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What is Viagra used for? Viagra is used to treat impotence in men. Viagra increases the body’s ability to achieve and maintain an erection during sexual stimulation. Viagra does not protect you from getting sexually transmitted diseases, including HIV. take Viagra? Men who are currently using medicines that contain nitrates, such as nitroglycerin should not use Viagra because taken together they can lower the blood pressure too much. Viagra should not be used by women or children. You should have a complete medical history and exam to determine the cause of your impotence before taking Viagra. Men who have medical conditions that may cause a sustained erection such as sickle cell anemia, leukemia or multiple myeloma or who have an abnormally shaped penis may not be able to take Viagra. There are several medications that are known to interact with Viagra, so be sure to tell your doctor about all medications you are taking including those you can get without a prescription. Viagra has not been studied with other treatments for impotence, so use in combination with other treatments is not recommended. How should I take Viagra? Your healthcare provider may prescribe Viagra as one tablet once a day, about 1 hour before sexual activity. However, Viagra may be taken anywhere from 30 minutes to 4 hours before sexual activity. What are some possible side effects of Viagra? a complete list of side effects reported with Viagra. Your healthcare provider can discuss with you a more complete list of side effects. Viagra is generally well tolerated. If any side effects are experienced, they are usually mild and temporary. The following is a listing of the most common side effects: Visual changes such as mild and temporary changes in blue/green colors or increased sensitivity to light. For more detailed information on Viagra, ask your healthcare provider. More Articles... If you have any questions or comments on senior health nutrition, fitness, etc., go to the is for educational / reference use only.bingo buy game online viagra Impotence and erectile dysfunction affect many men, and in recent years, have become more widely discussed. Various treatments have been developed to cure such problems, the most popular and widely available being Viagra. There are more and more alternatives to Viagra appearing on the market, some of which are more reliable and trustworthy than others! Read on to discover a legitimate and safe alternatives to Viagra. Firstly, some men experience side effects from using Viagra. Although this isn't widespread amongst users, Viagra alternatives don't involve any risk of side effects. Side effects such as dizziness, loss of vision, headaches, flushing and low blood pressure can occur. In more extreme cases some men have experienced priapism( a painful condition when a man's penis fails to return to its natural flaccid state. The Viagra alternative extracts such side effects as the non- chemical remedies consist of natural herbal ingredients. Such alternatives are widely available and their increased use by male consumers on the rise. Secondly, such herbal alternatives are available over the counter or on the internet (as are Viagra however), without a prescription, and are relatively cheap, ranging from $1- 1.50 a pill. Generic Viagra treatments however are also available without a prescription, and although are slightly more expensive they still appear to be the most popular choice amongst consumers. Thirdly, an alternative Viagra treatment takes 30- 45 minutes to work, however the length of its effect varies widely. Certain herbal ingredients work effectively such as Epicedium (commonly known as the horny goat weed), which is a great sex drive booster. Viagra however, whilst taking about the same time to have an effect on a man's penis normally lasts for around 1-2 hours (sometimes more) from the time of ingestion, and so guarantees a man sexual pleasure. It is important for each individual male to weigh up the pro's and cons to his preferred treatment of erectile dysfunction, taking into account all the available information. viagra 6 free samples Viagra has made a significant difference in the quality of life of millions of men and their partners. When the FDA approved the first oral medication for the treatment of erectile dysfunction in 1998, it gave rise to a new world of possibilities that would restore men to healthy sex routine. For plenty of these individuals, the ability to have reliable erections has brought them and their partners’ sexual satisfaction and a tremendous sense of emotional comfort in their lives. Many times, the return to sexual potency greatly enriches overall relationship satisfaction. Thanks to the advantages of Viagra, many men have come to the conclusion that they enjoy sex and had sex more frequently. While Viagra is not an aphrodisiac, men have reported an enhancement in sexual desire and arousal. Some are of the opinion that their orgasms felt more intense and enjoyable. Rather than being directly attached to Viagra, these sorts of opinions are most likely because of an increase in the man's general interest in sex, which is due to their Viagra-assisted reliable erections. Even with the sexual success that having a good erection allows, there are a wide array of psychological and relationship aspects involved in a couple's sexual routine. The continued quality of a couple's sexual routine will still be dependent on past, present and future relationship factors. To illustrate this point, consider The following factors: the sort of changes that occurred in the relationship when, thanks to Viagra, erectile problems were no longer a factor Some couples may enjoy renewed sexual routine, but others might feel that sex will now be required on demand. This can place unnecessary pressure on either partner to perform. If the erectile issues were due to problems between the partners, they need to be addressed. It is not unusual for men to be of the view that everything is in order once modern medicine has restored his erections. This is where work must be done to avoid future problems involving intimacy and communication about sex. Even with the restoration of a man's erections, the same sort of sexual turn-offs and difficulties surrounding sex, (timing, frequency, life-style, routines and methods) can still be crucial issues in judging overall sexual satisfaction..
Life is, of course, all about managing death. or rather, it's all about managing pain and pollution and disease and gravity and germs and bacteria and poison and dick cheney and those little shards of glass in your burrito; it's all about, in short, how you sort through the sundry and ever-increasing laundry list of things in your immediate world that want to torment and toxify and destroy you because oh my god they are legion and they are ready and they are . . did you know? it shouldn't come as much of a surprise, really, given how many millions of drug-blasted americans inhale prescription meds by the fistful and then hit the bathroom and the water flows and the treatment plant churns and pumps it all back into municipal water pipes, still brimming with trace amounts of xanax and zoloft and medrol and norvasc, asthma drugs and cholesterol drugs and birth control pills, cancer drugs and painkillers and diuretics and who the hell knows what else. hell, who needs vitamin water when there's lipitor in your ice cubes? this is the wacky fun reminder: living in the city is deadly and toxic a million ways from sunday. in every breath, electromagnetic waves in every gizmo, plastic off-gassing and high-voc paints and chemicals in the carpet and toxins in your very clothing and every modern home so packed with thriving bacteria and synthetic substances and venomous glade air fresheners it's a wonder we manage to stay upright at all. hell, they just discovered that even our national parks, the fish and trees and lakes and the snow itself, are hugely polluted, . go ahead, hug that tree. but be sure to wear a body condom. this is what we have to accept: you do not avoid poison. you do not escape toxin or chemical or gravity or modern synthetic residue even if you move to the woods and build a humble off-grid shack made only of fresh pine needles and bird dung and make your own jam out of river moss and beetle larvae because, hey look, up there in the sky, it's the very air itself, full of chemicals and pollutants drifting over from china and india and, um, marin county, and you're breathing it in and it's coating the very trees and raining down upon your organic tomatoes right now. sorry. please enjoy your salad. no, you do not escape. you cannot completely block. you merely minimize. you recognize the most dire sources and most abhorrent problems and you choose your battles wisely, as you acknowledge just how complicit you are in all of it, how much you contribute to the problem, and adjust and recalibrate your life accordingly. this is the first, mandatory, all-important step. but more important than that, you learn to shun the paranoia. you gotta mock the relentless direness and shrug off the gods of death, every single day, even as they seem to be multiplying like rabid evangelicals at a colorado megachurch. you gotta keep perspective, recall how man has been under deadly pressure from himself since the dawn of time. otherwise, well, life is merely an army of demons and sins lined up and ready to take a bite out of your sweet, innocent flesh as you stroll by like a virgin at a porn convention. you know? wait, did i mention sin? good thing. because apparently they've . did you hear? indeed, a dour red-robed figure just slithered out of the shadows of the vatican and proclaimed some new additions to the master list of thou shalt nots, adding juicy tidbits like pedophilia and pollution and the taking/dealing of drugs (then you'd best not drink the water, father) and questions of bioethics (stem cell research, cloning, whatnot) to the massive catalog of things that make god scowl and angels whine and for which we are all surely going to hell like, a billion times over. is this not delightful, in a deeply pathetic and insulting sort of way? is it not amusing that, after 2,000 years, they're finally saying, hey gosh, trashing the planet and abusing creation itself is sort of wrong? or that they — the catholic church! — dared to add pedophilia to the list, which is a bit like mcdonald's announcing that beef is bad for you? yo, preacher: heal thyself, ok? as for bioethics, well, of course they worry that we'll try to "play god," which is just sort of cute and ridiculous given how most of us, you know, , every single day, by defying death and tormenting our bodies and launching brutal unwinnable wars (in the name of god, natch), choosing whether or not to eat meat and destroy plants and get pregnant or fall in love or hate gay people or buy an escalade or enjoy adam sandler movies. playing god? who the hell is playing? god, that's where the real action is. and now, the bad news: they didn't remove a single damnable thing. they did not say, ok, we've added some vile and obvious new sins, so just for the sake of balance and just so you don't think we're authoritarian cretins, let's remove a few of the outdated, insulting ones, shall we? condoms? birth control? go for it (they should've said). pre-marital sex? have at it, children. in fact, it's now highly recommended. especially if you do it right. and often. and develop some mad skills so if you ever get married you can keep surprising each other with delightful new ways to enjoy various kitchen tools and yoga straps and viagra chewing gum. praise jesus. better yet, they should take it a step further, and for every new sin they add, they should remove . this way, eventually we'll whittle it down to just one grand sin, one terrifically all-encompassing god-mocking insult. which is, of course, the idea of sin itself. believe in sin? believe that we're all, at our core, corrupt and evil and mortally flawed and that life is basically a grueling slog against disease and pain and pollution and 10,000 household poisons until you eventually whimper and sigh and lay yourself in a chemical-soaked pine box and sink it six feet under? baby, that's the biggest sin of all. and you are hereby absolved. thoughts about this column? . This medicine is a phosphodiesterase inhibitor used to treat sexual function problems such as impotence or erectile dysfunction. In combination with sexual stimulation, this medicine works by helping the blood flow into the penis to achieve and maintain an erection. This medicine is not intended for use in women or children. This medicine will not protect against sexually transmitted diseases including HIV infection. Use "safe sex" practices such as latex condoms. Contact your doctor or pharmacist for more details. Some medicines or medical conditions may interact with this medicine. INFORM YOUR DOCTOR OR PHARMACIST of all prescription and over-the-counter medicine that you are taking. DO NOT TAKE THIS MEDICINE if you are taking any form of nitroglycerin, (such as tablet, patch, or ointment dose forms) or other nitrates (such as isosorbide), nitroprusside (or any "nitric oxide donor" medicine), or recreational drugs called "poppers" containing amyl or butyl nitrate because very serious interactions may occur. If you are not sure whether a certain medicine is a nitrate, contact your doctor or pharmacist. If you are currently using any of these medicines, tell your doctor or pharmacist before using sildenafil. ADDITIONAL MONITORING OF YOUR DOSE OR CONDITION may be needed if you are taking other medicines for impotence, antifungals (such as itraconazole or ketoconazole), cimetidine, delavirdine, erythromycin, mibefradil, or rifampin. If you are taking an HIV protease inhibitor (such as ritonavir or saquinavir), do not take more than a 25 mg dose of sildenafil in a 48-hour period. If you are taking more than a 25 mg dose of sildenafil and are also taking an alpha-blocker medicine (such as doxazosin, prazosin, or terazosin) for various conditions (such as enlarged prostate), separate the time between taking these medicines by more than 4 hours. DO NOT START OR STOP any medicine without doctor or pharmacist approval. Inform your doctor of any other medical conditions including penis conditions (such as angulation, fibrosis/scarring, or Peyronie's disease), history of painful/prolonged erection (priapism), sickle cell anemia, blood system