PDE5 Inhibitor drugs - Benefit and side effects of PDE5 Inhibitor drugs and their safety, danger
Feb 28 2014

The PDE-5 inhibitors sildenafil (Viagra) vardenafil (Levitra) and tadalafil (Cialis) are erectile dysfunction drugs have been taken by tens of millions of men as an erectile dysfunction treatment. There have been dozens of cases of nonarteritic anterior ischemic optic neuropathy (NAION) described in patients using PDE5 Inhibitor drugs. NAION is a common optic neuropathy in patients in the age group using these drugs and the question arises whether or not PDE-5 inhibitors are causing NAION. There is some evidence to support PDE-5 inhibitors as a cause of NAION. PDE-5 inhibitors probably are a cause of a common ischemic disorder of the optic disc. PDE5 Inhibitor must be avoided in men who have already experienced NAION in one eye. Patients should be warned to seek medical attention if they have visual field or acuity loss after using PDE-5 inhibitors. Icariin is a natural PDE5 inhibitor found in the the plant Horny-Goat-Weed.

PDE 5 inhibitors and MDMA
Phosphodiesterase 5 PDE 5 inhibitors prevent 3,4-methylenedioxymethamphetamine-induced 5-HT deficits in the rat.
J Neurochem. 2009. Department of Pharmacology, School of Medicine, University of Navarra, Pamplona, Spain.
PDE5 inhibitors are often used in combination with club drugs such as 3,4-methylenedioxymethamphetamine (MDMA or ecstasy). We investigated the consequences of such combination in the serotonergic system of the rat. Oral administration of sildenafil citrate (1.5 or 8 mg/kg) increased brain cGMP levels and protected in a dose-dependent manner against 5-hydroxytryptamine depletions caused by MDMA (3 x 5 mg/kg, i.p., every 2 h) in the striatum, frontal cortex and hippocampus without altering the acute hyperthermic response to MDMA. IOur data show that the protective effect of sildenafil can be extended to vardenafil, another PDE5 inhibitor. Sildenafil protects against MDMA-induced long-term reduction of indoles by a mechanism involving increased production of cGMP and subsequent activation of PKG and mitochondrial ATP-sensitive K(+) channel opening.

Which PDE5 inhibitor to use?
Tadalafil and vardenafil vs sildenafil: a review of patient-preference PDE5 inhibitor studies.
BJU Int. 2009. Mirone V, Fusco F, Rossi A, Sicuteri R, Montorsi F. Ely Lilly Italy, Florence, Italy.
The immediate objective of PDE5 inhibitor treatment is to restore the ability of a man to achieve and/or maintain an erection adequate for sexual intercourse. The therapeutic success of PDE5 inhibitor drugs has an important subjective component, which is compounded by the subjective nature and complexity of sexual life in humans. PDE5 inhibitor drugs are typically used twice a week, so a patient would have to spend approximately 3 months trying the various compounds and dosages to achieve adequate exposure to all three PDE5 inhibitors; this would seem an unrealistic strategy in normal clinical practice. The acknowledgement that the patient has an important role in therapeutic decisions for ED has fuelled interest in the concept of patient preference. It has been established that patient preference depends on three factors, i.e. personal characteristics, e.g. age, duration of ED, frequency and dynamics of sexual relations, and the characteristics of their partners, e.g. age, menopausal status and level of interest in sexual activity and medication profile. Medication features of interest include efficacy in terms of quality of erection, consistency of effects, rapid onset of action, long duration of action, side-effect profile and route of administration; drug costs must also be considered if the medicinal product is not reimbursed.

Efficacy and safety of tadalafil for erectile dysfunction: an updated review
Zhonghua Nan Ke Xue. 2009; Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
As a long-acting phosphodiesterase type 5 (PDE5) inhibitor, tadalafil is administered orally as the first line therapy for erectile dysfunction (ED). Its efficacy and safety have been confirmed by many clinical studies in the treatment of ED in general patients, elderly patients and those with diabetes mellitus or spinal cord injury or after prostate cancer surgery. With its prolonged action of 36 hours, tadalafil can not only increase the self-esteem of ED men but also improve the quality of life of both the patients and their partners.

Use in Peyronie's disease
Treatment of Peyronie's disease with PDE5 inhibitors: an antifibrotic strategy.
Nat Rev Urol. 2010. Gonzalez-Cadavid NF, Rajfer J.Department of Urology, David Geffen School of Medicine at UCLA, and Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Building F-6, 1124 West Carson Street, Torrance, CA, USA.
Peyronie's disease is a localized fibrotic condition of the tunica albuginea that is associated with risk factors for corpora cavernosa fibrosis (such as advanced age and diabetes) and Dupuytren contracture, another localized fibrotic process. Most of the current pharmacological treatments for PD are not based on antifibrotic approaches that have shown promising results in animal models and clinical efficacy in other fibrotic conditions, which may explain why they are generally unsuccessful. Evidence gathered in human specimens and animal models of PD have elucidated aspects of its etiology and histopathology, showing that overexpression of transforming growth factor beta1, plasminogen activator inhibitor 1, reactive oxygen species and other profibrotic factors, which are, in most cases, assumed to be induced by trauma to the tunica albuginea, leads to myofibroblast accumulation and excessive deposition of collagen. At the same time, a steady overexpression of inducible nitric oxide synthase, leading to increased nitric oxide and cGMP levels, seems to act as an endogenous antifibrotic mechanism. This process has also been reported in corporal and cardiovascular fibrosis, and has led to the demonstration that long-term continuous administration of phosphodiesterase type 5 inhibitors counteracts the development of a PD-like fibrotic plaque in a rat model, and later extended to the prevention of corporal fibrosis in animal models of erectile dysfunction.

Eur J Heart Fail. 2013 Dec 31. Additional use of a phosphodiesterase 5 inhibitor in patients with pulmonary hypertension secondary to chronic systolic heart failure: a meta-analysis.