sildenafil-citrate and Gastroesophageal-Reflux

Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease with a median survival of 2 - 4 years after diagnosis. Since the publication of the German IPF guideline in 2013 new treatment trials have been published, necessitating an update of the pharmacological therapy of IPF. Different from the previous guideline, the GRADE system was discarded and replaced by the Oxford evidence classification system which allows a more differentiated judgement. The following pharmacological therapies were rated not suitable for the treatment of IPF patients (recommendation A; evidence 1-b): triple therapy with prednisolone, azathioprine and acetyl-cysteine; imatinib; ambrisentan; bosentan; macitentan. A less clear but still negative recommendation (B, 1-b) was attributed to the treatment of IPF with the phosphodiesterase-5-inhibitor sildenafil and acetyl-cysteine monotherapy. In contrast to the international guideline antacid therapy as a general treatment for IPF was rated negative, based on conflicting results of recent analyses (recommendation C; evidence 4). An unanimous positive recommendation was granted for the antifibrotic drugs nintedanib and pirfenidone for the treatment of IPF (A, 1-a). For some open questions in the management of IPF patients for which firm evidence is lacking the guideline also offers recommendations based on expert consensus.. Die idiopathische Lungenfibrose (idiopathische pulmonale Fibrose, IPF) ist eine schwerwiegende Lungenerkrankung, die häufig innerhalb von zwei bis vier Jahren nach Diagnosestellung zum Tod führt. Seit Veröffentlichung der deutschen IPF-Leitlinie im Jahr 2013 liegen neue Therapiestudien vor, die eine Neubewertung der Behandlungsstrategien erfordern. Abweichend von der Vorgängerleitlinie wurde in der aktuellen Überarbeitung nicht mehr das GRADE-System sondern die Oxford Evidenzsystematik mit drei Empfehlungsgraden (A, B, C) verwendet, weil dieses System eine differenziertere Betrachtung erlaubt. Folgende Medikamente wurden mit dem Empfehlungsgrad A und dem Evidenzgrad 1-b als nicht geeignet für die Behandlung der IPF klassifiziert: Triple-Therapie aus Prednisolon, Azathioprin und Acetylcystein; Antikoagulation mit Vitamin-K-Antagonisten; Imatinib; Ambrisentan; Bosentan; Macitentan. Weniger eindeutig ist die negative Bewertung des Phosphodiesterase-5-Inhibitors Sildenafil und der Acetylcystein-Monotherapie (Empfehlungsgrad B, Evidenzgrad 2-b). Eindeutig positiv fiel die Empfehlung für Nintedanib und Pirfenidon zur Behandlung von IPF-Patienten aus (Empfehlungsgrad A, Evidenzgrad 1-a). Mit Empfehlungsgrad C und Evidenzgrad 4 wurde der generelle Einsatz von Antazida zur Behandlung der IPF als nicht zu empfehlen bewertet, da die Datenlage widersprüchlich ist; hier weicht die deutsche Leitlinie auch am deutlichsten von der internationalen Leitlinie ab. Am Ende der Leitlinie wird aus Expertensicht zu offenen Fragen in der Therapie der IPF Stellung genommen, für die bisher keine ausreichende Evidenzbasis existiert.

Topics: Acetylcysteine; Adult; Aged; Aged, 80 and over; Antacids; Bosentan; Clinical Trials as Topic; Evidence-Based Medicine; Female; Gastroesophageal Reflux; Guideline Adherence; Humans; Idiopathic Pulmonary Fibrosis; Imatinib Mesylate; Indoles; Male; Middle Aged; Phenylpropionates; Pyridazines; Pyridones; Pyrimidines; Sildenafil Citrate; Sulfonamides

The mechanism underlying increased perception of food bolus passage in the absence of esophageal mechanical obstruction has not been completely elucidated. A correlation between the intensity of the symptom and the severity of esophageal dysfunction, either motility (manometry) or bolus transit (impedance) has not been clearly demonstrated. The aim of this study was to analyze the correlation between objective esophageal function assessment (with manometry and impedance) and perception of bolus passage in healthy volunteers (HV) with normal and pharmacologically-induced esophageal hypocontractility, and in patients with gastro-esophageal reflux disease (GERD) with and without ineffective esophageal motility (IEM).. Combined manometry-impedance was performed in 10 HV, 19 GERD patients without IEM and nine patients with IEM. Additionally, nine HV were studied after 50 mg sildenafil, which induced esophageal peristaltic failure. Perception of each 5 mL viscous swallow was evaluated using a 5-point scale. Manometry identified hypocontractility (contractions lower than 30 mmHg) and impedance identified incomplete bolus clearance.. In HV and in GERD patients with and without IEM, there was no association between either manometry or impedance and perception on per swallow analysis (OR: 0.842 and OR: 2.017, respectively), as well as on per subject analysis (P = 0.44 and P = 0.16, respectively). Lack of correlation was also found in HV with esophageal hypocontractility induced by sildenafil.. There is no agreement between objective measurements of esophageal function and subjective perception of bolus passage. These results suggest that increased bolus passage perception in patients without mechanical obstruction might be due to esophageal hypersensitivity.

