Feldene

Susan M. Harding, M.D.

• Assistant Professor of Medicine
• Pulmonary and Critical Care Medicine
• University of Alabama
• Birmingham, AL

It functions to break the chain of free radical reactions that result in lipid peroxidation arthritis pain diet mayo clinic order feldene amex. Vitamin C (ascorbate) is a water-soluble free radical scavenger that may help to inhibit lipid peroxidation arthritis pain emergency room purchase feldene pills in toronto. Vitamin A (carotinoids) has many diverse actions on systems name of arthritis in back discount feldene 20mg on-line, such as the immune system rheumatoid arthritis prognosis discount feldene 20 mg otc, in addition to being an antioxidant arthritis relief plus order feldene 20 mg amex. There is evidence from animal studies that it extends mean (average) life span arthritis relief for wrists cheap feldene 20mg fast delivery, but there is controversy as to whether it extends maximal life span. One of these models is the simulation of hypoxia and the resulting oxidative damage in young rats. In this rat model of hypoxia, vitamin E sup plementation prevented the oxidative damage seen with inadequate oxygen availability. With regard to aging itself, the protective effects of vitamin E have been studied in the brain tissue of aging rats. One study compared several biochemical markers in the brain cortex from young and old rats. These elevated markers were not observed in old animals fed a diet of vitamin E and ascorbate for 12 weeks. There are also increases in lipid peroxidation and in ammation in old animals that may be related to increased oxidative stress. Brain striatal slices from young and old rats were studied directly in perfusion chambers. Slices from old animals were more sensitive to oxidative stress than slices from young animals. However, preincubation with vitamin E reversed the sensitivity to oxidative stress. This suggests that the old striatum has decreased antioxidant capacity compared to the young, but that this capacity can be boosted by exogenous antioxidants. For example, culturing primary rat embryonic hippocampal neurons with the full-length peptide (Abeta(1-42)) results 16 Geriatric Nutrition in increased protein oxidation, oxygen radical formation, and neurotoxicity. In addition to possible protective effects in the brain, dietary vitamin E has been shown to be bene cial to the immune system. Feeding vitamin E for 6 weeks boosted the immune response of aged mice to that seen in young mice. In a direct test of immune function, old mice were challenged with in uenza virus. These effects of vitamin E may be independent of its antioxidant properties, since other antioxidants had no effect in the same study. Traditionally, the bene cial effects of the avonoids have been attributed to their ability to act as antiox idants by neutralizing free radical compounds. However, recent studies have indi cated that avonoids can also modulate cell signaling pathways independent of their antioxidant properties. In intact mouse studies, this preparation was found to considerably prolong the survival time of mice undergoing lethal hypoxia. In one study using rat cerebellar neurons, pretreatment with Ginkgo extract increased the survival of cells subsequently challenged by oxidative stress induced by hydrogen peroxide. This has led to the study of the possible bene ts of fruit and vegetable polyphenolic compounds. Rats were fed diets containing 1 to 2% extracts of strawberry or spinach from 6 to 14 months of age. These behavioral changes correlated with retar dation of age-related changes in brain biochemical function. The spinach extract had the most bene cial effect, but the strawberry extract was also effective. These results prompted the question of whether fruit extracts could reverse already existing de cits. The effects of strawberry, spinach, and blueberry extracts were studied in old rats with behavioral de cits. However, the blueberry diet stimulated hippocampal signaling pathways in ways associated with improved memory. This suggests that fruit polyphenols may have speci c effects in the brain not related to their antioxidant properties. These effects may include increasing receptor sensitivity, improving ion buffering, and reducing premature death of neuronal cells. Some of these proteins are components of the mitochondrial electron transport chain. Mitochondria perform many other functions in the cell in addition to generating energy, such as regulating intracellular calcium and participating in apoptotic pathways. This group proposes several ways by which nutri ents may have a positive effect on mitochondrial function: (1) protecting and enhanc ing mitochondrial enzymes, (2) increasing antioxidant defenses, (3) reducing oxidant stress by reducing free radical production, and (4) repairing mitochondrial structural damage. Three dietary compounds that may have one or more of these effects are L-carnitine, lipoic acid, and coenzyme Q. Its bene ts include antioxidant activity, improved mitochondrial energy production, and stabilization of intracellular membranes. This is consistent with a more recent report in mice that feeding CoQ10 produced gene alterations consistent with reduced oxidative stress in the 20 Geriatric Nutrition heart. It may be that the effects of CoQ10 are more evident when older animals are stressed rather than in longitudinal aging studies. At the cellular level, the mitochondria are both a source and a target for free radicals. In addition, the fate of the cell itself may lie in part with mitochondria, since they play a role in cell death, cell senescence, and apoptosis. As cellular function and cell cycles change with age, the regulatory systems of which they are a part also change. This results in the decreased capacity of an organism to regulate itself in the face of external stressors. In addition, increased longevity is associated with low insulin and glucose levels and increased sensitivity to insulin, such as in dwarf mice. When the gene for the growth hormone receptor/bind ing protein is disrupted in mice, they live signi cantly longer. However, long-term exposure to high glucocorticoid levels may have negative effects on the nervous system, including neuronal degeneration. It has been argued that the aging of the immune system may be due in part to chronic stress and elevated glucocorticoids. It has been known for many years that this signi cantly increases mean and maximal life span in rodents. Some studies show an increase in enzymatic activity associated with free radical defenses in some tissues. These changes in the glucose/insulin system are similar to those seen in long-lived dwarf mice. It has bene cial effects at