Mecanismos farmacológicos implicados en la función deglutoria

Abstract

The objective of this Doctoral Thesis has been to study, in an integrated way, different aspects related to drugs and oropharyngeal dysphagia (OD) in the adult patient. The Thesis has focused on the study of different pharmacological mechanisms involved in swallowing. The objective of the first study was to know which drugs can be associated with a detrimental effect and which ones in a beneficial effect in OD. For this purpose, we retrospectively studied 966 elderly patients admitted to an Acute Geriatric Unit (AGU), in which we systematically performed the volume-viscosity swallow test (V-VST) to assess the presence of OD, and reviewed their pharmacological treatment. We classified the drugs according to the level 4 (pharmacological and therapeutic classification) of the Anatomical, Therapeutics, Chemical (ATC) system. The results of this study suggested that antipsychotics (ATC code N06A), antidepressants (ATC code N02B) and anti-dementia drugs (ATC code N06D) were associated with a worsening of the swallowing function. However, none of them showed statistical significance when adjusted for pathology (including dementia and depression). Regarding the beneficial effects, we found that agents acting in the renin-angiotensin system (ATC code C08C), oral antidiabetics (ATC code A10B), calcium antagonists (ATC code C08C), anti-inflammatories and antirheumatic products, nonsteroidal (ATC code M01A) and beta-blockers (ATC code C07A) could have a protective effect on OD. However, only beta-blockers were statistically associated with OD after the multivariate analysis. The objective of the second study and the one included in the annex was to increase the knowledge of the effect of antipsychotics in OD. The study in the annex consisted of a systematic review of the evidence based on clinical studies that related OD with antipsychotics. We concluded that patients on antipsychotic treatment may develop dysphagia, but it is difficult to differentiate whether this effect is due to the drug or the disease itself. For this reason, the second study was conducted in patients with dementia. In this study, we compared swallowing parameters, evaluated by a videofluoroscopy (VFS) study, of patients with dementia in treatment with antipsychotics for behavioral symptoms of dementia with patients also with dementia but without treatment with antipsychotics. Similarly, the pathophysiology of swallowing of patients with dementia was compared with patients without dementia, finding differences in these two groups, but we did not found significant differences in patients with dementia with treatment with antipsychotics in comparison to those without treatment with antipsychotics. We only found a delay in the upper esophageal sphinchter time, but it was not clinically significant. Otherwise, we found an increase of the oropharyngeal motor response time in patients with dementia and a higher prevalence of swallowing safety alterations compared with patients without dementia. Finally, the objective of the third study was to explore the serum and saliva SP in patients who were in treatment with beta-blockers using an enzyme-linked immunosorbent assay (ELISA), and to know the relationship of SP levels with OD. From this study, we were able to obtain 3 conclusions: (i) SP serum and saliva levels of patients treated with beta-blockers were significantly higher in comparison with those patients who were not in treatment with beta-blockers; (ii) the prevalence of OD was significantly lower in patients taking beta-blockers; and (iii) patients with OD had significantly lower SP concentrations in saliva than patients without OD.

Date of Award	9 Jul 2018
Original language	Spanish
Supervisor	Laia Rofes Salsench (Director) & Carlos Guarner Aguilar (Tutor)