Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-three diabetic men were instructed in the use of phentolamine-papaverine injections for the treatment of erectile dysfunction over a two-year period. Of these, 12 reported a satisfactory response and 21 reported a nonsatisfactory response. The responders and the nonresponders were retrospectively studied to identify characteristics that would predict a satisfactory response. No difference was found between the two groups in the duration of diabetes, the presence of retinopathy, neuropathy, nephropathy, peripheral vascular disease, or ischemic heart disease. The utilization of insulin, the prevalence of type II diabetes, or the use of drugs which would cause impotence, did not differ between the two groups. There was no difference in the serum testosterone levels between the two groups. Age was the only predictive factor. Only 1 of 14 patients over age sixty had a satisfactory response to treatment while 11 of 19 patients under age sixty had a satisfactory response. Five of the responders and 2 of the nonresponders proceeded to penile implant surgery and reported satisfactory results. While older diabetic men may choose a trial of intracorporeal injections, they should be counselled regarding the high failure rate and alternative forms of therapy.
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PMID:Factors predicting efficacy of phentolamine-papaverine intracorporeal injection for treatment of erectile dysfunction in diabetic male. 162 10

Hypertension is often cited as a risk factor for erectile dysfunction. To clarify the relation between hypertension and erectile dysfunction, we evaluated 32 consecutive hypertensive and 78 normotensive impotent men with respect to multiple potential determinants and parameters of erectile function, including medical and sexual history, depression, hormonal profile, penile nocturnal tumescence, penile vascular supply, and pudendal nerve conduction. The hypertensive men were older, had higher body mass index, and used more medications than the normotensive men. The groups were not different with respect to the prevalence of smoking and peripheral vascular disease, but the hypertensive men had a marginally higher rate of ischemic heart disease (P = .06). The prevalence of depression, abnormal nocturnal penile tumescence, anomalous pudendal nerve conduction, and impairment in arterial supply as determined by penile brachial index were similar in the two groups. Testosterone and bioavailable testosterone levels were lower in the hypertensive men. After stratification by age and body mass index, hypertensive men younger than 50 years with body mass index less than 30 kg/m2 had significantly lower testosterone levels (12.0 +/- 1.7 versus 21.3 +/- 1.4 nmol/L, P < .02) but not bioavailable testosterone levels (3.9 +/- 0.7 versus 6.4 +/- 0.7 nmol/L, P < .17) than the corresponding normotensive group. Prolactin, follicle-stimulating hormone, and luteinizing hormone levels of the two groups were not significantly different. Contrary to common belief and with the exception of lower circulating testosterone levels, the overall analysis showed little difference between hypertensive and normotensive men with respect to a wide range of classic determinants of erectile function. Direct study of the local vascular erectile apparatus appears necessary for further elucidation of the mechanisms underlying erectile dysfunction in hypertensive men.
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PMID:Erectile dysfunction in hypertensive subjects. Assessment of potential determinants. 890 35

Erectile function in man depends upon a complex interaction of psychogenic, neurologic, hormonal and vascular factors, and therefore the management of erectile dysfunction (ED) reflects this complexity of control. Therapeutic options include psychological and non-pharmacological approaches as well as drug treatments. The effectiveness of the type-5 cGMP phosphodiesterase inhibitor sildenafil citrate (Viagra) confirms the pivotal role of the NO-cGMP axis in promoting and maintaining erection. Although widely acclaimed, sildenafil leaves many questions unanswered, especially regarding its susceptibility to pharmacokinetic drug interactions, and its safety in patients with ischaemic heart disease and those taking nitrates. In view of the epidemiological link between erectile dysfunction and cardiovascular disease in the elderly, this limitation might have much broader implications. The presently available scientific documentation, although less extensive, indicates that NO donors, such as topically applied nitroglycerin (GTN; for example, 1-2 puffs of an ordinary GTN spray applied to the shaft of the penis), might be a reasonable alternative. Further larger-scale research on the efficacy and tolerability of topical GTN is needed to establish its full therapeutic potential in the treatment of erectile dysfunction.
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PMID:Opportunities for the treatment of erectile dysfunction by modulation of the NO axis--alternatives to sildenafil citrate. 989 Nov 91