the molecular, cellular, and homeostatic systems levels in rodents. However, the restrictedness of the diet and its composition would make it impractical as a general intervention in a food-conscious Western society. In one study, the effects of feeding 2-deoxyglucose were compared to the effects of intermittent feeding, a type of dietary restriction, over a 6-month period in young rats. However, in addition to being antioxidants, they also have effects on fatty acid oxidation in mitochondria. Feeding a diet composed of vitamins, minerals, herbs, and antioxidants has been reported to extend longevity in mice. It increases stress hormone levels even as it increases life span and improves physiological functioning. However, Masoro proposes that the increase in glucocorticoids itself may be bene cial, perhaps by reducing in ammation. As an example, curcumin, an antioxidant derived from turmeric, a curry spice, also induces heat shock proteins, a stress response. This raises the interesting possibility that dietary intake of small amounts of compounds normally considered harmful may induce antioxidant defenses and have long-term bene cial effects. Recent studies suggest why certain nutrients may be bene cial and also suggest new strategies. Some of the nutritional interventions are very familiar, such as the antioxidant vitamins. However, even here there are some surprises, as antioxidants such as vitamin E seem to have speci c actions in cells that go far beyond their antioxidant properties. In recent years, it has become clearer how fruit polyphenols may have bene cial effects at the molecular level. These studies are exciting because this class of compounds is found in fruits such as strawberries, spinach, and blueberries. Studies of mitochondrial aging have suggested new nutritional interventions such as L-carnitine and lipoic acid. These compounds appear to have speci c effects on mitochondrial energy production and antioxidant capability. They have not yet been demonstrated to have an effect on longevity, but they do have an effect on cognitive function in old animals. This would have important implications if they were found to have the same effects in humans. Finally, recent studies suggest that a mechanism exists in rodents, probably in nonhuman primates and possibly in humans, that responds to caloric stress. This target is particularly attractive since the response to caloric stress is so robust. It may be that true caloric mimetics will be found given the great commercial interest. On the other hand, caloric stress may be just one of broader classes of stress responses. Activating these by nutritional means could potentially give the bene ts of an enhanced stress response while minimizing the unpleasant side effects. Membrane alteration as a basis of aging and the protective effects of calorie restriction. Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L-carnitine and/or R-alpha-lipoic acid. Effect of vitamin E supplementation on hypoxia-induced oxidative damage in male albino rats. Protective effect of vitamin E, beta-carotene and N-acetylcysteine from the brain oxidative stress induced in rats by lipopolysaccharide. Dietary supplementation with vitamin E reverses the age-related de cit in long term potentiation in dentate gyrus. Vitamin E supplementation suppresses prostaglandin E1(2) synthesis and enhances the immune response of aged mice. Effect of long-term dietary antioxidant supplementation on in uenza virus infection. A review of speci c dietary antioxidants and the effects on biochemical mechanisms related to neurode generative processes. Effects of Ginkgo biloba constituents related to protection against brain damage caused by hypoxia. Ginkgo biloba extract protects brain neurons against oxidative stress induced by hydrogen peroxide. Prevention of neuronal cell damage induced by oxidative stress in-vitro: effect of different Ginkgo biloba extracts. Reversing the deleterious effects of aging on neuronal communication and behavior: bene cial properties of fruit polyphenolic compounds. Long-term dietary strawberry, spinach, or vitamin E supplemen tation retards the onset of age-related neuronal signal-transduction and cognitive behavioral de cits. Reversals of age-related declines in neuronal signal transduction, cog nitive, and motor behavioral de cits with blueberry, spinach, or strawberry dietary supplementation. Blueberry supplementation enhances signaling and prevents behavioral de cits in an Alzheimer disease model. Minireview: the role of oxidative stress in relation to caloric restriction and longevity. Effect of ageing and caloric restriction on speci c markers of protein oxidative damage and membrane peroxi dizability in rat liver mitochondria. Mitochondrial decay in hepatocytes from old rats: membrane potential declines, heterogeneity and oxidants increase. Acetylcarnitine and cellular stress response: roles in nutritional redox homeostasis and regulation of longevity genes. Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress.

Accidental parenteral inoculation of the toxin is the primary hazard to laboratory personnel arthritis in knee from running order on line feldene. Because it is uncertain if tetanus toxin can be absorbed through mucous membranes rheumatoid arthritis research generic feldene 20mg with amex, the hazards associated with aerosols and droplets remain unclear arthritis knee icd 10 feldene 20mg without a prescription. Special Issues Vaccines the vaccination status of workers should be considered in a risk assessment for workers with this organism and/or toxin rheumatoid arthritis methotrexate generic 20mg feldene fast delivery. While the risk of laboratory-associated tetanus is low arthritis in back of knee generic feldene 20 mg mastercard, the administration of an adult diphtheria tetanus toxoid at 10-year intervals further reduces the risk to laboratory and animal care personnel of toxin exposures and wound contamination arthritis pain home treatment buy feldene online, and is therefore highly recommended. Corynebacterium diphtheriae Corynebacterium diphtheriae is a pleomorphic gram-positive rod that is isolated from the nasopharynx and skin of humans. The organism is easily grown in the laboratory on media containing 5% sheep blood. Natural Modes of Infection the agent may be present in exudates or secretions of the nose, throat (tonsil), pharynx, larynx, wounds, in blood, and on the skin. Travel to endemic areas or close contact with persons who have returned recently from such areas, increases risk. Naturally occurring diphtheria is characterized by the development of grayish white membranous lesions involving the tonsils, pharynx, larynx, or nasal mucosa. An