NO is the physiologic signal essential to penile erection because NO is required for the activation of soluble guanylate cyclase to convert guanosine triphosphate to cyclic guanosine monophosphate (cGMP).
Recent studies show that natural agents, specifically, the NO-producing substrates, L-arginine and L-citrulline, can do so. Furthermore, L-arginine, in addition to its roles as substrate for NOS and arginase, is also a precursor for the synthesis of proteins, urea, creatine, vasopressin, and agmatine.
In contrast, L-citrulline escapes intestinal or liver metabolism, and enters the kidneys where it is rapidly converted into L-arginine.
Improvement in the erection hardness score from 3 (mild ED--penile rigidity that still allowed some kind of vaginal penetration, but not satisfactory penetration or completion of successful intercourse) to 4 (normal erectile function) occurred in 12 (50%) of the men when taking L-citrulline, and in 2 of the 24 men when taking placebo.
In 2008, it was shown that increased NO production induces corpus cavernosum smooth muscle cell synthesis and the secretion of vascular endothelial growth factor (VEGF), which can restore impaired endothelial function. Clinical Pearl: L-citrulline may be of great benefit for your female postmenopausal patients as well. Supplementation with the NO-boosting substances, L-citrulline and L-arginine, along with antioxidants, has been demonstrated to delay endothelial senescence despite high glucose levels or a high-cholesterol diet. Given PDE5-inhibitors’ potential for adverse side-effects, a trial of supplementation with L-citrulline, which has been proven to be safe, effective, and psychologically well accepted by patients, and is significantly less expensive than the PDE5-inhibitor drugs, certainly deserves consideration.
Even more importantly for your patient’s long term health and longevity, PDE5-inhibitors do nothing to improve NO production, while using L-citrulline to increase L-arginine availability does. Supplementation with L-citrulline may increase the body’s production of nitric oxide (NO) more effectively than L-arginine. The NO donor L-arginine is a semi-essential amino acid present in dietary proteins and produced in the body from L-citrulline, another semi-essential amino acid present in watermelon and synthesized in the intestinal tract from glutamine.
It has long been known that ASS1 argininosuccinate synthetase, involved in the synthesis of arginine and catalyzing that condensation of citrulline and aspartate to argininosuccinate using ATP, is co-adjacent to the ABO locus.
IMPORTANT QUESTION: Can one take Cialis or Viagra WITH Arginine and or Citruline as a way of potentiating the effects of the ED Medication. Lara Pizzorno is a member of the American Medical Writers Association with 25+ years of experience writing for physicians and the public, Lara is Editor for Longevity Medicine Review as well as Senior Medical Editor for SaluGenecists, Inc.
For most patients, the recommended dose is 50 mg taken, as needed, approximately 1 hour before sexual activity.
Based on effectiveness and toleration, the dose may be increased to a maximum recommended dose of 100 mg or decreased to 25 mg. SINEGRA (Generic VIAGRA) is supplied as blue, film-coated, rounded-diamond-shaped tablets containing sildenafil citrate equivalent to 25 mg, 50 mg, or 100 mg of sildenafil. After patients have taken SINEGRA (Generic VIAGRA), it is unknown when nitrates, if necessary, can be safely administered. SINEGRA (Generic VIAGRA) is contraindicated in patients with a known hypersensitivity to sildenafil, as contained in SINEGRA (Generic VIAGRA) and REVATIO, or any component of the tablet.
There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease. There are no controlled clinical data on the safety or efficacy of SINEGRA (Generic VIAGRA) in the following groups; if prescribed, this should be done with caution. Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been reported infrequently since market approval of SINEGRA (Generic VIAGRA).
