Gene/Protein Disease Symptom Drug Enzyme Compound
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Modern cardiac rehabilitation is a comprehensive program of secondary prevention for patients with heart disease. Moreover, it is an important context in which to broach issues of impaired sexual function. Sexual problems plague a large portion of our cardiac patient population. Unspoken+ concerns about impotence, now more correctly called erectile dysfunction (ED), are common, as are concerns about the safety of engaging in sexual activity, especially after major cardiac events or therapeutic interventions. A large proportion of patients do not return to normal sexual activity after a cardiac event. Many factors, including normal age-related changes in sexual response, medication-induced dysfunction, and vascular changes associated with risk factors (e.g., diabetes and dyslipidemia), as well as the emotional impact of symptomatic heart disease, may influence sexual function in these patients. These factors, occurring alone or in combination, probably explain the discouraging prevalence of sexual dysfunction in patients with manifest cardiac disease. Because so few patients have specific cardiac reasons for limiting sexual activity, a clear opportunity exists for cardiologists and their staff to help enhance the emotional well-being and overall quality of life of their cardiac patients.
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PMID:Sexual activity and the cardiovascular patient: guidelines. 1050 70

Apomorphine SL (TAP Holdings, Deerfield, IL) is a centrally acting treatment for erectile dysfunction (ED) that has been undergoing phase III trials. Over 3000 men have received apomorphine SL and over 75,000 doses have been taken. In the first three phase III parallel arm cross-over double-blind studies 854 patients were given a total of 8263 tablets of apomorphine SL in 2 and 4 mg doses. The patients were between 18 and 70 y old and outcome measures included per attempt rates of intercourse and erections firm enough for intercourse as well as psychometric instruments and partner responses. The majority (74.1%) had moderate and severe grades of ED on admission to the studies, 31% had hypertension, 16% had documented coronary artery disease, 16% had dyslipidemia and 16% had diabetes. Erections occurred rapidly (10-25 min) and in 54.4% of attempts at 4 mg (vs 33.8% placebo). A majority of the attempts at intercourse (50.6%) were successful at 4 mg in patients when recorded on a per-attempt basis. The most common but infrequent and mild side effect of nausea decreases with use. The phase III trials of apomorphine SL show that there is a clinically important restoration of erectile function from this new formulation of apomorphine. It has a rapid and safe effect through action in the central nervous system. Apomorphine SL brings a new choice to the management of ED that will further benefit the millions of couples affected. International Journal of Impotence Research (2000) 12, Suppl 4, S67-S73.
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PMID:Apomorphine: an update of clinical trial results. 1103 90

The central nervous system has the capacity to enhance the activity of dysfunctional penile tissue in men with erectile dysfunction (ED). Phase III clinical trials have been conducted using Apomorphine SL (TAP Pharmaceuticals, Deerfield, IL) as a centrally acting treatment for ED. Apomorphine SL has been administered to over 3,000 men in over 75,000 doses. In three phase III crossover double blind studies 854 patients were given a total of 8,263 tablets of apomorphine SL in 2 and 4 mg doses. The patients were between 18 and 70 years old and had multiple co-morbid conditions. Outcome measures included intercourse rates and erection rates on a per attempt basis as well as psychometric instruments and partner response evaluations. The results show that 74.1% of patients had moderate or severe grades of ED on inclusion into the studies, 31% had hypertension, 16% had documented coronary artery disease, 16% had dyslipidemia, and 16% had diabetes. Erections occurred rapidly (10-25 min). In 54.4% of attempts at 4 mg (vs 33.8% placebo, P < 0.001) erections suitable for intercourse were documented. A majority of the attempts at intercourse (50.6%, P < 0.001) were successful at 4 mg a doubling of baseline rates. Mild nausea was the most common but infrequent side effect and the rare occurrence of syncope was the most significant. No cardiac deaths were attributed. It is concluded that the clinical trials of apomorphine SL demonstrate a safe and significant rate of restoration of erectile function by means of a central mode of action. Efficacy has been shown in men with cardiovascular disease and severe grades of ED.
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PMID:Key issues from the clinical trials of apomorphine SL. 1128 67

