By C. Ketil. University of Tennessee Health Science Center.
Матеріали згруповано за провідними напрямками науково-дослідної та навчальної роботи Національного фармацевтичного університету buy 500 mg keppra. Розглянуто теоретичні та практичні аспекти синтезу біологічно-активних сполук і створення на їх основі лікарських субстанцій; стандартизації ліків buy 250mg keppra free shipping, фармацевтичного та хіміко-технологічного аналізу; вивчення рослинної сировини та створення фітопрепаратів; сучасної технології ліків та екстемпоральної рецептури; біотехнології у фармації; досягнень сучасної фармацевтичної мікробіології та імунології; доклінічних досліджень нових лікарських засобів; фармацевтичної опіки рецептурних та безрецептурних лікарських препаратів; доказової медицини; сучасної фармакотерапії generic keppra 500 mg online, соціально-економічних досліджень у фармації order keppra 500mg with visa, маркетингового менеджменту та фармакоекономіки на етапах створення, реалізації та використання лікарських засобів; управління якістю у галузі створення, виробництва і обігу лікарських засобів; інформаційниих технологій у фармації та медицині; основ педагогіки та психології; суспільствознавства; філології. Book of Abstracts includes materials of Scientific and Practical Conference of Young Scientists and Students «Actual questions of development of new drugs». Materials are groupped according to the main directions of scientific, research and educational work of the National University of Pharmacy. The development of science has always been one of the most important tasks for our university. Because we are both the greatest pharmaceutical educational institution in our country, and the developed research structure, we want to provide not only good specialists, but also new and safe medicines. Of course, nowadays we already have powerful scientific basement – well-known scientists, professors and their achievements. Today 371 medicines with wide range of pharmacological activities are in various stages of implementation. But in order to continue the development of current research areas in the future we need you – students and young scientists with a strong desire to make our life better, healthier, happier. Different Student Scientific Societies have been fruitfully working in every department for 70 years already. Nowadays they unite more than 700 students, among them – students from foreign countries too. Student Scientific Societies are 3 the first step for students and young scientists on the way of improving their skills. You can choose the most interesting for you research area in pharmacy: from synthesis of new biologically active molecules and their analysis to preclinical and clinical testing, industrial aspects or marketing research. You have brilliant opportunity to test yourself in order to find your own way in science during students‘ years. Because altogether we are working for our main goal – development of new, safe and efficient medicines. Thus our Conference «Topical issues of new drugs development» is the first step for you today. Nowadays publication of abstracts is carried out entirely in English, as well as our plenary sessions. The Conference is an important part of your scientific work – an interesting and challenging pathway that leads to PhD degree, then to the degree of Doctor of Science, to professorship. Almost 90 % of our teaching staff, as well as I‘m myself, has started their scientific career the same way. Someone can say that scientific work isn‘t always easy and straight, that it needs lots of energy and even money. But we must understand that without the development of national science it‘s just impossible to make our country strong and independent, as it will be for sure in the nearest future. That‘s why the main goal for us is making science fashionable for talented youth and creating all necessary conditions for your scientific work. Smoking is an act of burning dried tobacco leaves and is inhaled which is easily absorbed into the bloodstream. It is gotten from a tobacco plant, which is dried and folded into cylindrical shapes and called cigarettes. It is also an administration route since combusted substances can easily be absorbed into the bloodstream and work actively in the various parts of the body. Cigarettes have additives substances called Nicotine, it causes aerosol and gases to have deep penetration in the lungs, which can be easily absorbed and causes the addictive character. The aim of the study was identification of harmful substances in cigarettes and their influence on the human body as activator of genetic and non- genetic conditions. Burning incense was also a means of Smoking which was mainly practiced by Babylonians, Chinese and Indians for ritual and religious purposes.
