History: How Sildenafil Became a Medication
» Sildenafil first was synthesized in England by Brand company’s chemists. Their initial purpose was to study if sildenafil’s molecules have effect on systemic heart disease, more precisely, on its symptom - angina pectoris. The trials turned out to be in vain, but unexpectedly the chemists discovered that sildenafil was able to help men with erectile dysfunction. So, in 1996 the drug got the name Viagra and was since 1998 sold for treating impotence. Later its generic versions appeared and became widely used by men around the world.
Pharmacokinetics: How Sildenafil Acts in the Body
When taken orally, Sildenafil gets quickly absorbed and in one hour reaches its peak concentration, and at this moment its effectiveness is the highest. But these terms depend to some extent on the person’s metabolism. Sildenafil partially degrades due to liver’s work, and because of that only 40% of the substance stays in the body. Older patients or other people with hepatic problems experience stronger and 3,5 times more long-lasting effect of sildenafil. The drug remains in the blood approximately for 4 hours, after that liver and kidneys start bringing it out of the body.
Pharmacodinamics: How Sildenafil Works
The action of Sildenafil is based on its ability to elevate levels of cGMP in the smooth muscle cells, being a PDE5 (phosphodiesterase type 5) inhibitor. Phosphodiesterase type 5 destroys the bond of cGMP enzyme and makes it turn into GMP. The inhibitor reduces PDE levels in the penis, allowing cGMP to become more concentrated in the cytoplasm, thus relaxing the cells. Sildenafil analogues, such as vardenafil, avanafil, tadafil - act in the similar way.
When Does Sildenafil Help - Clinical Uses
Treatment of men’s erectile dysfunction. The drug relaxes the helicine arteries wall smooth cells, thus increasing diameter of the arteries and improving blood flow, which leads to corpus spongiosum and corpus cavernosum cells relaxation, preventing them from compressing urethra and making it easier to reach erection. If was also noticed that men who take sildenafil to treat impotence, also experience increase in testosterone levels. The studies showed that the drug may also influence central nervous system, helping serotonin and dopamine to release, thus helping men to be less nervous during sex.
Pulmonary hypertension. In case of acute form an increase of pressure in pulmonary arteries takes place. The chronic form may be idiopathic or accompany heart diseases, sickle cell disease, interstitial fibrosis, vasculitis, beta-talassemia, sleep apnea. Hypertension is the consequence of increased resistance in the arteries because of arteries cells’ proliferation and modification. Sildenafil makes arterial wall relax, thus decreasing arterial pressure. This also reduces load on heart, and heart failure symptoms improve. So, some doctors add sildenafil to the major therapies based on other treatment methods. But in very serious cases one should not count on sildenafil.
Muscular dystrophy. There are muscular dystrophies of different kinds, but they are often caused by lack of dystrophin - cytoskeletal protein. Sildenafil alleviates muscle ischemia and optimizes muscle perfusion. It increases synthesis of muscle protein and reduces fatigue in muscles.
Reducing negative consequences of Fontan procedure. Children, who have complex heart defects, sometimes go through surgical procedure that includes blood diversion to the pulmonary arteries from the right atrium, avoiding the morphologic right ventricle. But it is important that blood could flow easily in the lungs, and if this blood is pumped by the heart (which happens among children having high pulmonary vascular resistance), such children may feel themselves worse. Due to sildenafil’s vasodilator action, it is sometimes used to reduce the resistance and to stimulate pulmonary vessels’ blood circulation.
How Sildenafil Can Be Used in the Future
- Treatment of gastroenteritis. The idea is that sildenafil acts as a vasolidator, regulates ATP-sensitive potassium channels, and inhibits lipid peroxidation, thus reducing gastric damage induced by alcohol or Indomethacin assumption, clinical use of anti-inflammatory and non-steroidal drugs. The studies also showed the sildenafil’s ability to help in preventing different kind of colitis.
- Coping with obesity. Studies with mice showed that sildenafil can reduce pro-inflammatory hormones secretion, thus reducing the amount of unhealthy fat and turning it into healthier fat.
- Help for insulin-resistant patients in reducing vascular oxidative stress, by correcting hyperinsulinemia, hyperglycemia, and hypertriglyceridemia.
- Treatment of female infertility. Thanks to its vasodilator action, sildenafil can be used for ovulation induction and improvement of uterine blood flow, to provide a good endometrial texture and thickness and to make endometrium receptive enough.
- Dysmenorrea. Women suffering from menstrual cramps (moderate of severe) may find relief in sildenafil. In this case the drug is administered not orally but vaginally. The pain relief is reached by increasing blood flow to the uterus and dilating blood vessels.
- Scleroderma treatment. A chronic autoimmune disease, scleroderma is characterized by autoantibodies, vascular alterations, and fibrosis. It damages all organs by affecting arterioles in them. The smooth muscle cells and the endothelial cells degenerate, the tissues are substitute by fibrous material. It is still not known how to treat scleroderma, but it is possible to reach relief is some aspects, and sildenafil is helpful here.
» These positive effects of sildenafil are not studied enough yet, so the researches still have work to do before the drug can be used in the situation mentioned above.
Possible Side Effects
Like the majority of medications, sildenafil can cause a range of adverse effects, and the patient should be aware of them:
- Facial flushing (due to excessive blood flow in the face);
- Nasal congestion;
- Ophthalmic toxicity, which can lead to blurred vision, photophobia, ocular pain, conjunctival hyperemia, or altered color perception;
- Emesis (rare cases of post-coital vomiting).
This is not the full list of adverse effects. If your doctor prescribes you sildenafil, he must give you fuller information.
Contraindications and Precautions
Some patients should avoid taking sildenafil citrate in case of specific medical conditions or taking other drugs that are incompatible will sildenafil:
- Taking other drugs of treating erectile dysfunction.
- Taking nitrates, antihistamines, beta blockers, antihypertensives, diuretics, appetite suppressants, tranquilizers, and some other medications.
- Taking 3A4 inhibitors (Ritonavir, Nicorandil, grapefruit juice, etc.).
- Taking vitamin K antagonists (for example, coumarines and other drugs inhibiting coagulation), because of higher hemorrhagic risk.
- Cardiopathy (multiple system atrophy, aortic stenosis, hypotension): sildenafil can cause hypotension and put cardiopathic patients at risk, even risk of sudden cardiac death.
- Esophageal hypomotility: if such patients have to take sildenafil, they should drink much water with it, to reduce risk of esophageal ulcer.
- Aging: because of reduced hepatic activity, older people should take smaller dosages of sildenafil because of its stronger effect in them.
- Tendency to priapism.
Sildenafil – Widely Spread Drug Available Online
Sildenafil citrate is most widely known as a drug for treating erectile dysfunction (or impotence) among men – an active ingredient of famous generic Viagra and its more cheap but still high quality generic analogues. Medications with sildenafil as an active component are very popular nowadays and are widely sold in online pharmacies – Canadian, American, Australian, European, and others. If you are in search of medicines containing sildenafil, you can find them using our online service.