effective vaccine has been developed for diphtheria and this disease has become a rarity in countries with vaccination programs. Francisella tularensis Francisella tularensis is a small gram-negative coccobacillus that is carried in numerous animal species, especially rabbits, and is the causal agent of tularemia (Rabbit fever, Deer fy fever, Ohara disease, or Francis disease) in humans. Type A and Type B strains are highly infectious, requiring only 10-50 organisms to cause disease. The incubation period varies with the virulence of the strain, dose and route of introduction but ranges from 1-4 days with most cases exhibiting symptoms in 3-5 days. Occasional cases were linked to work with naturally or experimentally infected animals or their ectoparasites. Natural Modes of Infection Tick bites, handling or ingesting infectious animal tissues or fuids, ingestion of contaminated water or food and inhalation of infective aerosols are the primary transmission modes in nature. Occasionally, infections have occurred from bites or scratches by carnivores with contaminated mouthparts or claws. Direct contact of skin or mucous membranes with infectious materials, accidental parenteral inoculation, ingestion, and exposure to aerosols and infectious droplets has resulted in infection. Infection has been more commonly associated with cultures than with clinical materials and infected animals. Laboratory personnel should be informed of the possibility of tularemia as a differential diagnosis when samples are submitted for diagnostic tests. Helicobacter species Helicobacters are spiral or curved gram-negative rods isolated from gastrointestinal and hepatobiliary tracts of mammals and birds. There are currently 20 recognized species, including at least nine isolated from humans. Since its discovery in 1982, Helicobacter pylori has received increasing attention as an agent of gastritis. Natural Modes of Infection Chronic gastritis and duodenal ulcers are associated with H. Transmission, while incompletely understood, is thought to be by the fecal-oral or oral-oral route. Legionella pneumophila and other Legionella-like Agents Legionella are small, faintly staining gram-negative bacteria. They are obligately aerobic, slow-growing, nonfermentative organisms that have a unique requirement for L-cysteine and iron salts for in vitro growth. There are currently 48 known Legionella species, 20 of which have been associated with human disease. Natural Modes of Infection Legionella is commonly found in environmental sources, typically in man-made warm water systems. The mode of transmission from these reservoirs is aerosolization, aspiration or direct inoculation into the airway. The spectrum of illness caused by Legionella species ranges from a mild, self-limited fu-like illness (Pontiac fever) to a disseminated and often fatal disease characterized by pneumonia and respiratory failure (Legionnaires disease). Although rare, Legionella has been implicated in cases of sinusitis, cellulitis, pericarditis, and endocarditis. Surgery, especially involving transplantation, has been implicated as a risk factor for nosocomial transmission. Laboratory Safety and Containment Recommendations the agent may be present in respiratory tract specimens (sputum, pleural fuid, bronchoscopy specimens, lung tissue), and in extrapulmonary sites. A potential hazard may exist for generation of aerosols containing high concentrations of the agent. Leptospira the genus Leptospira is composed of spiral-shaped bacteria with hooked ends. Leptospires are ubiquitous in nature, either free-living in fresh water or associated with renal infection in animals. These organisms also have been characterized serologically, with more than 200 pathogenic and 60 saprophytic serovars identifed as of 2003. Growth of leptospires in the laboratory requires specialized media and culture techniques, and cases of leptospirosis are usually diagnosed by serology. Animals with chronic renal infection shed large numbers of leptospires in the urine continuously or intermittently, for long periods of time. Common routes of infection include abrasions, cuts in the skin or via the conjunctiva. Higher rates of infection observed in agricultural workers and other occupations associated with animal contact. Laboratory Safety and Containment Recommendations the organism may be present in urine, blood, and tissues of infected animals and humans. Ingestion, accidental parenteral inoculation, and direct and indirect contact of skin or mucous membranes, particularly the conjunctiva, with cultures or infected tissues or body fuids are the primary laboratory hazards. Gloves should be worn to handle and necropsy infected animals and to handle infectious materials and cultures in the laboratory. Listeria monocytogenes Listeria monocytogenes is a gram-positive, non-spore-forming, aerobic bacillus; that is weakly beta-hemolytic on sheep blood agar and catalase-positive. It may also be isolated from symptomatic/asymptomatic animals (particularly ruminants) and humans. Occupational Infections Cutaneous listeriosis, characterized by pustular or papular lesions on the arms and hands, has been described in veterinarians and farmers. In pregnant women, Listeria monocytogenes infections occur most often in the third trimester and may precipitate labor. While ingestion is the most common route of exposure, Listeria can also cause eye and skin infections following direct contact with the organism. Gloves and eye protection should be worn while handling infected or potentially infected materials. Due to potential risks to the fetus, pregnant women should be advised of the risk of exposure to L. Mycobacterium leprae Mycobacterium leprae is the causative agent of leprosy (Hansen disease). The organism has not been cultivated in laboratory medium but can be maintained in a metabolically active state for some period. Organisms are recovered from infected tissue and can be propagated in laboratory animals, specifcally armadillos and the footpads of mice. Occupational Infections There are no cases reported as a result of working in a laboratory with biopsy or other clinical materials of human or animal origin. However, inadvertent human-to human transmissions following an accidental needle stick by a surgeon and after use of a presumably contaminated tattoo needle were reported prior to 1950. Laboratory Safety and Containment Recommendations the infectious agent may be present in tissues and exudates from lesions of infected humans and experimentally or naturally infected animals. Direct contact of the skin and mucous membranes with infectious materials and accidental parenteral 144 Biosafety in Microbiological and Biomedical