SINEGRA (Generic VIAGRA) should be used with caution in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis or Peyronie's disease), or in patients who have conditions which may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia). Physicians should advise patients to stop use of all phosphodiesterase type 5 (PDE5) inhibitors, including SINEGRA (Generic VIAGRA), and seek medical attention in the event of a sudden loss of vision in one or both eyes. Physicians should consider whether their patients with underlying NAION risk factors could be adversely affected by use of PDE5 inhibitors. There are no controlled clinical data on the safety or efficacy of SINEGRA (Generic VIAGRA) in patients with retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases). Physicians should advise patients to stop taking PDE5 inhibitors, including SINEGRA (Generic VIAGRA), and seek prompt medical attention in the event of sudden decrease or loss of hearing.
Patients who demonstrate hemodynamic instability on alpha-blocker therapy alone are at increased risk of symptomatic hypotension with concomitant use of PDE5 inhibitors.
In those patients who are stable on alpha-blocker therapy, PDE5 inhibitors should be initiated at the lowest dose [see Dosage and Administration (2.3)]. In those patients already taking an optimized dose of a PDE5 inhibitor, alpha-blocker therapy should be initiated at the lowest dose. Safety of combined use of PDE5 inhibitors and alpha-blockers may be affected by other variables, including intravascular volume depletion and other anti-hypertensive drugs. SINEGRA (Generic VIAGRA) has systemic vasodilatory properties and may further lower blood pressure in patients taking anti-hypertensive medications.
The concomitant administration of the protease inhibitor ritonavir substantially increases serum concentrations of sildenafil (11-fold increase in AUC).
The safety and efficacy of combinations of SINEGRA (Generic VIAGRA) with other PDE5 Inhibitors, including REVATIO or other pulmonary arterial hypertension (PAH) treatments containing sildenafil, or other treatments for erectile dysfunction have not been studied.
There have been postmarketing reports of bleeding events in patients who have taken SINEGRA (Generic VIAGRA). The safety of SINEGRA (Generic VIAGRA) is unknown in patients with bleeding disorders and patients with active peptic ulceration.
The use of SINEGRA (Generic VIAGRA) offers no protection against sexually transmitted diseases.
The most common adverse reactions reported in clinical trials (? 2%) are headache, flushing, dyspepsia, abnormal vision, nasal congestion, back pain, myalgia, nausea, dizziness, and rash.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.


SINEGRA (Generic VIAGRA) was administered to over 3700 patients (aged 19–87 years) during pre-marketing clinical trials worldwide. Body as a Whole: face edema, photosensitivity reaction, shock, asthenia, pain, chills, accidental fall, abdominal pain, allergic reaction, chest pain, accidental injury. Cardiovascular: angina pectoris, AV block, migraine, syncope, tachycardia, palpitation, hypotension, postural hypotension, myocardial ischemia, cerebral thrombosis, cardiac arrest, heart failure, abnormal electrocardiogram, cardiomyopathy.
Digestive: vomiting, glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, dry mouth, liver function tests abnormal, rectal hemorrhage, gingivitis. Metabolic and Nutritional: thirst, edema, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemic reaction, hypernatremia.
Musculoskeletal: arthritis, arthrosis, myalgia, tendon rupture, tenosynovitis, bone pain, myasthenia, synovitis. Nervous: ataxia, hypertonia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression, insomnia, somnolence, abnormal dreams, reflexes decreased, hypesthesia. Respiratory: asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, sputum increased, cough increased. Skin and Appendages: urticaria, herpes simplex, pruritus, sweating, skin ulcer, contact dermatitis, exfoliative dermatitis.
Special Senses: sudden decrease or loss of hearing, mydriasis, conjunctivitis, photophobia, tinnitus, eye pain, ear pain, eye hemorrhage, cataract, dry eyes. Urogenital: cystitis, nocturia, urinary frequency, breast enlargement, urinary incontinence, abnormal ejaculation, genital edema and anorgasmia. Analysis of the safety database from controlled clinical trials showed no apparent difference in adverse reactions in patients taking SINEGRA (Generic VIAGRA) with and without anti-hypertensive medication. The following adverse reactions have been identified during post approval use of SINEGRA (Generic VIAGRA). Serious cardiovascular, cerebrovascular, and vascular events, including myocardial infarction, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, hypertension, subarachnoid and intracerebral hemorrhages, and pulmonary hemorrhage have been reported post-marketing in temporal association with the use of SINEGRA (Generic VIAGRA). Hearing: Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including SINEGRA (Generic VIAGRA). Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely post-marketing in temporal association with the use of phosphodiesterase type 5 (PDE5) inhibitors, including SINEGRA (Generic VIAGRA).
Administration of SINEGRA (Generic VIAGRA) with nitric oxide donors such as organic nitrates or organic nitrites in any form is contraindicated.
Use caution when co-administering alpha-blockers with SINEGRA (Generic VIAGRA) because of potential additive blood pressure-lowering effects. Co-administration of ritonavir, a strong CYP3A4 inhibitor, greatly increased the systemic exposure of sildenafil (11-fold increase in AUC).
Co-administration of erythromycin, a moderate CYP3A4 inhibitor, resulted in a 160% and 182% increases in sildenafil Cmax and AUC, respectively.
This cancer most often present in people over the age of 55 and statistically speaking, men are four times more likely than women to be diagnosed with the dreaded disease. Head and neck cancers usually begin in the tissue or cells that line the moist surfaces inside the head and neck like inside the mouth, the nose, and the throat. If you are experiencing any of the above symptoms, see your primary care physician as soon as possible. A biopsy: A small piece of tissue is taken from the area and sent to the lab to determine if the cells are cancerous. If cancerous cells are found, the workup will continue to determine the stage or extent of the disease to consider treatment options. Maurice T.  Judkins is a Radiation Therapist for the Department of Veterans Affairs in Durham North Carolina. L-arginine is produced in the body from L-citrulline, and the most recently published research (discussed below) suggests supplementation with L-citrulline, rather than L-arginine, is the better option. All patients reporting an erection hardness score improvement from 3 to 4 were highly satisfied. This provides a rationale for L-citrulline supplementation to not only manage, but reverse penile endothelial dysfunction by correcting the proximate cause of ED.
Supplementing your ED patients with L-citrulline can provide systemic as well as sexual performance benefits. This may explain why ABO seems to be a major distinguishing factor in the response by newborns to inhaled NO therapy. However, SINEGRA (Generic VIAGRA) may be taken anywhere from 30 minutes to 4 hours before sexual activity.
Tablets are debossed with PFIZER on one side and VGR25, VGR50 or VGR100 on the other to indicate the dosage strengths. Hypersensitivity reactions have been reported, including rash and urticaria [see Adverse Reactions (6.1)].
Therefore, treatments for erectile dysfunction, including SINEGRA (Generic VIAGRA), should not be generally used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status. While this normally would be expected to be of little consequence in most patients, prior to prescribing SINEGRA (Generic VIAGRA), physicians should carefully consider whether their patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects, especially in combination with sexual activity. In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance.
However, there are no controlled clinical data on the safety or efficacy of SINEGRA (Generic VIAGRA) in patients with sickle cell or related anemias. Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition and a cause of decreased vision including permanent loss of vision, that has been reported rarely post-marketing in temporal association with the use of all PDE5 inhibitors. These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including SINEGRA (Generic VIAGRA).


PDE5 inhibitors, including SINEGRA (Generic VIAGRA), and alpha-adrenergic blocking agents are both vasodilators with blood pressure lowering effects. Stepwise increase in alpha-blocker dose may be associated with further lowering of blood pressure when taking a PDE5 inhibitor. If SINEGRA (Generic VIAGRA) is prescribed to patients taking ritonavir, caution should be used. A causal relationship between SINEGRA (Generic VIAGRA) and these events has not been established. Counseling of patients about the protective measures necessary to guard against sexually transmitted diseases, including the Human Immunodeficiency Virus (HIV), may be considered. The type of adverse reactions in flexible-dose studies, which reflect the recommended dosage regimen, was similar to that for fixed-dose studies. This analysis was performed retrospectively, and was not powered to detect any pre-specified difference in adverse reactions.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The clinical relevance of this finding to men treated with SINEGRA (Generic VIAGRA) for ED is not known. In some of the cases, medical conditions and other factors were reported that may have also played a role in the otologic adverse events. Most, but not all, of these patients had underlying anatomic or vascular risk factors for developing NAION, including but not necessarily limited to: low cup to disc ratio ("crowded disc"), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking.