cancers (such as leukemia or myeloma), vision problems (such as retina diseases like retinitis pigmentosa) or history of vision loss, kidney or liver disease, bleeding disorders, active stomach ulcers, heart problems (such as recent heart attack or irregular heartbeat within past 6 months, heart failure, coronary artery disease with unstable angina, aortic stenosis or idiopathic hypertrophic subaortic stenosis), recent stroke within past 6 months, very high or low blood pressure, or allergies. Contact your doctor or pharmacist if you have any questions or concerns about taking this medicine. Follow the directions for using this medicine provided by your doctor. An additional patient information leaflet is available with this medicine. Read it carefully. Ask your doctor, nurse, or pharmacist any questions that you may have about this medicine. TAKE THIS MEDICINE by mouth as needed between four hours and one-half hour before sexual activity (about 1 hour before is most effective); or take as directed by your doctor. DO NOT TAKE THIS MEDICINE more often than once daily as needed. A high fat meal may delay the time of onset of this medicine. Your dosage is based on your medical condition, your response to therapy, and other medicines you are taking. Consult your doctor or pharmacist for more information. STORE THIS MEDICINE at room temperature 77 degrees F (25 degrees C) in a tightly-closed container, away from heat, moisture, and light. Brief storage between 59 and 86 degrees F (15 and 30 degrees C) is permitted. DO NOT TAKE THIS MEDICINE if you have had an allergic reaction to it in the past or to any other ingredient that is found in it. THIS MEDICINE MAY CAUSE VISION CHANGES. DO NOT DRIVE, OPERATE MACHINERY, OR DO ANYTHING ELSE THAT COULD BE DANGEROUS until you know how you react to this medicine. Using this medicine alone, with other medicines, or with alcohol may lessen your ability to drive or to perform other potentially dangerous tasks. TO MINIMIZE DIZZINESS OR LIGHTHEADEDNESS, sit up or stand slowly when rising from a seated or lying position. Your dose is based on your medical condition, response to therapy, and the other medicines you are taking. DO NOT EXCEED THE RECOMMENDED DOSE without checking with your doctor. Rarely, this medicine may change heart rhythm, especially if taken with other medicines that can change the heart rhythm. This change in heart rhythm can result in serious, rarely fatal, irregular heartbeats. Ask your doctor for more information and if you should stop taking any of your other medicines to reduce the risk of this side effect. BEFORE YOU BEGIN TAKING ANY NEW MEDICINE, either prescription or over-the-counter, check with your doctor or pharmacist. CAUTION IS ADVISED WHEN USING THIS MEDICINE IN THE ELDERLY because they may be more sensitive to the side effects of this medicine. THIS MEDICINE SHOULD NOT BE USED IN WOMEN OR CHILDREN. SIDE EFFECTS that may occur while taking this medicine include headache, flushing, stomach upset, heartburn, nasal stuffiness, diarrhea, dizziness, or lightheadedness. Vision changes such as increased sensitivity to light, blurred vision, or impaired blue/green color discrimination may also occur. If these continue or are bothersome, check with your doctor or pharmacist. CONTACT YOUR DOCTOR IMMEDIATELY if you experience vision loss in one or both eyes, hearing loss, ringing in the ears, or severe or persistent dizziness. Sexual activity may put extra strain on your heart, especially if you have heart problems. If you have heart problems and experience any serious side effects while having sex, stop having sex and tell your doctor immediately. These side effects include severe dizziness, fainting, chest pain, or nausea. In the unlikely event that you have a painful or prolonged erection (lasting more than 4 hours), stop using this medicine and seek immediate medical attention or permanent problems could occur. AN ALLERGIC REACTION TO THIS MEDICINE is unlikely, but seek immediate medical attention if it occurs. Symptoms of an allergic reaction include rash, itching, unusual swelling, severe dizziness, or trouble breathing. If you notice other effects not listed above, contact your doctor, nurse, or pharmacist. If overdose is suspected, contact your local poison control center or emergency room immediately. Symptoms of overdose may include severe dizziness, fainting, or prolonged erection. If your symptoms do not improve or if they become worse, check with your doctor. DO NOT SHARE THIS MEDICINE with others for whom it was not prescribed, since they may have a problem that is not effectively treated with this medicine, or they may have a condition that is complicated by this medicine. DO NOT USE THIS MEDICINE for other health conditions. KEEP THIS MEDICINE out of the reach of children and pets. IF USING THIS MEDICINE FOR AN EXTENDED PERIOD OF TIME, obtain refills before your supply runs out. Copyright 2008 Wolters Kluwer Health, Inc. - This information is not intended to substitute for professional medical advice. Be sure to contact your physician, pharmacist or other health care provider for more information about this medication. By searching these web site pages, you agree to our.
Nuts, crocodiles and witch trials may seem to have little to do with viagra -- but at one time or another, they've all been employed against erectile dysfunction. for centuries, doctors struggled to pinpoint the causes of male impotence, blaming such factors as stress, diet, the wrath of deities and unattractive women. ancient greek physician hippocrates attributed impotence to horseback riding; one of his contemporaries placed the blame on childhood trauma; egyptians to evil spells. the ancients also left behind an imaginative array of remedies: snacks of almonds, pistachios, dates, currant juice and bird eggs in persia; a mix of sesame, lentils, rice and sugar cane juice in ancient india -- or goat testicles boiled in milk or butter and boiled alligator testes rubbed on the feet. the egyptians were more direct, smearing remedies (such as crocodile hearts and wood oil) directly on the penis. in the islamic empire, impotence was sometimes blamed on an imbalance in the four fluids, or humors, thought to course through the body. doctors advised men to avoid sex after meals, in the bathroom and with old or unappealing partners. in medieval europe, impotent men believed they were under spells cast by witches, but also blamed their wives. impotence was grounds for divorce. in the victorian era, many thought impotence was due to a depletion of sperm. doctors cautioned against masturbation (a "waste" of sperm) and prescribed quinine, opium, digitalis and bleeding, to no avail. in the late 1800s, french professor of medicine charles edouard brown-sequard proposed that injections of animal sperm might restore vitality. he tested the theory by injecting himself with an extract of dog and guinea pig testicles. his colleagues, who agreed the professor looked good for a man of 72, agreed to test the extracts on their patients. soon the treatment, organotherapy, was all the rage. starting in the late 1910s, a few doctors went a step further, deciding to transplant whole testicles. in france, serge voronoff transplanted monkey testicles into the nether regions of more than 1,000 old men. in kansas, john brinkley ran a hospital that specialized in grafting goat testicles onto patients. at a california prison, leo stanley gave older inmates testicles of younger, executed prisoners. although many men claimed to feel rejuvenated by their testicular shots and transplants, few recovered their virility, and researchers continued their search. in the 1930s doctors experimented with surgical adjustment of penile muscles. in the 1940s and 1950s, they tried implants, inspired by the penile bones many animals have. in the 1960s, an effective option finally arrived. a georgia tire serviceman began work on a vacuum pump to treat his own impotence, which was ultimately approved by the food and drug administration in 1982. the pump appeared just as several researchers began to identify drug treatments for impotence, albeit few with the showmanship exhibited by british doctor giles brindley. at a 1983 urology meeting, brindley injected himself with a drug, phentolamine -- then took the stage, dropped his pants and shared his erection with his colleagues. brindley injected 33 drugs in his penis before finding one that worked, which may have rendered him slightly envious of the discoverers of viagra. british researchers ian osterloh and gill samuels were developing a drug to improve blood flow to the heart when they realized that the drug, sildenafil citrate, was much more effective at improving blood flow to the penis -- and causing erections. in viagra's first month on the market, doctors wrote well over 500,000 prescriptions. considering men's history of options -- crocodile hearts, prayer, testicular shots and grafts -- perhaps the blue pill's lasting popularity should come as no surprise. Levitra and Viagra are different drugs used to treat one common issue, Erectile Dysfunction (impotence). There are lots of similarities as well as differences when looking at Levitra vs. Viagra. Advice from your health care provider is the ideal way to conclude which drug is the perfect choice for treating your ED. One should never diagnose and treat ED on their own; it could turn out to be a life threatening move. It is mandatory for men with ED to understand the fact that they are not alone. As a matter of fact, millions of men all over the world suffer from ED each year. Fortunately, advancement in pharmaceutical technology has offered choices for these millions. When comparing Levitra with Viagra, the main point of difference is the main ingredient. While Levitra’s main ingredient consists of vardenfil, a PDE5 inhibitor, the main ingredient in Viagra is sildenafil citrate, which has been used not only to treat ED, but also pulmonary arterial hypertension Side effects arising from the use of vardenfil are: abdominal pain, back pain, photosensitivity, abnormal vision, eye pain, facial edema, hypertension, palpitation, tachycardia, arthralgia, myalgia, rash, itch, priapism, and in a few rare scenarios heart attack. Vardenfil should also not be taken if the patient is using any sort of nitrate medication. This is because it has the tendency to produce very low blood pressure. Health care providers will never prescribe Levitra to a patient at risk of experiencing serious side effects. Viagra was the first pill to be introduced to the market. Side effects of Viagra include: priapism, severe hypotension, myocardial infarction, ventricular arrhythmias, sudden death, stroke and enhanced intraocular pressure. The common side effects consist of sneezing, headache, flushing, dyspepsia, prolonged erections, palpitations, and photophobia. Visual changes including blurring of vision and a curious bluish tinge which have been reported in studies. Levitra and Viagra are nearly identical in that they are to be consumed anywhere from a half an hour to a couple of hours prior to sexual activity. Viagra may have been the starting point in the treatment of ED, but there is no doubt that Levitra has been seen as “new and better”. Levitra’s side effects are far and few versus Viagra, though response of drugs varies from person to person. A detailed analysis of your medical history is required to choose the ideal prescription drug for you. An oral therapy for erectile dysfunction, is the citrate salt of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Sildenafil citrate is designated chemically as 1 - [[3 - (6,7 - dihydro - 1 - methyl - 7 - oxo - 3 - propyl - 1H - pyrazolo[4,3 - d]pyrimidin - 5 - yl) - 4 - ethoxyphenyl]sulfonyl] - 4 - methylpiperazine citrate and has the following structural formula: Sildenafil citrate is a white to off-white crystalline powder with a solubility of 3.5 mg/mL in water and a molecular weight of 666.7. Viagra (sildenafil citrate) is formulated as blue, film-coated rounded-diamond-shaped tablets equivalent to 25 mg, 50 mg and 100 mg of sildenafil for oral administration. In addition to the active ingredient, sildenafil citrate, each tablet contains the following inactive ingredients: microcrystalline cellulose, anhydrous dibasic calcium phosphate, croscarmellose sodium, magnesium stearate, hypromellose, titanium dioxide, lactose, triacetin, and FD & C Blue #2 aluminum lake. The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum, but enhances the effect of nitric oxide (NO) by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum. When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum. Sildenafil at recommended doses has no effect in the absence of sexual stimulation. Studies in vitro have shown that sildenafil is selective for PDE5. Its effect is more potent on PDE5 than on other known phosphodiesterases (10-fold for PDE6, >80-fold for PDE1, >700-fold for PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11). The approximately 4,000-fold selectivity for PDE5 versus PDE3 is important because PDE3 is involved in control of cardiac contractility. Sildenafil is only about 10-fold as potent for PDE5 compared to PDE6, an enzyme found in the retina which is involved in the phototransduction pathway of the retina. This lower selectivity is thought to be the basis for abnormalities related to color vision observed with higher doses or plasma levels (see ). In addition to human corpus cavernosum smooth muscle, PDE5 is also found in lower concentrations in other tissues including platelets, vascular and visceral smooth muscle, and skeletal muscle. The inhibition of PDE5 in these tissues by sildenafil may be the basis for the enhanced platelet antiaggregatory activity of nitric oxide observed in vitro, an inhibition of platelet thrombus formation in vivo and peripheral arterial-venous dilatation in vivo. Viagra is rapidly absorbed after oral administration, with absolute bioavailability of about 40%. Its pharmacokinetics are dose-proportional over the recommended dose range. It is eliminated predominantly by hepatic metabolism (mainly cytochrome P450 3A4) and is converted to an active metabolite with properties similar to the parent, sildenafil. The concomitant use of potent cytochrome P450 3A4 inhibitors (e.g., erythromycin, ketoconazole, itraconazole) as well as the nonspecific CYP inhibitor, cimetidine, is associated with increased plasma levels of sildenafil (see ). Both sildenafil and the metabolite have terminal half lives of about 4 hours. in Healthy Male Volunteers. Viagra is rapidly absorbed. Maximum observed plasma concentrations are reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted state. When Viagra is taken with a high fat meal, the rate of absorption is reduced, with a mean delay in T of 29%. The mean steady state volume of distribution (Vss) for sildenafil is 105 L, indicating distribution into the tissues. Sildenafil and its major circulating N-desmethyl metabolite are both approximately 96% bound to plasma proteins. Protein binding is independent of total drug concentrations. Based upon measurements of sildenafil in semen of healthy volunteers 90 minutes after dosing, less than 0.001% of the administered dose may appear in the semen of patients. Sildenafil is cleared predominantly by the CYP3A4 (major route) and CYP2C9 (minor route) hepatic microsomal isoenzymes. The major circulating metabolite results from N-desmethylation of sildenafil, and is itself further metabolized. This metabolite has a PDE selectivity profile similar to sildenafil and an in vitro potency for PDE5 approximately 50% of the parent drug. Plasma concentrations of this metabolite are approximately 40% of those seen for sildenafil, so that the metabolite accounts for about 20% of sildenafil's pharmacologic effects. After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the feces (approximately 80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose). Similar values for pharmacokinetic parameters were seen in normal volunteers and in the patient population, using a population pharmacokinetic approach. Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil, with free plasma concentrations approximately 40% greater than those seen in healthy younger volunteers (18–45 years). In volunteers with mild (CLcr=50–80 mL/min) and moderate (CLcr=30–49 mL/min) renal impairment, the pharmacokinetics of a single oral dose of Viagra (50 mg) were not altered. In volunteers with severe (CLcr=<30 mL/min) renal impairment, sildenafil clearance was reduced, resulting in approximately doubling of AUC and C compared to age-matched volunteers with no renal impairment. In volunteers with hepatic cirrhosis (Child-Pugh A and B), sildenafil clearance was reduced, resulting in increases in AUC (84%) and C (47%) compared to age-matched volunteers with no hepatic impairment. Therefore, age >65, hepatic impairment and severe renal impairment are associated with increased plasma levels of sildenafil. A starting oral dose of 25 mg should be considered in those patients (see ). In eight double-blind, placebo-controlled crossover studies of patients with either organic or psychogenic erectile dysfunction, sexual stimulation resulted in improved erections, as assessed by an objective measurement of hardness and duration of erections (RigiScan ), after Viagra administration compared with placebo. Most studies assessed the efficacy of Viagra approximately 60 minutes post dose. The erectile response, as assessed by RigiScan , generally increased with increasing sildenafil dose and plasma concentration. The time course of effect was examined in one study, showing an effect for up to 4 hours but the response was diminished compared to 2 hours. Single oral doses of sildenafil (100 mg) administered to healthy volunteers produced decreases in supine blood pressure (mean maximum decrease in systolic/diastolic blood pressure of 8.4/5.5 mmHg). The decrease in blood pressure was most notable approximately 1–2 hours after dosing, and was not different than placebo at 8 hours. Similar effects on blood pressure were noted with 25 mg, 50 mg and 100 mg of Viagra, therefore the effects are not related to dose or plasma levels within this dosage range. Larger effects were recorded among patients receiving concomitant nitrates (see ). Systolic Blood Pressure, Healthy Volunteers. Single oral doses of sildenafil up to 100 mg produced no clinically relevant changes in the ECGs of normal male volunteers. Studies have produced relevant data on the effects of Viagra on cardiac output. In one small, open-label, uncontrolled, pilot study, eight patients with stable ischemic heart disease underwent Swan-Ganz catheterization. A total dose of 40 mg sildenafil was administered by four intravenous infusions. The results from this pilot study are shown in Table 1; the mean resting systolic and diastolic blood pressures decreased by 7% and 10% compared to baseline in these patients. Mean resting values for right atrial pressure, pulmonary artery pressure, pulmonary artery occluded pressure and cardiac output decreased by 28%, 28%, 20% and 7% respectively. Even though this total dosage produced plasma sildenafil concentrations which were approximately 2 to 5 times higher than the mean maximum plasma concentrations following a single oral dose of 100 mg in healthy male volunteers, the hemodynamic response to exercise was preserved in these patients. In a double-blind study, 144 patients with erectile dysfunction and chronic stable angina limited by exercise, not receiving chronic oral nitrates, were randomized to a single dose of placebo or Viagra 100 mg 1 hour prior to exercise testing. The primary endpoint was time to limiting angina in the evaluable cohort. The mean times (adjusted for baseline) to onset of limiting angina were 423.6 and 403.7 seconds for sildenafil (N=70) and placebo, respectively. These results demonstrated that the effect of Viagra on the primary endpoint was statistically non-inferior to placebo. At single oral doses of 100 mg and 200 mg, transient dose-related impairment of color discrimination (blue/green) was detected using the Farnsworth-Munsell 100-hue test, with peak effects near the time of peak plasma levels. This finding is consistent with the inhibition of PDE6, which is involved in phototransduction in the retina. An evaluation of visual function at doses up to twice the maximum recommended dose revealed no effects of Viagra on visual acuity, intraocular pressure, or pupillometry. In clinical studies, Viagra was assessed for its effect on the ability of men with erectile dysfunction (ED) to engage in sexual activity and in many cases specifically on the ability to achieve and maintain an erection sufficient for satisfactory sexual activity. Viagra was evaluated primarily at doses of 25 mg, 50 mg and 100 mg in 21 randomized, double-blind, placebo-controlled trials of up to 6 months in duration, using a variety of study designs (fixed dose, titration, parallel, crossover). Viagra was administered to more than 3,000 patients aged 19 to 87 years, with ED of various etiologies (organic, psychogenic, mixed) with a mean duration of 5 years. Viagra demonstrated statistically significant improvement compared to placebo in all 21 studies. The studies that established benefit demonstrated improvements in success rates for sexual intercourse compared with placebo. The effectiveness of Viagra was evaluated in most studies using several assessment instruments. The primary measure in the principal studies was a sexual function questionnaire (the International Index of Erectile Function - IIEF) administered during a 4-week treatment-free run-in period, at baseline, at follow-up visits, and at the end of double-blind, placebo-controlled, at-home treatment. Two of the questions from the IIEF served as primary study endpoints; categorical responses were elicited to questions about (1) the ability to achieve erections sufficient for sexual intercourse and (2) the maintenance of erections after penetration. The patient addressed both questions at the final visit for the last 4 weeks of the study. The possible categorical responses to these questions were (0) no attempted intercourse, (1) never or almost never, (2) a few times, (3) sometimes, (4) most times, and (5) almost always or always. Also collected as part of the IIEF was information about other aspects of sexual function, including information on erectile function, orgasm, desire, satisfaction with intercourse, and overall sexual satisfaction. Sexual function data were also recorded by patients in a daily diary. In addition, patients were asked a global efficacy question and an optional partner questionnaire was administered. The effect on one of the major end points, maintenance of erections after penetration, is shown in Figure 3, for the pooled results of 5 fixed-dose, dose-response studies of greater than one month duration, showing response according to baseline function. Results with all doses have been pooled, but scores showed greater improvement at the 50 and 100 mg doses than at 25 mg. The pattern of responses was similar for the other principal question, the ability to achieve an erection sufficient for intercourse. The titration studies, in which most patients received 100 mg, showed similar results. Figure 3 shows that regardless of the baseline levels of function, subsequent function in patients treated with Viagra was better than that seen in patients treated with placebo. At the same time, on-treatment function was better in treated patients who were less impaired at baseline. Figure 3. Effect of Viagra and Placebo on Maintenance of Erection by Baseline Score. The frequency of patients reporting improvement of erections in response to a global question in four of the randomized, double-blind, parallel, placebo-controlled fixed dose studies (1797 patients) of 12 to 24 weeks duration is shown in Figure 4. These patients had erectile dysfunction at baseline that was characterized by median categorical scores of 2 (a few times) on principal IIEF questions. Erectile dysfunction was attributed to organic (58%; generally not characterized, but including diabetes and excluding spinal cord injury), psychogenic (17%), or mixed (24%) etiologies. Sixty-three percent, 74%, and 82% of the patients on 25 mg, 50 mg and 100 mg of Viagra, respectively, reported an improvement in their erections, compared to 24% on placebo. In the titration studies (n=644) (with most patients eventually receiving 100 mg), results were similar. Figure 4. Percentage of Patients Reporting an Improvement in Erections. The patients in studies had varying degrees of ED. One-third to one-half of the subjects in these studies reported successful intercourse at least once during a 4-week, treatment-free run-in period. In many of the studies, of both fixed dose and titration designs, daily diaries were kept by patients. In these studies, involving about 1600 patients, analyses of patient diaries showed no effect of Viagra on rates of attempted intercourse (about 2 per week), but there was clear treatment-related improvement in sexual function: per patient weekly success rates averaged 1.3 on 50–100 mg of Viagra vs 0.4 on placebo; similarly, group mean success rates (total successes divided by total attempts) were about 66% on Viagra vs about 20% on placebo. During 3 to 6 months of double-blind treatment or longer-term (1 year), open-label studies, few patients withdrew from active treatment for any reason, including lack of effectiveness. At the end of the long-term study, 88% of patients reported that Viagra improved their erections. Men with untreated ED had relatively low baseline scores for all aspects of sexual function measured (again using a 5-point scale) in the IIEF. Viagra improved these aspects of sexual function: frequency, firmness and maintenance of erections; frequency of orgasm; frequency and level of desire; frequency, satisfaction and enjoyment of intercourse; and overall relationship satisfaction. One randomized, double-blind, flexible-dose, placebo-controlled study included only patients with erectile dysfunction attributed to complications of diabetes mellitus (n=268). As in the other titration studies, patients were started on 50 mg and allowed to adjust the dose up to 100 mg or down to 25 mg of Viagra; all patients, however, were receiving 50 mg or 100 mg at the end of the study. There were highly statistically significant improvements on the two principal IIEF questions (frequency of successful penetration during sexual activity and maintenance of erections after penetration) on Viagra compared to placebo. On a global improvement question, 57% of Viagra patients reported improved erections versus 10% on placebo. Diary data indicated that on Viagra, 48% of intercourse attempts were successful versus 12% on placebo. One randomized, double-blind, placebo-controlled, crossover, flexible-dose (up to 100 mg) study of patients with erectile dysfunction resulting from spinal cord injury (n=178) was conducted. The changes from baseline in scoring on the two end point questions (frequency of successful penetration during sexual activity and maintenance of erections after penetration) were highly statistically significantly in favor of Viagra. On a global improvement question, 83% of patients reported improved erections on Viagra versus 12% on placebo. Diary data indicated that on Viagra, 59% of attempts at sexual intercourse were successful compared to 13% on placebo. Across all trials, Viagra improved the erections of 43% of radical prostatectomy patients compared to 15% on placebo. Subgroup analyses of responses to a global improvement question in patients with psychogenic etiology in two fixed-dose studies (total n=179) and two titration studies (total n=149) showed 84% of Viagra patients reported improvement in erections compared with 26% of placebo. The changes from baseline in scoring on the two end point questions (frequency of successful penetration during sexual activity and maintenance of erections after penetration) were highly statistically significantly in favor of Viagra. Diary data in two of the studies (n=178) showed rates of successful intercourse per attempt of 70% for Viagra and 29% for placebo. A review of population subgroups demonstrated efficacy regardless of baseline severity, etiology, race and age. Viagra was effective in a broad range of ED patients, including those with a history of coronary artery disease, hypertension, other cardiac disease, peripheral vascular disease, diabetes mellitus, depression, coronary artery bypass graft (CABG), radical prostatectomy, transurethral resection of the prostate (TURP) and spinal cord injury, and in patients taking antidepressants/antipsychotics and antihypertensives/diuretics. Analysis of the safety database showed no apparent difference in the side effect profile in patients taking Viagra with and without antihypertensive medication. This analysis was performed retrospectively, and