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The six membered dihydrothiazine ring fused with a four membered ß-lactam ring (figure 1 discount hydrochlorothiazide 12.5mg line blood pressure high in the morning. Cephalosporins are highly effective antibiotics in the treatment of bacterial infections of the respiratory tract [4 purchase 25 mg hydrochlorothiazide with amex blood pressure medication used to treat acne,13]. As for the penicillins, many semi-synthetic cephalosporins were developed which are nowadays distinguished in several generations based upon their time of discovery and their range of activity [14]. Cefacetril, cefalonium, cefazolin, cefalexin and st rd cefapirin (all 1 generation), cefoperazone and ceftiofur (3 generation), and th cefquinome (4 generation) are all approved for veterinary use (figure 1. Another ß-lactam group consists of the carbapenems of which the first compound was isolated from Streptomyces cattleyain in 1971 [15]. The carbapenems are structurally very similar to the penicillins: the sulfur atom has been replaced by a carbon atom and an unsaturation has been introduced (figure 1. As a result the carbapenems possess the broadest antimicrobial activity amongst the ß-lactams [16]. The most common carbapenems are imipenem, meropenem, ertapenem, doripenem and biapenem (figure 1. The carbapenems are not registered for use in food-producing animals and are used off-label in companion animals [8]. Another important group of antibiotics was introduced by Benjamin Duggar: the tetracyclines, of which chlortetracycline, isolated from the soil bacteria Strepromyces aureofaciens, was the first [17]. In the same year, David Gottlieb reported the isolation of a new broad spectrum antibiotic from the soil bacterium Streptomyces venezuelae called chloramphenicol [18] (figure 1. Although, as these examples show, many antibiotics were first isolated from a natural source, most of them are now produced synthetically and new antibiotics are usually semisynthetic modifications thereof [19]. Molecular structure of the carbapenems: meropenem, imipenem, ertapenem, doripenem and biapenem. Antibiotics are used to treat bacterially infected animals but are also administered as a preventive measure. Furthermore, administration of antibiotics at sub-therapeutic doses has a growth promoting effects, making its use economically advantageous [22]. This is especially of interest since the ban of antimicrobial growth promoting substances in animal feed since 2006 [23,24]. Antibiotic usage in veterinary practice in the Netherlands is monitored to obtain insight in the exposure of farm animals to antibiotics. One way of monitoring antibiotic usage is registering antibiotic sales for therapeutic use. The livestock population remained roughly constant over the years [25] and thus is concluded that sales by the pharmaceutical industry of antibiotics for veterinary therapeutic use increased from 1999 to 2007. In all years monitored, tetracyclines are sold the most followed by sulfonamides/trimethoprim and penicillins/cephalosporins. In 2009, for pigs a tendency to reintroduce traditional antibiotics like tetracyclines and sulfonamides/trimethoprim was observed, whereas for veal calves and dairy cows, besides the traditional rd th antibiotics, newer antibiotics like 3 and 4 generation cephalosporins and fluoroquinolones were more frequently used. For broilers a severe increase of the use of penicillin antibiotics was observed in 2009 compared to previous years, possibly because penicillin administration results in the enhancement of the feed conversion and growth rate [26]. Adverse effects of antibiotic usage Excessive antibiotic usage in veterinary practice in food producing animals can have adverse effects on human health [27-29]. Some antibiotics are banned for use in veterinary practice because of their negative effects on health, like bone marrow toxicity, aplastic anemia and carcinogenicity [28,30]. If these antibiotics are illegally administered, residues might occur in food products of animal origin. The adverse effects of the occurrence of these antibiotics in the food chain do not need any further elaboration. Less obvious is that also the irresponsible and excessive use of regulated antibiotics is a risk to human health [4,27,29,31]. About six to eight percent of the population show a hypersensitive reaction to covalent penicillin-protein conjugates that can be present in food products from animals that have been treated with penicillin antibiotics [32]. Furthermore, the use of antibiotics in veterinary practice can result in the occurrence of resistant bacteria that can be disseminated throughout the food chain and the environment and thus possibly be transferred from animals to humans [31]. Furthermore, low levels of these antibiotics can end up in the human food chain or the environment and do contribute to the evolvement of bacterial resistance as well [29,33]. Resistance development to ß-lactam antibiotics is caused by the expression of ß- lactamases, which are enzymes that hydrolyse the four-membered ß-lactam ring and thus inactivates the antibiotics [4,43]. Steadily increasing antibiotic resistance and the lack of the development of new still effective antibiotics appear to result in a period during which treatment of infections will become increasingly difficult [49,50].
