Sildenafil - It's Not Just For Erections Anymore
By now, nearly everyone knows what sildenafil is, or at least knows it by the name it’s been most widely marketed as – Viagra®, the most commonly prescribed drug for erectile dysfunction (ED). Another drug, tadalafil (marketed as Cialis®) does approximately the same thing, and is the second most commonly prescribed drug for ED treatment. There are others, such as vardenafil, however sildenafil and tadalafil are, by all accounts, the most widely used due to their long track records of effectiveness in helping men get, and keep, erections. It’s worth noting here, that Riize Health provides the only compound medication for ED that combines both sildenafil and tadalafil on a highly effective oral dissolving strip. (It also contains oxytocin, for an added boost to the moment.) All that said, there are four reasons we’re going to focus on sildenafil for right now. That’s because: a) it was the first; b) it became the most popular; c) it is the only ED medication, so far, that’s been approved for other medical uses (as Revatio®); and d) it is the one that’s currently involved in, or generating, the most research into other therapeutic uses. Sildenafil has had an interesting story, and it seems it’s not over yet.
The story of sildenafil
Sildenafil was the first drug to be approved by the FDA for the treatment of erectile dysfunction, but it didn’t start out to be that. In 1989, the pharmaceutical company Pfizer, was researching for a drug to treat patients with angina pectoris. Angina pectoris, or simply angina, is a symptom of coronary artery disease, causing chest pain, and feelings of heaviness and tightness in the chest. Coronary artery disease is the result of the heart muscle not getting enough blood and oxygen.
The research was aimed at finding a medication to dilate coronary arteries, thus relieving some of the symptoms of angina. The result of the research was the synthesis of a molecule that was later named sildenafil. The clinical results found that while sildenafil did widen the arteries, it widened the healthy coronary arteries more than the diseased ones, and thus its efficacy in treating patients with angina was limited. However, in the research process, some subjects reported a significant increase in the occurrence of penile erections. Once it was realized that sildenafil had a newly discovered on-target effect, it was commercialized as an ED medication, and became Viagra®. From when it was first FDA approved in 1998, it was very successful in its association with male sexuality however, it didn’t take long for it to also become approved for a nonsexual condition. In 2005 the FDA approved sildenafil for pulmonary hypertension, as Revatio®. In recent years, the research has grown, as scientists have continued to investigate uses for sildenafil for a vast array of nonsexual vascular disorders, as well as other conditions.
How does sildenafil work?
How sildenafil became the superstar of ED medications can explain why there is increasing interest in other uses for it. It starts with how and why it works for ED. Basically, how it gives you an erection.
Normally, erections require only few basic things to happen. A receptive state of mind, or arousal, stimulation, adequate testosterone levels, and overall healthy arteries, veins and nerves. With these things in place, it begins with the release of nitric oxide (N.O.), which is produced by a thin layer of cells that line the blood vessels. Nitric oxide is chemical messenger that transmits arousal impulses between nerves and relaxes arteries, widening them. At the same time, N.O. signals arterial cells to produce a chemical called cGMP, which increases blood flow to the penis. And, there it is! Your erection!
However, at the same time nitric oxide is doing its thing, tissue in the penis is producing an enzyme called PDE-5. What PDE-5 does, is breakdown the cGMP, essentially countering its ability to keep the increased blood flow, keeping the erection going. Normally this is not a problem, because PDE-5 usually comes into the picture after-the-fact, so to speak, decreasing the erection only after orgasm has been achieved. With erectile dysfunction, the normal function of PDE-5 has gotten out of sync. What sildenafil does is take over. It is a PDE-5 inhibitor, and stops the PDE-5 enzyme from breaking down the cGMP, so the erection can be maintained.
The point of all this is that, it’s the interaction of sildenafil with PDE-5, along with its effects on arterial dilation led to continued and expanded research into its possible use in other treatment and clinical applications where PDE-5 and vascular factors are involved.
