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(16) The drug has better coverage against Gram-positive cocci and atypical pathogens, and it is able to achieve excellent penetration into respiratory fluids and tissues. One particular adverse effect of the drug is that it may result in gastrointestinal disturbances, and thereby affect the individual's metabolism. (17) e) How does metabolism influence clearance, bioactivity and elimination?
At times, the metabolism does tend to affect the absorption and the clearance of the drug from the system. For example, the changes in the INR or the International Normalized Ratio may happen in certain patients who have been receiving oral anticoagulants, with antibiotics, such as Moxifloxacin. The age, the state of the infectious disease, and so on are all risk factors. However, the drug does not interfere with the 1A2 subtypes of cytochrome P450 enzymes, and in the same way, there was no significant effect on apparent body clearance and also on the renal clearance of moxifloxacin on a human being. (4) f) Is the drug mainly excreted in urine or faeces?
Moxifloxacin is mainly bound to serum albumin, and it is therefore widely distributed throughout the body. It is also distributed to the saliva, nasal and bronchial secretions, and to the sinus mucosa. Therefore, the elimination rates from the tissues generally correspond with the elimination through plasma. Most of the drug is metabolized in the liver, and most of it is excreted in the feces, and a small part of it in the urine. (18)
3. Mechanism of action a) How does the drug exert its effect?
The drug Moxifloxacin, a fluoroquinolone, being a broad spectrum antibiotic, with a concentration dependent bactericidal action, exerts its mechanism by either binding to or inhibiting topoisomerase II, or the DNA gyrase, and the topoisomerase IV. These are the bacterial enzymes that are responsible for the coiling and the uncoiling of DNA, which are always required for the bacterial cell repair, and for their replication within the body. (19) b) What are the targets of the drug and what aspects of its structure relate to efficacy?
When the in vitro activity of the drug was studied, and its intracellular activities were also studied, it was found that the first step mutants bore amino acid substitutions at position 81 in the Gyr A subunit of DNA gyrase. This was indicative of the fact that moxifloxacin targets the Gyr A subunit of DNA gyrase as an initial lethal event, and this was precisely the action needed against pneumonia bacteria. (20) The third generation fluoroquinolone moxifloxacin have a typical gram positive, atypical and an anaerobic coverage as compared with the first and second generation fluoroquinolones. This is a drug that is not at all affected by bacterial efflux mechanisms because of the fact that they possess a bulky side chain moiety at position 7, which as a matter of fact, serves to affect export. It also exceeds the mutant prevention concentrations for S. Pneumoniae. (21)
Does the drug have other targets/actions other than its main therapeutic action?
Since moxifloxacin is made up or composed of a number of quinolones, and if one small alteration or variation were to be brought out with regard to one of the side chains of quinolones, then it could be said that in the entire anti-bacterial structure there would be alterations, and therefore, one should understand that the basic structure of the drug must be left as it is, so that there is no change being brought about in its efficacy. (22) It must be stated however that the mechanism of the action of quinolones is not yet fully known, and in susceptible bacterial infections, it serves to inhibit the activity of DNA gyrase. (6) d) Are there abnormalities/diseases that influence its activity?
Although it is today widely acknowledged that moxifloxacin is one of the most active fluoroquinolones that can fight against tuberculosis in vitro, relevant data about its efficacy has not yet become fully available, and, according to one particular study conducted on tuberculosis patients, it was found that calculated early bactericidal activities for isoniazid and moxifloxacin were 0.209 and 0.273 log10 CFU per ml of sputum per day, accordingly, and this meant that the drug moxifloxacin showed an early bactericidal activity that it was possible to compare with that of an isoniazid. Therefore, it may be said that tuberculosis may be one disease that may have an impact on the activity of the drug Moxifloxacin. (23)
Moxifloxacin can be utilized for the treatment of community acquired tuberculosis, and new evidence shows that the agent may be less likely to be selected for resistant SP subpopulations, wherein this resistance may happen in a series of gradual steps, as and when the organisms start to acquire mutations in their genes which encode the two topoisomerases, gyr, and par. (24)
4. Therapeutic applications/effects a) What is the evidence that the drug is effective in treating its particular condition?
Pneumonia is a disease wherein there is a serious inflammation of the lung, and which is caused by bacteria, viruses, and several other organisms. It generally occurs when an individual's immune system has been compromised due to some reason or the other, and where there is a bacterial growth along the upper respiratory tract. About 10% of all hospitalizations in the U.S.A. are due to this disease, and as far as the treatment is concerned, antibiotics are the only option. The quinolones levofloxacin and gatifloxacin are generally recommended for its treatment. These medicines interfere with the bacteria's genetic material so that it cannot reproduce, and this arrests the disease. The fourth generation moxifloxacin is safe against many gram negative and gram positive bacteria. (25)
Moxifloxacin is also at times referred to as being 'genetically smart' flouroquinolone. This is because the drug, because of its unique structure has improved potency against gram positive bacteria, and the kill curves for the drug are infinitely higher than ciprofloxacin. It has the adual mechanism; wherein it acts on two sides, and these are on the DNA gyrase side and on the topoisomerase IV, which should as a matter of fact, delay in the emergence of resistance. (26) b) What patients or conditions is it effective for?
The drug is useful for the treatment of almost all respiratory tract infections, and it kills the common bacteria that are responsible for such infections in adults. (27)
What aspects of disease/symptoms are alleviated by the drug?
Moxifloxacin has an excellent gram negative quality and also a moderate gram positive activity. This is in fact referred to as a broad spectrum of activity, and since they also have a unique mechanism of action, they are the best agents of the study of empiric therapy. This, in combination with its high levels of bioavailability, makes it something that is very attractive and perhaps this is why it is so widely used, and at times, indiscriminately as well. (28) "Airway obstruction, airway destruction, airway inflammation, and emphysema" are some of the symptoms of disease that are being alleviated by Moxifloxacin. (29) d) Is therapeutic monitoring required?
Monitoring is indeed required when taking moxifloxacin, because there are any people who are allergic to the drug. This is especially true when the patient is at present taking any other medication for any other types of ailment that he may have at that time, even if they are merely vitamins or herbal products. Moxifloxacin cannot be taken along with antacids which contain either magnesium or aluminum, like for example, Milk of Magnesia, Mylanta, and Maalox. In the same way, the drug must not be taken along with iron or zinc or any other vitamin supplements. When treating children, extreme caution and care must be taken, and the doctor must be informed if the child is on any other medication for any reason whatsoever. Pregnant women, and also women in the reproductive age are often advised not to take moxifloxacin, because of the adverse side effects it may have. (30)
Even breast feeding mothers must be closely monitored therapeutically. Unnecessary exposure to bright sunlight must be avoided at any cost, and the reason for this is that the drug has the result of making an individual extremely sensitive to light and the sun. If the patient is planning to have surgery of any kind, especially dental, then the doctor must be told that the patient is on Moxifloxacin. The drug has been known to cause lightheadedness and dizziness, and one must be aware of these facts before taking the medicine so that he may be able to avoid potentially dangerous situations. (30) e) Is the drug used in combination with other drugs/approaches?
The traditional gram negative coverage of moxifloxacin has today been extended to include certain gram positive coverage as well, and these are specifically gram positive organisms like upper and lower respiratory tract infections, gastrointestinal infections, gynecologic infections, and sometimes, sexually transmitted diseases. However, one must remember that inappropriate usage of the drug would have certain extreme adverse reactions in the patient. When it is used in combination with…[continue]
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