BERKELEY, CA (UroToday.com) - Phosphodiesterase (PDE) is the enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP) and cyclic adenine monophosphate (cAMP) to GMP and AMP, respectively.
There are at least 11 isoenzymes of PDE in the body, and this may have therapeutic implications for a wide variety of conditions.
Sildenafil (Viagra) is an inhibitor of PDE type 5 (PDE5) and, to a lesser degree, PDE type 6 (PDE6). Other PDE5 inhibitors include vardenafil (Levitra) and tadalafil (Cialis). Sildenafil has been the most extensively studied PDE5 inhibitor. Inhibition of PDE5 by sildenafil increases the levels of cGMP, which causes smooth-muscle relaxation of the corpora cavernosa and penile arteriolar smooth muscles. This relaxation leads to a drop in arterial resistance and increases blood flow into these tissues. In addition to the vasculature of the penis, PDE5 was found in the lungs. The relaxing effect of sildenafil on arterial smooth muscles has extended its use to involve the treatment of pulmonary arterial hypertension (PAH). Recent studies have shown promising results of this drug in the management of PAH secondary to underlying lung diseases, such as chronic obstructive pulmonary disease (COPD). Sildenafil is being investigated for the treatment of acute myocardial infarction in humans and acute stroke in animal models.
This class of drugs affects the systemic vasculature causing transient hypotension, headache, flushing, dyspepsia, and nasal congestion. These drugs are contraindicated in patients taking nitrates because they cause a critical drop in blood pressure.
It is well documented that PDE5 inhibitors are associated with mild, transient visual symptoms. The most common visual symptoms that have been linked to PDE5 inhibitors include changes in color perception, characterized by a blue tinge to the environment, and changes in brightness perception, usually in the form of increased sensitivity to light. These symptoms occur in 3 to 11% of sildenafil (25 to 100 mg) users, 0.3 to 2% of vardenafil users, and 0.1% of tadalafil users. These symptoms are mild, dose dependent, and completely reversible. On the other hand, serious ocular complications associated with PDE5 inhibitors have been previously reported. These complications include nonarteritic anterior ischemic optic neuropathy (NAAION) with attendant vision loss; cilio-retinal artery occlusion; central retinal vein occlusion; and pupil-sparing, third-nerve palsy.
NAAION—the most commonly reported serious complication—is divided into anterior and posterior. NAAION is the most common acute optic neuropathy in people older than 50. It has an annual incidence of 2.3 to 10.2 per 100 000 adults aged over 50 in the United States. In the postmarketing safety database, events suggestive of NAAION were reported at a rate of 0.8% (333/39 277); i.e., similar to the incidence of NAAION in the general population. As of March 2006, the FDA's Adverse Event Reporting System had accumulated 43 cases of NAION in PDE5 inhibitor users. Thirty-eight cases were associated with sildenafil use, 4 with tadalafil, and 1 with vardenafil.
We conducted a critical search for case reports in peer-reviewed English literature involving vision-threatening ocular complications in relation to the use of PDE5 inhibitors (using Medline, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Library, Global Health, and MD Consult) between January 2006 and 2011. We identified 8 papers that reported vision-threatening ocular complications in relation to the use of PDE5 inhibitors. Vision-threatening ocular complications discussed in these case reports included NAAION, both anterior and posterior (NAAION and PION), optic atrophy, CRVO, cilio-retinal artery occlusion, and acute-angle closure glaucoma.
In order to analyze and assess the cause and effect relationship between the reported adverse drug reactions and the offending drug, we applied both the World Health Organization (WHO) Probability Scale and the criteria utilized by the National Registry of Drug-Induced Ocular Side Effects. Incomplete fulfillment of the criteria attributing vision-threatening adverse effects to PDE5 inhibitors was found.
The rarity of vision-threatening adverse effects in PDE5 inhibitor users, the wide use of PDE5 inhibitors, and the incomplete fulfillment of the criteria attributing vision-threatening adverse effects to PDE5 inhibitors provide evidence that PDE5 inhibitors are not vision threatening. Men who use PDE5 inhibitors appear to suffer vision-threatening complications at the same frequency as the general population. However, minor visual adverse effects occur in up to 11% of users, and they are transient and reversible.
Written by:
Faris Azzouni and Khawla Abu Samra as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
