Results of the IMPRESSION trial published in 2015 proved that morphine use in patients with acute coronary syndromes (ACS) is associated with undesirable impact on pharmacokinetics (PK) and pharmacodynamics (PD) of ticagrelor. Despite that, morphine is still a standard analgesic treatment in ACS patients and it should not be routinely withdrawn. Based on contemporary knowledge, morphine, acting via mi-opioid receptors, was found to inhibit gastrointestinal motility or induce adverse effects such as nausea or vomiting.~We decided to design a clinical study aiming to evaluate the impact of methoxyflurane on PD of ticagrelor in patients diagnosed with unstable angina pectoris (UA). Methoxyflurane is an inhaled anesthetic, registered in Poland in emergency medicine for pain alleviation in trauma patients. The drug was widely used in 1960s to induce general anesthesia, however its clinical utility was reduced with the development of novel anesthetic agents. Taking into account its different mechanism of action, it can be presumed that, contrary to morphine, no respiratory depression should be observed as well as no attenuation or delay of antiaggregatory effect of ticagrelor should occur, as no interaction with mi-receptor in gastrointestinal tract is related to activity of methoxyflurane.~Patients will be randomized in a 1:1:1 ratio into the study arms as follows: 1) 180 mg ticagrelor (2 integral tablets of 90 mg ticagrelor) followed by 3 mg inhaled methoxyflurane, 2) 180 mg ticagrelor followed by 5 mg intravenous morphine, 3) 180 mg ticagrelor alone
The purpose of this study is to evaluate differences in the pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite in patients who received ticagrelor followed with methoxyflurane versus ticagrelor followed with morphine or ticagrelor alone due to unstable angina pectoris