Erectile dysfunction (ED, formerly referred to as impotence, is a common (especially in diabetic and older men) and distressing condition. Several risk factors have been identified; among these are smoking, hyperlipidaemia, hypertension and diabetes mellitus. These risk factors are shared with atherosclerotic vascular disease (e.g. ischaemic heart disease). This observation underlies a common vascular pathology. Smoking may cause ED by several mechanisms, including adversely affecting intrapenile blood flow. It is important to be aware of the link between smoking and ED since this information may motivate some male smokers to quit. In this context, it is important to be aware of the link between smoking and ED since this information may motivate smokers to quit. In this context, it is relevant that there is evidence that quitting may restore/improve erectile function.
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PMID:Cigarette smoking and erectile dysfunction. 1007 52

Nitric oxide (NO) induces the formation of intracellular cyclic guanosine monophosphate (cGMP) by guanylate cyclase. Sildenafil, which selectively inhibits phosphodiesterase type 5 (PDE5) found predominantly in the corpora cavernosa of the penis, effectively blocks the degradation of cGMP and enhances erectile function in men with erectile dysfunction. The NO-cGMP pathway also plays an important role in mediating blood pressure. It is, therefore, possible that the therapeutic doses of sildenafil used to treat erectile dysfunction may have clinically significant effects on human hemodynamics. Three studies were undertaken to assess the effects of intravenously, intra-arterially, and orally administered doses of sildenafil on blood pressure, heart rate, cardiac output, and forearm blood flow and venous compliance in healthy men. A fourth study evaluated the hemodynamic effects of intravenous sildenafil in men with stable ischemic heart disease. In healthy men, significant (p <0.01) decreases in supine systolic and diastolic blood pressures were observed with intravenous sildenafil (20, 40, and 80 mg) at the end of the infusion period when plasma levels of sildenafil were highest (mean decreases from baseline of 7.0/6.9 and 9.2/6.7 mm Hg, for the 40- and 80-mg doses, respectively). These changes were transient and not dose related. Modest reductions in systemic vascular resistance also were observed (maximum decrease 16%), although heart rate was not affected by sildenafil administration when compared with placebo. Single oral doses of sildenafil (100, 150, and 200 mg) produced no significant changes in cardiac index from 1-12 hours postdose between placebo- and sildenafil-treated subjects. The approved dosage strengths of sildenafil citrate are 25 mg, 50 mg, and 100 mg. The 80-mg intravenous dose and the 200-mg oral dose of sildenafil produced comparable plasma levels at twice the maximum therapeutic dose (recommended range, 25-100 mg). After brachial artery infusion of sildenafil (up to 300 microg/min), there was a modest vasodilation of resistance arteries and a reversal of norepinephrine-induced preconstriction of forearm veins. These hemodynamic effects were similar to but smaller in magnitude than those of nitrates. In a small pilot study of men with ischemic heart disease, decreases from baseline in pulmonary arterial pressure (-27% at rest and -19% during exercise) and cardiac output (-7% at rest and -11% during exercise) were observed after 40-mg intravenous doses of sildenafil. Sildenafil was well tolerated by subjects and patients in all studies, with headache and other symptoms of vasodilation the most commonly reported adverse effects of treatment. Modest, transient hemodynamic changes were observed in healthy men after single intravenous or oral doses of sildenafil even at supratherapeutic doses. In men with stable ischemic heart disease, sildenafil produced modest effects on hemodynamic parameters at rest and during exercise.
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PMID:Effects of sildenafil citrate on human hemodynamics. 1007 38