If different processes or equipment are used keppra 250 mg, support discount 250mg keppra fast delivery, for example order keppra 250mg mastercard, the photostability of a product under more site-speciﬁc batches or longer duration of data are in-use conditions or the photostability of analytical sam- recommended buy keppra 500 mg amex. For example, if a product has been The extent of drug product testing should be established determined to photodegrade on direct exposure but is ade- by assessing whether acceptable change has occurred quately protected by packaging, an in-use study may be at the end of the light exposure testing. Light Sources Under some circumstances, photostability studies should be repeated if certain postapproval or supplemental changes, The light sources described below may be used for pho- such as changes in formulation or packaging, are made to tostability testing. The applicant should either maintain an the product or if a new dosage form is proposed. Whether appropriate control of temperature to minimize the effect these studies should be repeated depends on the photosta- of localized temperature changes or include a dark control bility characteristics determined at the time of initial ﬁling in the same environment unless otherwise justiﬁed. For example, if initial studies both options 1 and 2, a pharmaceutical manufacturer or demonstrate that an active moiety in a simple solution applicant can rely on the spectral distribution speciﬁcation degrades on exposure to light and the tablet drug product is of the light-source manufacturer. Option 1 dosage form may warrant additional studies to characterize Option 1 is any light source that is designed to produce the photostability characteristics of the new dosage form. If deviations in packaging or labeling state- source emitting signiﬁcant radiation below 320 nm, an ments are made, additional studies may be recommended. Option 2 The intrinsic photostability characteristics of new drug For option 2 the same sample should be exposed to both substances and products should be evaluated to demon- the cool white ﬂuorescent and the near-ultraviolet lamp. An example of an actino- should be chosen to provide minimal interference with the metric procedure is provided in the Annex. For drug substances, photostability testing should consist Solid drug substances should be spread across the con- of two parts: forced degradation testing and conﬁrmatory tainer to give a thickness of typically not more than 3 mm. Drug substances that are liquids should be exposed in The purpose of forced degradation testing studies is chemically inert and transparent containers. This testing may involve the drug substance At the end of the exposure period, the samples should alone or in simple solutions or suspensions to validate the be examined for any changes in physical properties analytical procedures. In these assay and degradants by a method suitably validated for forced degradation studies, a variety of exposure condi- products likely to arise from photochemical degradation tions may be used, depending on the photosensitivity of processes. For development and validation purposes, sampling should ensure that a representative portion is it is appropriate to limit exposure and end the studies if used in individual tests. For photostable materi- ations, such as homogenization of the entire sample, als, studies may be terminated after an appropriate expo- apply to other materials that may not be homogeneous sure level has been used. The analysis of the exposed sample is left to the applicant’s discretion, although the exposure should be performed concomitantly with that of any levels used should be justiﬁed. Judgment of Results may be useful in developing and validating suitable ana- The forced degradation studies should be designed to pro- lytical methods. If, in practice, it has been demonstrated vide suitable information to develop and validate test they are not formed in the conﬁrmatory studies, these methods for the conﬁrmatory studies. If the results of the con- of the drug product and if light-resistant packaging is ﬁrmatory study are equivocal, testing of up to two additional needed. Samples should be selected ies to determine whether change caused by exposure to as described in the parent guidance. Some adjustment of testing conditions may have to be made when testing large-volume containers Normally, the studies on drug products should be carried (e. Analysis of Samples product in the immediate pack and then in the marketing At the end of the exposure period, the samples should be pack. Testing should progress until the results demonstrate examined for any changes in physical properties (e. For solid oral dosage–form products, testing should conﬁrmatory study are equivocal, testing of up to two be conducted on an appropriately sized composite of, for additional batches should be conducted. Similar sampling consid- For some products where it has been demonstrated that erations, such as homogenization or solubilization of the the immediate pack is completely impenetrable to light, entire sample, apply to other materials that may not be such as aluminum tubes or cans, testing should normally homogeneous after exposure (e. The analysis of the exposed sample should be It may be appropriate to test certain products, such as performed concomitantly with that of any protected sam- infusion liquids or dermal creams, to support their photo- ples used as dark controls if they are used in the test. Judgment of Results on and relate to the directions for use and is left to the applicant’s discretion. Depending on the extent of change, special labeling or The analytical procedures used should be suitably val- packaging may be needed to mitigate exposure to light. When evaluating the results of photostability studies to determine whether change caused by exposure to light is a.
