• Please paraphrase the following paragraphs, check the plagiarism • Keep each paragraph in its position don’t mix or minimize (this lab report)The tetracycline class of antibiotics comprises a distinct family of substituted hydronaphthalene compounds produced by strains of Streptomyces aureofaciens and Streptomyces rimosus. The first member of the group to be discovered was chlorotetracycline (Aureomycin) in the late 1940s by Dr. Benjamin Duggar, a scientist employed by Lederle Laboratories, who derived the substance from a soil-dwelling bacterium named Streptomyces aureofaciens. For more than half a century, tetracycline antibiotics have been used to treat infectious diseases. As one of the earliest antibiotics to be marketed following penicillin and streptomycin, and because of their convenient oral dosing, tetracyclines quickly achieved wide clinical usage.
Unfortunately, this extensive use in clinical practice and agriculture has resulted in widespread resistance that ultimately has limited the clinical utility of the entire family of the tetracycline antibiotics. Tetracyclines inhibit bacterial growth by inhibiting protein synthesis. In general, they bind to the bacterial 30S ribosomal subunit and prevent aminocyl-t-RNA binding to the ribosomal A site, thus preventing the addition of amino acids to the growing polypeptide chain. In the past decade, there has been renewed interest in this antibiotics class, with attempts being made to modify existing compounds so that they are not affected by common bacterial tetracycline resistance mechanism.
Tetracyclines are amphoteric compounds, and are more stable in acid, then under alkaline conditions. They are thus suitable for oral administration, and are absorbed satisfactorily. However, because of the sequence of phenol and carbonyl substituents in the structures, they act as chelators and complex with metal ions, especially calcium, aluminium, iron and magnesium. Accordingly, they should not be administered with food such as milk and dairy products, aluminium and magnesium–based antacid preparations, iron supplements, otherwise erratic and unsatisfactory absorption will occur.Phototoxic reactions and increased vulnerability to sunburn have occurred. Porphyria-like skin changes and pigmentation of the nails have also been reported. A useful feature of doxycycline and Minocycline is that their absorptions are much less affected by metal ions.
Minocycline is a semisynthetic derivative of tetracycline that has excellent oral absorption and wide tissue penetration. Like other tetracyclines, minocycline is believed to act by binding to bacterial ribosomes and inhibiting protein synthesis. Minocycline has a broad spectrum of activity against both gram positive and gram negative organisms. Minocycline was approved for use in the United States in 1971 and it continues in wide use with more than 4 million prescriptions being filled yearly.
Current indications are for therapy of susceptible infections, including gonorrhoea, syphilis, non-gonococcal urethritis, chlamydia infections, cholera, leprosy, and the meningococcal carrier state. Perhaps the major use of minocycline is chronic use for treatment of acne and suppression of staphylococcal bacterial flora that contribute to it. It is much more lipophilic than its precursors, gives excellent blood levels following oral administration (90% to 100% available), and can be given once a day. However, its absorption is lowered by about 20% when taken with food or milk. It is less dependent on the active uptake mechanism and has a somewhat broader antimicrobial spectrum. It has vestibular toxicities e.g. vertigo, ataxia and nausea not generally shared by other tetracyclines.
The main objective of this expermint was to investigate the interaction of minocycline with each metal ions by measuring the spectra of minocycline standard and minocycline - metal ions complexes. Aluminium, Lithium, Sodium, Magnesium, Copper and Iron were used as metal ions.
The method that was used for this experiment was divided into three steps.Initially, the provided metal ions solutions 1%w/v, which are Aluminium, Lithium, Magnesium, Sodium, Copper and Iron, were diluted by using 2mL of each metal ion solution (1%w/v) with 4mL of distilled water each test tube contained 6mL.
