Hepatotoxicity following separate administration of two phosphodiesterase-5 inhibitors (sildenafil and tadalafil) and opioid (tramadol); evaluation of possible reversal following their withdrawal

Victor Nna,Ubom Akpan,Victoria Okon,Item Atangwho

doi:10.7324/japs.2015.50817

Abstract

The use of phosphodiesterase-5 inhibitors (PDE5i) and tramadol in the absence of erectile and ejaculatory dysfunctions in Nigeria has become a norm. In this study, we comparatively assess the effects of chronic use of these drugs on hepatotoxicity. Fifty male albino wistar rats weighing 180–200g were randomly assigned into 5 groups (n=10) as follows; control, sildenafil (1mg/100g b.w), tadalafil (1mg/100g b.w), tramadol (2mg/100g b.w) and sildenafil+tramadol treated group (1mg/100g and 2mg/100g b.w, respectively). Drugs were orally administered, once, every two days for 8weeks, at the end of which five animals were sacrificed per group (batch 1), while the remaining five animals per group were allowed for another 8weeks without drug administration (batch 2). Serum concentration of liver enzymes (AST, ALT and ALP) and bilirubin were assessed in both batches. Serum concentrations of AST, ALT, ALP, total bilirubin and unconjugated bilirubin were significantly (p

Highlights

Sildenafil citrate and tadalafil are widely used for treatment of erectile dysfunction (ED) of various etiologies (Nurnberg et al, 2001; Benchekroun et al, 2003; Gopalakrishnan et al, 2006; Kokkinos et al, 2015)
Serum concentrations of aspartate transaminase (AST) and alanine transaminase (ALT) were significantly reduced in sildenafil (p
These drugs belong to a class of drugs called phosphodiesterase-5 inhibitors (PDE5i), owing to their potent and selective inhibition of phosphodiesterase type 5 enzyme that breaks down cyclic guanosine monophosphate (Boolell et al, 1996)

Summary

Introduction

Sildenafil citrate (common name–viagra) and tadalafil (common name–cialis) are widely used for treatment of erectile dysfunction (ED) of various etiologies (Nurnberg et al, 2001; Benchekroun et al, 2003; Gopalakrishnan et al, 2006; Kokkinos et al, 2015). It is conceivable that there are other side effects which may not be discernible like headache and stomach pain, but may be serious enough to affect one’s health. It is against this backdrop that the present study seeks to ascertain the effect of chronic use of these drugs (sildenafil, tadalafil and tramadol) on hepatotoxicity, since the liver will be constantly bombarded with large concentrations of these medications. The present study investigates the possibility of reversal of hepatotoxicity following the withdrawal of these drugs

Methods

Results

Discussion

Conclusion