Cardiovascular and pulmonary responses following etomidate induction of anesthesia in patients with demonstrated cardiac disease cheap 500 mg keppra otc. Sympathetic responses to induction of anesthesia in humans with propofol or etomidate generic keppra 250 mg fast delivery. Pharmacokinetics and pharmacodynamics of ketamine enantiomers in surgical patients using a stereoselective analytical method generic keppra 500 mg on-line. Differential effects of ketamine isomers on neuronal and extraneuronal catecholamine uptake mechanisms purchase 500 mg keppra free shipping. Ketamine decrease plasma catecholamines and improves outcome from complete cerebral ischemia in rats. Khan Z, Ferguson C, Jones R: Alpha-2 and imidazoline receptor agonists: their pharmacology and therapeutic role. Pharmacological treatment of lipid disorders is used according to guidelines published in 1992 (Table 13-2). New pediatric lipid guidelines are being developed and will likely reflect this type of thinking. Although atherosclerosis is known to begin in childhood, extensive outcome data are lacking in pediat- rics, and parental and/or patient preferences are usually included in the decision- making process. Nonpharmacological Lipid Lowering Diet and Activity Dietary counseling for abnormal lipid levels should be tailored to address the lipid profile of the child and the circumstances of the family. The Step 2 diet, which severely restricts saturated fat (≤7%) and dietary cholesterol (≤200mg/day), is probably too difficult for a child to follow and is not recommended. Low-fat diets are not recommended for children younger than age 2 years because of concerns regarding adequate neuronal myeli- nation. Pharmacotherapy Lipid-lowering medications are usually initiated if diet and exercise changes fail to improve values sufficiently (Table 13-2). Mechanism of Action Positively charged sequestrants bind to negatively charged bile acids in the intestines and prevent the reabsorption of cholesterol-con- taining bile. Pharmacokinetics Absorption: the sequestrants remain in the gut and are not systemically absorbed, thus, the side effect profile is minimal. Adverse Effects Gastrointestinal: bloating, constipation can be reduced by allowing the preparation to sit for several hours before taking (it should be refrigerated), and by increasing fiber (dietary or psyllium supplements) and liquid intake Decreased compliance: because of gritty powder or large pills. One study showed approximately 40% noncompliance in children with familial hypercholesterolemia over 18 weeks of treatment7 322 S. Both male and female subjects are included, and the subjects are primarily those with familial hypercholesterolemia. The trials are relatively small, with the larg- est including 214 participants, and the agents evaluated include simvastatin,11,12 lovastatin,13,14 pravastatin,15,16 and atorvastatin. However, there are no long-term safety data, and no trial specifically addressed whether puberty is affected, a concern because cholesterol is a precursor for sex steroid hormones. Niacin and fibrate and low glycemic load data are taken from adult experience because of the lack of pediatric data (reference 3 and 21). Atorvastatin levels are increased in those drinking more than 1 quart/day of grapefruit juice. Statins tend to increase intestinal absorption of cholesterol, which means they combine well with cholesterol absorption inhibitors. Con- comitant dosing of any statin may be acceptable if the statin is administered at 25% of usual dose (maximum 20mg for most statins, 10mg for rosuvas- tatin) with careful monitoring. Pediatric trials are small, but they also have not shown significant side effects, including rhabdomyolysis. The muscle ache is similar to the myalgias accompanying influenza, starting in the extremities and accompanied by weakness and fatigue. Of those with true myopathy, more than 50% are receiving other drugs that increase risk, have medical problems such as hepatic or renal insufficiency, older age (particularly > 80 yr), or are small in size (relevant for pediatrics). In a 1-week multiple-dose trial, ado- lescents showed similar pharmacokinetics to those seen in adults. Pharmacokinetics Absorption and metabolism: ezetimibe is glucuronidated in the intestinal wall and circulated enterohepatically; there is presumably minimal sys- temic exposure, which may explain the low side effect profile Elimination: most is excreted in the feces Drug-Drug Interactions Concomitant administration with cyclosporine or gemfi- brozil raises the concentrations of both drugs. Adverse Effects Gastrointestinal: diarrhea, nausea, taste changes, pancreatitis, cholelithiasis Muscular: may potentiate statin-induced myopathy 326 S.
