What is Sildenafil?
Sildenafil, marketed under names such as Viagra among others, is a medication used to treat erectile dysfunction and pulmonary arterial hypertension. Its effectiveness in treating sexual dysfunction in women has not been demonstrated.
Sildenafil acts by blocking phosphodiesterase 5 (PDE5), an enzyme that promotes the breakdown of cGMP, which regulates blood flow in the penis. It requires sexual arousal, however, to work. Sildenafil has been a common treatment for erectile dysfunction; its primary competitors on the market are tadalafil (Cialis) and vardenafil (Levitra).
For pulmonary arterial hypertension, sildenafil improves some markers of the disease but does not appear to affect the risk of death or serious side effects as of 2014.
This medication is taken by mouth or injection into a vein. Common side effects include headaches, heartburn, and flushed skin. Caution is advised in those with cardiovascular disease. Rare but serious side effects include a prolonged erection that can lead to damage to the penis, vision problems, and hearing loss. Sildenafil should not be taken by people on nitrates such as nitroglycerin (glycerin trinitrate), as this may result in a serious drop in blood pressure.
Sildenafil was patented in 1996 and approved for use in erectile dysfunction by the United States Food and Drug Administration (FDA) in 1998. It became available as a generic medication in December 2017. It is on the World Health Organization’s List of Essential Medicines.
How Sildenafil Works
Sildenafil works by targeting the biochemical pathway that regulates blood flow in the penis and lungs. Here’s a detailed explanation of its mechanism of action:
In Erectile Dysfunction
- Phosphodiesterase Type 5 Inhibition: Sildenafil specifically inhibits the enzyme phosphodiesterase type 5 (PDE5) located primarily in the corpus cavernosum of the penis, as well as in other tissues. This enzyme is responsible for breaking down cyclic guanosine monophosphate (cGMP).
- Increase in cGMP Levels: By inhibiting PDE5, sildenafil prevents the breakdown of cGMP, leading to an increase in its levels. cGMP is a substance that relaxes smooth muscle cells and allows blood vessels to dilate, a process known as vasodilation.
- Enhanced Blood Flow: The increased levels of cGMP result in the relaxation of smooth muscle cells in the blood vessels of the penis. This vasodilation leads to enhanced blood flow into the spongy tissue of the penis, causing an erection.
- Role of Sexual Stimulation: It’s important to note that sildenafil’s effectiveness requires sexual stimulation. The initiation of the erectile process starts with the release of nitric oxide (NO) during sexual arousal. NO activates an enzyme that produces cGMP. Sildenafil’s role is to sustain the levels of cGMP by inhibiting its breakdown, but the initial production of cGMP still depends on sexual arousal signals.
In Pulmonary Arterial Hypertension
- Vasodilation in the Lungs: Similar to its effect in the penis, sildenafil causes vasodilation in the pulmonary blood vessels by inhibiting PDE5 and increasing cGMP levels. This reduces the pressure in the pulmonary artery.
- Improved Oxygenation and Exercise Capacity: By lowering pulmonary arterial pressure, sildenafil improves the oxygenation of blood and reduces the effort required by the heart to pump blood through the lungs. This can lead to an improvement in exercise capacity and a reduction in symptoms of pulmonary arterial hypertension.
Medical Uses
Sildenafil has a variety of medical uses, both approved and off-label, stemming from its ability to relax blood vessels and improve blood flow. Below are the primary and some investigational uses of sildenafil:
Treatment of Erectile Dysfunction
- Primary Use: Sildenafil is primarily used to treat erectile dysfunction (ED). By inhibiting the enzyme phosphodiesterase type 5 (PDE5), it helps to increase blood flow to the penis during sexual stimulation, facilitating the achievement and maintenance of an erection.
- Effectiveness: It is effective for a broad range of causes of ED, including those related to diabetes, post-prostatectomy recovery, and spinal cord injury.
