Drug Treatment of Erectile Dysfunction

Oral Agents (Pills)
Viagra (Sildenafil citrate)
Viagra? is the first oral agent with proven benefit in the treatment of erectile dysfunction. Early media coverage generated worldwide demand for this medication. It is an effective and safe first line medication. What every physician and patient should know about this drug follows.

Sildenafil citrate is an inhibitor of an enzyme that is concentrated in penile erectile tissue (although it is present in some other tissues). This enzyme, known as phosphodiesterase type 5 (PDE5), turns off erection, therefore, Viagra by blocking it promotes the development and maintenance of an erection. Sildenafil is rapidly absorbed, with maximal blood concentrations occurring within one hour after administration. Its effect last on average 4 hours, that is, after taking the medication, there is a 4-hour window in which to pursue sexual activity. In my experience there are some men in whom the effect may last as long as 8 hours. It is best taken on an empty stomach as fatty food interferes with its absorption. Therefore, patients are instructed to take the medication 2 1-2 hours after a meal and wait another hour before starting sexual stimulation. Stimulation is required for Viagra to work. There is also a suggestion that alcohol may interfere with the medication's absorption.

In my experience, treatment with Viagra allows approximately 65% of men to resume sexual intercourse. Viagra has been shown to be effective across a wide spectrum of medical conditions, although it is least effective in certain diabetics and early after radical prostatectomy. Headache, flushing, transient visual disturbances and dyspepsia are the most common side effects occurring in 6-18% of men using Viagra.

The benefit of sildenafil in men with angina or a history of heart attacks who have ED who are NOT taking nitrates has been shown to be similar to men without these conditions. From a safety standpoint, in carefully selected patients there is no evidence to show that Viagra is associated with heart attacks or an increased incidence of death. The overall incidence of cardiac side effects is approximately 5% for those with a history or compared to 3% in men without coronary artery disease. These figures are the same as for placebo (sugar pill) in the Viagra trials. More recent studies confirm the safety of Viagra and it can be concluded that for patients with coronary artery disease who are not taking nitrate (nitroglycerin) therapy, sildenafil is a well tolerated and effective treatment for ED.

Viagra should not be used by certain patients: patients who are on any form of nitrate therapy (pill, spray, paste, or patch) as the combination of the 2 drugs has been shown to lower the blood pressure to a dangerous level. Men with significant cardiac disease are at higher risk of problems. These patients include: heart attack within the last 3 months; poorly controlled high blood pressure; poorly controlled angina (cardiac chest pain); stroke within the last 3 months; severe congestive heart failure; and heart valve disease. There is a group of men with cardiovascular disease who may benefit from a cardiologist's input prior to starting Viagra and these include: men with moderate angina; mild congestive heart failure; heart attack or stroke in the recent past (more than 3 months less than 6 months ago).

The advantage of this medication is the simplicity of its use. After thorough discussion of the potential side effects and review of medications, those patients who are considered safe candidates are simply given a prescription for six 50 mg tablets. They are instructed to take only one dose per 24-hour period. For the first dose, the patient is instructed to take one pill one hour before planned intercourse. If this dose is ineffective on two different occasions, the patient doubles the dose (100mgs). At the end of this home trial, the patient speaks with his or her doctor or a nurse for a refill of the minimum, effective dose. Patients who are not successful are asked to return to consider alternative forms of therapy.

Currently there are 2 other agents that work in a similar fashion to Viagra that are under FDA review, both of which have received approvable letters, indicating the likelihood of release in 2003. Tadalafil (proposed trade name, Cialis) is being developed by Lilly-ICOS and vardenafil (proposed trade name, Nuviva) is being developed by Bayer. Both of these drugs have been shown to be effective and safe in trials to date. It is likely that the precautions used for Viagra prescribing will be used also for these newer agents. As more information comes to light on these agents it will be posted on this website.

Trazodone
Trazodone is an anti-depressant with the uncommon side-effect of prolonged erection (priapism). This occurs in approximately 1/10,000-20,000 users. It has been used for the treatment of erectile dysfunction without any clear evidence that it is truly effective. Its mechanism of action in promoting erection is not well known, but it is believed that it exerts its primary effect by stimulation of the serotonin receptors in the brain. The medication has been used at the dose of 50-200 mg by mouth each night at bed time (no relationship to intercourse timing). While some studies have cited trazodone?s effectiveness to be as high as 60%, the arrival of Viagra has decreased the use of this medication significantly. The side effects of trazadone include drowsiness in 31%, dry mouth in 1% and fatigue in 19%. At the Sexual Medicine Program at New York Presbyterian Hospital the combination of trazadone and Viagra is not allowed.

