sildenafil-citrate and Esophageal-Achalasia

Esophageal motility disorders are a group of disorders associated with dysfunctional swallowing resulting from impaired neuromuscular coordination. Phosphodiesterase 5 (PDE-5) inhibitors induce smooth relaxation and are proposed as a treatment option for esophageal motility disorders such as achalasia.. This study is conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We systematically searched MEDLINE/ PubMed, Scopus, EMBASE, and Web of Science databases for esophageal outcomes of individuals treated with PDE5 inhibitors. A random effect meta-analysis was conducted.. A total of 14 studies were included. They were conducted in different countries, with Korea and Italy having the highest number of articles. The main drug assessed was sildenafil. PDE-5 inhibitors resulted in a significant reduction in lower esophageal sphincter pressure (SMD - 1.69, 95% CI: -2.39 to -0.99) and the amplitude of contractions (SMD - 2.04, 95% CI: -2.97 to -1.11). Residual pressure was not significantly different between the placebo and sildenafil groups (SMD - 0.24, 95% CI: -1.20 to 0.72). Furthermore, a recent study reported contractile integral, stating that ingestion of sildenafil leads to a significant reduction in distal contractile integral and a significant increase in proximal contractile integral.. PDE-5 inhibitors significantly reduce LES resting pressure and esophageal peristaltic vigor, decreasing esophageal body contractility and contraction reserve. Therefore, using these drugs in patients affected by esophageal motility disorders may potentially improve their condition regarding symptom relief and prevention of further associated complications. Future reports investigating larger sample size is necessary in order to establish definite evidence regarding the efficacy of these drugs.

Topics: Cyclic Nucleotide Phosphodiesterases, Type 5; Esophageal Achalasia; Humans; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Achalasia is a primary esophageal disorder involving the body of the esophagus and lower esophageal sphincter affecting equally both genders and all ages. While its etiology remains unclear, the pathophysiologic mechanism involves the destruction of the myenteric plexi responsible for esophageal peristalsis. Given the slow, initially oligosymptomatic progression and relative low prevalence of disease, achalasia can remain undiagnosed for years. In terms of diagnosis, esophageal manometry is the gold standard to diagnose achalasia. Still, its role in post-treatment surveillance remains controversial. Radiological studies support the initial diagnosis of achalasia and have been proposed for detecting pre-clinical symptomatic recurrence. Although endoscopy is considered to have a poor sensitivity and specificity in the diagnosis of achalasia, it has an important role in ruling out secondary causes of achalasia (i.e. pseudoachalasia). With respect to treatment, laparoscopic myotomy and pneumatic balloon dilatations of the lower esophageal sphincter are considered definitive treatments for achalasia. Both treatment options offer sustained clinical responses, with head-to-head trials being currently underway. Botulinum toxin injection in the lower esophageal sphincter is considered an acceptable alternative in patients who are not candidates for surgery or balloon dilatation or as proof of concept in difficult to diagnose patients. Pharmacologic therapies for achalasia offer mild, transient improvement at best. In summary, diagnosis achalasia requires shrewd history taking and dedicated esophageal testing. In experienced hands, treatment of achalasia can provide long-term sustained clinical improvement.

Topics: Adult; Age Factors; Aged; Barium Sulfate; Botulinum Toxins, Type A; Calcium Channel Blockers; Catheterization; Controlled Clinical Trials as Topic; Esophageal Achalasia; Female; Humans; Incidence; Male; Manometry; Meta-Analysis as Topic; Middle Aged; Neuromuscular Agents; Phosphodiesterase Inhibitors; Piperazines; Prevalence; Purines; Radiography; Sensitivity and Specificity; Sex Factors; Sildenafil Citrate; Sulfones

To determine whether delivery of compounded liquid sildenafil directly to the stomach of dogs with megaesophagus (ME) would affect esophageal clearance, regurgitation frequency, body weight, or quality of life.. 10 client-owned otherwise healthy dogs with stable ME.. A randomized crossover study was performed. Dogs received either sildenafil (1 mg/kg, PO, q 12 h) or a placebo for 14 days, followed by a 7-day washout period, then the opposite treatment for 14 days. Esophageal clearance time was assessed by means of videofluoroscopy prior to treatment and on day 1 of each treatment period. Owners maintained logs of regurgitation episodes and quality of life.. Compounded liquid sildenafil moved into the stomach during 21 of 30 (70%) videofluoroscopy sessions. Sildenafil resulted in a significant reduction in the number of regurgitation episodes (median, 3.5 episodes/wk; range, 0 to 14.5 episodes/wk), compared with baseline (median, 6.5 episodes/wk; range, 1.5 to 19.5 episodes/wk) and the placebo (median, 4 episodes/wk; range, 0 to 28 episodes/wk), and a significant increase in body weight (median, 22.05 kg; range, 6 to 26.3 kg), compared with baseline (median, 21.55 kg; range, 5.1 to 26.2 kg) and the placebo (median, 22.9 kg; range, 5.8 to 25.9 kg). There were no differences in esophageal clearance times or quality-of life-scores between sildenafil and placebo.. Although significant differences with placebo administration were identified, clinically relevant improvements were not seen with the use of compounded liquid sildenafil in dogs with ME.

Topics: Animals; Cross-Over Studies; Dog Diseases; Dogs; Double-Blind Method; Esophageal Achalasia; Quality of Life; Sildenafil Citrate

We evaluated the efficacy of oral sildenafil citrate in dogs with congenital idiopathic megaoesophagus (CIM). Twenty-one puppies were randomly assigned to two groups (treatment and control). The dogs were given sildenafil oral suspension 1 mg/kg every 12 hours for 14 days or placebo in a masked fashion. Clinical signs (frequency of regurgitation and weight gain) and oesophagrams (relative oesophageal diameter, ROD) were evaluated in order to assess the efficacy of drug treatment, by examiners who were unaware of the study protocol. In addition, a set of in vitro experiments on isolated samples of canine lower oesophageal sphincter (LOS) was performed, and the effects of increasing concentrations of sildenafil on basal tone and electrically-stimulated motility were assessed. Sildenafil administration significantly reduced the number of regurgitation episodes (0.88±1.40 v 2.65±1.56, P<0.0001) and significantly increased weight gain in the treated dogs compared to controls (79.76±28.30 per cent v 53.40±19.30 per cent, P=0.034). ROD values, at the end of the treatment period, were significantly decreased in the sildenafil group, compared to pre-treatment values (0.97±0.19 v 0.24±0.14, P<0.0001), in contrast to control subjects (0.98±0.17 v 1.10±0.25, P=0.480). In accordance with the in vivo findings, sildenafil dose-dependently reduced basal tone and increased electrically-induced relaxation of dog LOS samples. These results suggest that sildenafil citrate helps ameliorate clinical and radiographic signs in dogs with CIM by reducing LOS tone, and could represent a novel therapeutic tool for the treatment of this disease.

Topics: Animals; Dog Diseases; Dogs; Esophageal Achalasia; Female; Male; Radiography; Sildenafil Citrate; Treatment Outcome

Sildenafil shows an intense and prolonged inhibitory effect on the smooth muscle cells of the human corpus cavernosum by blocking phosphodiesterase type 5 that destroys nitric oxide-stimulated cyclic guanosine monophosphate. We investigated if sildenafil possesses a similar effect on the esophageal musculature of patients with achalasia, where there is an impairment of nitric oxide production similar to that of functional impotence.. In 14 patients affected by achalasia with an esophageal diameter of

Topics: Adult; Deglutition; Double-Blind Method; Esophageal Achalasia; Esophagus; Female; Humans; Male; Middle Aged; Muscle Contraction; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones