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)

Sexual dysfunction is highly prevalent in both sexes. Considerable progress has been made in the development of new pharmacologic treatments since the approval of sildenafil in 1998. A variety of oral erectogenic agents are available or are in late-phase development, including centrally active dopamine agonists (e.g., sublingual apomorphine), peripheral nonselective alpha-blockers (e.g., oral phentolamine), and other phosphodiesterase type-5 inhibitors (e.g., vardenafil). These drugs have recently been evaluated for the treatment of female sexual arousal disorder, although results to date have been inconclusive. Pharmacologic therapies have also been proposed for the treatment of premature ejaculation and hypoactive sexual desire disorder. Strong evidence exists for the value of serotonergic drugs (e.g., selective serotonin reuptake inhibitors) in the treatment of premature ejaculation. Further research is needed, particularly on the effects of these drugs on female sexual dysfunction.
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PMID:Sexual pharmacology in the 21st century. 1125 55

Sexual dysfunction related to antidepressants, particularly serotonin reuptake inhibitors is a major cause of premature treatment discontinuation. This places patients at increased risk for recurrence, relapse, chronicity, and mortality (eg, suicide). The clinical assessment requires a comprehensive evaluation of sexual function, including libido, arousal, orgasm, and resolution prior to affective disorder, disturbances associated with the emergence of depression, and changes or dysfunctions associated with antidepressant treatment. Other factors to be included for evaluating sexual dysfunction include inquiry for concurrent medical conditions, somatic treatments, lifestyle risk factors, and response to antidepressants. Current treatment approaches to antidepressant-associated sexual dysfunction have relied on open-label reports, literature reviews, and clinical wisdom. Without double-blind, placebo-controlled studies to support them, too much non-evidence-based treatment may be offered to patients. Advances into nonadrenergic-noncholinergic novel signal transduction, specifically phosphodiesterase type-5 inhibitors, offer new opportunities for developing evidence-based treatments for this side effect and improving depression disease management outcomes.
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PMID:Selective phosphodiesterase type-5 inhibitor treatment of serotonergic reuptake inhibitor antidepressant-associated sexual dysfunction: a review of diagnosis, treatment, and relevance. 1259 14

Pelvic surgeries are among the most common causes of organic sexual dysfunction in men and women. The impact of nerve-sparing surgery on potency has been well documented in radical prostatectomy. However, its impact on potency needs to be evaluated in other pelvic surgeries. Sexual dysfunction is highly prevalent even after multiple technical advances in the field of oncological surgeries. The prevalence varies from 8 to 82%, depending on the type of pelvic surgery. In females, sexual dysfunction has not been evaluated adequately using validated questionnaires. However, in subspecialized circles, treatment for female sexual dysfunction is becoming routine. Currently, physicians have several options for the treatment of erectile dysfunction (ED) in men. Since the introduction of oral PDE-5 inhibitors, oral therapy has become the first-line treatment option for ED, irrespective of etiology. Currently available treatment options for the female sexual dysfunction include estrogens, androgens, phosphodiesterase inhibitors, and dopamine receptor antagonists. Initial reports regarding the role of early rehabilitation are encouraging and may become the part of routine practice in the management of ED after pelvic surgery. In this article, we summarize the sexual dysfunction following pelvic surgeries and their management.
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PMID:Sexual dysfunction after pelvic surgery. 1598 45

Sexual dysfunction is a common side effect of many antidepressants, especially those that increase serotonin. Many strategies have been reported to assist patients in minimizing impairment, with variable degrees of success. One of the newer approaches is to augment with phosphodiesterase type-5 inhibitors. Our report using the most recently released agent in this class, tadalafil is the first demonstrating potential benefit in women. We report here of three women who derived benefit from using 20 mg of tadalafil before anticipated sexual activity to reverse medication-induced sexual dysfunction. Tadalafil utility was maintained over time and was well tolerated.
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PMID:Tadalafil reversal of sexual dysfunction caused by serotonin enhancing medications in women. 1623 21

Sexual dysfunction associated with radical retropubic prostatectomy (RRP) may start before the surgery. Men undergoing RRP frequently have some degree of sexual dysfunction. In addition to the psychological stress of the diagnosis, the biopsy may itself have a detrimental effect. After surgery, all men will experience loss of ejaculate, because the organ responsible for ejaculate has been removed. Orgasm quality is adversely affected in many men. Erectile dysfunction is immediate and recovery from it is slow. Initially, phosphodiesterase (PDE)-5 inhibitors do not work, and they take up to 18 months for their effect to be maximized. Younger men who have had bilateral nerve-sparing procedures respond the best. Combination treatment with prostaglandin E1 or high-dose PDE-5 inhibitors may provide salvage therapy when initial PDE-5 inhibitor therapy has failed.
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PMID:Sexual dysfunction after radical prostatectomy. 1698 95

Sexual dysfunction is prevalent among psychiatric patients and may be related to both the psychopathology and the pharmacotherapy. The negative symptoms of schizophrenia limit the capability for interpersonal and sexual relationships. The first-generation antipsychotics cause further deterioration in erectile and orgasmic function. Due to their weak antagonistic activity at D2 receptors, second-generation antipsychotics are associated with fewer sexual side effects, and thus may provide an option for schizophrenia patients with sexual dysfunction. Depression and anxiety are a cause for sexual dysfunction that may be aggravated by antidepressants, especially selective serotonin reuptake inhibitors (SSRIs). SSRI-induced sexual dysfunction may be overcome by lowering doses, switching to an antidepressant with low propensity to cause sexual dysfunction (bupropion, mirtazapine, nefazodone, reboxetine), addition of 5HT2 antagonists (mirtazapine, mianserin) or coadministration of 5-phosphodiesterase inhibitors. Eating disorders and personality disorders, mainly borderline personality disorder, are also associated with sexual dysfunction. Sexual dysfunction in these cases stems from impaired interpersonal relationships and may respond to adequate psychosexual therapy. It is mandatory to identify the specific sexual dysfunction and to treat the patients according to his/her individual psychopathology, current pharmacotherapy and interpersonal relationships.
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PMID:The impact of mental illness on sexual dysfunction. 1839 59

