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)

In recognition of the large number of sufferers of sexual dysfunction worldwide, and the variety of etiologies of the condition, investigation into effective pharmacological agents has been expanded. One method of intervention is inhibition of the phosphodiesterase type 5 (PDE5) enzyme, which has already been exploited with a considerable degree--though not complete--success. A number of new agents that inhibit PDE5 are under development. Notable among these is tadalafil, which has demonstrated a high level of selectivity for PDE5 over the other phosphodiesterases and has shown efficacy in improving erectile function and sexual satisfaction in phase III trials. Throughout the clinical development program for tadalafil, the drug has been well tolerated and without serious side effects. The manufacturer, Lilly ICOS, received an approvable letter from the US Food and Drug Administration for use of the drug as a treatment for erectile dysfunction on April 30, 2002. Lilly ICOS hopes to market tadalafil, with the trade name Cialis, in the USA in 2003.
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PMID:Tadalafil, a further innovation in the treatment of sexual dysfunction. 1269 5

The relaxation of the smooth muscle in the vagina and clitoris and the increase of blood flow into these organs is thought to be essential in the female sexual response. Vardenafil is a type 5 phosphodiesterase (PDE5) inhibitor that potentiates the nitric oxide (NO)/cGMP pathway facilitating penile smooth muscle relaxation and improving penile erection in men. Although the potentiation of the NO/cGMP pathway through PDE5 inhibitors can clearly enhance blood flow into the penis and is used in the therapy of male sexual dysfunction, there is controversy about the efficacy of these agents in improving female sexual function. The aim of this work was to evaluate the effects of vardenafil on the increase of blood flow into the vagina and clitoris induced by pelvic nerve electrical stimulation (PNES) in a female dog model. Application of PNES produced consistent and frequency-related increased blood flow into the vagina and clitoris of anesthetized female dogs. The magnitude and duration of the blood flow responses to PNES were variable among the different animals but remained stable over time within the same animal. The intravenous administration of vardenafil (1 mg/kg) significantly potentiated the increases in blood flow produced by PNES into the vagina (381.4 and 206.2% of control response at 5 and 10 Hz, respectively, P<0.01, n=6) and clitoris (379.4 and 238.5% of control response at 5 and 10 Hz, respectively, P<0.01, n=6) 20 min after administration. The significant enhancement of PNES-induced responses was maintained 50 min (224.5 and 181.0%, P<0.01 in vagina; 294.8 and 258.9%, P<0.05 in clitoris) and 80 min after vardenafil administration (209.5 and 156.9%, P<0.05 in vagina; 268.9 and 194.9%, P<0.05 in clitoris). Here we present a feasible model for research into female sexual function. Our results show that vardenafil effectively potentiates the blood flow responses to PNES in the genitalia of female dogs. These results emphasize the role of the NO/cGMP pathway in the local vasodilatory response in female sexual organs and provide a rationale for testing PDE5 inhibitors, such as vardenafil, as a treatment for certain forms of female sexual dysfunction.
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PMID:Vardenafil enhances clitoral and vaginal blood flow responses to pelvic nerve stimulation in female dogs. 1278 94

Erectile dysfunction (ED) is a serious condition that becomes more common as men age. Many older men, however, report satisfactory erectile capacity and enjoy satisfying sexual relationships. Physicians have been slow to discuss ED with patients even in the presence of multiple risk factors. New information provides strong reasons for ED inquiry and management in the primary care physician's office. The presence of ED can reveal as yet undiscovered neurovascular and psychological disorders including diabetes, hypertension, dyslipidaemia, depression and anxiety as well as early neuromuscular disorders. By inquiring about ED, physicians can better decrease iatrogenic sexual dysfunction caused by certain commonly used medications. The successful management of ED, made much easier by the development of phosphodiesterase type 5 inhibitors, has additional potential benefits including improvement of quality of life for both the patient and his partner; decreasing the symptoms of depression in depressed men who also have ED; improving relationships, a significant factor related to good health; and enhancing overall patient health. Other potential values for the physician include a better clinician-patient and increased physician work satisfaction. Primary care physicians need to recognise the value of ED inquiry and management and integrate these activities into practice.
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PMID:The potential value of erectile dysfunction inquiry and management. 1452 62

