Finasteride (marketed as Proscar, Propecia, Fincar, Finpecia, Finax, Finast, Finara, Finalo, Prosteride, Gefina, Finasterid IVAX) is an antiandrogen which acts by inhibiting type II 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone (DHT). It is used as a treatment in benign prostatic hyperplasia (BPH) in low doses, and prostate cancer in higher doses. It is also indicated for use in combination with doxazosin therapy to reduce the risk for symptomatic progression of BPH. Additionally, it is registered in many countries for androgenetic alopecia (male-pattern baldness).Finasteride was approved initially in 1992 as Proscar, a treatment for prostate enlargement, but the sponsor had studied 1 mg of finasteride and demonstrated hair growth in male pattern hair loss. On December 22, 1997, the FDA approved finasteride to treat male pattern hair loss.

The Prostate Cancer Prevention Trial (PCPT) showed at a dosage of 5mg per day, as is commonly prescribed for BPH, though much higher than the 1mg generally prescribed for hair loss, participants taking finasteride were 25% less likely to have developed prostate cancer at the end of the trial compared to those taking a placebo. Further, finasteride increased the specificity and selectivity of prostate cancer detection, thus, a seemly increased rate of high Gleason grade tumor.

Recognized side effects, experienced by around >1% of users, include erectile dysfunction, and less often gynecomastia (breast gland enlargement).As expected from its short 6-8 hour half-life, in trial studies, side effects ceased after dosage was discontinued.

What is the most important information I should know about Propecia?
• Women who are or who may become pregnant must not handle crushed or broken Propecia tablets. The medication could be absorbed through the skin. Propecia is known to cause birth defects in a developing male baby. Exposure to whole tablets should be avoided whenever possible, however exposure to whole tablets is not expected to be harmful as long as the tablets are not swallowed.
What is Propecia?
• Propecia prevents the conversion of testosterone to dihydrotestosterone (DHT) in the body. DHT is involved in the development of benign prostatic hyperplasia (BPH) and hair loss.
• Proscar is used to treat benign prostatic hyperplasia (enlarged prostate). Propecia is also used to reduce hair loss due to male pattern baldness.
• Propecia may also be used for purposes other than those listed in this medication guide.
What should I discuss with my healthcare provider before taking Propecia?
• Before taking this medication, tell your doctor if you have liver disease. You may not be able to take Propecia, or you may need a lower dose or special monitoring during treatment.
• Propecia is intended for use by men only.
• Propecia is not indicated for use by women. Do not take or handle this medication if you are pregnant or are could become pregnant during treatment. Propecia is in the FDA pregnancy category X. This means that it is known to cause birth defects in an unborn baby. Women who are or who may become pregnant must not handle crushed or broken Propecia tablets. The medication could be absorbed through the skin. Propecia is known to cause birth defects in a developing male baby. Exposure to whole tablets should be avoided whenever possible, however exposure to whole tablets is not expected to be harmful as long as the tablets are not swallowed.
• It is not known whether Propecia passes into breast milk. Propecia is not intended for use by women. Do not take this medication if you are breast-feeding a baby.
How should I take Propecia?
• Take Propecia exactly as directed by your doctor. If you do not understand these instructions, ask your pharmacist, nurse, or doctor to explain them to you.
• Take each dose with a full glass of water.
• Propecia can be taken with or without food.
• It is important to take Propecia regularly to get the most benefit.
• Your doctor may perform blood tests or other forms of monitoring during treatment with Propecia. One of the tests that may be performed is called PSA (prostate-specific antigen). This test is used to help detect prostate cancer. Propecia will reduce the amount of PSA measured in the blood. Your doctor is aware of this effect and can still use PSA to help detect prostate cancer.
• Store this medication at room temperature away from moisture and heat.
• Women who are or who may become pregnant must not handle crushed or broken Propecia tablets. The medication could be absorbed through the skin. Propecia is known to cause birth defects in a developing male baby. Exposure to whole tablets should be avoided whenever possible, however exposure to whole tablets is not expected to be harmful as long as the tablets are not swallowed.
What is Propecia?
• Propecia prevents the conversion of testosterone to dihydrotestosterone (DHT) in the body. DHT is involved in the development of benign prostatic hyperplasia (BPH) and hair loss.
• Proscar is used to treat benign prostatic hyperplasia (enlarged prostate). Propecia is also used to reduce hair loss due to male pattern baldness.
• Propecia may also be used for purposes other than those listed in this medication guide.
What should I discuss with my healthcare provider before taking Propecia?
• Before taking this medication, tell your doctor if you have liver disease. You may not be able to take Propecia, or you may need a lower dose or special monitoring during treatment.
• Propecia is intended for use by men only.
• Propecia is not indicated for use by women. Do not take or handle this medication if you are pregnant or are could become pregnant during treatment. Propecia is in the FDA pregnancy category X. This means that it is known to cause birth defects in an unborn baby. Women who are or who may become pregnant must not handle crushed or broken Propecia tablets. The medication could be absorbed through the skin. Propecia is known to cause birth defects in a developing male baby. Exposure to whole tablets should be avoided whenever possible, however exposure to whole tablets is not expected to be harmful as long as the tablets are not swallowed.
• It is not known whether Propecia passes into breast milk. Propecia is not intended for use by women. Do not take this medication if you are breast-feeding a baby.
How should I take Propecia?
• Take Propecia exactly as directed by your doctor. If you do not understand these instructions, ask your pharmacist, nurse, or doctor to explain them to you.
• Take each dose with a full glass of water.
• Propecia can be taken with or without food.
• It is important to take Propecia regularly to get the most benefit.
• Your doctor may perform blood tests or other forms of monitoring during treatment with Propecia. One of the tests that may be performed is called PSA (prostate-specific antigen). This test is used to help detect prostate cancer. Propecia will reduce the amount of PSA measured in the blood. Your doctor is aware of this effect and can still use PSA to help detect prostate cancer.
• Store this medication at room temperature away from moisture and heat.

