Indications PDE5 Inhibitors

The inability to consistently get or sustain an erection strong enough for satisfying sexual performance is known as erectile dysfunction (ED).1. Data from the Massachusetts Male Ageing Study indicate that up to 52% of men in the 40–70 age range suffer from ED.2. According to data from the National Health and Nutrition Examination Survey (NHANES) conducted in 2001–2002, 18.4% of American males aged 20 and above are thought to have ED.

Historically, the only options for treating ED were intracavernosal injections, intraurethral suppositories, prosthetic implants, and vacuum-constriction devices due to a poor understanding of the physiological basis of erections.4 The class of drugs known as type-5 phosphodiesterase (PDE5) inhibitors has transformed the treatment of ED since its introduction. As advised by the American Urological Association (AUA) and the European Association of Urology (EAU), PDE5 inhibitors are now the first-line treatment for ED.4, 5

The four oral PDE5 inhibitors that are marketed commercially in the United States are vardenafil (Levitra and Staxyn), tadalafil (Cialis); and avanafil (Stendra), which was approved more recently. This class’s expansion has made it possible to prescribe more freely in light of each patient’s unique response.

PDE5 Inhibitors inhibitors: what are they?

Targeted therapies such as phosphodiesterase 5 (PDE 5) inhibitors treat pulmonary hypertension (PH). Targeted treatments can even partially restore the damage to the heart and lungs while slowing the growth of PH.

PDE 5 inhibitors are being used to treat PH in two different ways:

Sildenafil (brand-named, as in Revatio, Viagra, and now “generic”)

Adcirca and now “generic,” or not branded, tadalafil.

Additionally, erectile dysfunction is treated with PDE 5 inhibitors. This is because the blood arteries in the lungs and the penis are made of the same type of cells in the body. Since 1998, erectile dysfunction has been treated with Viagra (sildenafil).

PDE 5 inhibitors are almost always given as pills.  For brief periods, such as during surgery, when a patient cannot eat or drink, sildenafil injections are available.

How Do Inhibitors of PDE5 Operate?

PDE5 inhibitors help the blood arteries relax and enhance blood flow in the penis by having a vasodilating action.

The principles of erection science

Getting an erection is a complicated procedure. You have a parasympathetic nervous system activation when you are stimulated sexually. Nitric oxide (NO), which is released as a result of this brain activity, stimulates the synthesis of cyclic GMP, another molecule.

Cyclic GMP boosts blood flow by 20–40 times by relaxing the smooth muscles inside your penis’ blood arteries. Trusted Source.

Cyclic GMP molecules are broken down by an enzyme called PDE5, reversing the erection process. PDE5 inhibitors, on the other hand, bind to PDE5 to prevent this breakdown and share a structure with cyclic GMP. This function serves to increase blood flow and strengthens the effects of NO.

Which PDE5 Inhibitors are the best?

Sildenafil

Sildenafil is sold under the brand name Viagra. Following clinical testing, it is said that the oral dosage of sildenafil is expected to have a 30-minute start to action and a one-hour maximum effect.

Nevertheless, this medication has a four-hour serum half-life. Furthermore, because this medication is a lipophilic molecule, taking a dose of it soon after eating a fatty meal decreases the effectiveness of sildenafil.

Here are several more Viagra substitutes, such as Cenforce 100mg.

Tadalafil

Tadalafil is available on the market under the brand names Adcirca and Cialis. One of the greatest treatments for benign prostatic hyperplasia and erectile dysfunction is the commercially available medication Cialis. One drug that is sold to treat pulmonary arterial hypertension is called Adcirca.

It has been demonstrated that tadalafil works as early as 16 minutes in. Furthermore, taking this medication right before or right after a fatty meal does not affect Tadalafil’s effectiveness. Here are several more Viagra substitutes, such as Vidalista 20.

Vardenafil

There are three brands of vardenafil available on the market: Levitra, and Staxyn. It’s one of the medications that’s suggested for treating erectile dysfunction.

Thirty to one hour is the recommended time to take vardenafil before sexual activity. Additionally, because it may impact the drug’s effectiveness, experts advise taking it one to two hours before or after meals. This medication takes five to seven hours to take effect.

Adverse Reactions

In general, all PDE5 inhibitors are well tolerated. They share a lot of adverse effects because their mechanisms of action are similar. While severe adverse effects need stopping medication and getting medical assistance right once, the majority of side effects are mild to manageable.

PDE5 inhibitor adverse effects that are frequently experienced include:

• Headache
• Lightheadedness
• Flushing
• Upset stomach
• Congestion in the nose
• Aches in the muscles
• Nausea (mostly when taking Levitra and Viagra)
• Backache (mostly after using Stendra, Staxyn, and Cialis)
• Bluish vision abnormalities (mostly after taking Viagra)

With dosage, adverse effects are more likely to occur and to be more severe. PDE5 inhibitors can quickly lower blood pressure and induce syncope, or fainting if used in excess.

Precautions and Contraindications

PDE5 inhibitors function by making more nitric oxide available in the circulation. PDE5 inhibitors and any organic nitrate drug that has the same effect should never be combined for this reason. A hypotensive crisis—a potentially fatal drop in blood pressure—can result from the combination.9.

Medications containing nitrates include:

• Nitroglycerin
• Amyl nitrate
• “Poppers” are alkyl nitrites.
• Monosodium isosorbide
• Dinitrate of isosorbide
• Nitroprusside sodium

Individuals with severe renal or liver illness may additionally need to stay away from PDE5 inhibitors: 9.

If you have a severe liver impairment (designated as Child-Pugh Class C), you should never take Cialis, Levitra, Staxyn (the dissolvable form of Levitra), or Stendra.

It is not recommended to use Levitra, Stanxyn, or Stendra if you are on kidney dialysis.

In both of these populations, 25 milligrams (mg) of Viagra is the lowest dosage that can be used.2.

In summary

For males with ED, PDE5 inhibitors are a significant first-line oral treatment option. The frequency of ED and its effects on health are extensive. Due to the upcoming shift in the oral PDE5 inhibitor market from brand to generic medications, cost will no longer be as much of a determining factor for patients and providers. While numerous data indicate that the four main PDE5 inhibitors are generally equally safe and effective, tadalafil has been recommended to be the better option when used appropriately, since it offers better efficacy in terms of instability and successful completion of sexual activity. Key elements in customizing therapy include adverse events (AEs), timing and duration of action, administration issues, precautions, and cost. A conversation between the patient and the physician focusing on comprehending the different qualities can help boost the likelihood of satisfaction when choosing an oral PDE5 inhibitor medication.