Erectile dysfunction is a common condition in men with cardiovascular disease, probably as a result of shared factors that impair hemodynamic mechanisms in the penile and ischemic vasculature. Sildenafil citrate, an orally active, selective inhibitor of phosphodiesterase type 5 (PDE5), has demonstrated excellent efficacy and safety profiles in men with erectile dysfunction of various etiologies. Sildenafil administration is contraindicated in patients who are taking nitrates or nitric oxide donors. This retrospective subanalysis of data from double-blind, placebo-controlled studies assessed the efficacy (9 studies) and safety (11 studies) of sildenafil in patients with erectile dysfunction and ischemic heart disease who were not taking nitrates. Of 3,672 patients randomized to receive sildenafil (5-200 mg) or placebo for 4-24 weeks in 11 double-blind, placebo-controlled studies, 357 (10%) reported a history (past or present) of ischemic heart disease and were not taking nitrates. Efficacy was assessed using end-of-treatment responses to Question 3 (ability to achieve an erection) and Question 4 (ability to maintain an erection) of the International Index of Erectile Function (IIEF), scores for the 5 domains of male sexual function assessed by the IIEF (erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction), and responses to a global efficacy question ("Did the treatment improve your erections?"). The responses to the 2 IIEF questions were graded on a scale of 1 (almost never or never) to 5 (almost always or always), with a score of 0 indicating no attempt at sexual intercourse. At the end of treatment, the mean scores for Question 3 and Question 4 of the IIEF for patients with erectile dysfunction and ischemic heart disease were significantly higher for the sildenafil group than for the placebo group (p <0.0001). Mean end-of-treatment scores for the IIEF domains also demonstrated significant increases for sildenafil-treated patients compared with those receiving placebo (p <0.05). At the end of treatment, improved erections were reported by 70% of patients who received sildenafil and by 20% of those in the placebo group p <0.0001). For the sildenafil group, the incidences of the most common adverse events (headache 25%, flushing 14%, and dyspepsia 12%) for patients with ischemic heart disease were similar to those in patients without this concomitant illness (21%, 15%, and 10%, respectively). Moreover, the overall incidence of cardiovascular adverse events other than flushing was comparable in patients with and without ischemic heart disease for both treatment groups. Since there is a degree of cardiac risk associated with sexual activity, clinicians should consider the patient's cardiovascular status before initiating any treatment for erectile dysfunction. Physicians should be aware that patients with underlying cardiovascular disease could be adversely affected by the vasodilator effects of sildenafil, especially in combination with sexual activity. The results of the present subanalysis indicate that oral sildenafil significantly improves erectile function and is well tolerated in patients with erectile dysfunction and ischemic heart disease who are not taking nitrate therapy.
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PMID:Efficacy and safety of sildenafil citrate in the treatment of erectile dysfunction in patients with ischemic heart disease. 1007 40

Sildenafil, a selective inhibitor of phosphodiesterase type 5 (PDE5), is the first in a new class of orally effective treatments for erectile dysfunction. During sexual stimulation, the cavernous nerves release nitric oxide (NO), which induces cyclic guanosine monophosphate (cGMP) formation and smooth muscle relaxation in the corpus cavernosum. Sildenafil facilitates the erectile process during sexual stimulation by inhibiting PDE5 and thus blocking the breakdown of cGMP. Sildenafil alone can cause mean peak reductions in systolic/diastolic blood pressure of 10/7 mm Hg that are not dose related, whereas the heart rate is unchanged. Sildenafil and nitrates both increase cGMP levels in the systemic circulation but at different points along the NO-cGMP pathway. The combination is contraindicated because they synergistically potentiate vasodilation and may cause excessive reductions in blood pressure. Erectile dysfunction is a significant medical condition that shares numerous risk factors with ischemic heart disease, and hence a substantial overlap exists between these patient groups. From extensive clinical trials, the most commonly reported cardiovascular adverse events in patients treated with sildenafil were headache (16%), flushing (10%), and dizziness (2%). The incidences of hypotension, orthostatic hypotension, and syncope and the rate of discontinuation of treatment due to adverse events were <2% and were the same in patients taking sildenafil and those taking placebo. Retrospective analysis of the concomitant use of antihypertensive medications (beta blockers, alpha blockers, diuretics, angiotensin-converting enzyme inhibitors, and calcium antagonists) in patients taking sildenafil did not indicate an increase in the reports of adverse events or significant episodes of hypotension compared with patients treated with sildenafil alone. In clinical trials, the incidence of serious cardiovascular adverse events, including stroke and myocardial infarction, was the same for patients treated with sildenafil or placebo. Concurrent disease states, such as renal or hepatic impairment, or concomitant use of inhibitors of the cytochrome P450 isozyme CYP3A4 could increase systemic exposure to sildenafil. Since the US market launch in April 1998, monitoring of spontaneous adverse event reports in association with sildenafil has demonstrated a pattern that is generally consistent with the experience observed during clinical development, with the exception of infrequent reports of priapism. In conclusion, extensive clinical testing has shown that overall treatment with sildenafil for up to 1 year is well tolerated and is associated with a low incidence of adverse events that result in discontinuation of treatment in <3% of patients.
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PMID:Overall cardiovascular profile of sildenafil citrate. 1007 41

