Dose-dependency and Time-course of Electrophysiologic Short-term Effects of VIAGRA®: A Case Study

Abstract

The dose-dependency and time-course of the short-term visual effects of sildenafil citrate (VIAGRA) were tested in two subjects. Blood pressure was measured and samples of blood taken at 30 min intervals before and after drug administration. In the first experiment, prolongations of the implicit times of the scotopic maximum a-wave, cone a- and b-wave, 33 Hz flicker, ON-response a- and b-wave and 3.3 Hz a- and b-wave electroretinogram (ERG) recordings and of the oscillatory potentials OP1, OP2, and OP3 were observed for both eyes of both subjects, following 100 or 200 mg dosings. Interestingly, no prolongation was found for OP4, to which the OFF-bipolar cell pathway significantly contributes. In the second experiment, in which visual function was repeatedly assessed following a 200 mg dose, similar prolongations were found in both eyes of one subject for the implicit times of the oscillatory potential OP2, the cone b-wave response and the 3.3 Hz a-wave. Moreover, the steady-state (A0) and immediate extinction (B0) blue target thresholds of transient tritanopia were raised relative to the pre-drug administration baseline effects. While the maximum lowering of both systolic and diastolic blood pressure approximately correlated with the peak plasma concentration of sildenafil (c. 30-60 min after administration), the peak magnitudes of most visual effects were found at c. 110 min, consistent with a second compartment kinetic.

Retinal Effects of 6 Months of Daily Use of Tadalafil or Sildenafil

“…[29][30][31][32] The most consistent finding has been a reversible prolongation of b-wave implicit time in the cones (rods may be affected also). 29 This is evident in both full-field and multifocal ERG, and in the a-wave of the dark-adapted combined standard response.…”

ERG evaluation of daily, high-dose sildenafil usage

“…PDE-6 is a critical regulator of the photoreceptor transduction cascade. Human ERG studies have shown mild and somewhat variable reductions in full-field and mfERG amplitude in subjects after a single, large dose of sildenafil [4][5][6]. The most consistent finding has been a modest increase in cone b-wave implicit time.…”

“…The most consistent finding has been a modest increase in cone b-wave implicit time. Oscillatory potentials may be delayed as well [4].…”

“…Furthermore, although the drug half-life is typically listed as 3-4 h, some physiological and visual effects may persist longer so that a longer clearance period would have been desirable [4,17]. That was not feasible in this clinical study because of respiratory discomfort.…”

“…Sporadic vascular and optic nerve complications have been reported, although these may not directly reflect toxicity [2,3]. Sildenafil can cause transient, mild electroretinogram (ERG) changes in healthy individuals taking large single doses (e.g., 100-200 mg) [4][5][6]. Since it has now been approved for chronic use in subjects with pulmonary arterial hypertension (PAH) [7] and is being explored for other chronic systemic indications [8,9], it is reasonable to ask whether sustained high-dose exposure might cause retinal dysfunction or damage.…”