Side effects
Finasteride is not indicated for use by women. Finasteride is in the FDA pregnancy category X. This means that it is known to cause birth defects in an unborn baby. Women who are or who may become pregnant must not handle crushed or broken finasteride tablets, because the medication could be absorbed through the skin. Finasteride is known to cause birth defects in a developing male baby. Exposure to whole tablets should be avoided whenever possible, however exposure to whole tablets is not expected to be harmful as long as the tablets are not swallowed. It is not known whether finasteride passes into breast milk, and thus should not be taken by breastfeeding women. Finasteride may pass into the semen of men, but Merck states that a pregnant woman’s contact with the semen of a man taking finasteride is not an issue for concern.[2]

Finasteride has been linked with depression [3] The drug also caused reductions in allopregnanolone, a potent, endogenous positive modulator of the GABA-A receptor, in very large doses in rodent studies.[4]

Finasteride can also be used to mask steroid abuse, and many professional sports have banned finasteride use for this reason. [5]

Finasteride is under investigation by the Swedish Medical Products Agency for possibly causing irreversible sexual side effects [6].
Use as a treatment for hair loss
In a 5-year study of men with mild to moderate hair loss, 48% of those treated with Propecia (finasteride 1mg) experienced some regrowth of hair, and 42% had no further loss. Average hair count in the treatment group remained above baseline, and showed an increasing difference from hair count in the placebo group, for all five years of the study.[5]. Propecia is effective only for as long as it is taken; the hair gained or maintained is lost within 6-12 months of ceasing therapy.[7] In clinical studies, Propecia, like minoxidil, was shown to work on both the crown area and the hairline,[8] but is most successful in the crown area.

Some users, in an effort to save money, buy Proscar instead of Propecia, and split the Proscar pills to approximate the Propecia dosage. Doing so is generally considered unadvisable if women of pregnancy age are in the household; this is because finasteride, even in small concentrations, can cause birth defects in a developing male fetus. The birth defects involve the development of male genitalia (no such effects have been noted in developing female fetuses). On most product inserts, it will be mentioned that the dust or crumbs from broken Propecia tablets should be kept away from pregnant women.

