Xylometazoline and oxymetazoline - unusual effects of everyday drugs (literature review)

The aim of the study is to systematize the knowledge about xylometazoline and oxymetazoline - commonly used nasal sprays with sympathicomimetic effect, mainly directly on α-adrenergic receptors [1]. A review of recent reports on possible side effects and new therapeutic options will be presented. Results: Over several years, reports have been published regarding descriptions of unusual cases of side effects, such as angina attack [4], a case of respiratory failure in a newborn [5], ischemic stroke [6], or anaphylactic reaction during routine surgery. In experiments using rats, on the other hand, it has been shown that these substances can also cause increased inflammation of the lower respiratory tract [7], as well as numerous ophthalmic problems [8]. Recent reports also suggest new uses for xylometazoline and oxymetazoline. In combination with lidocaine, an intranasal solution of xylometazoline has shown efficacy in the anesthesia of maxillary teeth in patients with minor carious lesions [9], and a beneficial therapeutic combination of oxymetazoline and dye laser (PDL) has also been reported for the treatment of rosacea, among others [10]. Conclusions: Although imidazoline derivatives were admitted to the drug list decades ago, still their pharmacological potential has not been fully exploited. Finding applications of these drugs in dermatology and dentistry may not only improve the efficacy and comfort of treatment, but also significantly reduce the costs of the whole therapy. The aforementioned reports on the side effects of xylometazoline and oxymetazoline should not be forgotten. It is possible that the presented examples will increase awareness to use these drugs with more respect, according to the recommendations on the leaflet.

3332Exercise training ameliorates vasodilator capacity of coronary microvessels in patients with vasospastic angina - A new therapeutic approach for the coronary functional disorder

Background We have recently demonstrated that coronary vasospasm could develop in both epicardial coronary arteries and intramuscular coronary microvessels in patients with vasospastic angina (VSA). However, it remains to be examined whether vasodilator capacity of coronary microvessels is impaired in VSA patients and if so, whether exercise training could ameliorate vasodilator capacity of coronary microvessels on the top of calcium channel blockers. The effectiveness of exercise training is established for organic coronary artery disease but remained to be examined for VSA. Purpose We thus examined whether vasodilator capacity of coronary microvessels is impaired in VSA patients without organic coronary stenosis using an adenosine-stress dynamic computed tomography perfusion (CTP) that can measure absolute value of myocardial blood flow (MBF). We also examined whether exercise training ameliorates not only vasodilator capacity of coronary microvessels but also exercise capacity and frequency of angina attack. Methods In the first protocol, we measured MBF using CTP in consecutive 32 VSA patients with acetylcholine-induced diffuse coronary spasm in the left anterior descending coronary arteries (LAD) and 12 non-VSA controls. In the second protocol, we conducted a randomized controlled trial (RCT; Exercise VSA trial, UMIN: ehz745.008423996), where 20 VSA patients were randomly assigned to either exercise group (Ex group: supervised exercise training session for 30-min using bicycle ergometer, once/week at the hospital and more than 3 times/week at home) or non-exercise group (Non-Ex group) (n=10 each) (Figure A). Before and 3 months after exercise training, we measured MBF with adenosine-stress dynamic CTP and peak VO2 by cardiopulmonary exercise tests, and also assessed angina attack with Seattle Angina Questionnaire (SAQ). Results In the first protocol, CTP showed that adenosine-stress MBF was significantly decreased in the VSA group compared with the non-VSA group (VSA, 137.2±6.6 vs. Non-VSA, 174.4±10.7 ml/100g/min, P<0.01) (Figure B), although patient characteristics were comparable between the 2 groups. In the second protocol, exercise training was performed safely in all patients, and RCT showed that MBF was significantly increased in the Ex group compared with the non-Ex group (Figures C, D), although patient characteristics were also comparable between the 2 groups. Furthermore, peak VO2 was significantly increased in the Ex group compared with the non-Ex group (Figure E), and frequency of angina was significantly decreased in the Ex group compared with the non-Ex group (Figure F). Finally, there was a significant positive correlation between the extents of the changes in peak VO2 and the SAQ score for angina frequency in the Ex group (P<0.01, R=0.67). Figures Conclusions These results provide the first evidence that vasodilator capacity of coronary microvessels is impaired in VSA patients, which can be ameliorated by exercise training.

Effectiveness of the original trimetazidine MR in patients with stable coronary heart disease and angina attacks resistant to trimetazidine generics (ETALON study)

Aim. To assess the clinical benefits of the original trimetazidine medication (Preductal® MR) in patients with stable coronary heart disease and angina attacks resistant to trimetazidine generics. Material and methods. The study included 112 patients with stable coronary heart disease (CHD), who experienced angina attacks, despite the treatment with trimetazidine generics added to the standard CHD therapy (antiaggregants, statins, β-аadrenoblockers, ACE inhibitors). All participants received Preductal® MR (35 mg twice a day) instead of trimetazidine generics. The follow-up duration was 3 months. Treatment effectiveness was assessed by the changes in angina attack incidence, short-acting nitrate consumption, and general status, using a visual analogue scale (VAS). In addition, pharmaco-economic analysis of the treatment effectiveness was performed. Results. The replacement of trimetazidine generics with Preductal® MR was associated with a reduction in angina attack incidence by 63 % and in the number of nitroglycerine tablets/doses by 65 % (p<0,01). VAS score increased from 45,3±13,8 to 71,6±11,9 (р<0,0001). Preductal® MR therapy is the best pharmaco-economic option, since the ratio between weekly treatment costs (RUB) and the weekly number of prevented angina attacks is minimal for this original medication. Conclusion. In patients with stable CHD and angina attacks, resistant to trimetazidine generics, Preductal® МR therapy is associated with a significant reduction in angina attack incidence and consumption of short-acting nitrates. Preductal® MR is the most cost-effective medication, providing optimal effectiveness with minimal costs.