was not powered to detect any pre-specified difference in adverse reactions. Viagra is indicated for the treatment of erectile dysfunction. ), Viagra was shown to potentiate the hypotensive effects of nitrates, and its administration to patients who are using organic nitrates, either regularly and/or intermittently, in any form is therefore contraindicated. After patients have taken Viagra, it is unknown when nitrates, if necessary, can be safely administered. Based on the pharmacokinetic profile of a single 100 mg oral dose given to healthy normal volunteers, the plasma levels of sildenafil at 24 hours post dose are approximately 2 ng/mL (compared to peak plasma levels of approximately 440 ng/mL) (see ). In the following patients: age >65, hepatic impairment (e.g., cirrhosis), severe renal impairment (e.g., creatinine clearance <30 mL/min), and concomitant use of potent cytochrome P450 3A4 inhibitors (erythromycin), plasma levels of sildenafil at 24 hours post dose have been found to be 3 to 8 times higher than those seen in healthy volunteers. Although plasma levels of sildenafil at 24 hours post dose are much lower than at peak concentration, it is unknown whether nitrates can be safely coadministered at this time point. Viagra is contraindicated in patients with a known hypersensitivity to any component of the tablet. There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease. Therefore, treatments for erectile dysfunction, including Viagra, should not be generally used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status. Viagra has systemic vasodilatory properties that resulted in transient decreases in supine blood pressure in healthy volunteers (mean maximum decrease of 8.4/5.5 mmHg), (see ). While this normally would be expected to be of little consequence in most patients, prior to prescribing 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. Patients with the following underlying conditions can be particularly sensitive to the actions of vasodilators including Viagra – those with left ventricular outflow obstruction (e.g. aortic stenosis, idiopathic hypertrophic subaortic stenosis) and those with severely impaired autonomic control of blood pressure. There is no controlled clinical data on the safety or efficacy of Viagra in the following groups; if prescribed, this should be done with caution. Patients who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months; Patients with retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases). Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been reported infrequently since market approval of Viagra. In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency could result. The concomitant administration of the protease inhibitor ritonavir substantially increases serum concentrations of sildenafil (11-fold increase in AUC). If Viagra is prescribed to patients taking ritonavir, caution should be used. Data from subjects exposed to high systemic levels of sildenafil are limited. Visual disturbances occurred more commonly at higher levels of sildenafil exposure. Decreased blood pressure, syncope, and prolonged erection were reported in some healthy volunteers exposed to high doses of sildenafil (200–800 mg). To decrease the chance of adverse events in patients taking ritonavir, a decrease in sildenafil dosage is recommended (see , ). The evaluation of erectile dysfunction should include a determination of potential underlying causes and the identification of appropriate treatment following a complete medical assessment. Before prescribing Viagra, it is important to note the following: Caution is advised when Phosphodiesterase Type 5 (PDE5) inhibitors are co-administered with alpha-blockers. PDE5 inhibitors, including Viagra, and alpha-adrenergic blocking agents are both vasodilators with blood pressure lowering effects. When vasodilators are used in combination, an additive effect on blood pressure may be anticipated. In some patients, concomitant use of these two drug classes can lower blood pressure significantly (see ) leading to symptomatic hypotension (e.g. dizziness, lightheadedness, fainting). Patients should be stable on alpha-blocker therapy prior to initiating a PDE5 inhibitor. 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. In those patients already taking an optimized dose of a PDE5 inhibitor, alpha-blocker therapy should be initiated at the lowest dose. Stepwise increase in alpha-blocker dose may be associated with further lowering of blood pressure when taking a PDE5 inhibitor. 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. Viagra has systemic vasodilatory properties and may augment the blood pressure lowering effect of other anti-hypertensive medications. Patients on multiple antihypertensive medications were included in the pivotal clinical trials for Viagra. In a separate drug interaction study, when amlodipine, 5 mg or 10 mg, and Viagra, 100 mg were orally administered concomitantly to hypertensive patients mean additional blood pressure reduction of 8 mmHg systolic and 7 mmHg diastolic were noted (see ). The safety of Viagra is unknown in patients with bleeding disorders and patients with active peptic ulceration. 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). The safety and efficacy of combinations of Viagra with other treatments for erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended. In humans, Viagra has no effect on bleeding time when taken alone or with aspirin. In vitro studies with human platelets indicate that sildenafil potentiates the antiaggregatory effect of sodium nitroprusside (a nitric oxide donor). The combination of heparin and Viagra had an additive effect on bleeding time in the anesthetized rabbit, but this interaction has not been studied in humans. Physicians should discuss with patients the contraindication of Viagra with regular and/or intermittent use of organic nitrates. Physicians should advise patients of the potential for Viagra to augment the blood pressure lowering effect of alpha-blockers and anti-hypertensive medications. Concomitant administration of Viagra and an alpha-blocker may lead to symptomatic hypotension in some patients. Therefore, when Viagra is co-administered with alpha-blockers, patients should be stable on alpha-blocker therapy prior to initiating Viagra treatment and Viagra should be initiated at the lowest dose. Physicians should discuss with patients the potential cardiac risk of sexual activity in patients with preexisting cardiovascular risk factors. Patients who experience symptoms (e.g., angina pectoris, dizziness, nausea) upon initiation of sexual activity should be advised to refrain from further activity and should discuss the episode with their physician. Physicians should advise patients to stop use of all PDE5 inhibitors, including Viagra, and seek medical attention in the event of a sudden loss of vision in one or both eyes. Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), 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. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors. Physicians should also discuss with patients the increased risk of NAION in individuals who have already experienced NAION in one eye, including whether such individuals could be adversely affected by use of vasodilators, such as PDE5 inhibitors (see ). Physicians should advise patients to stop taking PDE5 inhibitors, including Viagra, and seek prompt medical attention in the event of sudden decrease or loss of hearing. These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including Viagra. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors (see , ). Physicians should warn patients that prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been reported infrequently since market approval of Viagra. In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result. The use of Viagra offers no protection against sexually transmitted diseases. Counseling of patients about the protective measures necessary to guard against sexually transmitted diseases, including the Human Immunodeficiency Virus (HIV), may be considered. Sildenafil metabolism is principally mediated by the cytochrome P450 (CYP) isoforms 3A4 (major route) and 2C9 (minor route). Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance. Cimetidine (800 mg), a nonspecific CYP inhibitor, caused a 56% increase in plasma sildenafil concentrations when coadministered with Viagra (50 mg) to healthy volunteers. When a single 100 mg dose of Viagra was administered with erythromycin, a specific CYP3A4 inhibitor, at steady state (500 mg bid for 5 days), there was a 182% increase in sildenafil systemic exposure (AUC). In addition, in a study performed in healthy male volunteers, coadministration of the HIV protease inhibitor saquinavir, also a CYP3A4 inhibitor, at steady state (1200 mg tid) with Viagra (100 mg single dose) resulted in a 140% increase in sildenafil C and a 210% increase in sildenafil AUC. Viagra had no effect on saquinavir pharmacokinetics. Stronger CYP3A4 inhibitors such as ketoconazole or itraconazole would be expected to have still greater effects, and population data from patients in clinical trials did indicate a reduction in sildenafil clearance when it was coadministered with CYP3A4 inhibitors (such as ketoconazole, erythromycin, or cimetidine) (see ). In another study in healthy male volunteers, coadministration with the HIV protease inhibitor ritonavir, which is a highly potent P450 inhibitor, at steady state (500 mg bid) with Viagra (100 mg single dose) resulted in a 300% (4-fold) increase in sildenafil C and a 1000% (11-fold) increase in sildenafil plasma AUC. At 24 hours the plasma levels of sildenafil were still approximately 200 ng/mL, compared to approximately 5 ng/mL when sildenafil was dosed alone. This is consistent with ritonavir's marked effects on a broad range of P450 substrates. Viagra had no effect on ritonavir pharmacokinetics (see ). Although the interaction between other protease inhibitors and sildenafil has not been studied, their concomitant use is expected to increase sildenafil levels. In a study of healthy male volunteers, co-administration of sildenafil at steady state (80 mg t.i.d.) with endothelin receptor antagonist bosentan (a moderate inducer of CYP3A4, CYP2C9 and possibly of cytochrome P450 2C19) at steady state (125 mg b.i.d.) resulted in a 63% decrease of sildenafil AUC and a 55% decrease in sildenafil C . Concomitant administration of strong CYP3A4 inducers, such as rifampin, is expected to cause greater decreases in plasma levels of sildenafil. Single doses of antacid (magnesium hydroxide/aluminum hydroxide) did not affect the bioavailability of Viagra. Pharmacokinetic data from patients in clinical trials showed no effect on sildenafil pharmacokinetics of CYP2C9 inhibitors (such as tolbutamide, warfarin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and related diuretics, ACE inhibitors, and calcium channel blockers. The AUC of the active metabolite, N-desmethyl sildenafil, was increased 62% by loop and potassium-sparing diuretics and 102% by nonspecific beta-blockers. These effects on the metabolite are not expected to be of clinical consequence. Sildenafil is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 >150 µM). Given sildenafil peak plasma concentrations of approximately 1 µM after recommended doses, it is unlikely that Viagra will alter the clearance of substrates of these isoenzymes. Three double-blind, placebo-controlled, randomized, two-way crossover studies were conducted to assess the interaction of Viagra with doxazosin, an alpha-adrenergic blocking agent. In the first study, a single oral dose of Viagra 100 mg or matching placebo was administered in a 2-period crossover design to 4 generally healthy males with benign prostatic hyperplasia (BPH). Following at least 14 consecutive daily doses of doxazosin, Viagra 100 mg or matching placebo was administered simultaneously with doxazosin. Following a review of the data from these first 4 subjects (details provided below), the Viagra dose was reduced to 25 mg. Thereafter, 17 subjects were treated with Viagra 25 mg or matching placebo in combination with doxazosin 4 mg (15 subjects) or doxazosin 8mg (2 subjects). The mean subject age was 66.5 years. For the 17 subjects who received Viagra 25 mg and matching placebo, the placebo-subtracted mean maximum decreases from baseline (95% CI) in systolic blood pressure were as follows: Blood pressure was measured immediately pre-dose and at 15, 30, 45 minutes, and 1, 1.5, 2, 2.5, 3, 4, 6 and 8 hours after Viagra or matching placebo. Outliers were defined as subjects with a standing systolic blood pressure of <85 mmHg or a decrease from baseline in standing systolic blood pressure of >30 mmHg at one or more timepoints. There were no subjects treated with Viagra 25 mg who had a standing SBP < 85mmHg. There were three subjects with a decrease from baseline in standing systolic BP >30mmHg following Viagra 25 mg, one subject with a decrease from baseline in standing systolic BP > 30 mmHg following placebo and two subjects with a decrease from baseline in standing systolic BP > 30 mmHg following both Viagra and placebo. No severe adverse events potentially related to blood pressure effects were reported in this group. Of the four subjects who received Viagra 100 mg in the first part of this study, a severe adverse event related to blood pressure effect was reported in one patient (postural hypotension that began 35 minutes after dosing with Viagra with symptoms lasting for 8 hours), and mild adverse events potentially related to blood pressure effects were reported in two others (dizziness, headache and fatigue at 1 hour after dosing; and dizziness, lightheadedness and nausea at 4 hours after dosing). There were no reports of syncope among these patients. For these four subjects, the placebo-subtracted mean maximum decreases from baseline in supine and standing systolic blood pressures were 14.8 mmHg and 21.5 mmHg, respectively. Two of these subjects had a standing SBP < 85mmHg. Both of these subjects were protocol violators, one due to a low baseline standing SBP, and the other due to baseline orthostatic hypotension. In the second study, a single oral dose of Viagra 50 mg or matching placebo was administered in a 2-period crossover design to 20 generally healthy males with BPH. Following at least 14 consecutive days of doxazosin, Viagra 50mg or matching placebo was administered simultaneously with doxazosin 4 mg (17 