Pulmonary Arterial Hypertension (PAH)
- Approved Use: Sildenafil is approved for the treatment of pulmonary arterial hypertension, a condition characterized by high blood pressure in the arteries that supply the lungs. It works by relaxing the blood vessels in the lungs, which lowers pulmonary blood pressure and improves symptoms.
- Benefits: It improves exercise capacity and delays clinical worsening of the condition.
Off-label Uses and Research
- Raynaud’s Phenomenon: Sildenafil has been used off-label to treat Raynaud’s phenomenon, a condition where the fingers and toes become cold and numb due to constriction of blood vessels in response to cold or stress. Sildenafil can help by improving blood flow.
- High-Altitude Pulmonary Edema (HAPE): It is sometimes used to prevent or treat HAPE, a condition that can affect mountain climbers at high altitudes. Sildenafil, by dilating blood vessels, can help reduce pulmonary artery pressure and alleviate symptoms.
- Heart Disease: Research has explored the use of sildenafil for the treatment of heart diseases, including heart failure, because of its potential to improve blood flow and reduce the workload on the heart.
- Women’s Health Issues: Although its effectiveness is not well-established, some studies have looked into using sildenafil for women’s health issues such as female sexual arousal disorder. However, the evidence supporting its use for these conditions is mixed and more research is needed.
Investigational Uses
- Neonatal Conditions: There is ongoing research into the use of sildenafil for treating conditions in newborns, such as persistent pulmonary hypertension of the newborn (PPHN), though its safety and efficacy in this population require more evidence.
- Stroke Recovery: Some early research suggests sildenafil may have neuroprotective effects that could aid in stroke recovery, but more research is needed to confirm these findings.
Alternatives to Sildenafil
For those seeking alternatives to sildenafil for the treatment of erectile dysfunction (ED) or other conditions, there are several options available, ranging from other medications to non-pharmacological therapies. Here’s a look at some of the alternatives:
Other Phosphodiesterase Type 5 (PDE5) Inhibitors
- Tadalafil (Cialis): Known for its longer duration of action, tadalafil can be effective for up to 36 hours, offering a longer window of opportunity compared to sildenafil.
- Vardenafil (Levitra, Staxyn): Similar to sildenafil, vardenafil is used to treat ED but may have a slightly different side effect profile.
- Avanafil (Stendra): A newer PDE5 inhibitor with a fast onset of action, avanafil can start working in as little as 15 minutes.
Hormonal Therapy
- Testosterone Replacement Therapy (TRT): For men with ED caused by low levels of testosterone (hypogonadism), TRT can help improve symptoms along with ED.
Vacuum Erection Devices
- Penis Pumps: These devices create a vacuum around the penis, drawing blood into it and causing an erection. A ring is then applied at the base of the penis to maintain the erection.
Penile Injections
- Alprostadil (Caverject, Edex): This medication can be injected directly into the penis to induce an erection. It can also be used as a urethral suppository.
Surgical Options
- Penile Implants: Surgical implants can offer a permanent solution to ED when other treatments have failed. There are inflatable and malleable (bendable) types available.
Lifestyle Changes and Natural Remedies
- Exercise and Diet: Improving cardiovascular health through regular exercise and a healthy diet can help reduce ED symptoms.
- Psychotherapy and Counseling: For ED with a psychological cause, therapy can be beneficial in addressing anxiety, depression, or relationship issues.
- Herbal Supplements: Some people turn to herbal supplements like ginseng, L-arginine, or yohimbine, though evidence of their effectiveness varies and they’re not regulated like prescription medications.
Treatment for Pulmonary Arterial Hypertension (PAH)
- Endothelin Receptor Antagonists (e.g., bosentan)
- Prostacyclin Analogues (e.g., epoprostenol)
- Soluble Guanylate Cyclase (sGC) Stimulators (e.g., riociguat)
Other Considerations
When considering alternatives to sildenafil, it’s important to consult with a healthcare provider to determine the most appropriate treatment based on the individual’s health status, the cause of their condition, and potential side effects. What works best can vary significantly from person to person, and some treatments may not be suitable for everyone due to underlying health issues or interactions with other medications.