Phetolamine
Oral administration of the phentolamine, which blocks the action of adrenaline in the penis (the major inhibitor of erection) has been shown to result in erection in men with mild ED. Recently, this drug has received recognition as Vasomax? (Schering-Plough, NJ, USA) and has in a number of trials, in men with low-grade ED, been shown to be better than placebo. It has yet to be put before the FDA for final approval and it is unclear if this drug will ever come to the market.

Yohimbine
This drug is derived from a tree bark and acts on receptors in the brain to stimulate area that are believed to be involved in sexual function. It has been used for many years, however, there is no good evidence to show that this drug is any better than placebo (sugar pill). Currently, its role as therapy in men with erectile dysfunction is minimal. It is associated with potentially serious side effects such as palpitations and high blood pressure, especially in patients with cardiovascular disease.

Apomorphine
Apomorphine has been used as a pharmacologic agent for over a century. Previously, it has been used primarily in Parkinson?s disease and is approved in a number of countries for this indication. The route of administration for this has been both by pill and injection with doses used up to 30 mg. It is a stimulator of dopamine receptors in an area of the brain (hypothalamus) that is key to the triggering of erection. TAP Pharmaceuticals licensed apomorphine for the treatment of erectile dysfunction in 1996 and the medication has been reformulated so that it can be delivered in under the tongue. The trade name for the drug is Uprima? and is available is Europe and Asia at 2mg and 3 mg doses. It is currently under review by the FDA. It appears from trials that this agent is an effective drug in men who have some erectile function left (mild and moderate ED) and who have had ED for a short period of time (less than 2 years). The medication is rapidly-acting, causing erections to occur as quickly as 5 minutes after administration. In men who get erections in response to Uprima? about 70% get the erection within 20 minutes. Sexual stimulation is required for this medication to work. Because it is given under the tongue, it may be taken with food. The medication dissolves in about 10 minutes. It is a safe medication whose most common side effects include (at 3mg) nausea, headache, and dizziness (which occur in less than 5% of men). It is unclear when this drug will come to market.

Intraurethral Agents (Suppositories)
Alprostadil (MUSE?)
Intra-urethral administration of alprostadil suppository (MUSE, Vivus, Menlo Park, CA, USA) induces an erection sufficient for sexual intercourse in 30-40% of men. A pellet, the size of a grain of rice, is placed 1 inch into the urine channel following urination while the patient is standing. The reported side effects include pain and dizziness, albeit in less than 5% and 2% of men respectively. PGE1 has four dosage strengths (125, 250, 500, and 1000 mg), although the lower doses are not effective in the average man with ED. MUSE was introduced as a treatment for the impotent male in 1997. It bypassed the need for the direct injection of a drug into the penis. This factor alone has made it appealing to many physicians as well as patients. In the program's history experience, MUSE has an average overall success rate of 35% on office administration, as defined by the ability to obtain an erection sufficiently rigid for sex. It also showed that the at-home consistency rate was 55% in men with established in-office drug efficacy. No significant side effects have occurred in our patients. The incidence of priapism (prolonged erections) is negligible, with one study reporting 1,373 home administrations without the incidence of priapism or fainting, which is consistent with our experience.

Administration of intraurethral suppositories, while less intimidating than intracavernosal injection, is also somewhat complex. These medications should be given initially in the clinic, with instruction and demonstration of competence as well as effectiveness prior to dispensing a prescription for at-home use. In our experience, lack of effectiveness is the reason for patient drop-out with this route of administration. We currently use this medication in selected patients. A starting dose of 500 or 1000 mcg is used. The patient is instructed to void just prior to use of the medication. This lubricates the urethra and makes the administration of the suppository easier. To minimize venous leak and promote absorption, the patient is instructed to stand while the medication is absorbed. Gentle massage helps absorption. The effectiveness is assessed at 5, 10, and 30 minutes. Loss of erection is expected within one hour. Recently, the company has supplied a constriction device (ACTIS) that is placed at the base of the penis just prior to medication administration. This theoretically will increase intracavernosal concentrations and decrease systemic absorption. It may be worn during intercourse if desired. The effectiveness of MUSE? in combination with the ACTIS device is under investigation.

Penile Injections
Virag and Brindley were the first authors to report the ability of penile injection to produce an erection, using papaverine and phenoxybenzamine, respectively. To date, a number of medications have been used for this purpose, most commonly papaverine, phentolamine and alprostadil. These medications have been administered in a variety of combinations with good effect. The success rate, defined by the production of an erection rigid enough for intercourse, has been in excess of 75%.

While Viagra has become the most prescribed medication for the treatment of ED, injection therapy still represents a cornerstone of therapy. In a recent study patients were asked to compare penile injections to sildenafil with regard to hardness of erection, overall sexual satisfaction, and preference for future use. All patients, regardless of etiology of ED, reported a more rigid erection using injections versus sildenafil. The majority of patients chose to continue using injections as their preferred treatment.

The use of combination agents is preferred to single agents to minimize side effects and maximize effectiveness. For example, the combination of papaverine, phentolamine, and alproastadil was shown to be more effective than high dose alprostadil alone, but has a lower incidence of painful erections (due to the lower concentration of alprostadil). The advantage of intracavernosal agents compared to currently available oral agents, is that these medications induce erection even in the presence of only minimal stimulation. The disadvantages include more complex route of administration, potential for bleeding, bruising, and penile fibrosis, and a higher incidence of priapism (albeit all uncommon side effects).

It is mandatory that the patient receive detailed instructions on the use of this type of therapy and is administered his first dose in the clinic. In our clinic, each visit is an important combination of physician assessment, trial dose administration, and patient education. The patient is given instructions on cleaning the phallus. An alcohol swab is used to cleanse the intended area of injection. An insulin type syringe is then used to administer the medication. The injection is given at the ten or two o?clock position on the penis (away from the ventrally located urethra), away from visible veins, and never in the midline. To minimize the chance of scar formation, the sight is changed with each dose. The needle is aimed at a right angle to the skin and pushed in to the hub, ensuring delivery of the medication into the correct location. After administration of the medication, the patient holds direct pressure to the area of injection for a few minutes. Patients taking blood thinners are advised to continue pressure for 6 minutes. The staff gives the first dose with the patient watching. This is a very low dose (which varies depending on the choice of drug). Patients with pure nerve damage ED are started lower than those with suspected vascular ED. After administration and assessment of erectile response 5, 10, and 30 minutes later, the patient waits in the clinic until the erection goes away. With each visit the dose of medication is increased. The patient?s role in administration of the medication also progressively increases. The dosage goal is to produce an in-clinic erection of 60% maximum (barely adequate for penetration) that lasts less than one hour. It is presumed that at home with less anxiety, more appropriate stimulation, etc., the effect will be greater. Ultimately, the patient (or his partner) must also demonstrate the ability to draw up the drug and properly inject it with an aseptic technique without staff assistance. At this point, he is graduated from the clinic and given prescriptions for at-home use. As with all forms of medical therapy, the patient is given instructions to seek prompt medical attention for prolonged erections.

The potential side effects of scarring, priapism (see page on Priapism on this website), bleeding, bruising, can be thus minimized by using combination medications, carefully titrating to the correct dose in the clinic, and thoroughly educating the patient on injection technique. Scarring can occur as a nodule, plaque, or penile curvature. Patients in our clinic are instructed that prolonged erections constitute a medical emergency. If the patient has an erection that lasts longer than two hours that is not relieved by ejaculation, they are instructed to call the answering service for advice and should be in the Emergency Department by the fourth hour.

Topical Administration (Creams and Gels)
Two companies at present (Nexmed and Macrochem) are developing medications, in the form of gels that are applied to the penis that are absorbed into the erectile bodies and cause erection. These medications obviously have great appeal to patients given the absence of a needle and minimal side effects. It is unclear at this time, based on early trials, how effective these drugs will be in the general population of men with ED. As new information becomes available it will be posted on this website.