Secondly, minocycline standard was prepared by using 1mL of original minocycline solution (10-3 M) with 3mL of distilled water.The produced solution (standard) was poured into a cuvette, and the spectrum of standard minocycline was determined by placing the sample in a spectrophotometer and measuring the absorbances from 300 nm to 500 nm at 2 nm intervals. Distilled water was used as a blank. The obtained results were plotted in Excel to produce a graph.
Thirdly, the formation of minocycline-metal ions complexes, 3mL of each metal ion solution that produced in step one was pipetted into a separate test tube and 1mL of the minocycline (original) was added to each test tube by using a glass pipette to form minocycline-metal ion complexes. The minocycline-metal ion complexes were poured into a separated cuvette and placed into the spectrophotometer; the remaining 3 mL of metal ion solution from step one was used as a blank for each ion. Then, the spectrum was measured at 2 nm intervals and the readings were printed for each complex.The obtained results were plotted in Excel in addition to that produced in step two.
The graph illustrates the absorption of Minocycline standard compared with the absorbance of minocycline-metal ion complexes. The absorbance of minocycline increased at the start, reached a peak of 1.325 at 348nm then declined steadily downward in a slope towards 400nm. Similarly, a complex of minocycline with sodium and magnesium had a maximum absorbance of 1.324 & 1.288 respectively, and at the wavelength, which are 348 and 352nm. Graphically, it can be seen that magnesium and sodium mimic minocycline standard. Whereas the lithium shows the strong complex formation followed by copper and aluminium.
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Chelation is an important feature of the chemical and clinical properties of the tetracyclines. This acidic functions of the tetracyclines are capable of forming salts through chelation with metal ions. The salts of polyvalent metal ions, such as Fe2+, Mg2+, and Al3+, are all quite insoluble at neural pHs (Fig 2). This insolubility is not only inconvenient for the preparation of solutions, but also interferes with blood levels on oral administration. However, the different tetracyclines are absorbed to different extents from the gastrointestinal tract, ranging from oxytetetacycline at 58% absorption to minocycline, which is completely absorbed. In contrast to the shorter acting preparation, the absorption of minocycline is not affected by food.
The experiment was carried out in vitro environment. The results obtained from the experiment were plotted using Excel to get the graph use in interpreting the data. By looking at the graph shown in (Fig.1) it can be seen that the highest absorbance for minocycline was 1.325 at 350nm. Sodium and magnesium complexes follow almost the same pattern as minocycline standard. This mimicry indicates that food containing sodium or magnesium ions will not reduce the effectiveness (bioavailability) of the minocycline as no shift to the right was observed. This may due to the fact that the sodium has a smaller positive charge, therefore a weaker complex formed. It seems that the magnesium as divalent metal ions exhibit the same pattern for minocycline standard.
On the other hand, the graph shows that the absorbance spectrum of minocycline was affected in the presence of copper and aluminium ions as minocycline graph shifted to the right (Bathochromic shift). They reached their peaks max at around 376 to 378nm and the absorbance readings at this peak were 1.643 and 1.596 respectively. This is due to the fact that tetracyclines (minocycline) have hydroxyl groups and are capable to interact with these divalent and trivalent metal ions (Al3+,Cu2+) and that means minocycline has formed strong complexes with these metal ions. So, these metal ions will affect the absorption and bioavailability of minocycline if they are taken together.
A case report has suggested that tetracycline may increase serum lithium levels and may lead to toxicity, although this conclusion was not substantiated by a small crossover study. Patients who must take both drugs probably should be monitored for clinical and laboratory evidence of lithium toxicity.
Iron did not fit the general trend, there were no absorbable readings presented by the spectrophotometer, whereas all the other ions gave absorbable readings for the different values. This indicates that the iron, possibly precipitated out of the solution and hence no absorbance value was detected at wavelengths from 300-388nm. In cases where iron administration is warranted, physicians prescribing tetracycline antibiotics are advised to inform patients of the probable pharmacokinetics interaction between iron and the medication and so recommend separating oral intake by at least 3 hours.