PMID- 30696282
OWN - NLM
STAT- MEDLINE
DCOM- 20200421
LR  - 20200421
IS  - 1556-9519 (Electronic)
IS  - 1556-3650 (Linking)
VI  - 57
IP  - 7
DP  - 2019 Jul
TI  - COPD and asthma therapeutics for supportive treatment in organophosphate 
      poisoning.
PG  - 644-651
LID - 10.1080/15563650.2018.1540785 [doi]
AB  - Context: Nerve agents like sarin or VX have repeatedly been used in military 
      conflicts or homicidal attacks, as seen in Syria or Malaysia 2017. Together with 
      pesticides, nerve agents assort as organophosphorus compounds (OP), which inhibit 
      the enzyme acetylcholinesterase. To counteract subsequent fatal symptoms due to 
      acetylcholine (ACh) accumulation, oximes plus atropine are administered, a 
      regimen that lacks efficacy in several cases of OP poisoning. New therapeutics 
      are in development, but still need evaluation before clinical employment. 
      Supportive treatment with already approved drugs presents an alternative, whereby 
      compounds from COPD and asthma therapy are likely options. A recent pilot study 
      by Chowdhury et al. included beta2-agonist salbutamol in the treatment of 
      OP-pesticide poisoned patients, yielding ambiguous results concerning the 
      addition. Here, we provide experimental data for further investigations regarding 
      the value of these drugs in OP poisoning. Methods: By video-microscopy, changes 
      in airway area were analyzed in VX-poisoned rat precision cut lung slices (PCLS) 
      after ACh-induced airway contraction and subsequent application of selected 
      anticholinergics/beta2-agonists. Results: Glycopyrrolate and ipratropium efficiently 
      antagonized an ACh-induced airway contraction in VX-poisoned PCLS (EC(50) 
      glycopyrrolate 15.8 nmol/L, EC(50) ipratropium 2.3 nmol/L). beta2-agonists 
      formoterol and salbutamol had only negligible effects when solely applied in the 
      same setting. However, combination of formoterol or salbutamol with low dosed 
      glycopyrrolate or atropine led to an additive effect compared to the sole 
      application [50.6 +/- 8.8% airway area increase after 10 nmol/L formoterol 
      +1 nmol/L atropine versus 11.7 +/- 9.2% (10 nmol/L formoterol) or 8.6 +/- 5.9% 
      (1 nmol/L atropine)]. Discussion: We showed antagonizing effects of 
      anticholinergics and beta2-agonists on ACh-induced airway contractions in 
      VX-poisoned PCLS, thus providing experimental data to support a prospective 
      comprehensive clinical study. Conclusions: Our results indicate that COPD and 
      asthma therapeutics could be a valuable addition to the treatment of OP 
      poisoning.
FAU - Herbert, Julia
AU  - Herbert J
AD  - a Bundeswehr Institute of Pharmacology and Toxicology , Neuherbergstrasse 11, 
      Munich , Germany.
FAU - Thiermann, Horst
AU  - Thiermann H
AD  - a Bundeswehr Institute of Pharmacology and Toxicology , Neuherbergstrasse 11, 
      Munich , Germany.
FAU - Worek, Franz
AU  - Worek F
AD  - a Bundeswehr Institute of Pharmacology and Toxicology , Neuherbergstrasse 11, 
      Munich , Germany.
FAU - Wille, Timo
AU  - Wille T
AD  - a Bundeswehr Institute of Pharmacology and Toxicology , Neuherbergstrasse 11, 
      Munich , Germany.
LA  - eng
PT  - Journal Article
DEP - 20190130
PL  - England
TA  - Clin Toxicol (Phila)
JT  - Clinical toxicology (Philadelphia, Pa.)
JID - 101241654
RN  - 0 (Adrenergic beta-2 Receptor Agonists)
RN  - 0 (Anti-Asthmatic Agents)
RN  - 0 (Chemical Warfare Agents)
RN  - 0 (Cholinergic Antagonists)
RN  - 0 (Organothiophosphorus Compounds)
RN  - 9A4381183B (VX)
SB  - IM
MH  - Adrenergic beta-2 Receptor Agonists/administration & dosage/*pharmacology
MH  - Animals
MH  - Anti-Asthmatic Agents/administration & dosage/pharmacology
MH  - Chemical Warfare Agents/*poisoning
MH  - Cholinergic Antagonists/administration & dosage/*pharmacology
MH  - Disease Models, Animal
MH  - Male
MH  - Microscopy, Video
MH  - Organophosphate Poisoning/*drug therapy/physiopathology
MH  - Organothiophosphorus Compounds/*poisoning
MH  - Rats
MH  - Rats, Wistar
OTO - NOTNLM
OT  - COPD
OT  - Organophosphate poisoning
OT  - PCLS
OT  - asthma
OT  - nerve agents
EDAT- 2019/01/31 06:00
MHDA- 2020/04/22 06:00
CRDT- 2019/01/31 06:00
PHST- 2019/01/31 06:00 [pubmed]
PHST- 2020/04/22 06:00 [medline]
PHST- 2019/01/31 06:00 [entrez]
AID - 10.1080/15563650.2018.1540785 [doi]
PST - ppublish
SO  - Clin Toxicol (Phila). 2019 Jul;57(7):644-651. doi: 10.1080/15563650.2018.1540785. 
      Epub 2019 Jan 30.