Erectile dysfunction and impotence has a high prevalence among male hypertensive patients. Whether this relates mainly to specific drug side effects or to primary pathogenic disorders is unknown. In the present study 101 male patients from our outpatient hypertension clinic answered detailed questionnaires about hypertension and sexual function. Patients with perceived impotence were offered a thorough penile evaluation and examination performed by specialists in the urology department. Twenty-seven (27%) men had impotence. The main cause of impotence was an arterial dysfunction (89%). The prevalence of impotence was related to the degree of secondary organ manifestation, reflected by World Health Organization (WHO) classification I-III (P = .01). Intermittent claudication (P = .001) and ischemic heart disease (P = .005) were the best determinants in this respect. Twelve impotent patients (44%) ascribed onset of impotence to drug initiation. A variety of drugs were incriminated in the occurrence of drug-induced impotence. In summary our results indicate that impotence in hypertensive men is caused mainly by penile arterial vascular changes, probably atherosclerosis. Drug-induced impotence could well be the result of blood pressure reduction itself and not specific drug side effects.
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PMID:The prevalence and etiology of impotence in 101 male hypertensive outpatients. 1019 29

Sildenafil citrate is the first orally active therapy proved to be effective and safe treatment for erectile dysfunction (ED). Because men with cardiovascular disease are at increased risk of developing ED, and because ED and cardiovascular disease share important risk factors, attention has focused recently on the use of sildenafil in these men. When used in combination with nitroglycerin and other nitric oxide (NO) donors, sildenafil may potentiate major drops in blood pressure. Use of nitrate antianginal agents are an absolute contraindication to sildenafil use. In normotensive men and in men receiving antihypertensive medications evaluated in Phase II/III clinical trials, sildenafil use at the recommended doses (25-100 mg 1 hour before sexual intercourse and no more than once daily) was associated with modest, transient reductions in blood pressure and negligible effects on heart rate. In a more recent study, sildenafil was well tolerated in patients receiving antihypertensive medications and was not associated with major decreases in blood pressure. From the time of its approval in the United States in March 1998 through mid-November 1998, with approximately 6 million prescriptions written, 130 deaths were reported by the US Food and Drug Administration (FDA). Seventy-seven of the men who died had documented cardiovascular events. Sixteen men took or were administered nitroglycerin or an organic nitrate; 3 others had nitroglycerin in their possession. Physician prescribing guidelines issued by the American College of Cardiology/American Heart Association (ACC/AHA) recommend caution when prescribing sildenafil to men with certain cardiovascular conditions, liver or kidney disease, and to those taking medications that may prolong sildenafil's half-life (e.g., erythromycin or cimetidine). Those with known or suspected coronary artery disease may benefit from an exercise test to determine whether resumption of sexual activity with use of sildenafil is likely to be associated with an increased risk of myocardial ischemia.
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PMID:Cardiovascular effects of sildenafil citrate and recommendations for its use. 1050 71

There is convincing evidence that the prevalence of erectile dysfunction is increased among men with ischaemic heart disease. This association may be attributed to the fact that both erectile dysfunction and ischaemic heart disease share similar risk factors (e.g. hypertension, dyslipidaemia, diabetes and smoking). Nitric oxide (NO) activity is adversely affected, in penile and vascular tissue, by these risk factors. It is therefore not surprising that a defect in NO activity is thought to play a role in the pathogenesis of both erectile dysfunction and ischaemic heart disease. We consider this evidence and propose that defective NO activity provides a unifying explanation for the association between these two conditions. Further research in this area may improve our understanding of the pathogenesis of cardiovascular diseases as a whole.
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PMID:Nitric oxide and penile erection: is erectile dysfunction another manifestation of vascular disease? 1069 Mar 37


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