PurposeThe aim of this review was to assess the efficacy of cannabis preparations for relieving pain in patients with malignant diseases, through a systematic review of randomized controlled trials (RCTs), which were predominantly double-blind trials that compared cannabis preparation to a placebo.MethodsAn electronic search of all literature published until June 2017 was made in MEDLINE/PubMed, Embase, The Cochrane Controlled Trials Register and specific web pages devoted to cannabis.ResultsFifteen of the 18 trials demonstrated a significant analgesic effect of cannabinoids as compared to placebo. The most commonly reported adverse effects were generally well tolerated, mild to moderate. The main side effects were drowsiness, nausea, vomiting and dry mouth. There is evidence that cannabinoids are safe and modestly effective in neuropathic pain and also for relieving pain in patients with malignant diseases. The proportion of “responders” (patients who at the end of 2 weeks of treatment reported ≥30% reduction in pain intensity on a scale of 0–10, which is considered to be clinically important) was 43% in comparison with placebo (21%).ConclusionThe target dose for relieving pain in patients with malignant diseases is most likely about 10 actuations per day, which is about 27 mg tetrahydrocannabinol (THC) and 25 mg cannabidiol (CBD), and the highest approved recommended dose is 12 actuations per day (32 mg THC/30 mg CBD). Further large studies of cannabinoids in homogeneous populations are required.

Patients suffering from malignant diseases receive very often highly emetogenic chemotherapy as part of their treatment. With the aim of assessing the efficacy of cannabinoids in treating chemotherapy-induced nausea and vomiting (CINV), we searched the literature published until April 2020 in Medline/PubMed, Embase, the Cochrane Controlled Trials Register, and in specific web pages. Randomized clinical trials comparing cannabinoids efficacy in managing CINV with that of placebo reported absence of vomit-ing (3 trials, 168 patients) and absence of nausea and vomiting (3 trials, 288 participants). In comparison with patients receiving other antiemetics, patients receiving cannabinoids reported no nausea (5 trials, 258 participants), no vomiting (4 trials, 209 participants), and absence of both (4 trials, 414 patients). Across all trials, cannabinoids were more effective in relieving the symptoms of nausea and vomiting induced by cytotoxic therapy than placebo was and slightly better than conventional antiemetics. A retrospective review com-paring nabilone, dronabinol, delta-9-THC, and delta 8-THC with other antiemetics used to manage CINV in pediatric patients showed that these drugs could also be used as adjuvant antiemetics. Cancer patients on highly emetogenic chemotherapy but with insufficiently effective standard antiemetic therapy can be given cannabis preparations containing similar amounts of tetrahydrocannabinol and can-nabidiol, which should be received in strict compliance with the professional guidelines for the treatment of CINV. 

Tirofiban hydrochloride is a reversible antagonist of fibrinogen binding to the GPIIb/IIIa receptor, used for the treatment of acute coronary syndrome. A novel RP-HPLC method has been developed and validated for the determination of Tirofiban in serum of Wistar rats with and without deep acute venous thrombosis. The chromatographic separation was carried out using a reverse-phase HPLC column Purospher® RP-18e (150 mm  4.6 mm i.d.; 5 μm) coupled with a guard column LiChrosorb® (4 mm  4 mm i.d.; 7 μm) and mobile phase consisting of the mixture of 1-octane sulfonic acid in water (pH 3.0, adjusted with orthophosphoric acid) and acetonitrile, with a ratio of 60 : 40 (v/v) and a flow rate of 1.0 ml/min, at a wavelength of 277 nm. The serum concentrations of Tirofiban in the group of rats with DVT were lower than those in the control group, and it could be explained with the binding of Tirofiban with the GPIIb/IIIa receptors.Keywords: Tirofiban; deep acute venous thrombosis (DVT); HPLC determination; rat serum РАЗВОЈ НА АЛТЕРНАТИВНA HPLC-МЕТОДA ЗА ОПРЕДЕЛУВАЊЕ ТИРОФИБАН ВО СЕРУМОТ НА СТАОРЕЦТирофибан хидрохлорид е реверзибилен антагонист на фибриногенот врзувајќи се за рецепторот GPIIb/IIIa, и се користи за третман на акутен коронарен синдром. Нова RP-HPLC-метода е развиена и валидирана за определување на тирофибанот во серумот на Wistar стаорци со и без длабока акутна венска тромбоза. Хроматографското раздвојување се врши со помош на реверзно фазна HPLC-колона Purospher ® RP-18E (150 mm  4.6 mm; 5 μm) во комбинација со претколона LiChrosorb ® (4 mm  4 mm; 7 μm) и мобилна фаза која се состои од смеса на 1-октанска сулфонска киселина во вода (pH 3.0, се регулира со ортофосфорна киселина) и ацетонитрил во сооднос 60 : 40 (v/v) и проток од 1,0 ml/min, на бранова должина од 277 nm. Серумските концентрации на тирофибанот во групата стаорци со ДВТ беа пониски од оние во контролната група, што би можело да се објасни со врзување на тирофибанот за рецепторите GPIIb/IIIa. Клучни зборови: тирофибан; длабока акутна венска тромбоза (ДВТ); HPLC-определување; серум на стаорец