Laboratories inoculation are the primary laboratory hazards associated with handling infectious clinical materials. Extraordinary care should be taken to avoid accidental parenteral inoculation with contaminated sharp instruments. Mycobacterium tuberculosis complex the Mycobacterium tuberculosis complex includes M. The organism has a thick, lipid-rich cell wall that renders bacilli resistant to harsh treatments including alkali and detergents and allows them to stain acid-fast. The primary focus of infection is the lungs, but most other organs can be involved. It is spread to humans, primarily children, by consumption of non pasteurized milk and milk products, by handling of infected carcasses, and by inhalation. Exposure to laboratory-generated aerosols is the most important hazard encountered. Tubercle bacilli may survive in heat-fxed smears108 and may be aerosolized in the preparation of frozen sections and during manipulation of liquid cultures. Use of a slide-warming tray, rather than a fame, is recommended for fxation of slides. However, considerable care must be exercised to verify the identity of the strain and to ensure that cultures are not contaminated with virulent M. Many of the species are common environmental organisms, and approximately 25 of them are associated with infections in humans. All of these species are considered opportunistic pathogens in humans and none are considered communicable. Mycobacteria are frequently isolated from clinical samples but may not be associated with disease. Agent Summary Statements: Bacterial Agents 147 Occupational Infections Laboratory-acquired infections with Mycobacterium spp. Natural Modes of Infection Person-to-person transmission has not been demonstrated. Presumably, pulmonary infections are the result of inhalation of aerosolized bacilli, most likely from the surface of contaminated water. They are also common in potable water supplies, perhaps as the result of the formation of bioflms. Laboratory Safety and Containment Recommendations Various species of mycobacteria may be present in sputa, exudates from lesions, tissues, and in environmental samples. Direct contact of skin or mucous membranes with infectious materials, ingestion, and accidental parenteral inoculation are the primary laboratory hazards associated with clinical materials and cultures. Aerosols created during the manipulation of broth cultures or tissue homogenates of these organisms also pose a potential infection hazard. Selection of an appropriate tuberculocidal disinfectant is an important consideration for laboratories working with mycobacteria. Neisseria gonorrhoeae Neisseria gonorrhoeae is a gram-negative, oxidase-positive diplococcus associated with gonorrhea, a sexually transmitted disease of humans. The organism may be isolated from clinical specimens and cultivated in the laboratory using specialized growth media. Natural Modes of Infection Gonorrhea is a sexually transmitted disease of worldwide importance. The 2004 rate of reported infections for this disease in the United States was 112 per 100,000 population. This usually occurs by sexual activity, although newborns may also become infected during birth. Accidental parenteral inoculation and direct or indirect contact of mucous membranes with infectious clinical materials are known primary laboratory hazards. Gloves should be worn when handling infected laboratory animals and when there is the likelihood of direct skin contact with infectious materials. Neisseria meningitidis Neisseria meningitidis is a gram-negative coccus responsible for serious acute meningitis and septicemia in humans. Thirteen different capsular serotypes have been identifed, with types A, B, C, Y, and W135 associated with the highest incidence Agent Summary Statements: Bacterial Agents 149 of disease. Almost all the microbiologists had manipulated sterile site isolates on an open laboratory bench. Natural Modes of Infection the human upper respiratory tract is the natural reservoir for N. Invasion of organisms from the respiratory mucosa into the circulatory system causes infection that can range in severity from subclinical to fulminant fatal disease. Transmission is person-to-person and is usually mediated by direct contact with respiratory droplets from infected individuals. Parenteral inoculation, droplet exposure of mucous membranes, infectious aerosol and ingestion are the primary hazards to laboratory personnel. Based on the mechanism of natural infection and the risk associated with handling of isolates on an open laboratory bench, exposure to droplets or aerosols of N. Special Issues Vaccines the quadrivalent meningococcal polysaccharide vaccine, which includes serogroups A, C, Y, and W-135, will decrease but not eliminate the risk of infection, because it is less than 100% effective and does not provide protection against serogroup B, which caused one-half of the laboratory-acquired cases in the United States in 2000. Typhi Salmonellae are gram-negative enteric bacteria associated with diarrheal illness in humans. They are motile oxidase-negative organisms that are easily cultivated on standard bacteriologic media, although enrichment and selective media may be required for isolation from clinical materials. Occupational Infections Salmonellosis is a documented hazard to laboratory personnel. Case reports of laboratory-acquired infections indicate a presentation of symptoms (fever, severe diarrhea, abdominal cramping) similar to those of naturally-acquired infections, although one case also developed erythema nodosum and reactive arthritis. An estimated 5 million cases of salmonellosis occur annually in the United States. A wide range of domestic and feral animals (poultry, swine, rodents, cattle, iguanas, turtles, Agent Summary Statements: Bacterial Agents 151 chicks, dogs, cats) may serve as reservoirs for this disease, as well as humans.

