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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Med+Hypotheses
2020 ; 143
(ä): 110051
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Harnessing adenosine A2A receptors as a strategy for suppressing the lung
inflammation and thrombotic complications of COVID-19: Potential of
pentoxifylline and dipyridamole
#MMPMID32650197
DiNicolantonio JJ
; Barroso-Aranda J
Med Hypotheses
2020[Oct]; 143
(ä): 110051
PMID32650197
show ga
Counterproductive lung inflammation and dysregulated thrombosis contribute
importantly to the lethality of advanced COVID-19. Adenosine A2A receptors
(A2AR), expressed by a wide range of immune cells, as well as endothelial cells
and platelets, exert cAMP-mediated anti-inflammatory and anti-thrombotic effects
that potentially could be highly protective in this regard. The venerable drug
pentoxifylline (PTX) exerts both anti-inflammatory and antithrombotic effects
that reflect its ability to boost the responsiveness of A2AR to extracellular
adenosine. The platelet-stabilizing drug dipyridamole (DIP) blocks intracellular
uptake of extracellularly-generated adenosine, thereby up-regulating A2AR
signaling in a way that should be functionally complementary to the impact of PTX
in that regard. Moreover, DIP has recently been reported to slow the cellular
replication of SARS-CoV-2 in clinically feasible concentrations. Both PTX and DIP
are reasonably safe, well-tolerated, widely available, and inexpensive drugs.
When COVID-19 patients can be treated within several days of symptom onset, using
PTX + DIP in conjunction with hydroxychloroquine (HCQ) and an antibiotic -
azithromycin (AZM) or doxycycline - might be warranted. HCQ and AZM can suppress
SARS-CoV-2 proliferation in vitro and may slow the cell-to-cell spread of the
virus; a large case series evaluating this combination in early-stage patients
reported an impressively low mortality rate. However, whereas HCQ and AZM can
promote QT interval lengthening and may be contraindicated in more advanced
COVID-19 entailing cardiac damage, doxycycline has no such effect and exerts a
potentially beneficial anti-inflammatory action. In contrast to HCQ, we propose
that the combination of PTX + DIP can be used in both early and advanced stages
of COVID-19. Concurrent use of certain nutraceuticals - yeast beta-glucan, zinc,
vitamin D, spirulina, phase 2 inducers, N-acetylcysteine, glucosamine, quercetin,
and magnesium - might also improve therapeutic outcomes in COVID-19.