In males, aging, health and disease are processes that occur over physiologic time and involve a cascade of hormonal, biochemical and physiological changes that accompany the down-regulation of the hypothalamic-anterior pituitary-testicular axis. As aging progresses there are relative increases of body fat and decreases in muscle mass. The increased adipose tissue mass is associated with the production of a number of newly generated factors. These include aromatase, leptin, PAI-1, insulin resistance, and the dyslipidemias, all of which can lead to tissue damage. Fatty tissue becomes the focal point for study as it represents the intersection between energy storage and mobilization. The increase in adipose tissue is associated with an increase in the enzyme aromatase that converts testosterone to estradiol and leads to diminished testosterone levels that favor the preferential deposition of visceral fat. As the total body fat mass increases, hormone resistance develops for leptin and insulin. Increasing leptin fails to prevent weight gain and the hypogonadal-obesity cycle ensues causing further visceral obesity and insulin resistance. The progressive insulin resistance leads to a high triglyceride-low HDL pattern of dyslipidemia and increased cardiovascular risk. All of these factors eventually contribute to the CHAOS Complex: coronary disease, hypertension, adult-onset diabetes mellitus, obesity and/or stroke as permanent changes unfold. Other consequences of the chronic hypogonadal state include osteopenia, extreme fatigue, depression, insomnia, loss of aggressiveness and erectile dysfunction all of which develop over variable periods of time.
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PMID:Aromatase, adiposity, aging and disease. The hypogonadal-metabolic-atherogenic-disease and aging connection. 1139 22

Aging is a complex process modulated by multiple interactions between environmental and genetic factors. Myotonic dystrophy (DM1) is an autosomal dominant disorder caused by an unstable (CTG)n repeat expansion in the DM1 protein kinase (DMPK) gene. The affected male patients' life expectancy at birth (53.2 years) is more than two decades below that observed in most occidental populations. The DMPK gene expression is pleiotropic and includes the premature expression of several age-related signs, symptoms and metabolic disturbances including hormonal dysfunctions, progressive decrease in muscular mass, presenile cataracts, alopecia, reduced alertness, insulin resistance, dyslipidemia, erectile dysfunction and hypogonadism. The aim of this study was to analyze the relationship between aging covariates and the severity of DM1 expression in 136 DM1 male subjects. DM1 clinical expression was assessed on a validated neuromuscular disability rating scale and was correlated with plasma total testosterone (rs = -0.31, p < 0.001), luteinizing hormone (LH) (rs = 0.52, p < 0.001) and follicle stimulating hormone (FSH) (rs = 0.54, p < 0.001) levels. Following LH releasing hormone stimulation, FSH and LH concentrations increased as a function of DM1 severity (p < 0.05). Muscular disability in DM1 was also positively associated with fasting plasma insulin and triglyceride concentrations (p < 0.05). The association of plasma apolipoprotein B and low-density lipoprotein cholesterol levels with DM1 was not linear across their distribution and tended to reflect cell membrane damage progression. These results suggest that DM1, a simple Mendelian trait, can represent a valuable model to illustrate the complex relationships between variables associated with male aging.
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PMID:The pleiotropic expression of the myotonic dystrophy protein kinase gene illustrates the complex relationships between genetic, biological and clinical covariates of male aging. 1263 69

After the acute phase, a patient who is diagnosed with cardiac or vascular disease becomes "chronically ill". This patient will then still spend many years without symptoms or impairments. One day, a percentage of such patients will be confronted with the problem of erectile dysfunction. Various studies have demonstrated that this problem occurs with a higher frequency in patients with cardiovascular diseases, in particular when they have to be treated for hypertension, diabetes mellitus or dyslipidemia. Very rarely are stenoses or occlusions found in the arteries responsible for penile circulation. More recent data indicates that a diffuse anomaly of the vascular endothelium is present, for which erectile dysfunction is a marker. Nowadays, medical care has achieved a better degree of standardization, not only thanks to knowledge about the effects of cardiovascular medication, but also because the physician can now prescribe drugs that treat erectile dysfunction.
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PMID:[Erectile dysfunction in cardiovascular diseases]. 1279 21

This article examines the relationships among depression, ischemic heart disease, and erectile dysfunction. Depression is an independent risk factor for the development of ischemic heart disease, and depression in the post-myocardial infarction patient is associated with increased morbidity and mortality. Ischemic heart disease and erectile dysfunction are also frequently comorbid and share many common risk factors including age, hypertension, diabetes, dyslipidemia, obesity, sedentary lifestyle, and smoking. Depression and erectile dysfunction often occur together; however, the causal relation may be difficult to determine because erectile dysfunction may be a symptom of depression, social distress accompanying erectile dysfunction may precipitate depressive symptoms, or both conditions may result from a common factor such as vascular disease.
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PMID:Depression: links with ischemic heart disease and erectile dysfunction. 1297 13