Tick out the drug belonging to non-narcotic antitussives: a) Libexine b) Tusuprex c) Codeine d) Aethylmorphine hydrochloride 005 arthritis in the knee cure discount feldene 20mg. Indicate the expectorant with the reflex mechanism: a) Sodium benzoate b) Derivatives of Ipecacucnha and Thermopsis c) Trypsin d) Ambroxol 006 arthritis young living purchase feldene 20mg visa. Tick the antitussive agent with a peripheral effect: a) Codeine b) Tusuprex c) Libexine d) Glaucine hydrochloride 007 rheumatoid arthritis quality of life questionnaire feldene 20 mg. Tick the drug belonging to non-selective beta2-adrenomimics: a) Salbutamol b) Isoprenaline c) Salmeterol d) Terbutaline 013 arthritis diet recommendations feldene 20 mg discount. Select the side-effect characteristic for non-selective beta2-adrenomimics: a) Depression of the breathing centre b) Tachycardia c) Peripheral vasoconstriction d) Dry mouth 014 arthritis after back fusion purchase generic feldene line. Pick out the bronchodilator drug related to xanthine: a) Atropine b) Orciprenaline c) Adrenaline d) Theophylline 015 reactive arthritis diet mayo clinic buy feldene cheap online. Pick out the bronchodilator drug belonging to sympathomimics: a) Isoprenaline b) Ephedrine c) Atropine d) Salbutamol 016. The property of prolonged theophyllines is the prevention of night asthmatic attacks. The mechanism of methylxanthines action is: a) Inhibition of the enzyme phosphodiesterase b) Beta2 -adrenoreceptor stimulation c) Inhibition of the production of inflammatory cytokines d) Inhibition of M-cholinoreceptors 018. Which of the following M-cholinoblocking agents is used especially as an anti-asthmatic Indicate the side effect of Theophylline: a) Bradycardia b) Increased myocardial demands for oxygen c) Depression of respiratory centre d) Elevation of the arterial blood pressure 020. Choose the drug belonging to membranestabilizing agents: a) Zileutin b) Sodium cromoglycate c) Zafirlucast d) Montelucast 022. Tick the drug which is a 5-lipoxygenase inhibitor: 70 a) Budesonide b) Sodium cromoglycate c) Zileutin d) Beclometazone 023. Indicate the drug which is a leucotriene receptor antagonist: a) Sodium cromoglycate b) Zafirlucast c) Zileutin d) Triamcinolone 025. Tick the main approach of peptic ulcer treatment: a) Neutralization of gastric acid b) Eradication of Helicobacter pylori c) Inhibition of gastric acid secretion d) All the above 002. Indicate the drug belonging to proton pump inhibitors: a) Pirenzepine b) Ranitidine c) Omeprazole d) Trimethaphan 004. Choose the drug which is a H2-receptor antagonist: a) Omeprazole b) Pirenzepine c) Carbenoxolone d) Ranitidine 007. Indicate the drug belonging to M1-cholinoblockers: a) Cimetidine b) Ranitidine c) Pirenzepin d) Omeprazole 009. Select the drug stimulating the protective function of the mucous barrier and the stability of the mucous membrane against damaging factors: a) De-nol b) Sucralfate c) Misoprostol d) Omeprazole 014. Antacids are weak bases that react with gastric hydrochloric acid to form salt and water. Indicate the drug that cause metabolic alkalosis: a) Sodium bicarbonate b) Cimetidine c) Pepto-Bismol d) Carbenoxolone 017. Choose the drug that causes constipation: a) Sodium bicarbonate b) Aluminium hydroxide c) Calcium carbonate d) Magnesium oxide 018. Select an anorexigenic agent affecting serotoninergic system: a) Fenfluramine b) Fepranone c) Desopimone d) Masindole 021. Choose an emetic drug of central action: a) Ipecacuanha derivatives b) Promethazine c) Tropisetron d) Apomorphine hydrochloride 024. Select the emetic agent having a reflex action: a) Ipecacuanha derivatives b) Apomorphine hydroclorid c) Chlorpromazine d) Metoclopramide 026. Indicate an antiemetic agent which is related to neuroleptics: a) Metoclopramide b) Nabilone c) Tropisetron d) Prochlorperazine 028. Indicate the laxative drug belonging to osmotic laxatives: a) Docusate sodium b) Bisacodyl c) Phenolphthalein d) Sodium phosphate 030. The mechanism of stimulant purgatives is: a) Increasing the volume of non-absorbable solid residue b) Increasing motility and secretion c) Altering the consistency of the feces d) Increasing the water content 031. Choose the drug irritating the gut and causing increased peristalsis: a) Phenolphthalein b) Methyl cellulose c) Proserine d) Mineral oil 032. Tick the stimulant of bile production of vegetable origin: a) Oxaphenamide b) Papaverine c) Cholenzyme d) Cholosas 034. Select the drug which inhibits peristalsis: a) Castor oil b) Bisacodyl c) Loperamide d) Sorbitol 035. Choose the drug depressing erythrogenesis: a) Radioactive phosphorus 32 b) Ferrous sulfate c) Molgramostim d) Folic acid 003. Iron deficiency anemia leads to pallor, fatigue, dizziness, exertional dyspnea and other symptoms of tissue ischemia. Tick the drug for parenteral iron therapy: a) Ferrous sulfate b) Fercoven c) Ferrous lactate d) Ferrous fumarate 007. Indicate the drug which increases absorption of iron from intestine: a) Cyanocobalamin b) Folic acid c) Ascorbic acid d) Erythropoetin 008. Pernicious anemia is developed due to deficiency of: a) Erythropoetin b) Vitamin B12 c) Iron d) Vitamin B6 010. Select the drug used for pernicious anemia: a) Ferrous lactate b) Cyanocobalamin c) Iron dextran d) Ferrous gluconate 011. An adverse effect of oral iron therapy is: a) Anemia b) Thrombocytopenia c) Headache d) Constipation 012. Choose the drug which contains cobalt atom: 74 a) Folic acid b) Iron dextran c) Cyanocobalamine d) Ferrous gluconate 013. Tick the drug used in aplastic anemia: a) Fercoven b) Cyanocobalamine c) Epoetin alpha d) Folic acid 014. Which of the following substances is synthesized within vessel walls and inhibits thrombogenesis Pick out the drug belonging to anticoagulants of direct action: a) Aspirin b) Heparin c) Dicumarol d) Phenprocoumon 005. Indicate the drug belonging to antagonists of heparin: a) Aspirin b) Dicumarol c) Dalteparin d) Protamine sulfate 007. Tick the drug used as an oral anticoagulant: a) Heparin b) Daltreparin c) Dicumarol d) Enoxaparin 008. Indicate the drug belonging to fibrinoliytic inhibitors: a) Aminocapronic acid b) Ticlopidine c) Streptokinase d) Vitamin K 021. Aminocapronic acid is a drug of choice for treatment of: a) Acute myocardial infarction b) Bleeding from fibrinolytic therapy c) Heart failure d) Multiple pulmonary emboli 022. The non-glycoside positive inotropic drug is: a) Digoxin b) Strophantin K c) Dobutamine d) Digitoxin 006. Sugar molecules in the structure of glycosides influence: a) Cardiotonic action b) Pharmacokinetic properties c) Toxic properties d) All of the above 007. Aglycone is essential for: a) Plasma protein binding b) Half-life c) Cardiotonic action d) Metabolism 008. Choose the derivative of the plant Foxglove (Digitalis): a) Digoxin b) Strophantin K c) Dobutamine d) Amrinone 009. Digoxin is thought to increase intracellular concentrations of calcium in myocardial cells by indirectly slowing the action of the sodium-calcium exchanger. Compare the half-life of digoxin and the half-life of digitoxin: a) Digoxin is greater than digitoxin b) Digitoxin is greater than digoxin 013. The most cardiac manifestation of glycosides intoxication is: a) Atrioventricular junctional rhythm b) Second-degree atrioventricular blockade c) Ventricular tachycardia d) All the above 016. The manifestations of glycosides intoxication are: a) Visual changes b) Ventricular tachyarrhythmias c) Gastrointestinal disturbances d) All the above 017. For digitalis-induced arrhythmias the following