Propecia has been shown to be ineffective for treating hair loss in women.[citation needed] However, Propecia’s supporters respond that the study was on post-menopausal women whose hair loss was more likely related to the loss of estrogen versus a sensitivity to testosterone. Many doctors prescribe it for women, but not without either careful birth control measures or assurance that the woman cannot become pregnant.
Possible health concerns
The UC Berkeley Wellness Letter expressed concern in March 2003 about the unproven long-term safety of Propecia and recommended cutting a standard 1 milligram dose of Propecia into quarters to reduce the cost without reducing its effectiveness. This claim appears to be supported by clinical pharmacological data reviewed by the FDA during Propecia’s approval process that suggested that the advantage of taking 1 mg per day over 0.2 mg per day is statisticially small.[9] Some people have unsuccessfully petitioned the FDA to re-examine the approved dosage in light of the statistical evidence and unknown long-term risks.[10] The FDA responded and said that just because the level of DHT found in the scalp was not significantly different does not mean there is a correlation with hair loss. A study would have to show that the benefits of using 0.2 mg and 1 mg were not statistically different. According to the FDA such a study has been performed and a 1 mg dose has a greater benefit whilst remaining equally safe. The same study also concluded that doses of 0.01 mg per day were found to be ineffective in treating hair loss.[10]

In the Prostate Cancer Prevention Trial (PCPT), 25 percent fewer men taking the drug finasteride developed prostate cancer than men not taking the drug. However, men who developed prostate cancer while taking finasteride were more likely to have high-grade cancers, which can spread quickly even if the tumors are small. [11]
Propecia’s effects in detail
DHT is a derivative hormone (metabolite) of testosterone that has been shown to be critical to the initiation and progression of follicular miniaturization and eventual destruction of hair follicles in male pattern baldness. DHT is a steroid hormone just like testosterone but with greater affinity for the androgen receptor. Converting testosterone to DHT thus increases many of its effects.

While the mechanism by which DHT is involved in hair loss is not confirmed, many dermatologists and research scientists specializing in hair loss believe DHT molecules may diffuse into the interior of hair follicle cells (the cytoplasm or cytosol) and bind with androgen receptors. This complex, both the receptor and the DHT molecule, then enters the nucleus of the cell. In the nucleus of the hair follicle cell this complex could then alter the rate of protein synthesis in men who are genetically predisposed to baldness.[citation needed]

However, DHT also plays an important role in the functioning of the central nervous system (the brain), the testicles and prostate, and almost everything but muscle tissue. In muscle tissue testosterone is the dominant hormone, which is why some bodybuilders inject testosterone derivatives to aid in muscular development.

Propecia (and other products containing finasteride) cause a rise in testosterone levels because testosterone that would normally be converted into DHT remains testosterone. Continual high levels of testosterone in the body could possibly have negative side effects.
Artificially low levels of DHT in the body could cause some unwanted conditions. DHT is an antagonist of estrogen. Men’s bodies also produce the female hormone estrogen in the adrenal glands, although this is just one-tenth of the estrogen that premenopausal women produce in their ovaries. By reducing DHT with drugs, a man’s protection from the effects of estrogen may also be reduced. This could result in gynecomastia.
Even though both finasteride and dutasteride were developed to combat benign prostatic hyperplasia by reducing DHT in prostate tissue, some scientists question the wisdom of using these 5-alpha reductase inhibitors in younger men who have no problem with their prostates. A research chemist, Patrick Arnold, says “Evidence is mounting that the existence of a high estrogen/androgen ratio – a condition common in older men – is highly correlated with the development of benign prostatic hyperplasia.”[citation needed] However, in apparent contradiction, individuals with 5-alpha-reductase deficiency (and thus a similar hormonal profile to users of DHT inhibitors) do not experience BPH.

Vardenafil (INN) is a PDE5 inhibitor used in the treatment of erectile dysfunction. It can assist men with this disorder in achieving and maintaining an erection during sexual activity. It is commonly marketed under the trade name Levitra (Bayer AG).

History
Vardenafil was co-marketed by Bayer Pharmaceuticals and GSK under the trade name Levitra. As of 2005, the co-promotion rights of GSK on Levitra have been “transferred back” to Bayer in many markets outside of the United States. In Italy, Bayer markets the product as Levitra and GSK markets the product as Vivanza. Due to European Union trade rules, parallel imports may result in the Vivanza branded packs being seen alongside Levitra packs in pharmacies in other EU member states.
Important Safety and Dosing Information

LEVITRA is a prescription medicine that is used to treat erectile dysfunction (ED). Men taking nitrate drugs, often used to control chest pain (also known as angina), should not take LEVITRA. Such combinations could cause blood pressure to drop to an unsafe level.

