Phosphodiesterase Inhibitors in Clinical Urology - An Overview

What Are Phosphodiesterase Inhibitors?

Phosphodiesterase inhibitors are a class of drugs that widen the blood vessels and allow the relaxation of smooth muscles in the heart, lungs, and genitals. Phosphodiesterase are a group of enzymes that play an essential role in regulating the release of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). These are "second messengers" regulating the primary effects of cells, hormones, and neurotransmitters. As the name suggests, these phosphodiesterase inhibitors work by inhibiting the phosphodiesterase enzymes. As a result, the levels of cAMP and cGMP increase, resulting in a decrease in calcium levels, which leads to vasodilation and smooth muscle relaxation.

What Are the Different Types of Phosphodiesterase Inhibitors?

Phosphodiesterase inhibitors are classified based on the phosphodiesterase enzymes they target. There are 11 types of phosphodiesterase enzymes, and there are different inhibitors for each of them. The different types of phosphodiesterase inhibitors are listed below:

• Phosphodiesterase 5 inhibitors (PDE 5) - They specifically target the penis and work by increasing the cGMP levels. They relax the smooth muscles, widen the blood vessels, and are used to treat erectile dysfunction.

• Phosphodiesterase 4 inhibitors (PDE 4) - They work by increasing cAMP levels and target the immune system, brain, skin, and lungs. Therefore, they are useful in the treatment of asthma, chronic obstructive pulmonary disease, psoriasis, and rheumatoid arthritis.

• Phosphodiesterase 3 inhibitors (PDE 3) - They are typically used for cardiac diseases and work by increasing cAMP levels. They inhibit platelet aggregation and increase the heart’s ability to pump blood. Therefore, they can be used to treat heart failure and other cardiac diseases.

• Nonspecific Inhibitors - They decrease the destruction of cAMP by phosphodiesterase enzymes, which cause phosphodiesterase enzymes, which cause bronchodilation and reduce inflammation of the airways.

What Is Clinical Urology?

Clinical urology is a branch of medicine that deals with studying conditions affecting the male and female urogenital tract. Urology addresses the problems of the urinary tract and the reproductive organs like the testes, ovaries, penis, scrotum, and prostate. Doctors who specialize in the field of urology are known as urologists. Clinical urology is similar to urology and deals with its practical applications. A urologist is trained to diagnose, detect, and treat conditions affecting the kidneys, bladder, ureters, and urethra. In males, a urologist might also resolve problems with the testis, scrotum, and penis. In contrast, the urologist deals with female reproductive organ issues such as the vagina, cervix, and other reproductive organs. Sometimes, the urologist might need to work with a radiotherapist and an oncologist to treat urinary cancer. Many advancements have been made in urology in recent years for the benefit of people.

Are Phosphodiesterase Inhibitors Used in Urology?

Phosphodiesterase inhibitors are used in urology to treat erectile dysfunction. Erectile dysfunction, or impotence, is a condition in which males are unable to keep an erection firm enough for sexual intercourse. The exact cause of erectile dysfunction is still unknown, but this condition was first noticed over 2000 years ago. During that time, not enough medical resources were available to diagnose it. However, with the advancement in medical science, researchers have been able to decipher the exact causes of this condition. Earlier, the treatment of erectile dysfunction was limited to arterial injections or intraurethral agents. But the discovery of oral medications has revolutionized the treatment of erectile dysfunction. Phosphodiesterase inhibitors are oral medications used to treat erectile dysfunction in urology.

What Is Erectile Dysfunction?

Erectile dysfunction is a common issue associated with the penis. The penis is one of the most crucial organs of the male reproductive system. During puberty, the penis develops completely and reaches its maximum size. The penis is attached to the urinary bladder through the urethra, allowing urine to leave the body. The penis contains spongy tissues that receive blood and increase in size. When the person is doing his normal activities, the arteries that supply blood to the penis are only partially open. However, when the person is sexually stimulated, the brain commands the arteries to open completely. The problem arises when medical conditions like atherosclerosis, heart disease, diabetes, and high cholesterol levels interfere with the mechanism of sexual arousal. As a result, the penis fails to remain erect for a prolonged period of time, and the patient suffers from erectile dysfunction.