drug is favored: a) Verapamil b) Amiodarone c) Lidocaine d) Propanolol 018. In very severe digitalis intoxication the best choice is to use: a) Lidocaine b) Digibind (Digoxin immune fab) c) Oral potassium supplementation d) Reducing the dose of the drug 019. This drug is a selective beta-1 agonist: a) Digoxin b) Dobutamine c) Amrinone d) Dopamine 021. Tolerance to this inotropic drug develops after a few days: a) Amrinone b) Amiodarone c) Dobutamine d) Adenosine 022. This drug is useful for treating heart failure because it increases the inotropic state and reduces afterload: a) Amiodarone b) Amrinone c) Propanolol d) Enalapril 024. Drugs most commonly used in chronic heart failure are: a) Cardiac glycosides b) Diuretics c) Angiotensin-converting enzyme inhibitors d) All the above 028. This drug prolongs repolarization: a) Flecainide b) Sotalol c) Lidocaine d) Verapamil 007. This drug is used in treating supraventricular tachycardias: a) Digoxin b) Dobutamine c) Amrinone d) Dopamine 009. This drug has beta-adrenergic blocking activity: a) Flecainide b) Sotalol c) Lidocaine d) Verapamil 011. This drug is useful in terminating atrial but not ventricular tachycardias: a) Flecainide b) Sotalol c) Lidocaine d) Verapamil 012. This is a drug of choice for acute treatment of ventricular tachycardias: a) Flecainide b) Sotalol c) Lidocaine d) Verapamil 013. The calcium channel blockers have direct negative inotropic effects because they reduce the inward movement of calcium during the action potential. This drug is contraindicated in patients with moderate to severe heart failure: a) Nifedipine b) Verapamil c) Both of the above d) None of the above 017. This drug is an effective bronchodilator: a) Nifedipine b) Verapamil c) Both of the above. This drug is used intravenously to terminate supraventricular tachycardias: a) Nifedipine b) Verapamil c) Both of the above d) None of the above 019. This drug has a little or no direct effect on chronotropy and dromotropy at normal doses a) Nifedipine b) Diltiazem c) Verapamil d) All of the above 020. Angina pectoris is: a) Severe constricting chest pain, often radiating from the precordium to the left shoulder and down the arm, due to insufficient blood supply to the heart that is usually caused by coronary disease b) An often fatal form of arrhythmia characterized by rapid, irregular fibrillar twitching of the ventricles of the heart instead of normal contractions, resulting in a loss of pulse c) the cardiovascular condition in which the heart ability to pump blood weakens d) All of the above 002. This drug group useful in angina decreases myocardial oxygen requirement (by decreasing the determinations of oxygen demand) and does not increase myocardial oxygen delivery (by reversing coronary arterial spasm): a) Nitrates and nitrite drugs (Nitroglycerin, Isosorbide dinitrate) b) Myotropic coronary dilators (Dipyridamole) c) Potassium channel openers (Minoxidil) d) Beta-adrenoceptor-blocking drugs (Atenolol, Mtoprolol) 004. This drug group useful in angina increase myocardial oxygen delivery (by reversing coronary arterial spasm) and does not decrease myocardial oxygen requirement (by decreasing the determinations of oxygen demand): a) Beta-adrenoceptor-blocking drugs (Atenolol, Metoprolol): b) Myotropic coronary dilators (Dipyridamole) c) Calcium channel blockers (Nifedipine, Nimodipine) d) Potassium channel openers (Minoxidil) 005. Which of the following nitrates and nitrite drugs is used for prevention of angina attack Duration of nitroglycerin action (sublingual) is: a) 10-30 minutes b) 6-8 hours c) 3-5 minutes d) 1. Which of the following cardiovascular system effects refers to a calcium channel blocker Main clinical use of calcium channel blockers is: a) Angina pectoris b) Hypertension c) Supraventricular tachyarrhythmias d) All of the above 016. Which of the following antianginal agents is a myotropic coronary dilator: a) Dipyridamole b) Validol c) Atenolol d) Alinidine 017. Which of the following antianginal agents is a beta-adrenoceptor-blocking drug: a) Dipyridamole b) Validol 82 c) Atenolol d) Alinidine 018. Which of the following antianginal agents refers to reflex coronary dilators: a) Dipyridamole b) Validol c) Atenolol d) Alinidine 021. Which of the following statements concerning Validol is true: a) Validol has a moderate reflex and vascular dilative action caused by the stimulation of sensitive nerve endings b) At sublingual administration the effect is produced in five minutes and 70 % of the preparation is released in 3 minutes c) It is used in cases of angina pectoris, motion sickness, nausea, vomiting when seasick or airsick and headaches due to taking nitrates d) All of the above 022. Which of the following antianginal agents is the specific bradycardic drug: a) Dipyridamole b) Validol c) Atenolol d) Alinidine 023. Which of the following antianginal agents is a potassium channel opener: a) Dipyridamole b) Validol c) Atenolol d) Minoxidil 026. A ganglioblocking drug for hypertension treatment is: a) Hydralazine b) Tubocurarine c) Trimethaphan d) Metoprolol 004. Pick out the sympatholythic drug: a) Labetalol b) Prazosin c) Guanethidine d) Clonidine 005. Tick the drug with nonselective beta-adrenoblocking activity: a) Atenolol b) Propranolol c) Metoprolol d) Nebivolol 006. Choose the selective blocker of beta-1 adrenoreceptors: a) Labetalol b) Prazosin c) Atenolol d) Propranolol 007. This drug inhibits the angiotensin-converting enzyme: a) Captopril b) Enalapril c) Ramipril d) All of the above 009. This drug is a directly acting vasodilator: a) Labetalol b) Clonidine c) Enalapril d) Nifedipine 010. Pick out the diuretic agent for hypertension treatment: a) Losartan b) Dichlothiazide c) Captopril d) Prazosin 011. This drug blocks alpha-1 adrenergic receptors: a) Prazosin b) Clonidine c) Enalapril d) Nifedipine 012. This drug activates alpha-2 adrenergic receptors: a) Labetalol b) Phentolamine c) Clonidine d) Enalapril 84 013. This drug is an inhibitor of renin synthesis: a) Propranolol b) Enalapril c) Diazoxide d) Losartan 014. This drug is a potassium channel activator: a) Nifedipine b) Saralasin c) Diazoxide d) Losartan 016. This drug is contraindicated in patients with bronchial asthma: a) Propranolol b) Clonidine c) Enalapril d) Nifedipine 018. This drug is converted to an active metabolite after absorption: a) Labetalol b) Clonidine c) Enalapril d) Nifedipine 019. This drug routinely produces some tachycardia: a) Propranolol b) Clonidine c) Enalapril d) Nifedipine 020. The reason of beta-blockers administration for hypertension treatment is: a) Peripheral vasodilatation b) Diminishing of blood volume c) Decreasing of heart work d) Depression of vasomotor center 024.