Simplified Approach To Drug Therapy For ED
ED is a common problem that affects men as they age. There are many effective forms of therapy available that should be offered to motivated patients. Consideration of the primary cause of ED is important in determining the likelihood of success with any given form of treatment. A history and physical examination are mandatory before the prescription of any form of erection-inducing medication. While the oral agent Viagra is currently the most popular first line medication, in patients who fail to respond to this agent, injection therapy should also be offered as second line therapy as it is easily the most effective treatment that exists. Viagra is absolutely contraindicated in patients who take nitrates of any kind but has proven to be safely used in combination with other blood pressure medications. Treatment with intraurethral alprostadil is a good option for patients who take nitrates, but are unable or unwilling to try penile injection therapy. Other oral agents, such as trazadone and yohimbine are probably, currently, of only historical value.

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Erectile dysfunction drugs affect other organ systems.

Ernst R. Schwarz, at Cedars-Sinai Medical Center, and colleagues concluded a review of the medical literature, as well as their own research findings and clinical data, to determine what actually is known about the effects of long-term use of phosphodiesterase-5 inhibitors ( PDE-5i ), on various organ systems.

Their findings are published in the International Journal of Impotence Research.

Studies so far suggest the phosphodiesterase-5 inhibitors produce mostly beneficial results, and not just for erectile dysfunction. The FDA recently approved a reformulation of Sildenafil ( Revatio ) for the treatment of primary pulmonary hypertension, a disease that tends to occur in young women, causing elevated blood pressures in the lung that can lead to heart failure and early death.

" When we look at all the different organ systems – the blood, the heart, the lungs, blood flow in the brain – there are hardly any negative side effects. In fact, just the opposite is true. There are beneficial effects for primary pulmonary hypertension, as well as for conditions such as heart failure and lack of oxygen in the heart, " said Schwarz. " The only issue is that the data we have are from relatively short-term studies. Viagra ( Sildenafil ) has been on the market since 1998 and the other two PDE-5 inhibitors, Levitra ( Vardenafil ) and Cialis ( Tadalafil ), were approved by the FDA in 2003. Therefore, we do not have multi-year follow-up studies. On the other hand, the drugs have been on the market for several years now and there have been no reports of negative long-term effects."

While there are some differences among the three medications, they have many properties in common and work by limiting the activity of the enzyme phosphodiesterase-5, which is found in tissues and vessels of the penis, blood platelets, and smooth muscle of blood vessels. For the treatment of erectile dysfunction, the drugs' constraint of the enzyme's action results in increased levels of cyclic guanosine monophosphate ( cGMP ) and nitric oxide ( NO ), biochemicals that promote smooth muscle relaxation and increased blood flow in erectile tissue.

PDE-5 inhibitors can be effective in treating erectile dysfunction even for many men who also have diabetes, those who are older, and those who have co-existing ischemic heart disease. Furthermore, say the authors, " since PDE-5 is found in smooth muscles of the systemic arteries and veins throughout the body, use of PDE-5i has been associated with various cardiovascular effects."

" The original intention was to develop PDE-5 inhibitors as a treatment for angina, chest pain that occurs when the heart is starved for oxygen," Schwarz said. "As such, their effects on the heart appear to be all beneficial. Nitrates and other substances commonly used to improve blood flow and oxygenation to the heart muscle have a side effect that we call the 'steal phenomenon,' in which blood is taken away from underperfused areas to improve blood flow in normal areas. In contrast, PDE-5 inhibitors actually improve blood flow even in areas where there is a blockage of an artery, thereby having a protective effect on the heart muscle."

The drugs' potential impact on visual function became a matter of controversy when a suspected link between PDE-5 inhibitors and vision loss led to lawsuits filed last year against the maker of Viagra. According to the article's authors, however, "analysis of clinical trial data in more than 13,000 men and on more than 35,000 patient-years of observation" found occurrence of the visual disorder to be similar to that of the general population. " Even though individual cases have been reported for all PDE-5i, these recently published data do not suggest an increased incidence of NAION ( non-arteric anterior ischemic optic neuropathy ) in men who took PDE-5i for ED," the article states.

Among other findings:

Although the enzyme PDE-5 has been found in tissue and arteries of the brain, Sildenafil does not appear to dilate cerebral arteries or have an effect on cerebral blood flow or blood flow velocity, an indication that there is no increased risk of stroke or hemorrhage.

PDE-5 exists in blood platelets, cells that play a major role in the blood clotting process, but Sildenafil appears to have no direct impact on platelet function. However, the drug's effects have not been specifically evaluated in patients with bleeding disorders or in those taking drugs that reduce clotting.