Other therapeutic roles for sildenafil
In the discovery of sildenafil, the original research did find that it did have positive dilation effects on arteries. Its effect on PDE-5, as an inhibitor, was discovered subsequently, with the reporting of frequent erections on the part of the test subjects. The fact is, PDE-5 plays a diverse number of roles, across different areas of the anatomy. It is pivotal in signaling cells to regulate muscle relaxation and blood vessel dilation, in more areas than just the penis. As a PDE-5 inhibitor, sildenafil may have a direct and unique effect for other pathologies in which PDE-5 plays a part. Recent studies have shown that exposure to PDE-5 inhibitors have shown positive indications for conditions related to blood flow and heart function. Repurposing of sildenafil is of great interest in the pharmaceutical and healthcare sectors, in pursuit of new, effective medical applications.
Pulmonary hypertension
Pulmonary hypertension is a serious problem when it occurs, and it is the only nonsexual condition for which sildenafil (as Revatio®) has been approved. Pulmonary hypertension is a type of high blood pressure specific to the arteries in the lungs and right side of the heart. Among its causes are various lung diseases, vascular diseases and heart disorders. It can also be caused by exercise when it increases the pulmonary artery pressure. High altitudes are still another possible cause. Clinical trials have demonstrated improved exercise tolerance and relief of symptoms, with few side effects, with the use of sildenafil.
Mountain sickness
High altitudes lower blood oxygen levels, in some cases to the point of causing pulmonary hypertension. The low oxygen levels narrow the pulmonary arteries, and make the heart work harder. In tests done in Germany and at a Mount Everest base camp, 50mg of sildenafil decreased pressures in the lungs’ blood vessels and increased the tolerance for physical activity.
Heart disease
After Viagra® was approved, research continued, with the focus on making sure it was safe for circulation, especially for men with heart disease. It was found that it was in most cases. It was also found that in some cases of patients with congestive heart failure, sildenafil improved oxygen consumption, pulmonary artery pressure and exercise capacity. Research also shows that sildenafil helps the heart muscle relax properly, possibly helping patients with heart failure due to diastolic dysfunction, where the heart doesn’t relax properly between beats. In addition, sildenafil has demonstrated the ability to protect the heart from excess adrenaline stimulation
Benign prostatic hyperplasia
Benign prostatic hyperplasia, or BPH, is a condition of non-cancerous enlarged prostate. Three studies reported that ED medications, including sildenafil, may ease the symptoms of BPH by inhibiting PDE-5 in the bladder, not the prostate. More research is being done.
Anti-inflammatory properties
Cancer treatment enhancement
Sildenafil has exhibited anti-inflammatory and neuroprotective properties through the regulation of certain protein functions and signaling pathways.
Sildenafil has also shown that it might make certain types of tumor cells more susceptible or vulnerable to the effects of chemotherapy agents.
Additional research
Additional uses of sildenafil as part of a therapeutic treatment are being explored for a wide range of conditions including Alzheimer’s, retinopathy, wound healing, depression and even stroke.
You can read some of the other articles about sildenafil on our blog page if you want to learn more about how it is an important ingredient in our ED strips for sexual wellness. Riize Health has led the way with innovations for both men’s and women’s sexual health, and for weight loss. Riize oral film strips use the latest in thin film manufacturing technology, and are made domestically, under strict guidelines. Through the Riize Health telemedicine platform, patients can get a free personalized assessment, with prescriptions from licensed medical professionals. Because of this, Riize Health is leading the way in the use of dissolving film strips for oral drug delivery.
SOURCES
- https://www.health.harvard.edu/newsletter_article/viagra-and-health-beyond-ed
- https://www.tandfonline.com/doi/full/10.3109/13685538.2013.801952
- https://www.ahajournals.org/doi/10.1161/01.cir.99.1.168
- https://www.nbcnews.com/health/heart-health/viagra-performs-not-only-bed-heart-n228256
- https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0185-3
- https://www.mdpi.com/1648-9144/59/12/2190
- https://www.popsci.com/health/sildenafil-heart-heart-benefits/
- https://www.everydayhealth.com/heart-health/viagra-and-cialis-may-cut-risk-of-early-death-from-heart-disease/
- https://www.nbcnews.com/health/health-news/viagra-may-offer-help-enlarged-hearts-flna1c9447992
- https://www.healthline.com/health/benefits-of-taking-viagra-daily