subjects) or with doxazosin 8 mg (3 subjects). The mean subject age in this study was 63.9 years. Twenty subjects received Viagra 50 mg, but only 19 subjects received matching placebo. One patient discontinued the study prematurely due to an adverse event of hypotension following dosing with Viagra 50 mg. This patient had been taking minoxidil, a potent vasodilator, during the study. For the 19 subjects who received both Viagra and matching placebo, the placebo-subtracted mean maximum decreases from baseline (95% CI) in systolic blood pressure were as follows: Blood pressure was measured after administration of Viagra at the same times as those specified for the first doxazosin study. There were two subjects who had a standing SBP of < 85 mmHg. In these two subjects, hypotension was reported as a moderately severe adverse event, beginning at approximately 1 hour after administration of Viagra 50 mg and resolving after approximately 7.5 hours. There was one subject with a decrease from baseline in standing systolic BP >30mmHg following Viagra 50 mg and one subject with a decrease from baseline in standing systolic BP > 30 mmHg following both Viagra 50 mg and placebo. There were no severe adverse events potentially related to blood pressure and no episodes of syncope reported in this study. In the third study, a single oral dose of Viagra 100 mg or matching placebo was administered in a 3-period crossover design to 20 generally healthy males with BPH. In dose period 1, subjects were administered open-label doxazosin and a single dose of Viagra 50 mg simultaneously, after at least 14 consecutive days of doxazosin. If a subject did not successfully complete this first dosing period, he was discontinued from the study. Subjects who had successfully completed the previous doxazosin interaction study (using Viagra 50 mg), including no significant hemodynamic adverse events, were allowed to skip dose period 1. Treatment with doxazosin continued for at least 7 days after dose period 1. Thereafter, Viagra 100mg or matching placebo was administered simultaneously with doxazosin 4 mg (14 subjects) or doxazosin 8 mg (6 subjects) in standard crossover fashion. The mean subject age in this study was 66.4 years. Twenty-five subjects were screened. Two were discontinued after study period 1: one failed to meet pre-dose screening qualifications and the other experienced symptomatic hypotension as a moderately severe adverse event 30 minutes after dosing with open-label Viagra 50 mg. Of the twenty subjects who were ultimately assigned to treatment, a total of 13 subjects successfully completed dose period 1, and seven had successfully completed the previous doxazosin study (using Viagra 50 mg). For the 20 subjects who received Viagra 100 mg and matching placebo, the placebo-subtracted mean maximum decreases from baseline (95% CI) in systolic blood pressure were as follows: Blood pressure was measured after administration of Viagra at the same times as those specified for the previous doxazosin studies. There were three subjects who had a standing SBP of < 85 mmHg. All three were taking Viagra 100 mg, and all three reported mild adverse events at the time of reductions in standing SBP, including vasodilation and lightheadedness. There were four subjects with a decrease from baseline in standing systolic BP >30mmHg following Viagra 100 mg, one subject with a decrease from baseline in standing systolic BP > 30 mmHg following placebo and one subject with a decrease from baseline in standing systolic BP > 30 mmHg following both Viagra and placebo. While there were no severe adverse events potentially related to blood pressure reported in this study, one subject reported moderate vasodilatation after both Viagra 50 mg and 100 mg. There were no episodes of syncope reported in this study. When Viagra 100 mg oral was coadministered with amlodipine, 5 mg or 10 mg oral, to hypertensive patients, the mean additional reduction on supine blood pressure was 8 mmHg systolic and 7 mmHg diastolic. No significant interactions were shown with tolbutamide (250 mg) or warfarin (40 mg), both of which are metabolized by CYP2C9. Viagra (50 mg) did not potentiate the increase in bleeding time caused by aspirin (150 mg). Viagra (50 mg) did not potentiate the hypotensive effect of alcohol in healthy volunteers with mean maximum blood alcohol levels of 0.08%. In a study of healthy male volunteers, sildenafil (100 mg) did not affect the steady state pharmacokinetics of the HIV protease inhibitors, saquinavir and ritonavir, both of which are CYP3A4 substrates. Sildenafil at steady state (80 mg t.i.d.) resulted in a 50% increase in AUC and a 42% increase in C of bosentan (125 mg b.i.d.). Carcinogenesis, Mutagenesis, Impairment of Fertility Sildenafil was not carcinogenic when administered to rats for 24 months at a dose resulting in total systemic drug exposure (AUCs) for unbound sildenafil and its major metabolite of 29- and 42-times, for male and female rats, respectively, the exposures observed in human males given the Maximum Recommended Human Dose (MRHD) of 100 mg. Sildenafil was not carcinogenic when administered to mice for 18–21 months at dosages up to the Maximum Tolerated Dose (MTD) of 10 mg/kg/day, approximately 0.6 times the MRHD on a mg/m basis. Sildenafil was negative in in vitro bacterial and Chinese hamster ovary cell assays to detect mutagenicity, and in vitro human lymphocytes and in vivo mouse micronucleus assays to detect clastogenicity. There was no impairment of fertility in rats given sildenafil up to 60 mg/kg/day for 36 days to females and 102 days to males, a dose producing an AUC value of more than 25 times the human male AUC. There was no effect on sperm motility or morphology after single 100 mg oral doses of Viagra in healthy volunteers. Pregnancy, Nursing Mothers and Pediatric Use Viagra is not indicated for use in newborns, children, or women. No evidence of teratogenicity, embryotoxicity or fetotoxicity was observed in rats and rabbits which received up to 200 mg/kg/day during organogenesis. These doses represent, respectively, about 20 and 40 times the MRHD on a mg/m basis in a 50 kg subject. In the rat pre- and postnatal development study, the no observed adverse effect dose was 30 mg/kg/day given for 36 days. In the nonpregnant rat the AUC at this dose was about 20 times human AUC. There are no adequate and well-controlled studies of sildenafil in pregnant women. ). Since higher plasma levels may increase both the efficacy and incidence of adverse events, a starting dose of 25 mg should be considered (see ). Viagra was administered to over 3700 patients (aged 19–87 years) during pre-marketing clinical trials worldwide. Over 550 patients were treated for longer than one year. In placebo-controlled clinical studies, the discontinuation rate due to adverse events for Viagra (2.5%) was not significantly different from placebo (2.3%). The adverse events were generally transient and mild to moderate in nature. In trials of all designs, adverse events reported by patients receiving Viagra were generally similar. In fixed-dose studies, the incidence of some adverse events increased with dose. The nature of the adverse events in flexible-dose studies, which more closely reflect the recommended dosage regimen, was similar to that for fixed-dose studies. When Viagra was taken as recommended (on an as-needed basis) in flexible-dose, placebo-controlled clinical trials, the following adverse events were reported: Other adverse reactions occurred at a rate of >2%, but equally common on placebo: respiratory tract infection, back pain, flu syndrome, and arthralgia. In fixed-dose studies, dyspepsia (17%) and abnormal vision (11%) were more common at 100 mg than at lower doses. At doses above the recommended dose range, adverse events were similar to those detailed above but generally were reported more frequently. The following events occurred in <2% of patients in controlled clinical trials; a causal relationship to Viagra is uncertain. Reported events include those with a plausible relation to drug use; omitted are minor events and reports too imprecise to be meaningful: 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. Hemic and Lymphatic: anemia and leukopenia. 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. 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 Viagra. Most, but not all, of these patients had preexisting cardiovascular risk 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 Viagra without sexual activity. Others were reported to have occurred hours to days after the use of Viagra and sexual activity. It is not possible to determine whether these events are related directly to Viagra, to sexual activity, to the patient's underlying cardiovascular disease, to a combination of these factors, or to other factors (see for further important cardiovascular information). Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including Viagra. In some of the cases, medical conditions and other factors were reported that may have also played a role in the otologic adverse events. In many cases, medical follow-up information was limited. It is not possible to determine whether these reported events are related directly to the use of Viagra, to the patient’s underlying risk factors for hearing loss, a combination of these factors, or to other factors (see ). Nervous: seizure and anxiety. Urogenital: prolonged erection, priapism (see ), and hematuria. Special Senses: diplopia, temporary vision loss/decreased vision, ocular redness or bloodshot appearance, ocular burning, ocular swelling/pressure, increased intraocular pressure, retinal vascular disease or bleeding, vitreous detachment/traction, paramacular edema and epistaxis. 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 Viagra. 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. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors, to the patient's underlying vascular risk factors or anatomical defects, to a combination of these factors, or to other factors (see ). In studies with healthy volunteers of single doses up to 800 mg, adverse events were similar to those seen at lower doses but incidence rates were increased. In cases of overdose, standard supportive measures should be adopted as required. Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and it is not eliminated in the urine. For most patients, the recommended dose is 50 mg taken, as needed, approximately 1 hour before sexual activity. However, Viagra may be taken anywhere from 4 hours to 0.5 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. The maximum recommended dosing frequency is once per day. The following factors are associated with increased plasma levels of sildenafil: age >65 (40% increase in AUC), hepatic impairment (e.g., cirrhosis, 80%), severe renal impairment (creatinine clearance <30 mL/min, 100%), and concomitant use of potent cytochrome P450 3A4 inhibitors [ketoconazole, itraconazole, erythromycin (182%), saquinavir (210%)]. Since higher plasma levels may increase both the efficacy and incidence of adverse events, a starting dose of 25 mg should be considered in these patients. Ritonavir greatly increased the systemic level of sildenafil in a study of healthy, non-HIV infected volunteers (11-fold increase in AUC, see .) Based on these pharmacokinetic data, it is recommended not to exceed a maximum single dose of 25 mg of Viagra in a 48 hour period. Viagra was shown to potentiate the hypotensive effects of nitrates and its administration in patients who use nitric oxide donors or nitrates in any form is therefore contraindicated. When Viagra is co-administered with an alpha-blocker, patients should be stable on alpha-blocker therapy prior to initiating Viagra treatment and Viagra should be initiated at the lowest dose (see ). Viagra (sildenafil citrate) is supplied as blue, film-coated, rounded-diamond-shaped tablets containing sildenafil citrate equivalent to the nominally indicated amount of sildenafil as follows: Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature]. LAB-0221-8.0 ®. It is not meant to take the place of your doctor's instructions. Read this information carefully before you start taking Viagra. Ask your doctor or pharmacist if you do not understand any of this information or if you want to know more about Viagra. This medicine can help many men when it is used as prescribed by their doctors. However, Viagra is not for everyone. It is intended for use only by men who have a condition called erectile dysfunction. Viagra must never be used by men who are taking medicines that contain nitrates of any kind, at any time. This includes nitroglycerin. If you take Viagra with any nitrate medicine your blood pressure could suddenly drop to an unsafe or life threatening level. • WHAT IS Viagra? Viagra is a pill used to treat erectile dysfunction (impotence) in men. It can help many men who have erectile dysfunction get and keep an erection when they become sexually excited (stimulated). You will not get an erection just by taking this medicine. Viagra helps a man with erectile dysfunction get an erection only when he is sexually excited. When a man is sexually excited, the penis rapidly fills with more blood than usual. The penis then expands and hardens. This is called an erection. After the man is done having sex, this extra blood flows out of the penis back into the body. The erection goes away. If an erection lasts for a long time (more than 6 hours), it can permanently damage your penis. You should call a doctor immediately if you ever have a prolonged erection that lasts more than 4 hours. Some conditions and medicines interfere with this natural erection process. The penis cannot fill with enough blood. The man cannot have an erection. This is called erectile dysfunction if it becomes a frequent problem. During sex, your heart works harder. Therefore sexual activity may not be advisable for people who have heart problems. Before you start any treatment for erectile dysfunction, ask your doctor if your heart is healthy enough to handle the extra strain of having sex. If you have chest pains, dizziness or nausea during sex, stop having sex and immediately tell your doctor you have had this problem. Viagra enables many men with erectile dysfunction to respond to sexual stimulation. When a man is sexually excited, Viagra helps the penis fill with enough blood to cause an erection. After sex is over, the erection goes away. As noted above (How Sex Affects the Body), ask your doctor if your heart is healthy enough for sexual activity. If you take any medicines that contain nitrates – either regularly or as needed – you should never take Viagra. If you take Viagra with any nitrate medicine or recreational drug containing nitrates, your blood pressure could suddenly drop to an unsafe level. You could get dizzy, faint, or even have a heart attack or stroke. Nitrates are found in many prescription medicines that are used to treat angina (chest pain due to heart disease) such as: nitroglycerin (sprays, ointments, skin patches or pastes, and tablets that are swallowed or dissolved in the mouth) isosorbide mononitrate and isosorbide dinitrate (tablets that are swallowed, chewed, or dissolved in the mouth) Nitrates are also found in recreational drugs such as amyl nitrate or nitrite ("poppers"). If you are not sure if any of your medicines contain nitrates, or if you do not understand what nitrates are, ask your doctor or pharmacist. Viagra is only for patients with erectile dysfunction. Viagra is not for newborns, children, or women. Do not let anyone else take your Viagra. Viagra must be used only under a doctor's supervision. Viagra does not cure erectile dysfunction. It is a treatment for erectile dysfunction. Viagra does not protect you or your partner from getting sexually transmitted diseases, including HIV—the virus that causes AIDS. Viagra is not a hormone or an aphrodisiac. Only your doctor can decide if Viagra is right for you. Viagra can cause mild, temporary lowering of your blood pressure. You will need to have a thorough medical exam to diagnose your erectile dysfunction and to find out if you can safely take Viagra alone or with your other medicines. Your doctor should determine if your heart is healthy enough to handle the extra strain of having sex. have ever had any heart problems (e.g., angina, chest pain, heart failure, irregular heart beats, heart attack or narrowing of the aortic valve) have ever had any blood problems, including sickle cell anemia or leukemia have a deformed penis, Peyronie's disease, or ever had an erection that lasted more than 4 hours Some medicines can change the way Viagra works. Tell your doctor about any medicines you are taking. Do not start or stop taking any medicines before checking with your doctor or pharmacist. This includes prescription and nonprescription medicines or remedies: Remember, Viagra should never be used with medicines that contain nitrates (see Viagra Is Not for Everyone). If you are taking medicines called alpha-blockers for the treatment of high blood pressure or prostate problems, your blood pressure could suddenly drop. You could get dizzy or faint. If you are taking a protease inhibitor, your dose may be adjusted (please see Finding the Right Dose for You). Viagra should not be used with any other medical treatments that cause erections. These treatments include pills, medicines that are injected or inserted into the penis, implants or vacuum pumps. Viagra comes in different doses (25 mg, 50 mg and 100 mg). If you do not get the results you expect, talk with your doctor. You and your doctor can determine the dose that works best for you. Do not take more Viagra than your doctor prescribes. If you think you need a larger dose of Viagra, check with your doctor. Viagra should not be taken more than once a day. Your doctor may prescribe a lower dose of Viagra in certain circumstances. For example: If you are older than age 65, or have serious liver or kidney problems, your doctor may start you at the lowest dose (25 mg) of Viagra. If you are taking protease inhibitors, such as for the treatment of HIV, your doctor may recommend a 25 mg dose and may limit you to a maximum single dose of 25 mg of Viagra in a 48 hour period. If you have prostate problems or high blood pressure for which you take medicines called alpha blockers, your doctor may start you on a lower dose of Viagra. Take Viagra about one hour before you plan to have sex. Beginning in about 30 minutes and for up to 4 hours, Viagra can help you get an erection if you are sexually excited. If you take Viagra after a high-fat meal (such as a cheeseburger and french fries), the medicine may take a little longer to start working. Viagra can help you get an erection when you are sexually excited. You will not get an erection just by taking the pill. Like all medicines, Viagra can cause some side effects. These effects are usually mild to moderate and usually don't last longer than a few hours. Some of these side effects are more likely to occur with higher doses. The most common side effects of Viagra are headache, flushing of the face, and upset stomach. Less common side effects that may occur are temporary changes in color vision (such as trouble telling the difference between blue and green objects or having a blue color tinge to them), eyes being more sensitive to light, or blurred vision. In rare instances, men taking PDE5 inhibitors (oral erectile dysfunction medicines, including Viagra) reported a sudden decrease or loss of vision in one or both eyes. It is not possible to determine whether these events are related directly to these medicines, to other factors such as high blood pressure or diabetes, or to a combination of these. If you experience sudden decrease or loss of vision, stop taking PDE5 inhibitors, including Viagra, and call a doctor right away. In rare instances, men have reported an erection that lasts many hours. You should call a doctor immediately if you ever have an erection that lasts more than 4 hours. If not treated right away, permanent damage to your penis could occur (see How Sex Affects the Body). Sudden loss or decrease in hearing, sometimes with ringing in the ears and dizziness, has been rarely reported in people taking PDE5 inhibitors, including Viagra. It is not possible to determine whether these events are related directly to the PDE5 inhibitors, to other diseases or medications, to other factors, or to a combination of factors. If you experience these symptoms, stop taking Viagra and contact a doctor right away. Heart attack, stroke, irregular heart beats, and death have been reported rarely in men taking Viagra. Most, but not all, of these men had heart problems before taking this medicine. It is not possible to determine whether these events were directly related to Viagra. Viagra may cause other side effects besides those listed on this sheet. If you want more information or develop any side effects or symptoms you are concerned about, call your doctor. In case of accidental overdose, call your doctor right away. Keep Viagra out of the reach of children. Keep Viagra in its original container. Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature]. Viagra is a prescription medicine used to treat erectile dysfunction. Only your doctor can decide if it is right for you. This sheet is only a summary. If you have any questions or want more information about Viagra, talk with your doctor or pharmacist, visit www.Viagra.com, or call 1-888-4Viagra. LAB-0220-6.0

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A consistent inability to sustain an erection sufficient for sexual intercourse. Also commonly known as impotence. Medically, the term erectile dysfunction is used to differentiate impotence from other problems that interfere with sexual intercourse The following drugs and medications are in some way related to, or used in the treatment of Impotence. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The most widely used remedy for erectile dysfunction; research has indicated that Viagra has an effect on the condition of the human heart as well as a male's penis. The hormonal stress normally exerted on the human heart has been noted to be decreased in men who take Viagra. When conducted with mice, the testing was more noticeable, Viagra having the tendency to avert harmful and long term effects of chronic hypertension on their heart. The study, lead by the John Hopkins research team, found that there is potential benefits for the treatment of pulmonary hypertension, linked in with how Viagra dilates genital blood vessels. Viagra works by dulling the heart beat, which is increased during stress. It works to decrease the force which is needed to pump blood from the heart to the rest of the body. The research conducted by David Kass, cardiologist and senior researcher of the John Hopkins study noticed Viagra can be effective in blocking short- term consequences of hormonal stresses in the heart. Further evidence on the testing of mice (although further research is needed until this is applicable to humans), indicated that negative effects of heart failure and cardiac hypertrophy on weakened heart muscles can be reversed. Further research is need in this area on humans however. Thirty five men and women were tested and injected with Dobutamine (a synthetic derivative of dopamine that increases heart rate and contractions), which resulted in increased rate of 150%. The men and women were then separated into two groups, one of which were given sildenafil (Viagra) and the other given a placebo (fake) pill. Results showed that the first group's heart rate decreased by 50%, whilst the latter group's further increased. This has led to widespread scientific interest in the effects of sildenafil (Viagra) on the human heart condition. viagra side effects You have to be cautious. There are literally thousands of internet operations ready to sell you unregulated versions of Pfizer's Viagra. Often the sites claim to be selling the real thing, and it can be a daunting task to identify a safe resource for genuine, Pfizer Viagra. Ukmedix has had to compete with these fakes (which often are cheaper) and has even had to assist in identifying illegal operations (fakes are a threat to your safety, and ultimately Pfizer). In order to stand out from the crowd and reassure our customers Ukmedix produces useful customer tools e.g. a forum dedicated to viagra and makes sure that with every order sent batch numbers and manufacturer;s hall marks are always maintained. Dispatch pharmacists* are always available on receipt of your order for any further queries of authenticity. This means you can trace the product all the way back to Pfizer's manufacturing facility and even know the date your viagra was produced. *A UK pharmacist will always be able to assist you and any licensed pharmacy should be able to verify the viagra batch number. Apart from being unsafe and more then likely to be completely ineffective, fake viagra (wherever it has been produced) has passed no tests, is unregulated and for all you know may have been produced in a garden shed. In some instances dangerous substances have been found in this copied viagra, which would completely defeat the purpose of your seeking help with impotence in the first place! Ukmedix is obviously a business, but we care about our reputation and we care about our customers. We support Pfizer's Safe Drug Initiative which has been created to specifically find and close any illegal sellers of the unsubstantiated, fake viagra being sold on and offline. To this extent we want to know if you have been sold viagra that you think may be fake or viagra that doesn't look like it should. Contact ukmedix and we will gladly assist you and qualify your findings to Pfizer on your behalf. The fact is that fake viagra could have any substances in it and it is not to be trusted as a suitable replacement for the real thing. Impotence is a health condition that may be complex in its causes. Unnecessary e-mail spam on viagra or ludicrous claims that viagra will fix everything in your life are not what we are about. We never send out unsolicited e-mail and try to encourage you to research as much as you can yourself/ through your doctor and local pharmacists. Viagra has truly revolutionized many millions of lives, but viagra (that is Pfizer's viagra) is not suitable for everybody, and fake viagra is suitable for NO-ONE free online sample viagra According to recent study, for 1% of men who take Viagra, sex comes with nasty side effects that can sometimes lead to an untimely death. However, scientists have never linked the deaths directly to the drug, leaving open the possibility that the physical stress of an amorous routine could be the main cause of the whole issue. Scientists studying the blood component known as platelets have stumbled upon evidence that might implicate the drug instead of the sex. Platelets are tiny cell-like disks that collect and form blood clots at the site of an injury. Overactive platelets can clog blood vessels, which can lead to a heart attack or stroke. Viagra enhances blood concentrations of a compound that enhances the blood flow to the penis and stimulates production of an enzyme known as cGMP-dependent protein kinase (PKG). Researchers are aware of the fact that PKG keeps platelets from sticking together because they initially developed sildenafil (the main ingredient of Viagra) to treat heart disease. The dangers of Viagra are becoming increasingly evident: in 2006 alone, the FDA received 16 reports of death among men who took the drug and, though there is no direct evidence that proves the direct linkage with the pill, at least seven of these men (the majority of them elderly) died during or after intercourse. Some individuals are purchasing Viagra as a street drug (given the street name ‘Poke’). Often, this solves the immediate symptoms, but does not address the root cause and can lead to problems later. There are reports in the media that men are crushing the tablets and snorting them. This sort of routine may get some of the drug into the blood stream quickly, but it has the risk of all of the other chemicals being left in the lungs, resulting in long term health related risks. Most importantly, unprescribed users are not aware of the possible side effects of using Viagra with other unprescribed drugs. Viagra is quite a powerful drug and has a significant bearing on blood pressure. Because of this, doctors need to be able to discuss dos and don’ts with a man before he takes Viagra. It is worth mentioning that ‘poppers’ (amyl nitrate) also affect blood pressure and that taking the drugs concurrently can lead to heart failure, which can lead to death. Viagra does not leave the body instantly so you have to wait at least six hours before risking using amyl nitrate. Your doctor should be aware of this precaution and make sure you are not on medications that can lead to problems when using Viagra.

