Effect Of Diseased States On Transit

Oesophageal transit may be influenced by diseased states such as oropharyngeal dysphagia or achalasia. Oral pharyngeal dysphagia is a common problem particularly in the elderly which carries a significant morbidity and mortality33. Oral-pharyngeal dysphagia copuld be

Table 4.2 Potential risk factors for stricture development in subjects with pill-induced oesophageal damage38

Risk factor

Pill-induced oesophageal damage without stricture

Pill induced oesophageal stricture

36 ± 19

60 ± 16

43:95

18:17

14/155 (9%)

17/33 (52%)

60/121 (50%)

18/25 (72%)

11/119(9%)

15/25 (63%)

1/120(1%)

5/32(16%)

Number taking sustained release formulations Number in reclining position Number with left atrial engorgement Number with pre-existing oesophageal disease caused by neurogenic dysfunction, with stroke being the commonest cause, but could also be due to local structural lesions34. Achalasia is caused by local structural lesions in which transit is impaired by an oesophageal stricture or inability of the lower oesophageal sphincter to relax. Oesophageal retention of food results. Additionally, abnormalities in oesophageal function can occur as a result of a variety of diseased states such as diabetes mellitus, chronic alcoholism and scleroderma, although an abnormality of the oesophagus is not a prerequisite for adhesion of dosage forms. Oesophageal dysfunction has been shown to be more common in asthmatics than normal subjects35, so drugs such as theophylline may show an increased incidence of adhesion36.

Reflux of gastric contents can cause injury to the oesophageal mucosa and the oesophagitis produced can lead to stricture. The acid reflux may actually exacerbate the oesophageal damage produced by some drugs such as doxycycline monohydrate which are poorly water soluble and should produce little damage under normal conditions. If gastrooesophageal reflux of acid occurs, the monohydrate may be converted to the highly ulcerogenic hydrochloride. In humans, this problem would be compounded since delayed transit is associated with hiatus hernia and gastro-oesophageal reflux with typical clearance times of 50 s compared to 9.5 s in normals37.

Where there is an existing stricture due to reflux or previous 'pill-induced' damage, the likely hood of further damage is increased. Risk factors associated with age, posture and formulation for stricture and non-stricture groups illustrated in Table 4.238.

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