As with all ED drugs, there is a rare risk of an erection lasting longer than four hours. To avoid long-term injury, seek immediate medical attention. LEVITRA does not protect against sexually transmitted diseases. In rare instances, men taking PDE5 inhibitors (oral erectile dysfunction medicine, including LEVITRA) reported a sudden decrease or loss of vision in one or both eyes, or a sudden loss or decrease in hearing, sometimes with ringing in the ears and dizziness. It is not possible to determine whether these events are related directly to these medicines or to other factors. If you experience any of these symptoms, stop taking PDE5 inhibitors, including LEVITRA, and call a doctor right away.

Discuss your medical conditions, including heart problems, and medications, including alpha blockers prescribed for prostate problems or high blood pressure, with your doctor to ensure LEVITRA is right for you and that you are healthy enough for sexual activity. LEVITRA is not recommended for men with uncontrolled high blood pressure.

The starting dose of LEVITRA is 10 mg taken no more than once per day. Your doctor will decide the dose that is right for you. In patients taking alpha blockers, your doctor may start you on a lower dose of LEVITRA. In patients taking certain medications such as ritonavir, indinavir, saquinavir, atazanavir, ketoconazole, itraconazole, erythromycin and clarithromycin, lower doses of LEVITRA are recommended, and time between doses of LEVITRA may need to be extended.

In clinical trials, the most commonly reported side effects were headache, flushing, and stuffy or runny nose. LEVITRA is available in 2.5-mg, 5-mg, 10-mg, and 20-mg tablets.

LEVITRA MECHANISM

Levitra is an oral medicine for the treatment of erectile dysfunction. Vardenafil is the main ingredient of Levitra and monohydrochloride salt of vardenafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5). It is an inhibitor for corporal smooth muscle relaxation, resulting in increased blood flow in the penis in reaction to sexual stimulation.

PDE5 is an inhibitor that increases the blood flow to the penis and helps man attain erection and keep the erection strong and long enough to finish a successful sexual intercourse. The active ingredient in LEVITRA works during arousal when two large chambers in a man’s penis fill up with blood.

Levitra label says it takes 60 minutes before sexual activity, but medical studies have proved that it can work within 16 minutes of its oral administration. Levitra works properly at the very first time taken.

Levitra gives same result in a full stomach; the quality of erection will be strong and satisfactory without being affected by food or drink.

Levitra works quicker and better than Viagra and Cialis, as it can start working withing 16 minutes and it gives full and strong erection even though you have high blood pressure or diabetes type 1 and 2 or high cholesterol.

Before taking Levitra
Do not take Levitra if you are also using a nitrate drug for chest pain or heart problems. This includes nitroglycerin (Nitrostat, Nitrolingual, Nitro-Dur, Nitro-Bid, and others), isosorbide dinitrate (Dilatrate-SR, Isordil, Sorbitrate), and isosorbide mononitrate (Imdur, ISMO, Monoket). Nitrates are also found in some recreational drugs such as amyl nitrate or nitrite (”poppers”). Taking this medication with a nitrate medicine can cause a serious decrease in blood pressure, leading to fainting, stroke, or heart attack.

A small number of patients have had a sudden loss of eyesight after taking Levitra. This type of vision loss is caused by decreased blood flow to the optic nerve of the eye. It is not clear whether Levitra is the actual cause of such vision loss. Sudden vision loss with Levitra use has occurred most often in people with heart disease, diabetes, high blood pressure, high cholesterol, or certain pre-existing eye problems, and in those who smoke or are over 50 years old.

Before taking this medication, tell your doctor if you have:

*heart disease or heart rhythm problems;
*a recent history (in the past 6 months) of a heart attack, angina (chest pain), or congestive heart failure;
*a history of stroke or blood clots;
*a personal or family history of “Long QT syndrome”;
*high or low blood pressure;
*liver disease;
*kidney disease (or if you are on dialysis);
*a blood cell disorder such as sickle cell anemia, multiple myeloma, or leukemia;
*a bleeding disorder such as hemophilia;
*a stomach ulcer;
*retinitis pigmentosa (an inherited condition of the eye);
*a physical deformity of the penis (such as Peyronie’s disease); or
*if you have been told you should not have sexual intercourse for health reasons.

If you have any of these conditions, you may not be able to use Levitra or you may need a dosage adjustment or special tests during treatment.
FDA pregnancy category B: Although Levitra is not for use in women, this medication is not expected to be harmful to an unborn baby. Do not use this medication without telling your doctor if you are pregnant or plan to become pregnant during treatment. Although Levitra is not for use in women, it is not known if this medication passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. You may need a lower dose of this medication if you are older than 65. Follow your doctor’s instructions.
How should I take Levitra?

Take Levitra exactly as it was prescribed for you. Do not take it in larger doses or for longer than recommended by your doctor.
Take each dose with a full glass of water.

Levitra can be taken with or without food.

Levitra is usually taken only when needed, up to 60 minutes before sexual activity. The medication can help achieve an erection when sexual stimulation occurs. An erection will not occur just by taking a pill. Follow your doctor’s instructions.
Do not take Levitra more than once a day. Allow 24 hours to pass between doses. Contact your doctor or seek emergency medical attention if your erection is painful or lasts longer than 4 hours. A prolonged erection (priapism) can damage the penis. Store this medication at room temperature away from moisture and heat.

Levitra side effects
If you become dizzy or nauseated, or have pain, numbness, or tingling in your chest, arms, neck, or jaw during sexual activity, stop and call your doctor right away. You could be having a serious side effect of Levitra. Stop using Levitra and get emergency medical help if you have sudden vision loss. Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using Levitra and call your doctor at once if you have any of these serious side effects:

*chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;
*irregular heartbeat;
*swelling in your hands, ankles, or feet;
*shortness of breath;
*vision changes;
*feeling light-headed, fainting; or
* penis erection that is painful or lasts 4 hours or longer.

Continue taking this medication and talk with your doctor if you have any of these less serious side effects:

*warmth or redness in your face, neck, or chest;
*stuffy nose;
*headache;
*upset stomach; or
*back pain.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

Tadalafil is an orally administered drug used to treat male erectile dysfunction (impotence). It was initially developed by the biotechnology firm ICOS and subsequently developed and marketed worldwide by a joint venture of ICOS Corporation and Eli Lilly and Company (Lilly ICOS LLC) under the brand name Cialis.In the United States, tadalafil has Food and Drug Administration approval and became available in December, 2003 as the third impotence pill after sildenafil (Viagra) and vardenafil (Levitra). Due to its 36-hour effect it is also known as the weekend pill. As with sildenafil and vardenafil, it is recommended that tadalafil be used no more than once daily. Tadalafil is also currently undergoing Phase 3 clinical trials for the treatment of pulmonary arterial hypertension.
What is Cialis?

Cialis relaxes muscles and increases blood flow to particular areas of the body.

Cialis is used to treat erectile dysfunction (impotence).

Cialis may also be used for purposes other than those listed in this medication guide.

Important information about Cialis
Do not take Cialis if you are also using a nitrate drug for chest pain or heart problems. This includes nitroglycerin (Nitrostat, Nitrolingual, Nitro-Dur, Nitro-Bid, and others), isosorbide dinitrate (Dilatrate-SR, Isordil, Sorbitrate), and isosorbide mononitrate (Imdur, ISMO, Monoket). Nitrates are also found in some recreational drugs such as amyl nitrate or nitrite (”poppers”). Taking Cialis with a nitrate medicine can cause a serious decrease in blood pressure, leading to fainting, stroke, or heart attack. During sexual activity, if you become dizzy or nauseated, or have pain, numbness, or tingling in your chest, arms, neck, or jaw, stop and call your doctor right away. You could be having a serious side effect of Cialis Do not take this medication more than once a day. Allow 24 hours to pass between doses. Contact your doctor or seek emergency medical attention if your erection is painful or lasts longer than 4 hours. A prolonged erection (priapism) can damage the penis.

Cialis can decrease blood flow to the optic nerve of the eye, causing sudden vision loss. This has occurred in a small number of people taking Cialis, most of whom also had heart disease, diabetes, high blood pressure, high cholesterol, or certain pre-existing eye problems, and in those who smoke or are over 50 years old. It is not clear whether this medication is the actual cause of vision loss.
Stop using Cialis and get emergency medical help if you have sudden vision loss.

Cialis is by far the most effective and safe Erectile Dysfunction drug available for male Erectile Dysfunction problems. The famous blue pill Viagra that transformed treatment of sexual impotence in men five years ago has finally found a tough competitor in Cialis. You can purchase Cialis from reliable suppliers who offer guaranteed cheapest Cialis and free Cialis prescriptions.

Cialis stays in the system for up to 24 hours and with fewer side effects. Therefore, you can save money and enjoy longer with every Cialis pill purchase compared to Viagra. It is now available for sale in the US market. Your Cialis purchase is made easier from the comfort of your home as we provide you with one-stop resource on Cialis at cheap prices from trusted online pharmacies. We help you meet your goal to buy Cialis and save your time and money.

How Cialis Works
Cialis works by increasing the flow of blood to the penis during sexual stimulation. It allows most men to get and keep an erection long enough to complete sexual relations. When sex is over, the erection dissipates normally.

Advantage of Cialis
The effectiveness of most other ED tablets is just a few hours but Cialis works for up to 36 hours. This gives couples the freedom to relax and let the moment happen naturally. Cialis begins to work as quickly as half an hour after taking it, so it’s also possible to be more spontaneous.

Cialis works for mild, moderate or severe ED in most men. And because you can take Cialis with or without food, it’s easy to fit dosing into your schedule

How should I take Cialis? Take Cialis exactly as it was prescribed for you. Do not take it in larger doses or for longer than recommended by your doctor. Follow the directions on your prescription label.
Take this medication with a full glass of water.

Cialis can be taken with or without food.

Cialis is usually taken only when needed, just before sexual activity. The medication can help achieve an erection when sexual stimulation occurs. An erection will not occur just by taking a pill. Follow your doctor’s instructions.
Do not take Cialis more than once a day. Allow 24 hours to pass between doses. Contact your doctor or seek emergency medical attention if your erection is painful or lasts longer than 4 hours. A prolonged erection (priapism) can damage the penis. Store this medication at room temperature away from moisture and heat.
What happens if I miss a dose?

Since Cialis is used as needed, you are not likely to be on a dosing schedule.
What happens if I overdose?
Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include chest pain, nausea, irregular heartbeat, and feeling light-headed or fainting.

Mechanism of action
Although Viagra, Levitra, and Cialis all work by inhibition of PDE5, tadalafil’s distinguishing pharmacologic feature is its longer half-life (17.5 hours) compared with Viagra and Levitra (4-5 hours). This longer half-life results in a longer duration of action and is, in part, responsible for the Cialis nickname of the “weekend pill.” This longer half-life also is the basis of current investigation for tadalafil’s use in pulmonary arterial hypertension as a once-daily therapy. At present, sildenafil (trade name Revatio) is approved in various regions worldwide as a 3-times daily therapy for pulmonary arterial hypertension.

Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) enhances erectile function by increasing the amount of cGMP.Tadalafil (as well as sildenafil and vardenafil) inhibits PDE5. Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 by tadalafil has no effect in the absence of sexual stimulation. The recommended starting dose of Cialis in most patients is 10 mg, taken as needed before anticipated sexual activity (but no more than once daily). The dose may be increased to 20 mg or decreased to 5 mg, based on individual efficacy and tolerability. To avoid the inconvience of men with erectile dysfunction needing to plan use of Cialis around anticipated sexual activity, Lilly ICOS embarked upon a clinical development program to evaluate the benefits and risks of chronic (once-a-day) use. In June 2007, the European Commission approved low-dose (2.5 mg and 5 mg) Cialis to be used as a once-a-day therapy for men with erectile dysfunction.

Tadalafil is currently undergoing clinical trials for the treatment of pulmonary arterial hypertension. In patients with pulmonary arterial hypertension, it is believed that there is an imablance of the PDE5/NO system in the pulmonary vasculature that favors selective vasoconstriction of the pulmonary artery. Investigation of tadalafil in this disease assumes that PDE5 inhibition will result in pulmonary artery vasodilation, thus lowering pulmonary artery pressure and pulmonary vascular resistance. These physiologic changes may then reduce the workload of the right ventricle of the heart. Right heart failure is the main consequence of pulmonary arterial hypertension.
Side effects

Tadalafil has been used in approximately 15,000 men participating in clinical trials, and over 8 million men wordwide (primarily in the post-approval/post-marketing setting). The most common side effects when using tadalafil are headache, indigestion, back pain, muscle aches, flushing, and stuffy or runny nose. These side effects reflect the ability of PDE5 inhibition to vasodilate (cause blood vessels to widen) and usually go away after a few hours. Back pain and muscle aches can occur 12 to 24 hours after taking the drug, and the symptom usually disappears after 48 hours.