Co-administration of saquinavir, a strong CYP3A4 inhibitor, resulted in 140% and 210% increases in sildenafil Cmax and AUC, respectively.
There are five main types of head and neck cancers but we will focus mainly on cancer of the Larynx.
Using either alcohol or tobacco alone can be harmful but when they are combined the alcohol may alter the normal cells cycle which hinder their ability to repair damaged DNA caused by the harmful chemicals in tobacco. Ask your physician to inspect your neck to check your thyroid, larynx, and lymph nodes for abnormal lumps or swelling. The treatment options include surgery, radiation therapy, chemotherapy, or in some cases a combination of the three. I strongly urge you to talk to your physician if you are a loved one maybe suffering from any of the symptoms mentioned. At the month 2-visit, the men were informed they had received a commercially available nutrient and given the option to continue it or to receive a prescription for a PDE-5 inhibitor. Researchers have recently shown a close relationship between atherosclerosis and endothelial senescence--and that NO can prevent it—especially in a diabetic model. The evaluation of erectile dysfunction should include a determination of potential underlying causes and the identification of appropriate treatment following a complete medical assessment.
If priapism is not treated immediately, penile tissue damage and permanent loss of potency could result. Therefore, PDE5 inhibitors, including SINEGRA (Generic VIAGRA), should be used with caution in these patients and only when the anticipated benefits outweigh the risks. In humans, SINEGRA (Generic VIAGRA) has no effect on bleeding time when taken alone or with aspirin. At doses above the recommended dose range, adverse reactions were similar to those detailed in Table 1 below but generally were reported more frequently. These events have been chosen for inclusion either due to their seriousness, reporting frequency, lack of clear alternative causation, or a combination of these factors. Many of these events were reported to occur during or shortly after sexual activity, and a few were reported to occur shortly after the use of SINEGRA (Generic VIAGRA) without sexual activity. Stronger CYP3A4 inhibitors such as ketoconazole or itraconazole could be expected to have greater effects than seen with saquinavir.
If additional diagnostic exams are needed you may be referred to an Ear Eyes Nose and Throat Specialist (EENT). Visit the American Cancer Society website if you would like additional information about this or any other type of cancer. The purpose of this article is to provide useful health information. An observational study evaluated whether recent use of PDE5 inhibitors, as a class, was associated with acute onset of NAION. Individuals with "crowded" optic disc are also considered at greater risk for NAION compared to the general population, however, evidence is insufficient to support screening of prospective users of PDE5 inhibitors, including SINEGRA (Generic VIAGRA), for this uncommon condition. Decreased blood pressure, syncope, and prolonged erection were reported in some healthy volunteers exposed to high doses of sildenafil (200–800 mg). However, in vitro studies with human platelets indicate that sildenafil potentiates the antiaggregatory effect of sodium nitroprusside (a nitric oxide donor).
Others were reported to have occurred hours to days after the use of SINEGRA (Generic VIAGRA) and sexual activity. The results suggest an approximate 2 fold increase in the risk of NAION within 5 half-lives of PDE5 inhibitor use. In addition, the combination of heparin and SINEGRA (Generic VIAGRA) had an additive effect on bleeding time in the anesthetized rabbit, but this interaction has not been studied in humans.
From this information, it is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [see Adverse Reactions (6.2)]. Short-term effects of l-citrulline supplementation on arterial stiffness in middle-aged men..
Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction.



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