Determination of diclofenac residue in swine tissue following intramuscular administration

Diclofenac residue (DF) in swine tissue (liver, kidney, muscle, injection site) were examined using the method of High Performance Liquid Chromatography (HPLC) 15h, 72h,and 120h after i.m. administration of an individual therapeutic dose of diclofenac-sodium. At 15h after administration, the highest concentration of DF was found in the kidney (0.614 mg/kg), while a concentration about two times lower was found in the liver (0.316 mg/kg). At the injection site, the DF concentration was 0.432 mg/kg, while DF remained in a very low concentration (0.052 mg/kg) in the muscle outside the injection site, which was the lowest concentration in comparison with all the other examined tissues. At 72h after administration, DF was present in all examined tissues, but its concentrations were lower than the level that could be determined using the analytic procedure. Traces of the administered medicine disappeared after the waiting period of 120h in all tissues, except for the injection site. The longer presence of the medicine at the injection site could be a consequence of local inflammation, or irritation, that could cause a reduction in pH values of the area around the injection site, thus leading to slower dissolving and a longer presence of the DF at the injection site

Farmakokinetika inhalacionih kortikosteroida

The inhaled corticosteroids have improved asthma therapy significantly. The inhaled route allows the delivery of relatively small doses directly to the airway, providing a high local concentration and minimizing systemic adverse effects. Knowledge of pharmacokinetic properties of inhaled corticosteroids (deposition in respiratory system, rate of absorption, first-pass effect oral bioavailability, distribution and elimination) is a prerequisite for successful asthma therapy. Inhaled corticosteroids show various levels of oral bioavailability and significant differences in the rate of absorption. Rate of absorption is one of the most relevant properties of inhaled corticosteroids as it reflects pulmonary residence time and therefore duration of availability in the lungs. Significant hepatic first-pass metabolism of the swallowed dose of some corticosteroids (fluticasone propionate, budesonide) reduces oral bioavailability and systemic adverse effects. Pharmacokinetic properties could also be applied to predict and explain the systemic adverse effect profiles of inhaled corticosteroids. Taking into consideration the revealed differences in pharmacokinetic properties of inhaled corticosteroids enable individual therapeutic approach, better efficacy and safety of asthma treatment

Uloga farmaceuta u terapiji kardiovaskularnih bolesti

Sweeping changes continue to reshape the practice of pharmacy. The pharmacy professional needed today is a knowledgeable drug expert and skilled, persuasive communicator. Such pharmacist embraces a practice model-pharmacy care. Pharmacists play a major role in reducing the risk of vascular events via various interventions: promotion of health, prevention of disease, patient counseling for pharmacological and/or non-pharmacological treatment, support of adherence... Adherence to cardiovascular therapy is essential to optimal therapeutic outcomes. The common factors affecting adherence to cardiovascular therapy are: complexity of regimens, polypharmacy, frequent dosing times of some medicines, non-apparent effects on discontinuing medication, declined capability with increased age and patients health beliefs. The pivotal role of the pharmacist in optimizing adherence to cardiovascular therapy encompasses many actions: assessing the adherence problem, identifying predisposing factors, providing comprehensive counseling, and recommending specific adherence strategies targeted to the patient ,s needs

Farmakokinetika gastrointestinalnih lekova od značaja za racionalnu farmakoterapiju

Although much progress in the pharmacotherapeutic treatment of gastrointestinal diseases has been made during recent years, a lot of research is still needed in order to elucidate exact disease mechanisms, and to develop corresponding drugs. From the treatmens of Helicobacter pylori infections which are still far from ideal, through pharmacotherapy of irritable bowel syndrome which is not satisfactory, to directon for recognition and integration of important factors in pharmacotherapy of inflammatory bowel disease (genetic, infectious, immunologic and inflammatory), there are many open questions. The pharmacotherapy research today goes towards development of new drugs and vaccines based on the discovery of new receptors, appreciation of influence of important general and individual factors of diseases, as well as preventive and pharmacoeconomic treatment considerations. Pharmacokinetic principles considerations are necessary within all the pharmacotherapy ways, in order to develop drugs and drug products of better pharmacokinetics, and to provide individualized, effective and safe, as well as economic (rational) pharmacotherapy.Iako je tokom poslednjih godina učinjen veliki progres u farmakoterapiji gastrointestinalnih oboljenja, još uvek je potrebno mnogo istraživanja da bi se razjasnili egzaktni mehanizmi bolesti i razvili odgovarajući lekovi. Od tretmana infekcije sa Helicobacter pylori, koji se još uvek smatraju daleko od idealnih, preko farmakoterapije iritabilnog sindroma creva koja je nezadovoljavajuća, do usmeravanja na uvažavanje faktora značajnih za farmakoterapiju inflamatornog oboljenja creva (genetički, infektivni, imunološki i inflamatorni), još je mnogo otvorenih pitanja. Farmakoterapijska istraživanja danas idu u pravcu razvoja novih lekova i vakcina zasnovanih na otkriću novih receptora, uvažavanju uticaja značajnih opštih i individualnih faktora bolesti, kao i preventivnim i farmakoekonomskim razmatranjima lečenja. Razmatranje farmakokinetičkih principa je potrebno u okviru svih farmakoterapijskih pravaca, u cilju iznalaženja lekova i preparata bolje farmakokinetike i sprovođenja individualizovane, efikasne i bezbedne, kao i ekonomične (racionalne) farmakoterapije

Racionalna farmakoterapija kardiovaskularnih bolesti - značaj farmakokinetike, interakcija i neželjenih efekata lekova