Nearly two thirds of patients with cancer will undergo radiation therapy as part of their treatment plan. Given the increased use of radiation therapy and the growing number of cancer survivors, family physicians will increasingly care for patients experiencing adverse effects of radiation. Selective serotonin reuptake inhibitors have been shown to significantly improve symptoms of depression in patients undergoing chemotherapy, although they have little effect on cancer-related fatigue. Radiation dermatitis is treated with topical steroids and emollient creams. Skin washing with a mild, unscented soap is acceptable. Cardiovascular disease is a well-established adverse effect in patients receiving radiation therapy, although there are no consensus recommendations for cardiovascular screening in this population. Radiation pneumonitis is treated with oral prednisone and pentoxifylline. Radiation esophagitis is treated with dietary modification, proton pump inhibitors, promotility agents, and viscous lidocaine. Radiation-induced emesis is ameliorated with 5-hydroxytryptamine3 receptor antagonists and steroids. Symptomatic treatments for chronic radiation cystitis include anticholinergic agents and phenazopyridine. Sexual dysfunction from radiation therapy includes erectile dysfunction and vaginal stenosis, which are treated with phosphodiesterase type 5 inhibitors and vaginal dilators, respectively.
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PMID:Managing the adverse effects of radiation therapy. 2070 69

Sexual dysfunction is common in systemic sclerosis (SSc). Male erectile dysfunction (MED) has been reported in around 80% of subjects and more than half of female patients fulfill criteria for diagnosis as female sexual arousal Disorder (FSAD). While some evidence supports a role for cavernosal fibrosis, abundant data suggest that MED is yet another clinical feature of SSc related to vasculopathy. The contribution of vasculopathy to the more complex issues of female sexual dysfunction is less clear. Inhibitors of Type V phosphodiesterase are effective in men with MED secondary to SSc. Limited study in women suggests inconsistent effects on behavior (frequency) but not on measures related to perfusion. Sexual activity is an important component of quality of life and an important domain for the caregiver to address; it is not clear that it warrants primary consideration as a consistent measure of scleroderma-related vasculopathy.
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PMID:Vascular alterations and sexual function in systemic sclerosis. 2098 5

Pleasurable sexual activity is an essential component of many human relationships, providing a sense of physical, psychological, and social well-being. Epidemiological and clinical studies show that depressive symptoms and depressive illness are associated with impairments in sexual function and satisfaction, both in untreated and treated patients. The findings of randomized placebo-controlled trials demonstrate that most of the currently available antidepressant drugs are associated with the development or worsening of sexual dysfunction, in a substantial proportion of patients. Sexual difficulties during antidepressant treatment often resolve as depression lifts but can endure over long periods and may reduce self-esteem and affect mood and relationships adversely. Sexual dysfunction during antidepressant treatment is typically associated with many possible causes, but the risk and type of dysfunction vary with differing compounds and should be considered when making decisions about the relative merits and drawbacks of differing antidepressants. A range of interventions can be considered when managing patients with sexual dysfunction associated with antidepressants, including the prescription of phosphodiesterase-5 inhibitors, but none of these approaches can be considered "ideal." As treatment-emergent sexual dysfunction is less frequent with certain drugs, presumably related to differences in their pharmacological properties, and because current management approaches are less than ideal, a reduced burden of treatment-emergent sexual dysfunction represents a tolerability target in the development of novel antidepressants.
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PMID:Reduced treatment-emergent sexual dysfunction as a potential target in the development of new antidepressants. 2343 29

Systemic sclerosis (SSc) is a chronic, multisystem connective tissue disease with protean clinical manifestations. Recent advances in understanding the pathogenic mechanisms have led to development of target-oriented and vasomodulatory drugs which play a pivotal role in treating various dermatological manifestations. An exhaustive literature search was done using Medline, Embase, and Cochrane library to review the recent concepts regarding pathogenesis and evidence-based treatment of salient dermatological manifestations. The concept of shared genetic risk factors for the development of autoimmune diseases is seen in SSc. It is divided into fibroproliferative and inflammatory groups based on genome-wide molecular profiling. Genetic, infectious, and environmental factors play a key role; vascular injury, fibrosis, and immune activation are the chief pathogenic factors. Vitamin D deficiency has been documented in SSc and correlates with the severity of skin involvement. Skin sclerosis, Raynaud's phenomenon (RP) with digital vasculopathies, pigmentation, calcinosis, and leg ulcers affect the patient's quality of life. Immunosuppressives, biologicals, and hematopoietic stem cell transplantation are efficacious in skin sclerosis. Endothelin A receptor antagonists, calcium-channel blockers, angiotensin receptor inhibitors, prostacyclin analogs, and phosphodiesterase type 5 (PDE-5) inhibitors are the mainstay in RP and digital vasculopathies. Pigmentation in SSc has been attributed to melanogenic potential of endothelin-1 (ET-1); the role of ET 1 antagonists and vitamin D analogs needs to be investigated. Sexual dysfunction in both male and female patients has been attributed to vasculopathy and fibrosis, wherein PDE-5 inhibitors are found to be useful. The future concepts of treating SSc may be based on the gene expression signature.
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PMID:Systemic sclerosis: current concepts in pathogenesis and therapeutic aspects of dermatological manifestations. 2391 94


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