Читать книгу The Esophagus - Группа авторов - Страница 61

Since the underlying pathophysiology for primary achalasia, DES, and esophageal hypercontractility (i.e. jackhammer esophagus) remains poorly understood, the evidence‐based best practice pharmacologic recommendations are weak. The primary goal of available therapy aims to improve peristalsis and smooth muscle relaxation at the level of the LES. Ideally, this approach will translate into improved patient symptoms. Calcium channel blockers (CCBs) and nitrates remain the most commonly used drugs for the treatment of esophageal chest pain, but evidence to support this is limited.

The CCBs act by inhibiting calcium‐dependent myocyte contraction, leading to smooth muscle relaxation, although much of the data surrounding their use is both mixed and relatively dated. In these studies, nifedipine 10–30 mg three times daily was the most commonly used CCB, and in a small randomized crossover study of 16 patients it was shown to improve the chest pain index (severity × frequency) but not the chest pain frequency or intensity alone [152]. Diltiazem, another CCB, was used in a small trial of 14 patients and shown to decrease the chest pain score in patients with nutcracker esophagus (hypercontractile esophagus) [153]. The studies in this area, however, have significant methodological issues and small sampling sizes, precluding clear clinical benefit [152–156].

Nitrates are another pharmacologic agent used in the treatment of ECP related to motility disorders. As previously discussed, NO is thought to play a key role in the development of achalasia and DES. Small‐scale studies have suggested nitrates may improve manometric findings and chest pain in DES [157, 158]; however, data supporting its use in achalasia [159] and hypercontractile states [160] has been equivocal or lacking. More recently, phosphodiesterase‐5 inhibitors have recently emerged as a potential therapeutic option by acting to inhibit the degradation of NO, thus regulating smooth muscle relaxation. Bortolotti et al. evaluated in a double‐blind study the effect of sildenafil 50 mg/d vs. placebo on the esophageal musculature in 14 patients with achalasia [161]. Sildenafil inhibited contractile activity, decreased LES tone, residual pressure, and contraction amplitude as measured by a low‐compliance manometric system [161]. Eherer et al. investigated the effect of sildenafil on esophageal motility among six healthy male volunteers in a double‐blind study in which the participants underwent 12‐hour manometry on two separate days, once with sildenafil 50 mg and once with placebo [162]. The other arm was an open study on the effects of sildenafil 50 mg on manometric features and clinical responses in 11 patients with hypercontractility [162]. Results showed sildenafil lowered LES pressures and pressure amplitudes in the distal esophagus on esophageal manometry in all the healthy subjects, with a sustained effect for at least eight hours in three of the four patients who underwent prolonged manometric study. Among the patients with hypercontractility, they found manometric improvement in 9 of the 11 patients, however only 4 had symptomatic improvement, and 2 of those patients had to discontinue treatment due to side effects [162].

Finally, another potential therapy is the use of peppermint oil, which is postulated to have effects as a smooth relaxant. One group of investigators demonstrated that peppermint oil improved manometric findings in DES; however, repeat studies to date have failed to replicate this data [163]. More recent evidence has shown that its use improves difficulty swallowing and noncardiac chest pain, with 63% reporting improvement and 83% of patients with spastic esophageal disorders [164].