In May 2005, the U.S. Food and Drug Administration found that tadalafil (along with other PDE5 inhibitors) was associated with vision impairment related to NAION (non-arteritic anterior ischemic optic neuropathy) in certain patients taking these drugs in the post-marketing (outside of clinical trials) setting. Most, but not all, of these patients had underlying anatomic or vascular risk factors for development of NAION unrelated to PDE5 use, including: low cup to disc ratio (“crowded disc”), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking. Given the small number of NAION events with PDE5 use (less than 1 in 1 million), the large number of users of PDE5 inhibitors (millions) and the fact that this event occurs in a similar population to those who do not take these medicines, the FDA concluded that they were not able to draw a cause and effect relationship, given these patients underlying vascular risk factors or anatomical defects. However, the label of all three PDE5 inhibitors was changed to highlight clinicians to a possible association.

In October 2007, the FDA announced that the labeling for all PDE5 inhibitors, including tadalafil, requires a more prominent warning of the potential risk of sudden hearing loss as the result of postmarketing reports of deafness associated with use of PDE5 inhibitors.

What is Generic Viagra
Viagra is the brand name for sildenafil citrate and used for the treatment of erectile disfunction, otherwise known as male impotence. Generic Viagra is the same Sildenafil Citrate but marketed under different brand names and often at lower prices. Generic versions of brand name drugs have existed for a long time, but the generic version of Viagra is relatively new and brings new possibilites for affordable impotence treatment. You can expect generic Viagra to work in the same way as brand name Viagra because they contain the exact same active ingredient (Sildenafil Citrate). If Viagra is safe for you (as decided by your doctor) Generic Viagra is also safe for you and should be taken in the same doses as prescribed by your doctor.

How Does Viagra Work
When sexual stimulation begins nitric oxide (NO) is released into the spongy tissue of the penis. NO then activates an enzyme that increases the production of cyclic guanosine monophosphate (cGMP) the substance that relaxes the spongy tissue of the penis and facilitates an influx of blood. As specific enzymes slowly degrade cGMP the penis will slowly loose its ability to sustain an erection. Viagra works by inhibiting those enzymes that degrade cGMP, thereby enhancing ones ability to obtain and sustain an erection. 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.

How Effective is Viagra
Over 21 studies have been done to evaluate the efficacy of Viagra. Evaluation of drug activity was most often done using a self-assessment questionnaire. During a 6-month open labeled study, Viagra was found to improve sexual function in 88% of those treated. This included frequency, firmness, and maintenance of an erection; frequency of orgasm; frequency and level of desire; frequency, satisfaction and enjoyment of sexual intercourse; and overall relationship satisfaction.

History
Sildenafil (compound UK-92,480) was synthesized by a group of pharmaceutical chemists working at Pfizer’s Sandwich, Kent research facility in England. It was initially studied for use in hypertension (high blood pressure) and angina pectoris (a form of ischaemic cardiovascular disease). Phase I clinical trials under the direction of Ian Osterloh suggested that the drug had little effect on angina, but that it could induce marked penile erections. Pfizer therefore decided to market it for erectile dysfunction, rather than for angina. The drug was patented in 1996, approved for use in erectile dysfunction by the Food and Drug Administration on March 27, 1998, becoming the first pill approved to treat erectile dysfunction in the United States, and offered for sale in the United States later that year. It soon became a great success: annual sales of Viagra in the period 1999–2001 exceeded $1 billion.

The British press portrayed Peter Dunn and Albert Wood as the inventors of the drug, a claim which Pfizer disputes. Their names are on the manufacturing patent application drug, but Pfizer claims this is only for convenience.

Even though sildenafil is available by prescription from a doctor, it was advertised directly to consumers on US TV (famously being endorsed by former United States Senator Bob Dole and football star Pelé). Numerous sites on the Internet offer Viagra for sale after an “online consultation”, a mere web questionnaire. The “Viagra” name has become so well known that many fake aphrodisiacs now call themselves “herbal Viagra” or are presented as blue tablets imitating the shape and colour of Pfizer’s product. Viagra is also informally known as “Vitamin V”, “the Blue Pill”, as well as various other nicknames.