" Experimental and human studies indicate that PDE-5 inhibitors are effective and well tolerated, and there is evidence that they are not being used to their utmost potential. We suggest that these drugs may prove beneficial in treating a wide variety of disorders," said Schwarz. " Some studies are underway to determine the effects of long-term use of PDE-5 inhibitors, and others are warranted, especially in patients who are considered at high risk because of chronic cardiovascular disorders."

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Do erectile drugs put my life in danger?

This video should get you an idea...




The erectile drugs themselves aren't dangerous. Erectile drugs are proven to be safe. However, people that use them and mix them, if they have a heart disease or are taking nitro-glycerine, that's when the problems occur with different types of erectile dysfunction medication. However, it's usually not the erectile drug itself. The people that already have some type of heart ailment, they would still rather use the drug and prefer to die engaging in sex than refrain.

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Erectile disfunction: a very common problem.

What is erectile dysfunction?

Erectile dysfunction (ED), also known as impotence, is the inability to achieve or sustain an erection for satisfactory sexual activity. Erectile dysfunction is different from other conditions that interfere with sexual intercourse, such as lack of sexual desire and problems with ejaculation and orgasm. This article focuses on the evaluation and treatment of erectile dysfunction.


How common is erectile dysfunction?

Erectile dysfunction (ED, impotence) varies in severity; some men have a total inability to achieve an erection, others have an inconsistent ability to achieve an erection, and still others can sustain only brief erections. The variations in severity of erectile dysfunction make estimating its frequency difficult. Many men also are reluctant to discuss erectile dysfunction with their doctors, and thus the condition is under-diagnosed. Nevertheless, experts have estimated that erectile dysfunction affects 30 million men in the Untied States.

While erectile dysfunction can occur at any age, it is uncommon among young men and more common in the elderly. By age 45, most men have experienced erectile dysfunction at least some of the time. According to the Massachusetts Male Aging Study, complete impotence increases from 5% among men 40 years of age to 15% among men 70 years and older. Population studies conducted in the Netherlands found that some degree of erectile dysfunction occurred in 20% of men between ages 50 to 54, and in 50% of men between ages 70 to 78. In 1999, the National Ambulatory Medical Care Survey counted 1,520,000 doctor-office visits for erectile dysfunction.

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Cialis side effects, medical uses and interactions with other drugs.

USES: Tadalafil is used to treat male sexual function problems (impotence or erectile dysfunction) by blocking a certain enzyme (phosphodiesterase-PDE5) in the body. In combination with sexual stimulation, tadalafil helps blood flow into the penis to achieve and maintain an erection. This drug is not indicated for use in women. Use of this drug does not protect against sexually transmitted diseases (e.g., HIV, hepatitis B, gonorrhea, syphilis). Practice "safe sex" such as using latex condoms. Consult your doctor or pharmacist for more details.

HOW TO USE: This drug is taken by mouth as needed, at least 30 minutes before sexual activity with or without food; or use as directed by your doctor. This medication's effect on sexual ability may last up to 36 hours. Therefore, do not take more than once daily as needed. Avoid eating grapefruit or drinking grapefruit juice while being treated with this medication unless your doctor instructs you otherwise. Grapefruit juice can increase the amount of certain medications in your bloodstream. Consult your doctor or pharmacist for more details. The dosage is based on your medical condition, response to therapy, and other medications you may be taking (see also Drug Interactions section). Consult your doctor or pharmacist for more details. Read the patient information leaflet provided by your pharmacist and ask questions if any of the information is unclear.

SIDE EFFECTS: Headache, stomach upset, back pain, muscle pain, nasal stuffiness, flushing, pain in arms or legs, dizziness, or vision changes may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly. Sexual activity may put extra strain on your heart, especially if you have heart problems. If you have heart problems or experience any of the following serious side effects during sex, stop and tell your doctor immediately of: severe dizziness, fainting, chest pain. In the unlikely event you have a painful or prolonged erection (lasting more than 4 hours), stop using this drug and seek immediate medical attention or permanent problems could occur. A serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching, unusual swelling, severe dizziness, trouble breathing. If you notice other effects not listed above, contact your doctor or pharmacist.