Erectile dysfunction has multiple causes; most commonly the causes are mixed, a combination of physical and physiologic dysfunction. Two hypothetical case presentations provide the context for a discussion of the neurologic basis of erectile dysfunction and sexual dysfunction from the perspective of osteopathic medicine's holistic approach. Both offer osteopathic physicians the challenge of correcting structural, biological, and chemical defects to restore normal function. One of the cases is representative of patients who do not tell their physicians about sexual dysfunction unless their physicians specifically ask, and even then, these patients are most likely to lie to protect their self-esteem. The second hypothetical patient is representative of those patients who consult their physicians for any reason other than sexual dysfunction, expecting their physicians to figure out the real problem. Both of the hypothetical patients require not only support, but also education and counseling to motivate them to adopt healthier lifestyles and choices. Both would benefit from osteopathic manipulative treatment to correct structural abnormalities, and an oral medication such as a phosphodiesterase type 5 inhibitor offers both patients a good and easily accepted treatment option for erectile dysfunction.
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PMID:Osteopathic approach to sexual dysfunction: holistic care to improve patient satisfaction and prevent mortality and morbidity. 1499 20

The evaluation and treatment of male sexual dysfunction has evolved into a more extensive evaluation. This new evaluation should now include evaluation of hypogonadism, ejaculatory function, lower urinary tract symptoms, and depression. The evaluation may be readily accomplished with the use of questionnaires. The management of these entities is discussed, including the novel phosphodiesterase-5 for male erectile dysfunction. Inclusion of the partner in the evaluation and management scheme will provide added benefit and may produce a better outcome.
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PMID:Erectile dysfunction: etiology, evaluation, and treatment options. 1504 84

Autonomic pathways are important in the regulation of both lower urinary tract and sexual function, and their interruption in neurological pathologies predictably results in variable urogenital dysfunction, depending mainly on the level of the lesion. A normal neurological examination of a patient with urogenital complaints should exclude an underlying neurological pathology, and the neurologist should become involved in the management of symptoms. Electromyography can be of value in the diagnosis and management of cauda equina lesions and multiple system atrophy, but neurophysiological investigations are of no importance in the diagnosis of neurogenic sexual dysfunction. Urodynamic studies have proven helpful in determining the type and management of lower urinary tract dysfunction. Oral anticholinergics usually combined with clean intermittent catheterizations are the first-line treatment options for neurogenic lower urinary tract dysfunction, with intravesical treatments emerging as the main alternative in intractable incontinence. The availability of effective oral phosphodiesterase inhibitors has revolutionized the management of erectile dysfunction, but treatment of ejaculatory and orgasmic disorders as well as of female sexual dysfunction still remains problematic.
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PMID:Evaluation and treatment of autonomic disorders of the urogenital system. 1508 65

Recent studies suggest that erectile dysfunction (ED) may be an early marker of endothelial dysfunction and coronary artery disease (CAD). Conversely, patients with CAD commonly have ED. The phosphodiesterase 5 (PDE5) inhibitors are very effective for the treatment of ED in patients with CAD. Numerous studies show that this class of drugs is in general safe in patients with stable CAD and these agents do not exacerbate ischemia in men with CAD undergoing exercise stress testing. Analysis of placebo-controlled trials did not show an increase in cardiovascular events among men receiving PDE5 inhibitors, and post-marketing surveillance studies with sildenafil did not observe an increase in cardiovascular events compared to expected age-matched rates. Organic nitrates remain a contraindication for PDE5 inhibitors and alpha blockers have precautions/contraindications depending upon specific drugs. The Princeton Consensus Guidelines (soon to be updated) suggest a logical approach to the patient with CAD seeking therapy for sexual dysfunction.
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PMID:Erectile dysfunction in patients with coronary artery disease. 1572 74

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

Premature ejaculation is a common male sexual dysfunction. Treatment modalities as recommended by the British Association of Sexual Health and HIV include behavioural therapy, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs) and local anaesthetic creams. We audited the clinical cohort from our dedicated sexual dysfunction clinic to determine the success of prescribed treatment and co-existing prostatitis/male pelvic pain, erectile dysfunction, phosphodiesterase-5 (PDE5) inhibitor use and anxiety. The use of SSRIs was successful in the treatment of premature ejaculation with or without the use of local anaesthetic cream. Co-existing prostatitis/male pelvic pain, erectile dysfunction, PDE5 inhibitor use and anxiety were high.
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PMID:Pharmacological treatment for premature ejaculation. 1621 22

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


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