In February 2007, it was announced that Boots the Chemist would trial over the counter sales of Viagra in stores in Manchester, England. Men aged between 30 and 65 would be eligible to buy four tablets after a consultation with a pharmacist.

Pfizer’s worldwide patents on sildenafil citrate will expire in 2011–2013. The UK patent held by Pfizer on the use of PDE5 inhibitors as treatment of impotence was invalidated in 2000 because of obviousness; this decision was upheld on appeal in 2002.
Mechanism of action
Part of the physiological process of erection involves the parasympathetic nervous system causing the release of nitric oxide (NO) in the corpus cavernosum of the penis. NO binds to the receptors of the enzyme guanylate cyclase which results in increased levels of cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation (vasodilation) in the corpus cavernosum, resulting in increased inflow of blood and an erection.

Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum. The molecular structure of sildenafil is similar to that of cGMP and acts as a competitive binding agent of PDE5 in the corpus cavernosum, resulting in more cGMP and better erections. Without sexual stimulation, and therefore lack of activation of the NO/cGMP system, sildenafil should not cause an erection. Other drugs that operate by the same mechanism include tadalafil (Cialis®) and vardenafil (Levitra®).

Sildenafil is metabolised by hepatic enzymes and excreted by both the liver and kidneys. If taken with a high-fat meal, there may be a delay in absorption of sildenafil and the peak effect might be reduced slightly as the plasma concentration will be lowered.
Dosage and price
As with all prescription drugs, proper dosage is at the discretion of a licensed medical doctor. The dose of sildenafil is 25 mg to 100 mg taken once per day between 30 minutes and 4 hours prior to sexual intercourse.

It is usually recommended to start with a dosage of 50 mg and then lower or raise the dosage as appropriate. The drug is sold in three dosages (25, 50, and 100 mg), all three costing about US$10 per pill. Name-brand Viagra sildenafil is not scored and a fairly hard coating makes it more difficult to accurately cut the pills in half, even with a pill cutter.

Viagra pills are blue and diamond-shaped with the words “Pfizer” on one side, and “VGR xx” (where xx stands for “25″, “50″ or “100″, the dose of that pill in milligrams) on the other.
Contraindications
Contraindications include:

When taking nitric oxide donors, organic nitrites and nitrates, such as glyceryl trinitrate (nitroglycerin), sodium nitroprusside, amyl nitrite (”poppers”)
In men for whom sexual intercourse is inadvisable due to cardiovascular risk factors
Severe hepatic impairment (decreased liver function)
Severe impairment in renal function
Hypotension (low blood pressure)
Recent stroke or heart attack
Hereditary degenerative retinal disorders (including genetic disorders of retinal phosphodiesterases)

Viagra side effects
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. During sexual activity, if you become dizzy or nauseated, or have pain, numbness, or tingling in your chest, arms, neck, or jaw, stop and call your doctor right away. You could be having a serious side effect of Viagra.

Stop using Viagra and call your doctor at once if you have any of these serious side effects:

*sudden vision loss;
*chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;
*irregular heartbeat;
*swelling in your hands, ankles, or feet;
*shortness of breath;
*vision changes;
*feeling light-headed, fainting; or
* penis erection that is painful or lasts 4 hours or longer.

Less serious side effects may include:

*warmth or redness in your face, neck, or chest;
*stuffy nose;
*headache;
*upset stomach; or
*back pain.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect.

Absorption, Bioavailability

Viagra is rapidly absorbed. Maximum observed plasma concentrations
of Viagra are reached within 30 to 120 minutes (median 60 minutes) of
oral dosing in the fasted state. Viagra is about 40% biovailable. Viagra
is highly protein bound (96%). When Viagra is taken with a high fat
meal, the rate of absorption is reduced.

Metabolism, Half Life, Excretion

Viagra is mostly metabolized in the liver by an enzyme known as
CYP3A4 and to a lesser extent CYPC229. Viagra breakdown products
are excreted in the feces (80%) and in the urine (approximately 13%). Viagra’s mean half life is about 4 hours.

If you are going to take any of the PDE5 inhibitors such as Viagra, it is
very important that your doctor be aware if you have a liver condition
(such as cirrhosis) or kidney condition ( such as if you are on dialysis)
because you may need a special dosage adjustment.

Likewise, if you try to obtain Viagra on the internet, please make sure
that the person authorizing your prescription knows the true status of
your liver function and your kidney function.