You have been a mess from the get-go on here!
* However, none of the PDE5 inhibitors are truly selective for the PDE5 receptor, and the majority of the negative effects are caused by cross-reactivity with other PDE isoenzymes.64
* Back pain and myalgias are caused by a high concentration of the PDE11 enzyme in skeletal muscle, which has a strong cross-reactivity with tadalafil.
[URL unfurl="true"]https://journals.sagepub.com/doi/10.1177/0976500X221129008#bibr64-0976500X221129008[/URL]
Synthetic PDE5 Inhibitors and Risk Factors Associated with Their Uses
PDE5 inhibitors are the primary line of treatment for ED patients.62 However, as PDE5 receptors are ubiquitous in the pulmonary vasculature, brain, lower urinary tract, and heart, PDE5 inhibitors are also an essential treatment option for pulmonary hypertension, neurological diseases, cardiomyopathy, and cancer.40, 41, 46, 47–49 ED has become a big concern, with recent predictions estimating that 320 million men will be affected by the disease by 2025.63 FDA-approved sildenafil, vardenafil, tadalafil, and avanafil, as well as non-FDA approved lodenafil, udenafil, and mirodenafil, are among the PDE5 inhibitors available (Figure 3).8, 64 However, none of the PDE5 inhibitors are truly selective for the PDE5 receptor, and the majority of the negative effects are caused by cross-reactivity with other PDE isoenzymes.64 The majority of these effects are dose-dependent.
Mild headaches, flushing, dyspepsia, altered color vision, back discomfort, myalgias, priapism, melanoma, hypotension and dizziness, rhinitis, nonarteritic anterior ischemic optic neuropathy (NAION), and hearing loss are some of the most prevalent side effects associated with the use of PDE5 inhibitors.64, 65 The presence of a high concentration of PDE6 enzyme in the rods and cones of the retina makes these cells a vulnerable target for PDE5 inhibitors causing altered color vision, particularly by sildenafil, which has a high affinity for blocking both PDE6 and PDE5. This effect has not been linked to any retinal structural or functional alterations.66, 67 Back pain and myalgias are caused by a high concentration of the PDE11 enzyme in skeletal muscle, which has a strong cross-reactivity with tadalafil. The FDA issued a warning on the possibility of hearing loss linked with PDE5I usage due to the pathophysiology that causes sensorineural hearing loss, which has been described in a few case studies.64 Additionally, using nitrates or nitroglycerin alongside PDE5 inhibitors increases the risk of hypotension. Vardenafil, tadalafil, and sildenafil have all been linked to longer QT intervals in ECGs, with vardenafil having the longest QT intervals, tadalafil having the shortest QT intervals, and sildenafil having intermediate QT intervals. Patients taking PDE5Is should wait at least 1–2 days following their last PDE5I dose before taking nitrates, according to the American College of Cardiology.63, 68 Erythromycin and HIV protease inhibitors are two examples of medications that interact with PDE5 inhibitors since they share the same metabolic pathway.68