Fat restriction usually is lifted in 4 to 6 weeks hydrochlorothiazide 25 mg with mastercard arteria y vena esplenica, when the biliary ducts dilate to accommodate the volume of bile once held by the gallbladder and when the ampulla of Vater again functions effectively generic hydrochlorothiazide 12.5 mg visa arteria. After this time, when the patient eats fat, adequate bile will be released into the digestive tract to emulsify the fats and allow their digestion. This is in contrast to the condition before surgery, when fats may not be digested completely or adequately, and flatulence may occur. Monitoring and Managing Potential Complications Bleeding may occur as a result of inadvertent puncture or nicking of a major blood vessel. Postoperatively, the nurse closely monitors vital signs and inspects the surgical incisions and drains, if any are in place, for evidence of bleeding. The nurse also periodically assesses the patient for increased tenderness and rigidity of the abdomen. The nurse instructs the patient and family to report to the surgeon any change in the color of stools, because this may indicate complications. Gastrointestinal symptoms, although not common, may occur with manipulation of the intestines during surgery. After laparoscopic cholecystectomy, the nurse assesses the patient for loss of appetite, vomiting, pain, distention of the abdomen, and temperature elevation. These may indicate infection or disruption of the gastrointestinal tract and should be reported to the surgeon promptly. Because the patient is discharged soon after laparoscopic surgery, the patient and family are instructed verbally and in writing about the importance of reporting these symptoms promptly. Promoting Home and Community-Based Care Teaching Patients Self-Care The nurse instructs the patient about the medications that are prescribed (vitamins, anticholinergics, and antispasmodics) and their actions. It also is important to inform the patient and family about symptoms that should be reported to the physician, including jaundice, dark urine, pale-colored stools, pruritus, and signs of inflammation and infection, such as pain or fever. This is the result of a continual trickle of bile through the choledochoduodenal junction after cholecystectomy. Usually, such frequency diminishes over a period of a few weeks to several months. If a patient is discharged from the hospital with a drainage tube still in place, the patient and family need instructions about its management. The nurse instructs them in proper care of the drainage tube and the importance of reporting to the surgeon 95 promptly any changes in the amount or characteristics of drainage. Managing Pain You may experience pain or discomfort in your right shoulder from the gas used to inflate your abdominal area during surgery. Sitting upright in bed or a chair, walking, or use of a heating pad may ease the discomfort. Managing Follow-Up Care Make an appointment with your surgeon for 7 to 10 days after discharge. This is an abnormal response in which antibodies are directed against normal tissues of the body, responding to these tissues as if they were foreign. When excess glucose is excreted in the urine, it is accompanied by excessive loss of fluids and electrolytes. In addition, fat breakdown occurs, resulting in an increased production of ketone bodies, which are the byproducts of fat breakdown. Type 2 Diabetes Mellitus • Accounts for 90% of patients with diabetes • Usually occurs in people over 40 years of age • 80-90% of patients are overweight Etiology and Pathophysiology • Pancreas continues to produce some endogenous insulin • Insulin produced is either insufficient or poorly utilized by the tissues • Insulin resistance –Body tissues do not respond to insulin –Results in hyperglycemia • Inappropriate glucose production by the liver –Not considered a primary factor in the development of type 2 diabetes Normally, insulin binds to special receptors on cell surfaces and initiates a series of reactions involved in glucose metabolism. In type 2 diabetes, these intracellular reactions are diminished, making insulin less effective at stimulating glucose uptake by the tissues and at regulating glucose release by the liver. However, if the beta cells cannot keep up with the increased demand for insulin, the glucose level rises, and type 2 diabetes develops. One consequence of undetected diabetes is that long-term diabetes complications (eg, eye disease, peripheral neuropathy, peripheral vascular disease) may have developed before the actual diagnosis of diabetes is made Etiology (not well know) –Genetic factors –Increased weight. Secondary Diabetes • Results from another medical condition or due to the treatment of a medical condition that causes abnormal blood glucose levels –Cushing syndrome –Hyperthyroidism –Parenteral nutrition Clinical Manifestations Diabetes Mellitus • Polyuria • Polydipsia (excessive thirst) • Polyphagia • In Type I –Weight loss –Ketoacidosis Polyphagia (increased appetite) resulting from the catabolic state induced by insulin deficiency and the breakdown of proteins and fats Other symptoms include fatigue and weakness, sudden vision changes, tingling or numbness in hands or feet, dry skin, skin lesions or wounds that are slow to heal, and recurrent infections.