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Before proceeding to buy Viagra, we at UK Medix strongly advise that you read through the following information provided specifically on Viagra. We have provided it to answer all your unanswered questions on the medication, however we do understand that some may slip through and remain unanswered, in this case we would recommend that you seek advice from your prescribing physician or if you obtained your Viagra from UK Medix please feel free to contact our medical team for assistance. Please understand that this is not a comprehensive review of Viagra but a guide compiled by us at UK Medix regarding the use and effects. If any aspect of taking Viagra concerns you ensure to consult with your doctor before ordering. Should you take Viagra? Viagra was developed by Pfizer to treat men in their ongoing quest to tackle Erectile Dysfunction (aka impotence). It is a prescription medication that should only be taken if and when you wish to have sex and it is active only on arousal. This arousal may be physical or visual but either way you will need to be sexually aroused for Viagra to work; how aroused you need to be depends entirely on the patient and their individual degree of erectile dysfunction. At UK Medix, we insist that Viagra is not for female patients and thus should only be taken by men who obtain a prescription. It may be dangerous for females as studies have not been carried out and anyway for female impotence, UK Medix have heard of new medications coming out soon, such as a testosterone patch, currently known as Intrinsa. Viagra was originally developed as a compound to be trialed as just another medication for blood pressure and hypertension, not much excitement there really. However, it was in clinical trials that the scientists at Pfizer realized something that would change the course of sexual history worldwide; the side effects of this medication were that impotent men were getting erections. Eureka! (Quote - Archimedes) So, how exactly does Viagra work? Viagra works by causing the smooth muscles in your blood vessels to relax, increasing blood flow around and lowering the blood pressure. The active ingredient in Viagra, sildenafil, is also a PDE5 inhibitor; and it is this in particular that specifies an increase in blood flow to the penis. When a man is sexually stimulated his penile arteries go through a process to relax and enlarge. As they enlarge, the veins that remove blood from the penis are compressed thus restricting blood flow out of the penis, causing an erection. Although erectile dysfunction was originally thought to be purely psychological, the discovery of Viagra refuted this and it is now common fact that the nerves and blood vessels play a key role. If the nerves and blood vessels that facilitate the process of an erection do not work then erectile dysfunction occurs. How Long Does it work for? Viagra is seen to work on about 80% of patients and is active within an hour; it is thought to be one of the quickest medications on the market to work, however it only lasts up to 4 hours. UK Medix has seen this to be a bit of a problem to some patients as an element of planning is required. Other medications now out, such as Cialis, show lasting effects up to 36 hours but again they all have their problems, some patients have siad that , for example, does not start to work as quickly as Viagra. Viagra comes in 3 different dosages; 25mg, 50mg and 100mg. The starting dosage recommended by is 50mg and we here at UK Medix we agree with this; always start at this dosage and adjust accordingly if needs be. However, as with all medications ensure to follow the advice of your prescribing doctor on any of these matters. should be taken as one tablet, with or without meals, up to one hour before sexual activity and it should not then be take again for 24 hours. UK Medix recommend that you read carefully any leaflets that come supplied with your medication. 5 mg sildenafil citrate Life is, of course, all about managing death. Or rather, it's all about managing pain and pollution and disease and gravity and germs and bacteria and poison and Dick Cheney and those little shards of glass in your burrito; it's all about, in short, how you sort through the sundry and ever-increasing laundry list of things in your immediate world that want to torment and toxify and destroy you because oh my God they are legion and they are ready and they are . . Did you know? It shouldn't come as much of a surprise, really, given how many millions of drug-blasted Americans inhale prescription meds by the fistful and then hit the bathroom and the water flows and the treatment plant churns and pumps it all back into municipal water pipes, still brimming with trace amounts of Xanax and Zoloft and Medrol and Norvasc, asthma drugs and cholesterol drugs and birth control pills, cancer drugs and painkillers and diuretics and who the hell knows what else. Hell, who needs Vitamin Water when there's Lipitor in your ice cubes? This is the wacky fun reminder: Living in the city is deadly and toxic a million ways from Sunday. in every breath, electromagnetic waves in every gizmo, plastic off-gassing and high-VOC paints and chemicals in the carpet and toxins in your very clothing and every modern home so packed with thriving bacteria and synthetic substances and venomous Glade air fresheners it's a wonder we manage to stay upright at all. Hell, they just discovered that even our national parks, the fish and trees and lakes and the snow itself, are hugely polluted, . Go ahead, hug that tree. But be sure to wear a body condom. This is what we have to accept: You do not avoid poison. You do not escape toxin or chemical or gravity or modern synthetic residue even if you move to the woods and build a humble off-grid shack made only of fresh pine needles and bird dung and make your own jam out of river moss and beetle larvae because, hey look, up there in the sky, it's the very air itself, full of chemicals and pollutants drifting over from China and India and, um, Marin County, and you're breathing it in and it's coating the very trees and raining down upon your organic tomatoes right now. Sorry. Please enjoy your salad. No, you do not escape. You cannot completely block. You merely minimize. You recognize the most dire sources and most abhorrent problems and you choose your battles wisely, as you acknowledge just how complicit you are in all of it, how much you contribute to the problem, and adjust and recalibrate your life accordingly. This is the first, mandatory, all-important step. But more important than that, you learn to shun the paranoia. You gotta mock the relentless direness and shrug off the gods of death, every single day, even as they seem to be multiplying like rabid evangelicals at a Colorado megachurch. You gotta keep perspective, recall how man has been under deadly pressure from himself since the dawn of time. Otherwise, well, life is merely an army of demons and sins lined up and ready to take a bite out of your sweet, innocent flesh as you stroll by like a virgin at a porn convention. You know? Wait, did I mention sin? Good thing. Because apparently they've . Did you hear? Indeed, a dour red-robed figure just slithered out of the shadows of the Vatican and proclaimed some new additions to the master list of Thou Shalt Nots, adding juicy tidbits like pedophilia and pollution and the taking/dealing of drugs (then you'd best not drink the water, father) and questions of bioethics (stem cell research, cloning, whatnot) to the massive catalog of things that make God scowl and angels whine and for which we are all surely going to Hell like, a billion times over. Is this not delightful, in a deeply pathetic and insulting sort of way? Is it not amusing that, after 2,000 years, they're finally saying, hey gosh, trashing the planet and abusing creation itself is sort of wrong? Or that they — the Catholic Church! — dared to add pedophilia to the list, which is a bit like McDonald's announcing that beef is bad for you? Yo, preacher: Heal thyself, OK? As for bioethics, well, of course they worry that we'll try to "play God," which is just sort of cute and ridiculous given how most of us, you know, , every single day, by defying death and tormenting our bodies and launching brutal unwinnable wars (in the name of God, natch), choosing whether or not to eat meat and destroy plants and get pregnant or fall in love or hate gay people or buy an Escalade or enjoy Adam Sandler movies. Playing God? Who the hell is playing? God, that's where the real action is. And now, the bad news: They didn't remove a single damnable thing. They did not say, OK, we've added some vile and obvious new sins, so just for the sake of balance and just so you don't think we're authoritarian cretins, let's remove a few of the outdated, insulting ones, shall we? Condoms? Birth control? Go for it (they should've said). Pre-marital sex? Have at it, children. In fact, it's now highly recommended. Especially if you do it right. And often. And develop some mad skills so if you ever get married you can keep surprising each other with delightful new ways to enjoy various kitchen tools and yoga straps and Viagra chewing gum. Praise Jesus. Better yet, they should take it a step further, and for every new sin they add, they should remove . This way, eventually we'll whittle it down to just one grand sin, one terrifically all-encompassing God-mocking insult. Which is, of course, the idea of sin itself. Believe in sin? Believe that we're all, at our core, corrupt and evil and mortally flawed and that life is basically a grueling slog against disease and pain and pollution and 10,000 household poisons until you eventually whimper and sigh and lay yourself in a chemical-soaked pine box and sink it six feet under? Baby, that's the biggest sin of all. And you are hereby absolved. Thoughts about this column? .