PRECAUTIONS: Before taking tadalafil, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. Before using this medication, tell your doctor or pharmacist your medical history, especially of: penis conditions (e.g., angulation, fibrosis/scarring, Peyronie's disease), history of painful/prolonged erection (priapism), sickle cell anemia, blood system cancers (e.g., leukemia or myeloma), eye problems (e.g., retina diseases like retinitis pigmentosa), kidney disease, liver disease, bleeding disorders, active stomach ulcers, heart problems (e.g., recent heart attack or serious arrhythmia within past 6 months, heart failure, coronary artery disease with unstable angina, aortic stenosis, idiopathic hypertrophic subaortic stenosis), recent stroke within past 6 months, very high or low blood pressure. This drug may make you dizzy or cause vision changes; use caution engaging in activities requiring alertness such as driving or using machinery. Limit alcoholic beverages. To minimize dizziness and lightheadedness, get up slowly when rising from a seated or lying position. Alcohol may increase this effect. Limit alcoholic beverages. This drug is not indicated for use in women or children.

DRUG INTERACTIONS: See also How To Use section for drug-food interactions. This drug should not be used with the following medications because very serious (possibly fatal) interactions may occur: certain alpha-blocker medication (alfuzosin, doxazosin, prazosin, terazosin, or doses greater than 0.4mg daily of tamsulosin), nitrates (e.g., nitroglycerin, isosorbide), nitroprusside (or any "nitric oxide donor" drugs), recreational drugs called "poppers" containing amyl or butyl nitrite. If you are currently using any of these medications, tell your doctor or pharmacist before starting tadalafil. Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: drugs that affect certain liver enzymes (CYP 3A4 substrates, inhibitors and inducers such as cimetidine, rifamycins, St. John's wort, or certain anti-seizure drugs), high blood pressure medicines, other medications for impotence. If you are taking ritonavir, erythromycin, ketoconazole, or itraconazole (examples of potent inhibitors of CYP 3A4), do not take more than a 10mg dose of tadalafil in a 72 hour period. For more details contact your doctor or pharmacist. Do not start or stop any medicine without doctor or pharmacist approval.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly.

NOTES: Do not share this medication with others, since they may have a problem that is not effectively treated by this drug, or they may have a condition that is complicated by this drug.

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59 and 86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

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Is Viagra Cialis or Levitra best for you?

Older men who have less frequent sex and who are happy with the responses using Viagra should certainly continue Viagra. Some patients who do not get optimal responses to Cialis may find that Viagra is more to their liking. In general, all three drugs work and the patients should talk to their doctors about finding the one that works best for them and their sexual lifestyle. Three drugs now and others in various stages of clinical trials has not only further expanded the treatment options for ED, but in many ways has caused new confusion among physicians and patients. Add this to other medications and vacuum therapy and it's easy to see why patients and potential patients have questions.

For all practical purposes, these oral drugs are a first line of medical treatment. In certain circumstances in which the males are healthy, young, and laboratory blood tests and such are normal one should look for the physical cause of their erectile dysfunction before instituting treatment since the disease process may be more serious than the symptoms, i.e., the ED itself. In some cases, treatment of the primary disease may in fact resolve the sexual dysfunction. However, most men have other physical causes for ED as found in their health history and lab tests, making PDE-5 inhibitors a first line of choice. Selecting the appropriate drug is sometimes extremely difficult to do without proper information on each drug and a careful discussion about the sexual history of the patient and his partner.


advertisement Let us discuss the pros and cons of each of these three drugs and the sexual circumstances that may indicate the use of one drug over another. Viagra was the first and is probably the most famous of the three PDE-5 inhibitors used to treat erectile dysfunction. It had been researched for over a dozen years before becoming available to the American public. It works in about 70% of all men with all types of erectile dysfunction, although approximately 25% of them do not feel that the responses are optimal.

When initially doing the studies on Viagra, the endpoint of efficacy was improvement in sexual function; however, all patients in the Viagra studies had ED, whereas studies for the other two drugs were based on patients who had success with Viagra.Viagra's major drawbacks include decreased absorption due to food intake. You should take the pill on an empty stomach as absorption takes approximately 30 minutes. The drug takes about one hour for maximum effect, but loses 50% of its maximal concentration every four hours. Sexual stimulation is necessary to achieve erection. Of the three drugs, the maximal concentration for Viagra appears to be the therapeutic concentration. Side effects include mild headaches, facial flushing, stomach upset and unusual ocular disturbances including a bright vision and a blue-green halo around the vision.