Which Phosphodiesterase Inhibitors Are Used in Urology?

The phosphodiesterase inhibitors can be categorized into 11 different types based on their constituents. The tissues present in the human body express different types of phosphodiesterase enzymes. Certain enzymes are present in the blood vessels and smooth muscles of the penis that regulate erections. The problem arises when these enzymes are defective. In such cases, phosphodiesterase inhibitors come into action and aid in penile erections. The American Urological Association recommends the following phosphodiesterase inhibitors to treat urinary tract problems:

• Sildenafil - It was the first oral phosphodiesterase inhibitor used in the treatment of erectile dysfunction. Sildenafil gets activated after absorption, which accounts for its 20 percent pharmacological activity. People taking Sildenafil must avoid having a high-calorie diet because it slows down drug absorption. The clearance rate of this drug was noted to be high in males aged 65 or above. Therefore, it is recommended that males over 65 years of age and suffering from erectile dysfunction take only 25 mg of the drug an hour before sexual activity. Studies have reported that Sildenafil improves sexual activity and erections in 45 to 80 percent of males. Also, people suffering from depression after having reduced sexual functions have benefited a lot from phosphodiesterase inhibitors. The side effects of Sildenafil are headaches, flushing, abdominal problems, and abnormal vision.

• Vardenafil - Vardenafil is a type of phosphodiesterase inhibitor that was approved by the Food and Drug Administration in 2003 to treat erectile dysfunction. Vardenafil’s chemical structure is similar to that of Sildenafil, but there is a difference in the effectiveness of both drugs. Vardenafil is tolerated by both healthy people as well as those suffering from erectile dysfunction. During the clinical trials, 20 percent of patients reported side effects like headaches and flushing.

• Tadalafil - Tadalafil is a potent phosphodiesterase inhibitor that was approved by the Food and Drug Administration (FDA). The American Urological Association recommended it be used as a first-line treatment for erectile dysfunction. Tadalafil’s chemical structure is completely different from Vardenafil and Sildenafil, and the drug mainly works on the phosphodiesterase enzymes present in the muscle, prostate, kidney, liver, testes, and pituitary gland. Therefore, patients might experience headaches, back pain, and myalgia. According to the FDA, the daily dosage of Tadalafil must lie between 2.5 and 5 mg. The patient must also avoid the consumption of fatty foods and alcohol after these drugs as they slow down drug absorption.

• Avanafil - Avanafil is the newest phosphodiesterase inhibitor that was approved by FDA in 2012. During the clinical trials, it was discovered that Avanafil is fast-acting and causes minimal side effects. The drug was found to be effective in 45 to 77 percent of males.

What Are the Side Effects of Phosphodiesterase Inhibitors?

During the clinical trials, some patients presented with side effects due to phosphodiesterase inhibitors as they interfere with the body's chemical reactions. The side effects of phosphodiesterase inhibitors are listed below:

• Headache.

• Nasal congestion.

• Dyspepsia (pain or discomfort in the upper abdominal region).

• Flushing (skin becomes red and hot).

• Priapism (a painful erection that lasts for more than four to six hours).

• Vomiting, nausea, and diarrhea.

• Restlessness.

• Hypotension (reduced blood pressure).

• Ventricular arrhythmia (irregular heartbeat).

• Stomach problems.

Conclusion:

Phosphodiesterase inhibitors are drugs that work to stop the activity of phosphodiesterase enzymes. They target the enzymes in the heart, lungs, liver, and kidneys to dilate the blood vessels and relieve muscle cramps. They have also been shown to have a beneficial impact on people suffering from lower urinary tract diseases. Studies have also suggested that when phosphodiesterase inhibitors are used along with testosterone therapy, males have been able to replenish their testosterone levels. In urology, the primary aim of phosphodiesterase inhibitors is to resolve erectile dysfunction. As cases of erectile dysfunction have increased over the past few years, phosphodiesterase inhibitors have shown a wide spectrum of activity. Today, people prefer phosphodiesterase inhibitors over other treatments because they can be taken orally, and the patient is spared surgical trauma. Consult the doctor to know more about the treatment of erectile dysfunction.