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Should I Confront My Wife About Affair? TEN years ago I fell in love with a girl. She was 22 years younger than me and I was married. But the love I felt for her then - and still do - was overwhelming. So I left my wife for her. It was messy and my two grown-up children made it clear they wanted nothing to do with me after what I had done to their mum. I felt guilty but the dust settled and after the divorce I married my second wife. It was the happiest day of my life. We now have an eight-year-old and I've managed to patch things up with the older ones. My wife is 37 and I'll be 60 this year. The problem is I have been having trouble sustaining an erection. I'm taking Viagra which helps, but I don't have the same energy I used to have. I'm almost certain my wife is having an affair. We had a young guy, in his twenties, help get the garden in our new house into shape and I could see he was attracted to her. She's still an amazing-looking woman and doesn't look a year older than when I first saw her. She's been getting texts which she deletes immediately and I know for a fact when she told me she was round at her mum's that it was a lie. So I'm worried sick. I know I should tackle her about what's going on but I can't. I can't live without her and I don't like the thought of my ex-wife, most of my friends and my relatives pointing out that they all told me the age gap was too big and we wouldn't last. OF course you could carry on as you are with your head buried in the sand. There is the possibility your wife isn't having an affair or even if she is, it isn't serious and will soon blow itself out. Your problem keeping an erection could be affecting self-confidence and putting your imagination into overdrive. In some ways, sitting tight might be the sensible thing to do, especially as you have a young child but no intention of ending the marriage. But I don't think you can live with the uncertainty forever. Maybe you should give yourself a deadline of a few months. If you remain suspicious or get more solid evidence, I don't believe you can go on ignoring the issue. If she wants to save the marriage, counselling through Relate Scotland or Scottish Marriage Care is the next step. But if things can't be fixed, there's no point trying to glue it together just because you don't want those who warned you against marrying a younger woman crowing. If you have a problem, write to: Just Joan, Daily Record, One Central Quay, Glasgow G3 8DA or email j.burnie@dailyrecord.co.uk. I cannot reply personally.natural substitutes for viagra This is a summary of the most important information about Viagra. For details, talk to your healthcare professional. FDA ALERT [7/2005]: A small number of men have lost eyesight in one eye some time after taking Viagra, Cialis, or Levitra. This type of vision loss is called non-arteritic anterior ischemic optic neuropathy (NAION). NAION causes a sudden loss of eyesight because blood flow is blocked to the optic nerve. We do not know at this time if Viagra, Cialis, or Levitra causes NAION. NAION also happens in men who do not take these medicines. People who have a higher chance for NAION include those who: FDA has approved new labels for Viagra, Cialis, and Levitra to include information on possible eyesight loss (NAION). Stop using Viagra, Cialis, or Levitra if you have a loss in your eyesight. Get medical help right away. This information reflects FDA's current analysis of data available to FDA concerning this drug. FDA intends to update this sheet when additional information or analyses become available. What is Viagra? Viagra is a prescription medicine taken by mouth for the treatment of erectile dysfunction (ED) in men. ED is a condition where the penis does not harden and expand when a man is sexually excited, or when he cannot keep an erection. Viagra may help a man with ED get and keep an erection when he is sexually excited. Viagra must be used only under a doctor's care. protect a man or his partner from sexually transmitted diseases, including HIV. Speak to your healthcare professional about ways to guard against sexually transmitted diseases. Viagra is only for men with ED. Viagra is not for women or children. Viagra must be used only under a healthcare professional's care. Who Should Not Take Viagra? What are The Risks? The following are the major possible risks and side effects of Viagra therapy. This list is not complete. Viagra can cause your blood pressure to drop suddenly to an unsafe level if it is taken with certain other medicines such as nitrates and alpha-blockers, and recreational drugs that contain nitrates called "poppers". A sudden drop in your blood pressure could cause you to become dizzy, faint, or have a heart attack or stroke. Tell all your healthcare professionals that you take Viagra. If you need emergency medical care for a heart problem, it will be important for your healthcare professionals to know when you last took Viagra. vision changes, such as seeing a blue tinge to objects or having difficulty telling the difference between the colors blue and green What Should I Tell My Healthcare Professional? have retinitis pigmentosa, a rare genetic (runs in families) eye disease have blood cell problems such as sickle cell anemia, multiple myeloma, or leukemia Can Other Medicines or Food Affect Viagra? Viagra and certain other medicines can interact with each other. Tell your healthcare professional about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Know the medicines you take. Keep a list of them with you to show your healthcare professional. Date created: July 8, 2005, updated October 2, 2007 generic online viagra Levitra and Viagra are different drugs used to treat one common issue, Erectile Dysfunction (impotence). There are lots of similarities as well as differences when looking at Levitra vs. Viagra. Advice from your health care provider is the ideal way to conclude which drug is the perfect choice for treating your ED. One should never diagnose and treat ED on their own; it could turn out to be a life threatening move. It is mandatory for men with ED to understand the fact that they are not alone. As a matter of fact, millions of men all over the world suffer from ED each year. Fortunately, advancement in pharmaceutical technology has offered choices for these millions. When comparing Levitra with Viagra, the main point of difference is the main ingredient. While Levitra’s main ingredient consists of vardenfil, a PDE5 inhibitor, the main ingredient in Viagra is sildenafil citrate, which has been used not only to treat ED, but also pulmonary arterial hypertension Side effects arising from the use of vardenfil are: abdominal pain, back pain, photosensitivity, abnormal vision, eye pain, facial edema, hypertension, palpitation, tachycardia, arthralgia, myalgia, rash, itch, priapism, and in a few rare scenarios heart attack. Vardenfil should also not be taken if the patient is using any sort of nitrate medication. This is because it has the tendency to produce very low blood pressure. Health care providers will never prescribe Levitra to a patient at risk of experiencing serious side effects. Viagra was the first pill to be introduced to the market. Side effects of Viagra include: priapism, severe hypotension, myocardial infarction, ventricular arrhythmias, sudden death, stroke and enhanced intraocular pressure. The common side effects consist of sneezing, headache, flushing, dyspepsia, prolonged erections, palpitations, and photophobia. Visual changes including blurring of vision and a curious bluish tinge which have been reported in studies. Levitra and Viagra are nearly identical in that they are to be consumed anywhere from a half an hour to a couple of hours prior to sexual activity. Viagra may have been the starting point in the treatment of ED, but there is no doubt that Levitra has been seen as “new and better”. Levitra’s side effects are far and few versus Viagra, though response of drugs varies from person to person. A detailed analysis of your medical history is required to choose the ideal prescription drug for you. However discomfiting the commercials, the -- on March 27, 1998 -- is a landmark day in the history of sex. It seemed at the time like a biomedical revolution was upon us all, and about five minutes after word of the magical med went global, the question first was asked: Where is the women's version of Viagra? The short answer: They're still working on it. A bunch of companies have tried and failed to create "pink Viagra," as it's often called. Other companies have drugs in late stages of clinical testing, including a gel that recently began a make-or-break nationwide study with several thousand women. Give us five years, maybe less, say the most optimistic researchers and doctors. Though it's unclear exactly how many women would ask for a prescription, no one doubts that the first company that gets to market a remedy for female sexual dysfunction, as it's formally known, will earn a fortune. But as this race reaches what could be its final lap, not all of the spectators are cheering. Some, in fact, are booing as loudly as they can. A modest-size but fervent group of psychologists, academics and public health advocates contend that FSD isn't an authentic medical condition, or at least not the sort of problem that should be treated with drugs. These aren't the obtuse male physicians who for decades have been telling women distressed by their lack of libido that "it's all in your head." The anti-FSD crowd is mostly women, many of them self-described feminists. The most prominent is Leonore Tiefer, a psychotherapist and clinical associate professor at , who has long decried what she calls "the medicalization of women's sexuality." "Drug companies want to say to women, 'You don't need to know anything; you can have the satisfying sex life that you seek -- people dancing on TV, the whole bit -- without knowing anything. Just ask your doctor,' " she says. "I resent that, because there are specific harms that come from being ignorant and dependent in the world we live in. There may be lots of people who aren't interested in sex, but is there a medical reason for that, and do we diagnose that?" Tiefer's critique centers, in part, on the way that pink Viagra is sure to be marketed -- with ads day and night, suggesting that women who aren't feeling frisky have a medical problem. She and her allies -- organized as the New View Campaign -- are also galled that so much money and media attention are heaped on the lust drug, even before it exists, when for many women the solution to their libido problems isn't that exotic. Maybe they have a partner who hasn't a clue about technique.Maybe they're stressed out. Maybe they can't possibly get in the mood because they're so busy raising children. Therapy, counseling, even free day care, says the New View Campaign, might do more for women's sex lives than any drug company ever could. "People walk out of their doctors' offices with a prescription in hand 85 percent of the time," says Meika Loe, the author of "The Rise of Viagra" and a New View endorser. "But health insurers won't pay if you want to talk to a counselor or if you need advice about how to communicate your sexual desires. We've got a health-care system that is almost entirely focused on medical solutions." On the other side of the FSD divide, allied with the pharmaceutical companies, is a group of physicians who are prescribing off-label treatments for women vexed by their sex lives. (Off-label means the drug hasn't been approved by the FDA for that specific treatment.) The highest-profile of the bunch is Irwin Goldstein, the director of sexual medicine at San Diego's Alvarado Hospital. He and Tiefer have debated the topic of FSD for a decade, but as far as he's concerned, there's really nothing to discuss. He's been using hormones to treat women, and he'll happily put you in touch with patients who will rhapsodize about the results. Women like Virginia, a 60-year-old native of and an artist who, for privacy reasons, asked that her last name be omitted. She'd spent years asking doctors for medical help to boost her sex drive, which had once been voracious. All of them, she says, "rolled their eyes and harrumphed and tried to change the subject." "But when I was younger, a really strong libido was just part of who I was," she goes on. "Losing that was like losing a good friend." Three years ago, she heard Goldstein interviewed on . Within weeks she flew to , the site of his practice at the time, and she soon was taking several hormones. There was tinkering with the combination and the dosage, but a few weeks later she suddenly felt "perky" -- more confident about herself as a sexual being and more attractive. She also started having better sex.is generic viagra for real Dietary supplements marketed to provide male sexual enhancement contain undeclared erectile dysfunction drugs putting users at risk, the Food and Drug Administration warned Friday. The agency advised consumers to stay away from Shangai Chaojimengnan supplements sold under the names Super Shangai, Strong Testis, Shangai Ultra, Shangai Ultra X, Lady Shangai and Shangai Regular. The Chinese-made supplements are packaged and distributed by Shangai Distributor Inc. of Puerto Rico. Product testing indicates that some of these so-called supplements contain Viagra's active ingredient, sildenafil, or a compound with a chemical structure that mimics sildenafil. These chemicals could interact with nitrates in drugs taken for disorders commonly associated with erectile dysfunction, including diabetes, high blood pressure, high cholesterol and heart disease. The result could dangerously lower a user's blood pressure, according to the FDA. The agency also warned that the safety and purity of these illegal ingredients is unknown.

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An oral therapy for erectile dysfunction, is the citrate salt of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Sildenafil citrate is designated chemically as 1 - [[3 - (6,7 - dihydro - 1 - methyl - 7 - oxo - 3 - propyl - 1H - pyrazolo[4,3 - d]pyrimidin - 5 - yl) - 4 - ethoxyphenyl]sulfonyl] - 4 - methylpiperazine citrate and has the following structural formula: Sildenafil citrate is a white to off-white crystalline powder with a solubility of 3.5 mg/mL in water and a molecular weight of 666.7. Viagra (sildenafil citrate) is formulated as blue, film-coated rounded-diamond-shaped tablets equivalent to 25 mg, 50 mg and 100 mg of sildenafil for oral administration. In addition to the active ingredient, sildenafil citrate, each tablet contains the following inactive ingredients: microcrystalline cellulose, anhydrous dibasic calcium phosphate, croscarmellose sodium, magnesium stearate, hypromellose, titanium dioxide, lactose, triacetin, and FD & C Blue #2 aluminum lake. The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum, but enhances the effect of nitric oxide (NO) by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum. When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum. Sildenafil at recommended doses has no effect in the absence of sexual stimulation. Studies in vitro have shown that sildenafil is selective for PDE5. Its effect is more potent on PDE5 than on other known phosphodiesterases (10-fold for PDE6, >80-fold for PDE1, >700-fold for PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11). The approximately 4,000-fold selectivity for PDE5 versus PDE3 is important because PDE3 is involved in control of cardiac contractility. Sildenafil is only about 10-fold as potent for PDE5 compared to PDE6, an enzyme found in the retina which is involved in the phototransduction pathway of the retina. This lower selectivity is thought to be the basis for abnormalities related to color vision observed with higher doses or plasma levels (see ). In addition to human corpus cavernosum smooth muscle, PDE5 is also found in lower concentrations in other tissues including platelets, vascular and visceral smooth muscle, and skeletal muscle. The inhibition of PDE5 in these tissues by sildenafil may be the basis for the enhanced platelet antiaggregatory activity of nitric oxide observed in vitro, an inhibition of platelet thrombus formation in vivo and peripheral arterial-venous dilatation in vivo. Viagra is rapidly absorbed after oral administration, with absolute bioavailability of about 40%. Its pharmacokinetics are dose-proportional over the recommended dose range. It is eliminated predominantly by hepatic metabolism (mainly cytochrome P450 3A4) and is converted to an active metabolite with properties similar to the parent, sildenafil. The concomitant use of potent cytochrome P450 3A4 inhibitors (e.g., erythromycin, ketoconazole, itraconazole) as well as the nonspecific CYP inhibitor, cimetidine, is associated with increased plasma levels of sildenafil (see ). Both sildenafil and the metabolite have terminal half lives of about 4 hours. in Healthy Male Volunteers. Viagra is rapidly absorbed. Maximum observed plasma concentrations are reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted state. When Viagra is taken with a high fat meal, the rate of absorption is reduced, with a mean delay in T of 29%. The mean steady state volume of distribution (Vss) for sildenafil is 105 L, indicating distribution into the tissues. Sildenafil and its major circulating N-desmethyl metabolite are both approximately 96% bound to plasma proteins. Protein binding is independent of total drug concentrations. Based upon measurements of sildenafil in semen of healthy volunteers 90 minutes after dosing, less than 0.001% of the administered dose may appear in the semen of patients. Sildenafil is cleared predominantly by the CYP3A4 (major route) and CYP2C9 (minor route) hepatic microsomal isoenzymes. The major circulating metabolite results from N-desmethylation of sildenafil, and is itself further metabolized. This metabolite has a PDE selectivity profile similar to sildenafil and an in vitro potency for PDE5 approximately 50% of the parent drug. Plasma concentrations of this metabolite are approximately 40% of those seen for sildenafil, so that the metabolite accounts for about 20% of sildenafil's pharmacologic effects. After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the feces (approximately 80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose). Similar values for pharmacokinetic parameters were seen in normal volunteers and in the patient population, using a population pharmacokinetic approach. Healthy elderly volunteers (65 years or over) had a reduc