Physiology and pathology of the oesophagus in the elderly patient

Lock, Guntram

doi:10.1053/bega.2001.0250

Cited by 26 publications

(20 citation statements)

References 72 publications

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“…Many diseased conditions require the patient or customer to swallow several tablets at a time. The elderly, in particular, have difficulty in swallowing tablets because of underlying swallowing [110] and/or esophageal motility [111] disorders.…”

Section: Formulations Of Piroxicam-β-cyclodextrinmentioning

confidence: 99%

Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam

Scarpignato

2013

CMC

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Although NSAIDs are very effective drugs, their use is associated with a broad spectrum of adverse reactions in the liver, kidney, cardiovascular (CV) system, skin and gut. Gastrointestinal (GI) side effects are the most common and constitute a wide clinical spectrum ranging from dyspepsia, heartburn and abdominal discomfort to more serious events such as peptic ulcer with life-threatening complications of bleeding and perforation. The appreciation that CV risk is also increased further complicates the choices of physicians prescribing anti-inflammatory therapy. Despite prevention strategies should be implemented in patients at risk, gastroprotection is often underused and adherence to treatment is generally poor. A more appealing approach would be therefore to develop drugs that are devoid of or have reduced GI toxicity. Gastro-duodenal mucosa possesses many defensive mechanisms and NSAIDs have a deleterious effect on most of them. This results in a mucosa less able to cope with even a reduced acid load. NSAIDs cause gastro-duodenal damage, by two main mechanisms: a physiochemical disruption of the gastric mucosal barrier and systemic inhibition of gastric mucosal protection, through inhibition of cyclooxygenase (COX, PG endoperoxide G/H synthase) activity of the GI mucosa. However, against a background of COX inhibition by anti-inflammatory doses of NSAIDs, their physicochemical properties, in particular their acidity, underlie the topical effect leading to short-term damage. It has been shown that esterification of acidic NSAIDs suppresses their gastrotoxicity without adversely affecting anti-inflammatory activity. Another way to develop NSAIDs with better GI tolerability is to complex these molecules with cyclodextrins (CDs), giving rise to so-called “inclusion complexes” that can have physical, chemical and biological properties very different from either those of the drug or the cyclodextrin. Complexation of NSAIDs with β-cyclodextrin potentially leads to a more rapid onset of action after oral administration and improved GI tolerability because of minimization of the drug gastric effects. One such drug, piroxicam-β-cyclodextrin (PBC), has been used in Europe for 25 years. Preclinical and clinical pharmacology of PBC do show that the β-cyclodextrin inclusion complex of piroxicam is better tolerated from the upper GI tract than free piroxicam, while retaining all the analgesic and anti-inflammatory properties of the parent compound. In addition, the drug is endowed with a quick absorption rate, which translates into a faster onset of analgesic activity, an effect confirmed in several clinical studies. An analysis of the available trials show that PBC has a GI safety profile, which is better than that displayed by uncomplexed piroxicam. Being an inclusion complex of piroxicam, whose CV safety has been pointed out by several observational studies, PBC should be viewed as a CV safe anti-inflmmatory compound and a GI safer alternative to piroxicam. As a consequence, it should be considered as a useful addition t...

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Section: Formulations Of Piroxicam-β-cyclodextrinmentioning

confidence: 99%

Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam

Scarpignato

2013

CMC

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“…4 Age-related changes in swallowing, including esophageal function, are also well documented. [6][7][8][9] On videofluoroscopy, increased intraesophageal stasis is seen with increasing age. 7,8 Manometric studies have shown a reduction in pressure at the lower esophageal sphincter (LES), upper esophageal sphincter (UES), and reduction in peristaltic wave amplitude and velocity with increasing age.…”

Section: Introductionmentioning

confidence: 99%

Esophageal Swallowing Timing Measures in Healthy Adults During Videofluoroscopy

Miles

Clark

Jardine

et al. 2016

Ann Otol Rhinol Laryngol

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These normative values provide a standardized protocol and guidance in interpretation when completing esophageal visualization as part of videofluoroscopy. While measuring fluid ETT may support referral for further specialist investigations, slower paste and pill ETT may be normal findings. Age-related slowing in fluid ETT was seen in healthy adults. Further investigation of ETT is needed in both normal and dysphagic subjects.

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“…Esophagus-specific physiologic changes that would account for decreased effect from radiation were not found in our review of the literature. 26 There is, however, a body of evidence to suggest that there is decreased visceral pain sensation with advancing age. Lasch et al used intraesophageal balloon distension to demonstrate significantly decreased esophageal pain sensation in healthy individuals older than 65 compared to a younger population.…”

Section: Discussionmentioning

confidence: 99%

Lower Incidence of Esophagitis in the Elderly Undergoing Definitive Radiation Therapy for Lung Cancer

Soni

Boonstra

Schipper

et al. 2017

International Journal of Radiation Oncology*Biology*Physics

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Introduction-The majority of lung cancer patients are elderly and poorly represented in randomized clinical trials. They are often undertreated due to concerns about their ability to tolerate aggressive treatment. We tested the hypothesis that elderly patients undergoing definitive lung radiation might tolerate treatment differently from younger patients.Methods-125 patients who underwent definitive lung radiotherapy were identified from a prospective institutional database (UM cohort). Logistic regression modelling was performed to assess the impact of age on esophagitis grade ≥3 or ≥2 and pneumonitis grade ≥3 or ≥2, adjusting for esophageal and lung dose respectively, chemotherapy utilization, smoking status, and performance status. The analysis was validated in a large cohort of 691 patients from the Michigan Radiation Oncology Quality Consortium (MROQC) registry, an independent statewide prospective database.Results-In the UM Cohort, multivariable regression models revealed a significant inverse correlation between age and rate of esophagitis for both toxicity levels, (adjusted odds ratio=0.93 for both models, 95% confidence intervals of (0.88,0.98) and (0.87,0.99)), with AUC of 0.747 and 0.721, respectively, demonstrating good fit. This same association was noted in the MROQC cohort. There was no significant association between age and pneumonitis.Conclusions-There is a lower incidence of esophagitis with increasing age even after adjusting for use of chemotherapy. This is a novel finding in thoracic oncology. No age dependence was

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Physiology and pathology of the oesophagus in the elderly patient

Cited by 26 publications

References 72 publications

Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam

Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam

Esophageal Swallowing Timing Measures in Healthy Adults During Videofluoroscopy

Lower Incidence of Esophagitis in the Elderly Undergoing Definitive Radiation Therapy for Lung Cancer

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Physiology and pathology of the oesophagus in the elderly patient

Cited by 26 publications

References 72 publications

Piroxicam-&#946;-Cyclodextrin: A GI Safer Piroxicam

Piroxicam-&#946;-Cyclodextrin: A GI Safer Piroxicam

Esophageal Swallowing Timing Measures in Healthy Adults During Videofluoroscopy

Lower Incidence of Esophagitis in the Elderly Undergoing Definitive Radiation Therapy for Lung Cancer

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Product

Resources

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Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam

Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam