Sildenafil (Viagra) and Nitroglycerine are the mainstays of treatment for erectile dysfunction.
Sildenafil increases the sensitivity of contractile penile smooth muscle to calcium that causes increased blood flow to the penis and results in its erection, whereas Nitroglycerine is a muscle relaxant and a vasodilator; it increases blood flow to the deep artery of the penis and promotes erection.
Erectile dysfunction, formerly known as impotence, is a condition characterized by an erection that is not penetrative enough to have sexual intercourse (1). It is one of the most common sexual health concerns that are least talked about to avoid embarrassment, and the stress of not getting an erection worsens the condition.
Erectile dysfunction is the decreased contractility of penile smooth muscle due to reduced blood flow, factors being low cardiac output or fat blockage of penile arteries.
An erection occurs when muscles undergo relaxation, allowing blood to flow in (2). Sildenafil (Viagra) or Nitroglycerine are thought to be drugs used to treat erectile dysfunction (11).
Impotence may be physiological which is psychogenic and pathological, which occurs as a complication of cardiovascular diseases and should be treated accordingly.
Sildenafil and Nitroglycerin
Sildenafil or Viagra is orally effective with approximately 30 minutes duration of action and is capable of producing an erection that is penetrative enough (3). It should be taken 30 to 40 minutes before intercourse (4). The half-life of Viagra is between 2 to 4 hours. The side effects of Sildenafil are mainly due to its vasodilatory actions.
Common side effects of Viagra include: flushing, headaches, nasal congestion, impaired vision, increased intraocular pressure, photophobia, and prolong usage may cause priapism, a painful and lasting erection, heart attack, and ventricular arrhythmias (5).
Very rarely, but people do experience cyanopsia where everything appears to be tinged with blue; this is because Sildenafil is a phosphodiesterase inhibitor, and a similar enzyme is also present in the eye, known as phosphodiesterase 6, is also inhibited by it.
Inhibition of the enzyme in the eye makes rod cells ultra-sensitive at picking up blue-green light, resulting in a blue tinge (6).
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Nitroglycerine is given transcutaneously (7). When it is applied to the skin, it releases nitric oxides that expand blood vessels and increases blood flow. This is how the powerful, smooth muscle relaxant enhances erection.
The nitroglycerine gel is massaged on the head of the penis, and erection usually starts within 10 minutes and lasts between 30 to 60 minutes. Nitroglycerine is avoided to be given orally or sublingually for the treatment of erectile dysfunction because of its vasoactive nature.
Mechanism of Action
Although both drugs are used for erectile dysfunction, the mechanism by which they bring about erection is different.
Sildenafil works by protecting cyclic guanosine monophosphate (cGMP) from breakdown by inhibiting the phosphodiesterase-5 enzyme in the corpus cavernosum, and nitric oxide present in there increases the concentration of cGMP by binding with guanylate cyclase receptors (8).
This overall mechanism of action leads to smooth muscle relaxation, which, in turn, leads to vasodilation; this increases the blood inflow to penile arteries, causing an erection. If it is taken with a fatty meal, its absorption is reduced.
Sildenafil follows the hepatic route and is metabolized by cytochrome p450 enzymes, mainly by CYP450. The drug is excreted primarily in the feces and also in the urine, but to a lesser extent (9).
Nitroglycerin, on the other hand, works by dilating vessels. Venodilatation and smooth muscle relaxation lead to decreased preload, which reduces cardiac output, effective in treating high blood pressure (10).
Arteriolar dilatation leads to decreased peripheral resistance that lowers blood pressure (11). This allows blood to flow easily from the atherosclerotic sites.
Arteriolar dilatation also dilates vessels of the heart; this raises blood inflow to ischemic areas of the heart. Nitroglycerine is metabolized and is penetrated nitrates in the liver. Its metabolites are excreted in urine via the kidney.
Treatment of Pathological Erectile Dysfunction
Cardiovascular diseases, including atherosclerotic plaque, angina pectoris, and heart failure, either reduce blood supply to the heart or its pumping activity and leads to reduced blood supply to the rest of the arteries and eventually to organs.
Nitroglycerine is primarily used to treat heart failure and angina pectoris that is an ischemic heart. Due to ischemia, the heart is unable to pump blood to the body properly, and cavernous arteries might also be affected, resulting in erectile dysfunction.
Sildenafil vs. Nitroglycerine: Which One to Choose?
Nitroglycerine, being an effective vasodilator, increases coronary blood flow to the heart and every other part of the body via respective arteries; this includes deep arteries of the penis too.
In this way, nitroglycerine can treat pathologic erectile dysfunction, occurring as a complication of cardiovascular diseases, and is considered safe to be given to patients of cardiovascular diseases with erectile dysfunction (12).
All this might bring up with it some side effects due to prolonged use in the treatment; these side effects include throbbing headache, hypotension, and reflex tachycardia.
Sildenafil/Viagra, on the other hand, is considered good for treating patients of impotence without cardiac diseases and is avoided otherwise (13, 14).
Patients with low blood volume, low blood pressure, acute coronary ischemia, low cardiac output states, heart failure or even antihypertensive patients receive treatments which include drugs like Nitroglycerine and other vasodilatory drugs, are refrained from taking Sildenafil because these pharmacodynamically similar drugs can act synergistically together and cause blood pressure to drastically drop due to overwhelming vasodilation, eventually resulting in hypotension.
Sildenafil in Women?
Sildenafil, is, however, not approved to be used by women, but the drug has been seen taken by women with female sexual arousal disorder, loss of interest or decreased sex drive is common in women too.
The drug has also been found to be helpful to women; they have reported increased genital stimulation and satisfaction during intercourse (15).
Sildenafil and Nitroglycerine both drugs can be used to treat erectile dysfunction of pathologic and psychogenic causes. However, caution is needed to be taken in patients with cardiovascular diseases.
Being vasodilatory in action, the combination of these drugs is avoided to be introduced together as a result of their enhanced effect. Prolong penile muscle relaxation and vasodilation might treat Erectile dysfunction, but priapism can occur as a drug side effect.
Sildenafil produces a somewhat similar response in women, as they do in men. But Sildenafil is majorly used to treat erectile dysfunction. The correct treatment of erectile dysfunction, as the studies suggest, Sildenafil is suitable for patients without cardiovascular diseases, and Nitroglycerine is safe to be given to such patients (13, 14).
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