Levitra was the second oral PDE-5 inhibitor for erectile dysfunction to be FDA approved. In vitro, it is six to 10 more times more potent than Viagra, however, 15% of the drug is nonprotein-bound and bioactive. Studies on Levitra have excluded patients who did not have success with Viagra, therefore the efficacies are somewhat shifted toward the positive. In general, the thought is that Levitra is more potent and efficient than Viagra as demonstrated by the hard-to-treat groups of patients. Diabetics and post-radical-nerve-sparing-prostatectomy patients appear to have a higher incidence of success than for Viagra. In addition, the efficacy is based on sexual satisfaction or successful penetration rather than improvement, which were the endpoints for Viagra. Levitra reaches its peak concentration at 40 minutes, is only affected by a very high fat diet.

Most patients can eat and take the drug without affecting its absorption and maximal concentration. The half-life of Levitra is five hours; however, the therapeutic levels appear not to be the maximal concentration and therefore multiple half-lives may occur with efficacy of the drug. In Europe, Levitra is considered a 24-hour drug whereas in the United States the package insert states, "No duration of action for Levitra" although the majority of physicians consider it to be a drug that has efficacy longer than Viagra.

Overall the slight chemical change noted in Levitra appears to give it more potency, efficacy, longer duration, and probably more rapid onset. Levitra has shown that 25% of patients had optimal responses within 16 minutes of the oral intake of the pill. In recent studies, Viagra has also shown longer duration of action than four hours even though the package insert shows four hours of duration. However, if duration is the goal, Cialis appears to be the winner. Cialis has been approved for duration of 36 hours, yet, there are studies showing high efficacy out to 100 hours. It is not affected by any food whatsoever and in fact can be taken with pure fat.

The typical McDonald's double cheeseburger with French fries and malted milkshake would certainly inhibit the effect of Levitra, but a steak with potatoes, a glass of wine, salad, and dessert would probably not. Neither of these would affect the absorption of Cialis. Cialis is protein-bound that causes a serum peak concentration of two hours and a half-life anywhere between 16 and 22 hours depending on the age of the patient. The older the patient, the longer the half-life. Because of the long duration of action, the lack of absorption effects, and efficacy at least as good as Viagra, if not better. The paradigm of taking these PDE-5s may in fact change as people gain more and more experience with Cialis.

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Viagra or substitutes?

I've used them all.

I liked Kamagra for it's jelly-like dosing. It seemed the fastest acting, although it also tended to have the shortest effective lifespan after ingestion.

Viagra and Levitra (which I'm currently taking) both worked well enough on low dosage i.e. approx 1/4 available full dose, though the side-effect of a flushed face and skin appeared to be equally pronounced. Levitra seems to last in my system a little longer... not that there's anything wrong with that. :D (2 to 3 days in my case)

Finally, Cialis was definitely the winner for overall efficacy and longevity. It also won hands down for fewest side-effects in my case (the flushing). However, there is some current issue for persons with HIV that makes Cialis not a good fit. I'm not completely clear what it is though I've discussed it with my Dr. and will try to get more information.

In any event, none of the above will have much positive effect if you are not with someone you want to be with. These drugs help keep it up, not get it up and that seems to be a distinction that people don't often make when discussing them.

Finally, while I do not advocate drug use, I am not going to be hypocritical and say I've never done anything recreationally. I will say that none of the above really work well with something like good grade ecstasy. You can play until the cows come home (figure of speech of course) but when you are on ecstasy, you'll have a heckuva time maintaining an erection if you get one at all!

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Questions and answers about Viagra

Question:
Is Viagra safe to use?

Answer:
Generally speaking, yes. As you know, Viagra is a drug that was designed to help men who had problems having erections. Viagra improves the quality of the erections, it doesn't cause 'inappropriate' erections. That is, if a man took Viagra and did his income taxes, he wouldn't find himself sexually aroused.

Well, I know I wouldn't.

Some people who have taken Viagra have died. Generally, these have been people who have taken nitroglycerin or another similar drug, which react very badly with Viagra. They can cause a severe fall in blood pressure.

Other men who have died have been in very poor condition with serious medical problems, and it's been thought the exertion and excitement may have caused their deaths.

Generally speaking, though, if you're in fair physical condition (aside from the erectile dysfunction requiring Viagra), you shouldn't have a problem with it.

Of course, you can get it at very cheap at the following site