Viagra: History and Mechanism of Action
The drug Viagra is the brand name under which the Pfizer laboratory launched the active substance sildenafil. This drug is used to treat erectile dysfunction and pulmonary arterial hypertension.
Contrary to what many people may think, Viagra doesn’t work if there isn’t any sexual stimulation. Its effect is exclusively vasodilator and, therefore, it’s only indicated for the treatment of erectile dysfunction of this origin.
Some sports professionals have used Viagra in the belief that it could improve their blood flow in order to strengthen their muscles and, consequently, their sports performance.
Also, since it was released, Viagra has grown in popularity among young and middle-aged men. Due to its effects, it has led to recreational use, with people believing that the drug increases libido or improves the performance of the sexual act.
There is limited research on the effects it has when used by a patient without erectile dysfunction. However, it does suggest that the effect in these people is quite low.
On the other hand, there’s research that shows that a dose of 25 mg in these people doesn’t modify the erection. However, it can reduce the refractory time after ejaculation. A strong placebo effect was also demonstrated in the control group.
History of Viagra
The history of the discovery of Viagra is quite a well-known one in the world of science. Clinical trials were underway in Wales with sildenafil to treat high blood pressure and angina pectoris. During phase I studies, the drug was observed to produce a noticeable erection of the penis.
Because of this, it was the pharmaceutical company Pfizer decided to market it for the treatment of erectile dysfunction instead of treating angina. Viagra was finally patented in 1996 as the first drug for erectile dysfunction in the United States.
Also known as the “blue pill”, Viagra is sold by prescription, although attempts have been made to make it freely available in pharmacies. Its main competitors in the market are vardenafil / Levitra and tadalafil / Cialis.
Why does erectile dysfunction occur?
To understand how Viagra works a little better, it’s important to know about the condition it treats. Erectile dysfunction occurs when you have difficulty achieving or maintaining an erection. It’s usually more common as you get older, but it isn’t a natural part of this process.
Vascular and nervous mechanisms intervene in the erection, as well as hormonal factors. It’s the corpora cavernosa of the penis that’s responsible for taking blood to it, thus causing the erection. The causes of erection problems are divided into organic (90%) and psychic or nervous (10%).
Among the organic we can find:
- Diabetes: This causes the blood flow to the penis to decrease.
- Arterial hypertension: This is the second most frequent cause. It produces a peripheral vasoconstriction, making it difficult for blood to circulate to the penis.
- Altered or increased blood cholesterol: This causes the walls of the arteries to harden and, as a result, they don’t dilate enough to allow blood flow.
- Tobacco, alcohol, and drugs.
As for the psychological causes, we can mention the fear of failure, anxiety, stress, tension and nervousness. All of them have a negative influence, as they favor the production of adrenaline, a neurotransmitter that affects the heart rate and reduces the thickness of the arteries. Finally, there can also be mixed causes, both organic and psychic. We’ll now have a look at the following aspects about Viagra:
- Mechanism of action
- Pharmacokinetics
- Dosage
- Adverse reactions and contraindications
Viagra’s mechanism of action
Viagra belongs to a group of drugs called phosphodiesterase type 5 inhibitors. Phosphodiesterases are enzymes (a type of protein) that catalyze hydrolysis reactions in the body. Type 5 is only one of 11 that are currently known. This enzyme is found in cells of the aortic smooth muscle, heart, placenta, skeletal muscle, and, to a lesser extent, in the brain, liver, and lungs.
By inhibiting this enzyme, by means of some complex chemical mechanisms, the blood vessels of the penis dilate, favoring the flow of blood when sexually stimulated. As we’ve mentioned, Viagra doesn’t work if the patient doesn’t have adequate sexual stimulation.
Pharmacokinetics
Within this section, we’ll have a look at the following aspects: absorption, distribution, metabolism, and elimination.
Absorption
Here we’re referring to the process by which the active ingredient is absorbed by the body’s mucosa, and then passes into the bloodstream, in order to be distributed throughout the body. Sildenafil, after oral administration, is rapidly absorbed, with an absolute bioavailability of 40%.
It reaches its maximum concentration in plasma between 30 and 120 minutes after administration in the fasted state. Furthermore, we must take into account that when the drug is taken with food, the rate of absorption decreases. As a result, the time to reach peak concentrations is reduced by 29%.
Distribution
Sildenafil, and its main metabolite that we’ll look at later, N-dimethyl, are bound in a high percentage to plasma proteins (96%). This data is important, because, if it’s administered along with another drug that also binds to plasma proteins, they could interact. This would significantly increase the effects of Viagra, leading to toxic symptoms.
Metabolism
The term metabolism refers to the set of chemical reactions that the drug undergoes in the body in order to become more soluble in water to favor its elimination. In this way, Viagra is metabolized, mainly in the liver. This occurs thanks to the isoenzymes of the CYP 3A4 complex.
The main metabolite (the molecule resulting from metabolization reactions) is, as we’ve said, N-desmethyl. This molecule is also active, showing a selectivity for phosphodiesterases similar to the molecule of origin. However, its activity is reduced to approximately 50%.
Elimination
After being administered orally or intravenously, Viagra is mainly excreted and metabolized by feces. A smaller proportion, approximately 13%, is excreted in the urine. We must take into account that all these parameters may vary from one person to another, especially in the elderly and in patients with kidney or liver failure.
Dosage: how much and when to take it?
Viagra is administered orally. Depending on the population groups, the dosage of Viagra may vary:
- Adults: the recommended dose is 50 mg. It’s recommended to take it approximately one hour before sexual activity. The maximum recommended dose is 100 mg. However, it shouldn’t be taken more than once a day.
- Elderly: unlike many other drugs, this doesn’t require dose adjustment.
- Patients with renal insufficiency: when the insufficiency is mild or moderate, the dose for adults is maintained. If it’s severe, you might consider lowering it to 25 mg.
- Patients with hepatic impairment: the dose is normally reduced to 25 mg. However, based on efficacy and tolerance, the adult dosage can be maintained.
- Children and adolescents: Viagra isn’t recommended for this population group.
- Patients who are being treated with other medicinal products: With the exception of ritonavir (simultaneous administration is not recommended), an initial dose of 25 mg should be considered in patients receiving concomitant treatment with inhibitors of the isoenzyme CYP 3A4, since the concentrations of Viagra may be affected.
Adverse reactions and contraindications
Like all medicines, sildenafil can have side effects, although not everyone gets them. Adverse reactions observed with the use of this drug are generally mild to moderate in intensity and of short duration.
The most common side effect (1 person in 10) is headaches. Others are:
- Facial redness
- Dizziness
- Bleeding from the penis
- Muscle pain
- Fast or irregular heartbeat
- Fainting
Viagra is not recommended in patients allergic to the active principle or any other component of the formulation. Neither can it be taken if the patient is being treated with nitrates, as the combination can cause a dangerous drop in blood pressure. Nor can it be administered if the patient has a serious heart or liver problem. Other contraindications regarding the use of Viagra are:
- People who have suffered an ischemic stroke, heart attack, or have low blood pressure.
- Hereditary rare eye disease.
- If you have previously experienced a loss of vision due to optic neuropathy.
Remember, don’t take Viagra without a therapeutic purpose and without being under a prescription. Drugs are dangerous, so self-medication can cause serious problems, even death.