When the same animals received a cannula in the bile-duct and were given an oral dose generic 250 mg keppra with mastercard, 31% of the radiolabel was found in faeces generic keppra 500mg overnight delivery, 38% in urine and 22% in bile order keppra 250 mg on line. After an intra- venous dose buy keppra 250 mg low price, 11% was eliminated in faeces, 35% in urine and 43% in bile (Visek et al. The profile of systemic blood concentration–time for phenolphthalein during 24 h after a single intravenous bolus injection was described by a classical compartmental pharmacokinetics model, with evidence of enterohepatic recirculation (Colburn et al. In the two-year bioassays of the National Toxicology Program (1996), the concen- trations of total phenolphthalein in plasma were 100–200 μg/mL. As evidenced by the presence of radiolabel in peri- pheral organs (including the kidney, liver and skin), the compound was absorbed. After 2 h, it had arrived in the large intestine, and 4 h after administration, maximum radio- label was observed in the rectum. Serious side-effects were reported in cases of habitual phenol- phthalein consumption under conditions of abuse (Cooke, 1977; Pietrusko, 1977). The main target organ for the toxic effects of phenolphthalein is reported to be the intestine. Indiscriminate use of phenolphthalein results in chronic constipation and laxative dependence, loss of normal bowel function and bowel irritation. The clinical condition, which resembles chronic ulcerative colitis both radiologically and pathologically, involves thinning of the intestinal wall and loss of the normal mucosal pattern of the terminal ileum (Cummings, 1974; Cummings et al. Anecdotal cases of long-term use or overdose of phenolphthalein have been asso- ciated with abdominal pain, diarrhoea, vomiting, electrolyte imbalance (hypo- kalaemia, hypocalcaemia and/or metabolic acidosis or alkalosis), dehydration, mal- absorption, protein-losing gastroenteropathy, steatorrhoea, anorexia, weight loss, polydipsia, polyuria, cardiac arrhythmia, muscle weakness, prostration and histo- pathological lesions (Heizer et al. Kidney, muscle and central nervous system disturbances are thought to be due to electrolyte imbalance. Loss of intestinal sodium and water stimulates compensatory renin production and secondary aldosteronism, leading to sodium conservation and potassium loss by the kidney. The hypokalaemia contributes to renal insufficiency and is sometimes associated with rhabdomyolysis (Copeland, 1994). Abuse of phenolphthalein-containing laxatives has been associated with gastro- intestinal bleeding, iron-deficient anaemia (Weiss & Wood, 1982), acute pancreatitis (Lambrianides & Rosin, 1984) and multiple organ damage in cases of massive over- dose, including fulminant hepatic failure and disseminated intravascular coagulation (Sidhu et al. Allergy to phenolphthalein is often manifested as cutaneous inflammatory reactions or fixed drug eruptions, i. These lesions characteristically recur in the same location with each subsequent dose of phenolphthalein and generally leave residual hyperpigmentation that increases in intensity with each exposure; numerous melanin- containing dermal macrophages have been found in pigmented areas (Wyatt et al. Despite the profile of low acute toxicity documented in this study, cases of fatal poisoning of children have been reported; symptoms of pulmonary and cerebral oedema, multiple organ effects and encephalitis were attributed to hypersensitivity reactions (Cleves, 1932; Kendall, 1954; Sarcinelli et al. Repeated adminis- tration of phenolphthalein-containing laxatives to children has led to serious illness and multiple hospitalizations (Sugar et al. Phenolphthalein did not appear to be toxic in rats, and no laxative effect was observed. Treated rats showed increased relative (to body weight) kidney weights (males only) and elevated absolute and relative liver weights at concentrations of 12 000–50 000 ppm. Female rats showed no effect on body-weight gain, but those receiving concentrations of 6000–50 000 mg/kg had elevated liver weights. The primary treatment-related findings in mice involved the reproductive and haematopoietic systems. The haematopoietic changes included bone-marrow hypo- plasia (at 12 000–50 000 mg/kg) and increased splenic haematopoiesis (males only; 25 000 and 50 000 mg/kg) (National Toxicology Program, 1996). In female mice [strain not specified] fed 5, 25 or 50 mg/kg bw phenolphthalein per day orally for 135 days, no toxic manifestations or evidence of histopathological changes were found in the liver, kidney or gastrointestinal tract (Visek et al. Phenolphthalein at doses of 25 and 50 μg/mL was cytotoxic in cultured Chang liver cells, causing decreased cell growth and increased anaerobic glycolysis, i. Doses of 1–10 mg given subcutaneously twice daily for two days to female Wistar rats weighing 35–40 g induced a dose-related increase in uterine weight, but the maximum increase was only about half of that induced by oestradiol. Phenolphthalein was shown to bind to the oestrogen receptor and was a competitive antagonist to oestradiol (Nieto et al. In a study reported in an abstract, exposure of female B6C3F1 mice to 1895 mg/kg bw phenolphthalein orally [method not stated] daily for 30 or 60 days caused no changes in weight gain, oestrous cycles or the numbers of oocyte-containing follicles of any class (primordial, primary, growing or antral), or any detectable pathological change in ovarian cells (Hoyer et al. Pairs of 40 control and 20 treated mice were housed together and allowed to produce up to five litters, the last of which was reared and their reproductive performance measured. Significant reproductive toxicity was observed at the intermediate and high doses.