They are powerful engines for the development arthritis knee range of motion cheap feldene 20 mg visa, industrialization arthritis in neck injections purchase feldene cheap, registration rheumatoid arthritis and zoloft cheap 20 mg feldene visa, and marketing of vaccines arthritis pain home treatment feldene 20 mg, but are increasingly outsourcing some of these functions arthritis hip pain relief exercises feldene 20 mg overnight delivery. Biotechs concentrate on applied research zen arthritis cream purchase feldene with amex, pre-clinical development, and clinical development up to Phase 2 clinical trials. Although these companies are expected to play an increasingly important role in vaccine R&D, their ability to penetrate downstream functions such as Phase 3 clinical trials, and the industrialization and commercialization of vaccines, is often limited by structural, fnancial, and human constraints. As the recent case of Roche taking over Genentech in 2009 has demonstrated, the largest Biotech companies that manage to make their way to the market are usually taken over and absorbed by Big Pharma. They have strengthened their industrial capability and become credible players, prompting Big Pharma to seek alliances and partnerships with them, even though their innovation potential is still limited by their regulatory environment and fnancial capacity. Sub-contractors are increasingly engaged in all sectors of the pharmaceutical industry, including the vaccine business. Strategic restructuring may in the future enable some sub-contractor companies to become vaccine producers and suppliers in their own right. Big Pharma is expected to remain a major and indispensable driver of innovation in the feld of vaccines and immunization. New licensed vaccines Several new vaccines and new vaccine formulations have become available since the year 2000. These vaccines are not envisaged at the time of writing for use in large population groups. Vaccines in the pipeline A large number of vaccine products are currently in the pipeline and are expected to become available by 2012. According to recent unpublished data, more than 80 candidate vaccines are in the late stages of clinical testing. About 30 of these candidate vaccines aim to protect against major diseases for which no licensed vaccines exist, such as malaria and dengue. If successful, it would be the frst vaccine against a parasite that causes disease in humans. Several candidate vaccines are also under development against dengue, another mosquito-borne disease of major public health concern. Two candidate vaccines against dengue virus have been evaluated in children, and one candidate vaccine is currently being evaluated in a large-scale trial. However, researchers are hopeful that dengue vaccines will become available in the coming years. About 50 candidate vaccines target diseases for which vaccines already exist, such as pneumococcal disease, Japanese encephalitis, hepatitis A, and cholera: however, these candidates hold the promise of being more effective, more easily administered, and more affordable than the existing vaccines. Phase 3 malaria vaccine trial participants and their mothers (on bench) with Dr Salim Abdulla (standing left) and vaccination staff at the Bagamoyo Research and Training Centre of the Ifakara Health Institute in the United Republic of Tanzania. A new chapter in vaccine development Box 5 Product development partnerships Product development partnerships are typically not-for-proft entities mandated to accelerate the development and introduction of a product, such as a vaccine. They are funded by donors to promote research and development, often through links between developing country academic programmes, biotechnology companies, and vaccine manufacturers. Product development partnerships have encouraged investment in various aspects of vaccine development, including large-scale clinical trials of vaccines against diseases prevalent in the poorest countries of the world. The Meningitis Vaccine Project (launched in 2001) is involved in both vaccine development and introduction. Most of the expansion comes from sales in industrialized countries of newer, relatively more expensive vaccines, which account for more than half of the total value of vaccine sales worldwide (20). The commercial success of these products, according to a recent vaccine market analysis (21), is sparking renewed interest and investment in the vaccine industry, which had appeared moribund in the 1980s. A concentrated industry the vaccine supply scene is dominated by a small number of multinational manufacturers based in industrialized countries. The remaining revenue is divided among more than 40 manufacturers in developing countries. By contrast, in terms of volume, only 14% of the vaccine required to meet global vaccine demand comes from suppliers in industrialized countries. In 2000, 39% of vaccine doses purchased by these agencies came from suppliers in developing countries. A good part of the increase is due to the vaccine requirements of the initiatives mounted to eradicate polio, eliminate neonatal tetanus and maternal tetanus, and reduce deaths from measles. The manufacturers were able to supply these vaccines at a low price for at least three reasons. First, at that time, the richest and poorest countries were using much the same vaccines: by selling the same vaccines at higher prices to the richer countries and at lower prices to the poorer countries. Second, manufacturers tended to keep an excess production capacity for many of the traditional vaccines, which enabled them to supply vaccines at a low price to developing countries without having to invest in expanding production capacity. And third, up to the 1980s, there were enough vaccine suppliers to sustain competition among them, which kept vaccine prices low. No longer do manufacturers maintain excess production capacity: supply must be equivalent to demand, since the newer vaccines are more costly to make, and too costly or too perishable to keep. And in the traditional markets, with the exception of hepatitis B, there is no longer enough competition among suppliers to keep prices down: there are now far fewer suppliers from industrialized countries than before and those that remain tend increasingly to protect their products from competition through a system of patents and royalties. Box 6 Vaccine security In the late 1990s, a vaccine supply crisis began, which highlighted the need for a new approach to ensure the uninterrupted and sustainable supply of vaccines of assured quality. With growing divergence between the vaccines used in developing and industrialized countries, some manufacturers stopped production of the traditional vaccines and supplies plummeted. The