AimThe aim of this study was to investigate the possibility of using 99mtechnetium (99mTc)-labeled tirofiban (a reversible antagonist of glycoprotein IIb/IIIa) for detection of deep venous thrombosis (DVT) in rats without causing an antiplatelet effect.MethodsThe ability of in vitro tirofiban to inhibit adenosine 5′-diphosphate (ADP)-induced platelet aggregation was evaluated using optical aggregometer. Binding of 99mTc-tirofiban to platelets was evaluated. Serum levels of unlabeled (a validated high performance liquid chromatography method) and 99mTc-tirofiban after single intravenous injection were evaluated in male Wistar rats with or without induced DVT (femoral vein ligation model), and the rats were also subjected to whole body scintigraphy.ResultsTirofiban in vitro inhibits ADP-induced aggregation of human platelets in a dose- and concentration-dependent manner (10 nM to 2 μM), but only if it is added before ADP and not after ADP. 99mTc labeling did not affect the ability of tirofiban to bind to either human or rat platelets, nor did it affect tirofiban pharmacokinetics in intact rats or in animals with induced DVT. When 99mTc-tirofiban was injected to rats after induction of DVT, at a molar dose lower than the one showing only a weak antiaggregatory effect in vitro, whole body scintigraphy indicated localization of 99mTc-tirofiban around the place of the induced DVT.Conclusion99mTc labeling of tirofiban does not affect its ability to bind to glycoprotein IIb/IIIa or its in vivo pharmacokinetics in rats, either intact or with DVT. A low, nonantiaggregatory dose of 99mTc-tirofiban may be used to visualize DVT at an early stage.

One of the biggest achievements of the second half of the last century, in the field of medicine, was the antibiotics development. Today, their uncontrolled and inappropriate usage is considered as a huge public health problem, because of the occurrence of antibiotics resistance resistance of microorganisms to antimicrobial agents. Around 50% of the antibiotics prescribed during the hospitalization period of the patients are unnecessary or inappropriate. Endemic forms of occurrence and maintenance of resistant and multiresistant bacteria in hospitals, especially in intensive care units, increase morbidity, treatment costs and mortality of hospitalized patients. Aim: To confirm the information and knowledge of the antibiotics usage and antibiotics resistance among the population of the eastern region of Republic of North Macedonia. Material and Methods: The paper is a transphase study conducted in the period from 01.10.2018 30.11.2018 on the territory of the municipalities of Stip, Probistip, Kocani, Radovis and Strumica. Fur fulfilling the set goals, a specially designed questionnaire was made, and a total of 526 respondents fulfilled it voluntarily and anonymously. The descriptive and the analytical epidemiological method of work were used. Results: From the total number of 526 respondents, 230 (43,7%) were men, and 296 (56,3%) were women. The respondents were on the age from 18 to 70 years. 385 (73,2%) of them live in a city. The female population take antibiotics with a doctor's recommendation more in comparison with the male population. More than 50% of the respondents confirmed that the antibiotics affect both bacterias and viruses. 98 (42,6%) of the men, and 264 (56,1%) of the women responded that they are aware what antibiotics resistance is. From the total number of 264 respondents who said that know about antibiotics resistance, only 127 (48,1%) indicate that the doctors and tge pharmacists as the source of information. Conclusion: The population of the eastern region of our country is not informed enough for antibiotics usage and the antibiotics resistance. The information that only 127 (24,1%) respondents of a total number of 526 respondents has gained their information from doctors and pharmacists is worrying. The main reason for appearing of resistance to bacteria is excessive and unconscious use of antibiotics, their unnecessary consumption, discontinuation of the treatment before it is completed, taking inadequate (smaller) doses than necessary and disregarding the correct intervals when taking therapy.