Such technologies are concerned with delivering drugs to specific targets in the body and also to protect drugs from degradation and premature elimination buy hydrochlorothiazide 12.5mg with visa blood pressure stress. They include the use of: • soluble carriers buy hydrochlorothiazide 25mg on-line blood pressure ranges for elderly, such as monoclonal antibodies, dextrans, soluble synthetic polymers; • particulate carriers, such as liposomes, micro- and nano-particles, microspheres; • target-specific recognition moieties, such as monoclonal antibodies, carbohydrates and lectins. These technologies, and the various anatomical, physiological and pathological issues that pertain to their use, are discussed in detail in Chapter 5. Recent advances in biological and chemical sciences have led to the development of various “Smart” technologies to ensure more effective drug delivery and targeting of drugs to specific sites within the body. The advantages and limitations of these systems are discussed in detail in Chapter 16. Such systems are used to achieve site-specific drug delivery following parenteral administration. Release of the attached drug molecules at the target site can be achieved by enzymatic or hydrolytic cleavage. Larger complexes, some undergoing clinical trials, include drug conjugates with soluble natural, or synthetic, polymers. Nano- and microparticles Nanoparticles are solid colloidal particles, generally less than 200 nm. Such systems include poly (alky1- cyanoacrylate) nanoparticles used for parenteral drug delivery and targeting. Microparticles are colloidal particles in the micrometer scale, typically in the size range 0. Synthetic polymers, such as poly(lactide-co-glycolide), are widely used in the preparation of microparticulate drug delivery systems and also as biodegradable implantable devices. Natural polymers, such as albumin, gelatin and starch, are also used as microparticulate drug carriers. Liposomes, vesicular structures based on one or more lipid bilayer(s) encapsulating an aqueous core, represent highly versatile carriers. Liposomes can be prepared using a variety of techniques to give a wide range of sizes (approximately 30 nm–10 µm), structures and physicochemical properties, to facilitate the encapsulation of both water-soluble and lipid-soluble drugs (see Section 5. Commercial products based on liposome technology are available and many more products are in clinical trials, for a variety of indications. Macrodevices Macrodevices are widely used in many applications, including: • parenteral drug delivery, mechanical pumps, implantable devices; • oral drug delivery: solid dosage forms such as tablets and capsules which incorporate controlled release/ targeting technologies; • buccal drug delivery: buccal adhesive patches and films; • transdermal drug delivery: transdermal patches, iontophoretic devices; • nasal drug delivery: nasal sprays and drops; • pulmonary drug delivery: metered-dose inhalers, dry-powder inhalers, nebulizers; • vaginal drug delivery: vaginal rings, creams, sponges; • ophthalmic drug delivery: ophthalmic drops and sprays. This is painful for the patient, as well as generally requiring the intervention of medical professionals. The oral route, which involves merely swallowing a tablet, liquid or capsule, thus represents a much more convenient and attractive route for drug delivery. Some other dosage forms, for example nebulizers, pessaries and suppositories, may meet with more limited patient compliance. Ease of termination The dosage form should be easily removed either at the end of an application period, or in the case where continued drug delivery is contra-indicated. A transdermal adhesive system is easily removed if necessary, as is a buccal patch. However, non-biodegradable polymeric implants and osmotic pumps must be surgically retrieved at the end of treatment. Although a biodegradable polymeric implant does not require surgical retrieval, its continuing biodegradation makes it difficult to terminate drug delivery, or to maintain the correct dose at the end of its lifetime. Biocompatibility and absence of adverse effects The drug delivery system should be non-toxic and non-immunogenic. For example, concerns over the body’s responses to a foreign material often raise the issues of biocompatibility and safety of implantable devices. The use of dosage forms containing penetration enhancers, which potentiate drug absorption via a variety of mechanisms and are used in oral, buccal, transdermal, nasal, ophthalmic, pulmonary and vaginal drug delivery, has raised serious questions about the potential deleterious effects they exert on epithelial tissue. As well as the possibility of direct damage to the epithelium, the increased epithelial permeability may allow the ingress of potentially toxic agents. Large effective area of contact For drugs absorbed via passive mechanisms (see Section 1. The dosage form can influence the size of the area over which the drug is deposited. For example, the use of nasal drops offers a larger solution/ membrane surface area for immediate absorption than if the drug solution is delivered in the form of a nasal spray (see Section 9.
