay of PE treatment, and include techniques to decrease sensory input.
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PMID:Identifying and treating premature ejaculation: importance of the sexual history. 1754 31

Premature ejaculation (PE) is one of the most common sexual dysfunction problems, which has significant adverse effects on the life quality of the patients. Behavioral therapies have been the mainstay of PE management for many years. However, there is inadequate evidence for their long-term benefit. There are currently no medications licensed specifically for the treatment of PE. Current " off-label" pharmacotherapeutic approaches include topical anesthetics, phosphodiesterase-5 inhibitors, and serotonin reuptake inhibitors, all of which, however, fall short of the ideal therapy for PE. In the absence of a cure, the ideal treatment that researches aim at should be tolerable, effective from the first dose, rapid in onset of action, fast in elimination, and available as an oral medication. It is anticipated that agents being developed for the specific indication of PE will come closer to this ideal than the existing pharmacotherapeutic approaches.
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PMID:[Update of pharmacotherapy for premature ejaculation]. 1756 65

Premature ejaculation (PE) is a frequent male sexual complaint.This occurrence does not automatically imply the existence of a male sexual disorder. The current DSM definition of PE has a low positive predictive value with a high associated risk for false-positive diagnoses of PE. A new classification in four well-defined PE syndromes has recently been proposed for the pending DSM-V. According to this new classification there are different pathophysiologies and treatments of PE, dependent on the underlying PE syndrome. Some types are particularly neurobiologically or medically determined and need drug treatment; other types, which are mainly psychologically determined, need psychotherapy or both drug treatment and psychotherapy. A meta-analysis of all selective serotonin reuptake inhibitors (SSRIs) and clomipramine studies, which were performed according to current standards of evidence-based medicine, demonstrated a similar efficacy for the daily treatment with the serotonergic antidepressants paroxetine hemihydrate, clomipramine, sertraline, and fluoxetine, with paroxetine hemihydrate exerting the strongest effect on ejaculation. On-demand treatment with SSRIs generally exerts much less ejaculation delay than daily SSRI treatment. Other on-demand treatment options are the topical use of anesthetics, tramadol, and phosphodiesterase type 5 inhibitors. Caution is needed with tramadol with regard to its potential addictive properties. There is insufficient evidence for the ejaculation delaying effects of phosphodiesterase type 5 inhibitors and intracavernous injection of vasoactive drugs.
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PMID:Premature ejaculation: state of the art. 1798 99

Premature ejaculation (PE) is the most common male sexual problem worldwide affecting 22-38% of men. It has a significant morbidity both on patients and their partners, causing distress, anxiety and relationship difficulties. The mainstay of treatment is a combined approach using behavioural therapies and non-licensed medication such as topical anaesthetic preparations, selective serotonin re-uptake inhibitors and phosphodiesterase-5 inhibitors. In recent years, there has been a greater emphasis placed on researching novel treatments and exploring the on-demand use of current preparations. This review provides an overview of current accepted treatments and emerging agents for the use in PE.
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PMID:Premature ejaculation: treatment update. 2008 91


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