We investigated the characteristics of erectile dysfunction (ED) in ambulatory Saudi patients. A total of 680 male patients were assessed for ED using IIEF. Patients were also interviewed for sociodemographic data, medical history and risk factors for ED. Assessment for penile vasculature using color Doppler ultrasonography and rigidometer was performed. In all, 21.4% of the patients with severe ED were <50 y and 78.6% of them were > or =50 y (P<0.001). Of the patients, 20% had psychogenic, while 80% had organic causes of ED. Of the patients, 10% had mild, 39.3% had moderate and 50.7% had severe ED. There was a significant association between increasing severity of ED and the presence of diabetes, hypertension, dyslipidemia, smoking, increased BMI, increased values of EDV, decreased values of PSV, RI and rigidometer (P<0.001 for each). Moderate to severe ED is common among Saudi patients. This study provides a quantitative estimate of the characteristics of ED in ambulatory Saudi patients.
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PMID:Characteristics of erectile dysfunction in Saudi patients. 1496 66

Historically the province of urologists and sex therapists, erectile dysfunction (ED) is now managed predominantly by primary care practitioners. In recognition of this trend, simplified assessment and treatment models have been proposed. These new treatment models strongly emphasize the need for sexual inquiry in all middle-age and older men but deemphasize the value of intensive medical or psychologic assessment in most cases. New management guidelines emphasize the need for a brief sexual and medical history, physical examination, and standard laboratory tests to rule out diabetes, dyslipidemia, or hypogonadism.
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PMID:Evaluation of the patient with erectile dysfunction: history, questionnaires, and physical examination. 1514 87

Grapefruit juice can alter oral drug pharmacokinetics by different mechanisms. Irreversible inactivation of intestinal cytochrome P450 (CYP) 3A4 is produced by commercial grapefruit juice given as a single normal amount (e.g. 200-300 mL) or by whole fresh fruit segments. As a result, presystemic metabolism is reduced and oral drug bioavailability increased. Enhanced oral drug bioavailability can occur 24 hours after juice consumption. Inhibition of P-glycoprotein (P-gp) is a possible mechanism that increases oral drug bioavailability by reducing intestinal and/or hepatic efflux transport. Recently, inhibition of organic anion transporting polypeptides by grapefruit juice was observed in vitro; intestinal uptake transport appeared decreased as oral drug bioavailability was reduced. Numerous medications used in the prevention or treatment of coronary artery disease and its complications have been observed or are predicted to interact with grapefruit juice. Such interactions may increase the risk of rhabdomyolysis when dyslipidemia is treated with the HMG-CoA reductase inhibitors atorvastatin, lovastatin, or simvastatin. Potential alternative agents are pravastatin, fluvastatin, or rosuvastatin. Such interactions might also cause excessive vasodilatation when hypertension is managed with the dihydropyridines felodipine, nicardipine, nifedipine, nisoldipine, or nitrendipine. An alternative agent could be amlodipine. In contrast, the therapeutic effect of the angiotensin II type 1 receptor antagonist losartan may be reduced by grapefruit juice. Grapefruit juice interacting with the antidiabetic agent repaglinide may cause hypoglycemia, and interaction with the appetite suppressant sibutramine may cause elevated BP and HR. In angina pectoris, administration of grapefruit juice could result in atrioventricular conduction disorders with verapamil or attenuated antiplatelet activity with clopidrogel. Grapefruit juice may enhance drug toxicity for antiarrhythmic agents such as amiodarone, quinidine, disopyramide, or propafenone, and for the congestive heart failure drug, carvediol. Some drugs for the treatment of peripheral or central vascular disease also have the potential to interact with grapefruit juice. Interaction with sildenafil, tadalafil, or vardenafil for erectile dysfunction, may cause serious systemic vasodilatation especially when combined with a nitrate. Interaction between ergotamine for migraine and grapefruit juice may cause gangrene or stroke. In stroke, interaction with nimodipine may cause systemic hypotension. If a drug has low inherent oral bioavailability from presystemic metabolism by CYP3A4 or efflux transport by P-gp and the potential to produce serious overdose toxicity, avoidance of grapefruit juice entirely during pharmacotherapy appears mandatory. Although altered drug response is variable among individuals, the outcome is difficult to predict and avoiding the combination will guarantee toxicity is prevented. The elderly are at particular risk, as they are often prescribed medications and frequently consume grapefruit juice.
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PMID:Interactions between grapefruit juice and cardiovascular drugs. 1544 71


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