The active ingredient sildenafil has been marketed since 1998 by the American pharmaceutical company Pfitzer under the well-known brand name Viagra as a drug for erectile dysfunction. Sildenafil is also a component of various generic drugs and has been used since 2006 under the name Revatio as a treatment for pulmonary arterial hypertension.
What is sildenafil?
The active ingredient sildenafil is marketed by Pfitzer under the brand name Viagra as a drug for erectile dysfunction. Sildenafil is a synthetically produced so-called PDE-5 inhibitor. Drugs of this substance class (other examples are tadalafil and vardenafil, the active ingredients of the sexual enhancers Cialis and Levitra ) intervene in the regulation of the tone of the smooth muscle of the vascular walls and have a vasodilatory effect. Their action is based on the blocking of the cGMP-cleaving enzyme phosphodiesterase type 5 (PDE-5), which underlies both the potency-increasing and the blood pressure-lowering effects of sildenafil. Drugs containing sildenafil are available by prescription in Germany.
Pharmacologic effects
Regulation of blood pressure at the level of vascular smooth muscle, particularly in the pulmonary circulation and penis, is characterized by the interplay between the neurotransmitter nitric oxide (NO) and the enzyme phosphodiesterase 5 (PDE-5). Release of NO at nerve endings near blood vessels stimulates synthesis of the nucleotide cGMP (cyclic guanosine monophosphate cGMP is a relative of the universal energy molecule ATP). cGMP ultimately causes smooth muscle relaxation via another signaling cascade, thus dilating the cross-section of blood vessels. The blood pressure drops. During sexual arousal, this mechanism enables the corpus cavernosum of the penis to be filled with rapidly inflowing blood and thus contributes significantly to the development of an erection. The regulatory counterpart of NO is PDE-5, which breaks down cGMP again and thus promotes renewed constriction of the vessel walls. PDE-5 is often too active in men with hypertension and/or erection problems. When the enzyme is blocked by sildenafil, cGMP levels increase. This generally has a blood pressure lowering effect. The duration and strength of an erection are positively influenced by sildenafil.
Medical use and application
Sildenafil is used medicinally in the treatment of erectile dysfunction as well as hypertension. For erectile dysfunction, the drug is taken as needed – but not without first consulting with a doctor. The typical dose is between 25 and 100 milligrams, depending on the severity of the disorder. Sildenafil takes effect within about two hours and is active in the body for up to 10 hours after ingestion. An erection that develops can be effectively stabilized by the active ingredient within this period. Sildenafil alone does not trigger an erection – sexual arousal as well as intact mechanisms of NO release and cGMP synthesis are prerequisites for the effectiveness of drugs containing sildenafil. If sildenafil is prescribed for regular use as an antihypertensive, a dose of about 60 milligrams is usually distributed throughout the day.
Risks and side effects
The type and extent of side effects experienced by users of sildenafil vary from individual to individual. Most of these side effects are related to the vasodilator effect of the active ingredient. Sildenafil remains completely free of side effects for only about one-fifth of users. Headaches, stuffy or runny nose, facial flushing, stomach and digestive complaints, sweating and hot flashes, back and limb pain are common side effects. Rarely, users also complain of dizziness, delayed reaction time, or visual disturbances. Another side effect may be the undesirable persistence of an erection. These effects are not worrisome and subside within one to two days. Occasionally, hearing loss, i.e. sudden hearing loss, has occurred in regular users of high doses of sildenafil. Also very rarely, hypoxia of the optic nerve due to a severe drop in blood pressure in the eye (anterior ischemic optic neuropathy) has occurred, resulting in partial or complete loss of vision. However, these complications occurred only in men with additional risk factors for such damage.Since sildenafil lowers blood pressure, taking other blood pressure-lowering drugs or medications can cause a life-threatening drop in blood pressure. This is true for the scene drug amyl nitrite, known as poppers, and especially for nitrate-containing agents such as nitroglycerin, which are used in emergency medicine for heart failure.
