Abstract Respiratory failure is the predominant cause of death in humans and animals poisoned with anticholinesterases. Organophosphorus and carbamate anticholinesterases inhibit acetylcholinesterase irreversibly and reversibly, respectively. Some of them contain a quaternary atom that makes them lipophobic, limiting their action at the periphery, i.e. outside the central nervous system. They impair respiratory function primarily by inducing a desensitization block of nicotinic receptors in the neuromuscular synapse. Lipophilic anticholinesterases inhibit the acetylcholinesterase both in the brain and in other tissues, including respiratory muscles. Their doses needed for cessation of central respiratory drive are significantly less than doses needed for paralysis of the neuromuscular transmission. Antagonist of muscarinic receptors atropine blocks both the central and peripheral muscarinic receptors and effectively antagonizes the central respiratory depression produced by anticholinesterases. To manage the peripheral nicotinic receptor hyperstimulation phenomena, oximes as acetylcholinesterase reactivators are used. Addition of diazepam is useful for treatment of seizures, since they are cholinergic only in their initial phase and can contribute to the occurrence of central respiratory depression. Possible involvement of central nicotinic receptors as well as the other neurotransmitter systems – glutamatergic, opioidergic – necessitates further research of additional antidotes.

BACKGROUND/AIM Prescription of drugs is a fundamental care component of the elderly. Elderly patients often take multiple drugs, and it is known that polypharmacy may lead to drug interactions and adverse events. The aim of this study was to analyze the long-term drug use and the prevalence of polypharmacy among the elderly population in the Republic of Srpska, Bosnia and Herzegovina. METHODS; A retrospective study of outpatient drug use in 2005 and 2010 was conducted, analyzing prescriptions for patients aged ≥ 65 years reimbursed by the Health Insurance Fund. The study population was stratified by gender and age. Long-term drug use was defined as continuous drug dispensing for a whole year or at least two thirds of the year. Polypharmacy was defined as the use of 5 or more different reimbursed drugs. RESULTS Of all insured people aged ≥ 65 years, long-term drug use was identified in 10% (2005) and in 19% (2010), of whom 62% were women. Two to four different drugs were used by almost 49% (2005) and 54% (2010) of the elderly patients. The polypharmacy prevalence increased from 1.4% (2005) to 3.6% (2010); it increased in all the age groups of both genders. The largest increase was observed in the age group 65-74 years. Polypharmacy prevalence increase was higher in women. The most commonly used drugs were those for to treatment of cardiovascular diseases, in particular drugs for hypertension and cardiac treatment. CONCLUSION The study findings point out to the increase of elderly population with a long-term drug use. Over a half of elderly patients use 2-4 different drugs on the long-term basis. The polypharmacy prevalence was low. It increased in the period of 5 years in both genders. The increase was more prominent in women of all the age groups. The use of multiple drugs and polypharmacy increased with ageing.

Research on the renin-angiotensin system (RAS) has contributed significantly to advances in understanding cardiovascular and renal homeostasis and to the treatment of cardiovascular diseases. This review offers a brief history of the RAS with an overview of its major components and their functions, as well as blockers of the RAS, their clinical usage and current research that targets various components of the RAS. Because angiotensin-converting enzyme (ACE) metabolizes two biologically active peptides, one in the kallikrein-kinin system (KKS) and one in the RAS, it is the essential connection between the two systems. ACE releases very powerful hypertensive agent, angiotensin II and also inactivates strong hypotensive peptide, bradykinin. Inhibition of ACE thus has a dual effect, resulting in decreased angiotensin II and increased bradykinin. We described the KKS as well.

Introduction. Information on antibiotic utilization in the Republic of Srpska is limited. The aim of this study was to analyze antibiotic utilization in the community from 2007 to 2011 and to compare this data with antibiotic use in other European countries. Materials and Methods. We did a population-based study to analyze systemic antibiotic utilization by an outpatient population using Anatomical Therapeutic Chemical/Defi ned Daily Dose methodology. The results were expressed as the defi ned daily dose (DDD) per 1000 inhabitants per day. The data were obtained from the annual reports of the Agency for Drugs and Medical Devices of the Republic of Srpska and Public Health Institute. Results. Outpatient use of systemic antibiotics ranged between 21.51 DDD in the year with the highest use (2010) and 17.01 DDD in the year with the lowest use (2011). Penicillins were the most frequently prescribed antibiotic group, and amoxicillin was the most frequently prescribed drug. Cefalexin was the most frequently prescribed cephalosporin. Increased use of a second-generation cephalosporin, cefuroxime constituted almost a third of cefalexin consumption in 2011. Second-generation quinolones, mostly ciprofl oxacine, accounted for about 70% of total quinolones consumption, with rising third-generation drugs also in proportion to the increasing use. Erythromycine was the most frequently used macrolide, followed by long-acting azithomycin. Conclusion. Outpatient use of systemic antibiotics in the Republic of Srpska, at about 19 DDD, does not exceed that in Europe. As in other European countries, a shift between generations of drugs was noted for antibiotic use. Additional studies, including monitoring of seasonal variation impact on antibiotic use, are needed.

In this article the neurotoxic disorders appearing in patients poisoned with organophosphorus pesticides (OPs) are reviewed. OPs cause four important neurotoxic effects in humans: the cholinergic syndrome, the intermediate syndrome, organophosphate-induced delayed polyneuropathy and chronic organophosphateinduced neuropsychiatric disorder. Compared to the cholinergic syndrome, that causes millions of cases of poisoning with fatality of more than 15% each year, other disorders involve much smaller number of patients. This article is focused on neurotoxic disorders appearing after acute and chronic exposure to OPs with emphasis on clinical presentation, molecular mechanisms and possibilities of medical treatment.

Great scientifi c discoveries rarely originate from small and poor countries, especially if they are frequently engulfed in wars, like it was the case with Serbia, and other parts of the former Yugoslavia. Despite the odds, quite a few well educated, curious, wise, and brave minds have made signifi cant contributions under such circumstances. For example, the achievements of Laza K. Lazarević (18511891), Milutin Milankovic (1879-1958), Ivan Djaja (18841957), Pavao Stern (1913-1976), and several other Yugoslav researchers clearly show that some scientists are able to make great discoveries under limited resources. 1 Nikola Tesla (1856-1943), and two Nobel laureates of Yugoslav origin, Leopold Ruzicka (1887-1976) and Vladimir Prelog (1906-1998), are only mentioned here because their major scientifi c contributions had been mostly conducted in the USA and Switzerland.