aim is to ensure the uninterrupted and sustainable supply of vaccines that are both affordable and of assured quality. The strategy includes a focus on developing a healthy vaccine market through implementing specifc vaccine procurement strategies and ensuring that the key elements of accurate forecasting, timely funding, and appropriate contracts are in place. Industry reacted positively to the changes and the trend of decreasing vaccine availability was reversed. Today, the system in use in all industrialized countries and in a growing number of developing countries covers three main testing phases: preclinical laboratory testing, including animal tests; clinical trials in humans; and surveillance following regulatory approval for marketing. During the preclinical laboratory phase, a vaccine undergoes biochemical testing and evaluation in laboratory animals for, among other things, characterization of its biochemical components, potency, purity, genetic and biochemical stability, and safety in animals. In Phase 1, the vaccine is tested in a few volunteers for safety and effcacy (immunogenicity), and for an initial indication of the appropriate dose to be used (dose-ranging). Phase 2 tests for safety, immunity-stimulating capacity (immunogenicity), dose-ranging, and effcacy in up to several hundred volunteers. A regulatory authority will, among many other things, undertake a review of how the preclinical and clinical tests were conducted and what they found. The regulators will also inspect the production site and make a detailed review of 31 Chapter 2. Following licensure, post-marketing evaluation (Phase 4) involves surveillance for any adverse events. During the life cycle of a product, a manufacturer may wish to , or have to , introduce variations to the production process. In such cases, the variations are reported to the national regulatory authority for review and approval. In 1981, the Expert Committee on Biological Standardization called upon all countries to have a national regulatory authority. Having an independent and functional national regulatory authority is a good start for a country wishing to ensure that the vaccines it uses meet internationally agreed standards of safety, effcacy, and quality. For a country using or making vaccines, simply having a national regulatory authority is not enough. The national regulatory authority must be able to work independently (of vaccine manufacturers and of the government, for example); it must have the legal basis that defnes its mandate and enforcement power; and it should perform between two and six core functions, depending on how the country acquires its vaccines. Two additional core functions for countries that procure their vaccines directly in the domestic or international market are: (3) verifying consistency of the safety and quality of different batches of vaccine coming off the production line (lot release); (4) accessing, as needed, a national control laboratory in order to test vaccine samples. The sixth function is also recommended for any countries that host clinical trials of vaccines: (5) inspecting vaccine manufacturing sites and distribution channels; (6) authorizing and monitoring clinical trials to be held in the country. To achieve its objectives, the initiative undertakes a fve-step capacity development process tailor-made to the requirements of each individual country. Defning and then regularly updating benchmarks and other tools used to assess whether a national regulatory system is capable of ensuring that the vaccines used and/or made in its country are of the required standards of quality, effcacy, and safety. Using benchmark indicators and other pertinent tools to assess the national regulatory system. Implementing the institutional development plan, which may involve technical support or staff training to perform regulatory functions. Re-assessing the national regulatory authority within two years to evaluate progress. In 1997, 20 (38%) of the 52 vaccine producing countries had a reliable, functioning national regulatory authority. By the end of 2008, the numbers had risen to 33 (69%) of 48 vaccine producing countries. A regulatorsnetwork for developing countries the power of networking is being applied to the quest for stronger regulatory oversight in countries where regulation is lacking or inadequate. These countries are increasingly being asked by vaccine manufacturers to host clinical trials of vaccines intended for use in developing countries. Clearly, these vaccines must be tested for their safety and effcacy in the real-life conditions of these developing countries. The danger is that in countries with little or no regulatory capacity, the trials may take place without due respect for international standards of good clinical practice, of ethics, and of vaccine safety, quality, and effcacy. Network participants also inspect clinical trials for their adherence to good clinical practice. A new chapter in vaccine development Harmonizing and standardizing vaccine regulation Strengthening regulatory capacity also means bringing some uniformity to the way regulatory oversight is practised in different countries and, more importantly, to the standards of safety, effcacy, and quality they apply to vaccines. At the end of 2008, 58 countries possessed a reliable national regulatory authority, but not all were applying the same regulatory standards for vaccine licensure. Clearly, the diversity of regulatory standards from one country to another can seriously complicate international trade in vaccines. Vaccine quality testing by the Division of Biological Products at the Department of Medical Sciences, Ministry of Public Health, Thailand. In Europe, harmonization is a major objective of the European Medicines Agency, a regional regulatory authority. At present, vaccines for use in the European Union are regulated either by the European Medicines Agency itself or by a European Union Member State, in which case the licensure of the vaccine is recognized, through a mutual recognition agreement, by all other European Union states. The Conference, held every two years, brings together the regulatory authorities and pharmaceutical industry experts of Europe, Japan, and the United States. Their aim is to harmonize technical guidelines and licensing requirements for pharmaceutical products, including vaccines. Topics chosen for harmonization relate to criteria for assessing the safety, quality, and effcacy of these products. The Conference is credited with achieving substantial progress in harmonizing technical guidelines and applications for licensing. Generally speaking, progress towards harmonization of standards is slow but steady.

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