Topics: Adult; Deglutition; Deglutition Disorders; Electric Impedance; Esophagus; Female; Gastroesophageal Reflux; Humans; Male; Manometry; Middle Aged; Muscle Contraction; Perception; Piperazines; Purines; Sensitivity and Specificity; Sildenafil Citrate; Sulfones; Vasodilator Agents; Young Adult

Sildenafil is an inhibitor of type 5 phosphodiesterase. It relaxes or inhibits contraction of smooth muscle by increasing cellular concentrations of cyclic guanosine monophosphate. Multichannel intraluminal impedance manometry/pH allow the precise evaluation of oesophageal bolus transit and acid/non-acid reflux.. To investigate the effect of sildenafil on segmental oesophageal motor function and gastro-oesophageal reflux.. Eight healthy volunteers underwent multichannel intraluminal impedance manometry baseline, and 15, 30 and 45 min before and after a 50-mg dose of sildenafil successively. The subjects underwent 2-h multichannel intraluminal impedance/pH studies on two separate days after either water or sildenafil ingestion.. Sildenafil decreased the resting lower oesophageal sphincter pressure and prolonged the duration of lower oesophageal sphincter relaxation for the 45 min following its ingestion. At 15 min, distal onset velocity, total bolus transit time, bolus presence time and segmental transit time were delayed in the mid to distal oesophagus. At 30 min, distal onset velocity was restored but bolus presence time and bolus presence time were still delayed in distal smooth muscle segment. At 45 min, total bolus transit time and distal onset velocity were restored but bolus presence time and segmental transit time were delayed more in the transition zone. Sildenafil did not alter the reflux.. Sildenafil alters lower oesophageal sphincter function and oesophageal bolus transit, but not induce gastro-oesophageal reflux.

Topics: Adult; Esophageal Motility Disorders; Female; Gastroesophageal Reflux; Gastrointestinal Transit; Humans; Hydrogen-Ion Concentration; Male; Manometry; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Oesophageal clearance of acid reflux consists of an initial volume clearance followed by neutralisation of the acidified mucosa by swallowed saliva (chemical clearance). Ineffective oesophageal motility (IOM), a frequent finding in patients with gastro-oesophageal reflux disease (GORD), has been claimed to underlie prolonged acid clearance by affecting oesophageal emptying and saliva transport. Intraluminal impedance allows non-radiological monitoring of movement of oesophageal liquids.. To evaluate the relevance of IOM during oesophageal volume and chemical clearance using combined pH impedance measurements.. Impedance was validated with fluoroscopy to study volume clearance in three healthy subjects. Acid clearance tests were performed in 10 healthy subjects in the upright and supine positions, before and after oesophageal peristaltic disruption with sildenafil 50 mg.. After instillation of an acid bolus, simultaneous manometry, pH, and impedance were used to study oesophageal motility, chemical clearance, and volume clearance, respectively.. Impedance allowed assessment of volume clearance accurately, showing a strong correlation with fluoroscopy (r(2)=0.89). Sildenafil provoked a graded impairment in oesophageal motility in healthy subjects without affecting saliva secretion. In the upright position, volume clearance was slightly prolonged only with severe IOM (>80% abnormal peristaltic sequences). In the supine position, severe IOM significantly prolonged chemical and volume clearance. Moderate IOM (30-80% abnormal peristalsis) had no effect. With normal peristalsis and moderate IOM, clearance times were similar in the upright and supine positions. Severe IOM however had a greater impact on clearance in the supine than in the upright position.. Ineffective oesophageal motility has little effect on oesophageal clearance during upright acid reflux. With supine reflux, only severe IOM is associated with prolonged oesophageal clearance.

Topics: Acids; Adolescent; Adult; Analysis of Variance; Electric Impedance; Esophageal Motility Disorders; Esophagus; Female; Fluoroscopy; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Manometry; Middle Aged; Peristalsis; Phosphodiesterase Inhibitors; Piperazines; Purines; Saliva; Sildenafil Citrate; Sulfones; Supine Position