Cardiovascular diseases therapy is very complex task, primarily due to the fact that many of these diseases are simultaneous, that one class of drugs is used in several indications, and that the therapy is often of combined type. The knowledge of pharmacokinetics, interactions and side effects of the drugs used, significantly contribute to the rational pharmacotherapy, as well as the collaboration of all health care professionals. Beside the therapeutic drugs (ACE inhibitors, antiarrhytmics, cardiotonic glycosides, diuretics and nitrates), the complete knowledge on risk factors drugs , such as anticoagulants and hypolipemics, is also needed. For the pharmacist in health care team, therapeutic drug monitoring, direct such as with cardiac glycosides, or alternative with anticoagulant drugs, is also of great importance

Klinički značaj interakcija i neželjenih efekata gastrointestinalnih lekova

The most frequently prescribed drugs used for the treatment of gastrointestinal disorders and/or diseases are drugs for peptic ulcer disease, drugs against ulcerative colitis and Chron,s disease. The experience with ulcer-healing drugs suggests that this group belongs to relatively safe group of drugs with common adverse reactions such as: dizziness, fatigue, rash, diarrrhoea, headache, nausea, constipation, abdominal pain...H2 receptor antagonist (cimetidine, ranitidine) and proton pump inhibitors are metabolized by cytochrome P450 isoenzymes and can potentially interact with other drugs that undergo cytochrome P450 metabolism. A wide range of drugs (corticosteroids, aminosalicylates, immunosuppressive agents) is available for treatment of Chron,s disease and ulcerative colitis and these drugs are more vulnerable to adverse reactions than ulcer-healing drugs. Successful and safe therapy relies upon patients adhering to their drug therapy. Beside educating patients about the principle of prescribed therapy it is also important to inform patient about common adverse effects associated with drug regimen and how to cope with them. Knowledge of adverse effects profile of drugs for gastrointestinal disorders and their clinicaly significant interactions are important for prevention and treatment of unwanted effects.Neželjeni efekti lekova koji se koriste u terapiji gastrointestinalnih poremećaja i/ili oboljenja su veoma raznovrsni i imaju različit stepen ispoljavanja. Poznavanje mehanizama nastanka neželjenih efekata neophodno je za prevenciju i umanjenje njihovog ispoljavanja, dok su prepoznavanje i tretman ispoljenih neželjenih efekata od značaja za sprovođenjue racionalne terapije gastrointestinalnih poremećaja i/ili oboljenja. Jedan od čestih uzroka prestanka terapije i niskog stepena komplijanse jesu ispoljeni neželjeni efekti propisane terapije. Otuda je veoma važno upoznati pacijente o značaju poštovanja propisane terapije u cilju njenog uspeha, o mogućim ispoljenim neželjenim efektima, kao i načinu njihovog uklanjanja ili umanjenja. Poznavanje klinički značajnih interakcija gastrointestinalnih lekova sa drugim istovremeno primenjenim lekovima, takođe, je neophodno za efikasnu ali i bezbednu terapiju gastrointestinalnih poremećaja. Odgovornost farmaceuta i lekara je da objektivno informišu bolesnika o: principima terapije gastrointestinalnih oboljenja, značaju načina života i ishrane, važnosti redovne terapije, kao i načinu umanjenja neželjenih efekata koji prate propisanu terapiju

Genetički polimorfizam izoenzima Citohroma P450

The aim of this review is to explain genetic basis of interindividual variability in cytochrome P450 (CYP450) dependent drug metabolism and highlight the clinical significance of different polymorphisms. Nearly all CYP450 isoenzymes involved in drug metabolism have been shown to be polymorphic, although some of them are functionally well conserved (CYP2E1 and CYP3A4) in comparison with others (CYP2D6, CYP2C19 and CYP2C9). Genetic variability in drug metabolizing enzymes can be assessed at the level of phenotype (by investigating enzyme level/activity) and/or genotype (by determining which alleles are present). Polymorphism divides a population into at least two phenotypes: individuals with deficient metabolism are termed „poor metabolizers” (PM), as compared to normal or „extensive metabolizers” (EM). In case of CYP2D6, „ultrarapide metabolizers” (UM) with extremely high enzyme activity, have also been identified. The clinical significance of particular polymorphism depends on the importance of metabolic pathway under polymorphic control, therapeutic index (TI) of a drug and its active metabolites, and incidence of the polymorphism in a particular population. Therapeutic consequences vary from increased risk of adverse reactions in PM, to therapeutic failure at standard drug doses in UM (if drug metabolites are inactive). Drug dosage, especially for narrow TI drugs, should be adjusted to the metabolic capacity of a patient , by phenotyping/genotyping prior to drug therapy

Klinički značajne interakcije antibiotika i antimikotika sa drugim lekovima

Antibiotics (AB) and antifungals are large, heterogeneous, and commonly prescribed groups of drugs. Even thou, their use in therapy are considered to be safe, during concomitant use with other drugs the result can be clinically important interaction. Certain classes of AB or antifungal drugs are known to interact with many other drugs, but the interaction potential of them is not uniform among members of the class. Therefore, choosing the appropriate drug allows the possibility to avoid potentially dangerous drug-drug interactions.Antibiotici (AB) i antimikotici predstavljaju velike, heterogene i često propisivane grupe lekova. Iako se smatraju za relativno bezbedne lekove, pri istovremenoj primeni sa drugim lekovima mogu da stupe u klinički značajne interakcije. Određene grupe AB i antimikotika su poznate da stupaju u interakcije, ali potencijal za stupanje u interakcije unutar istih klasa lekova je različit, što pruža mogućnost da se odgovarajućim odabirom AB odnosno antimikotika izbegnu potencijalno štetne lek-lek interakcije