J Papp1, B Sandor1, Z Vamos2, D Botor1, A Toth1, M Rabai3, P Kenyeres1, P Cseplo4, I Juricskay1, E Mezosi1, A Koller5, K Toth1. 1. 1st Department of Medicine, School of Medicine, University of Pecs, Pecs, Hungary. 2. Department of Pathophysiology and Gerontology, School of Medicine, University of Pecs, Pecs, Hungary Hungarian National Ambulance Service, Pecs, Hungary. 3. 1st Department of Medicine, School of Medicine, University of Pecs, Pecs, Hungary Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. 4. 1st Department of Medicine, School of Medicine, University of Pecs, Pecs, Hungary Hungarian National Ambulance Service, Pecs, Hungary. 5. Department of Pathophysiology and Gerontology, School of Medicine, University of Pecs, Pecs, Hungary.
Abstract
BACKGROUND: Acetylsalicylic acid (ASA) plays an important role in the treatment and prevention of cardiovascular diseases. Metamizole (MET) is an analgesic and antipyretic medicine, it is not used as an antiplatelet drug. OBJECTIVES: We aimed to examine the antiplatelet effect of MET and the possible interactions between the drugs. METHODS: In our in vitro investigations different concentrations of ASA and MET solutions were added to blood. To examine the interactions MET and ASA were added together. In our in vivo crossover study intravenous MET, oral ASA or both drugs together were administered. Epinephrine and adenosine-diphosphate induced platelet aggregation was determined by optical aggregometry. RESULTS: Epinephrine-induced aggregation was completely inhibited in all ASA and MET concentrations in vitro. Lower, ineffective concentration of MET prevented the antiplatelet effect of ASA. The inhibition was completely restored when higher concentration of ASA was used or when ASA was added first. Our in vivo study showed that in the MET group rapid onset of inhibition was developed and there was no inhibition after one day. In the ASA group platelet aggregation decreased slowly but still had significant inhibitory effect after 72 hours. Combined therapy showed similar changes to the MET group. CONCLUSION: Antiplatelet effect of MET and ASA did not differ significantly in vitro. The observations may indicate a competitive interaction between the two drugs. The in vivo experiments showed that intravenously administered MET is an effective antiplatelet drug and can be considered as a therapeutic alternative, when ASA cannot be used in oral form.
BACKGROUND:Acetylsalicylic acid (ASA) plays an important role in the treatment and prevention of cardiovascular diseases. Metamizole (MET) is an analgesic and antipyretic medicine, it is not used as an antiplatelet drug. OBJECTIVES: We aimed to examine the antiplatelet effect of MET and the possible interactions between the drugs. METHODS: In our in vitro investigations different concentrations of ASA and MET solutions were added to blood. To examine the interactions MET and ASA were added together. In our in vivo crossover study intravenous MET, oral ASA or both drugs together were administered. Epinephrine and adenosine-diphosphate induced platelet aggregation was determined by optical aggregometry. RESULTS:Epinephrine-induced aggregation was completely inhibited in all ASA and MET concentrations in vitro. Lower, ineffective concentration of MET prevented the antiplatelet effect of ASA. The inhibition was completely restored when higher concentration of ASA was used or when ASA was added first. Our in vivo study showed that in the MET group rapid onset of inhibition was developed and there was no inhibition after one day. In the ASA group platelet aggregation decreased slowly but still had significant inhibitory effect after 72 hours. Combined therapy showed similar changes to the MET group. CONCLUSION: Antiplatelet effect of MET and ASA did not differ significantly in vitro. The observations may indicate a competitive interaction between the two drugs. The in vivo experiments showed that intravenously administered MET is an effective antiplatelet drug and can be considered as a therapeutic alternative, when ASA cannot be used in oral form.
Authors: Jan Hartinger; Robert Novotny; Jana Bilkova; Tomas Kvasnicka; Petr Mitas; Martin Sima; Jaroslav Hlubocky; Jan Kvasnicka; Ondrej Slanar; Jaroslav Lindner Journal: Med Princ Pract Date: 2018-05-13 Impact factor: 1.927