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Any use of this site constitutes your agreement to the Terms and Conditions and Privacy Policy linked below. This site complies with the HONcode standard for trustworthy health information: verify here. Various mechanism of action of tetracycline is related with the attachment of different species in the skeleton such as hydroxyl and amine groups. This breakage cause oxidative stress and ultimately death of bacterial cell.
Antibacterial tetracycline act in a different way as compared to antifungal and antitumor tetracycline. First, tetracycline get ahead of the eukaryotic cell to form complexes in different positions with calcium and magnesium ions present in the blood by changing the electronic balance equilibrium sequestering divalent ions. In the next step, tetracycline adopt typical and atypical mechanism against bacteria either by binding with ribosomal subunits to inhibit the synthesis of protein or by the direct killing of bacteria [2].
The typical mechanism of action of tetracycline contains the prevention of the association of aminoacyl-tRNA with bacterial ribosome to inhibit bacterial protein synthesis.
In gram positive and gram negative bacteria, tetracyclines intermingle with targets by passing through one or more membrane systems. Hence, mechanism of action of tetracycline requires understanding of uptake and ribosomal binding mechanism. Tetracycline crosses over the outer membrane of gram negative bacteria through outer membrane protein F and outer membrane protein C channels, as positively charged cation mostly magnesium -tetracycline coordination complexes. The Donnan potential of the outer membrane attract the cationic metal ion-antibiotic complex to mount up in the periplasm.
At this place, metal ion-tetracycline complex probably dissociate to release uncharged tetracycline, which is a weakly lipophilic molecule efficiently and diffuse through the lipid bilayer regions of the inner cytoplasmic membrane. Similarly, tetracycline in electroneutral and lipophilic forms transferred across the cytoplasmic membrane of gram positive bacteria. This uptake of tetracyclines across the cytoplasmic membrane is energy dependent.
Within the cytoplasm, tetracycline molecules become chelate at specific conditions when internal pH and divalent metal ion concentrations are higher compared to the conditions outside the cell. Magnesium tetracycline complex is an active drug species which binds to the ribosome of the bacteria. Bacteriostatic effects of antibiotics can be explained by understanding the association of tetracycline with ribosome during reversible reaction.
Pharmacokinetics and Pharmacodynamics studies of Tetracyclines. Pharmacokinetics is the study of mechanisms of absorption, distribution, chemical changes of a substance in the body and the effects, and the route of administration of metabolites of drugs in the body.
Many factors affect the pharmacokinetic properties of the drugs such as site of administration and the dose of administered drug. Pharmacokinetics is often studied in combination with pharmacodynamics, which is the study of the biochemical and physiological effects of the drug on the body, or microorganisms or parasites within or on the body.
The mechanism of drug action and relationship between drug concentration and effect are also studied in pharmacodynamics. Generally, tetracyclines can be divided into three main groups based on pharmacokinetics shown in Figure 3. Pharmacokinetics of members of the tetracycline class has been studied by using high performance liquid chromatography assays, spectrophotometric methods and biological assays.
Agents of group 1 include tetracyclines, oxytetracycline, chlortetracycline, demclocycline, lymecycline and methacycline and rolitetracyclines. All members give oral formulation except rolitetracycline which gives intravenously. Serum concentration progressively rises after oral administration with absorption occurring in the stomach, duodenum and small intestine. All these tetracycline reduce the absorption after forming insoluble complexes with calcium, magnesium, iron and aluminium.
Protein binding is variable. None of these agents undergo metabolism except tetracycline. In all of the agents of group 1, rolitetracycline gives the highest elimination. In blood, tetracycline first gives a slow rise then a slower drop, forming a plateau shaped course. In group 2 both doxycycline and minocycline give oral formulation.
Food has less effect on absorption, so more doxycycline enters the duodenum for absorption. In excretory organs, concentration exceeds by giving unchanged elimination by both renal and biliary routes.
Iron and antacids containing calcium and magnesium reduce the absorption of minocyclines. In group 3, two agents are included: glycylcycline and aminomethylcycline. Amino-methylcycline is in preclinical development while a little bit of pharmacokinetic data is available on tigecycline. There is no data on absorption of tigecycline, with limited data on oral formulation. Pharmacodynamics is the association between capacities of antimicrobial exposure with the antibacterial and toxicological effects of the drug in the body.
Several antibacterial measures are important but the most important measure of drug potency is minimum inhibitory concentration. The killing effects of doxycycline, minocycline and tigecycline have been studied by using the time-kill curve method Table 2.
Tetracycline and their analogues show non-antibiotic properties by inhibiting matrix metalloprotenases MMP and also play important roles in the remodeling of connective tissues and participate in wound healing; rheumatoid arthritis, tumor invasion and metastasis is also the non-antibiotic property of tetracycines [30]. Angiogenesis, construction of new blood vessels, occur in many diseases including benign e.
Minocycline and doxycycline hold down angiogenesis induced by implanted tumors in rabbit corneas [36]. The therapeutic implication of antiangiogenic effects of tetracycline in the inflammatory process accompanied by new blood vessel formation. Furthermore, recent studies indicated that tetracycline has antiapoptotic properties [26,37].
Doxycycline and minocycline both play crucial roles in bone metabolism. Doxycycline reduces the severity of canine osteoarthritis in dog anterior cruciate model, and minocycline avert the decrease in mineral density [38] osteoporosis observed in ovariectomized old rats Figure 4 [39]. Other clinical studies include both dermatologic and nondermatologic uses of tetracyclines in the diseases of skin, bullous dermatoses, cutaneous sarcoidosis, rosacea, and sarcoidosis.
Minocycline, because of having immunomodulatory and antiinflammatory properties, might be effective in the treatment of autoimmune disorders like rheumatoid arthritis, scleroderma, cancer, cardiovascular disorders and periodonititis. In short, tetracyclines and their analogues have been used not only in the treatment of different dermatologic and non-dermatologic diseases but also have anti-inflammatory and immunomodulatory effects. Because of extensive use of tetracycline, labeling of tetracycline with radioisotope was successfully done and used for the imaging of various diseases [40].
Radiolabeling of molecules is significantly important, which includes visualization, characterization and quantification of tumors and their biological processes. In therapy, particular radiations, such as alpha and beta particles and non-particulate like Auger electrons emitted by radiopharmaceuticals, are used for treatment and diagnosis. Alpha radiations give short tissue range with high localized energy deposition, which are damaging for healthy cells.
Beta radiations preferentially used for therapy having low toxicity due to lower deposition energy as compared to alpha radiations. The penetration range of beta radiations is several millimeter.
Thus, these radiations can easily target the cancerous cells located in the inner mass of tumors, even if penetration range of the pharmaceutical is low.
Electron capture and internal conversion emit gamma radiations which further triggers emission of Auger electrons which enter only few nanometers inside tissues, where energy deposition takes place which is significantly higher than beta radiation and lower than alpha radiations. This is the reason why non particulate emitters, such as gamma ray and positron emitter, which have low deposition energy are successfully used for therapy [42].
With all these aspects, this radioisotope Tcm has specific capabilities with favorable in vivo properties and vast clinical applications, which allow to develop radiolabeled compounds having excellent targeting properties [43]. In nuclear medicine, imaging modalities, such as Gamma camera scintigraphy and PET, are abruptly used to diagnose early stage abnormalities. These kinds of techniques require a radioisotope which emits proton, neutron and Gamma radiations.
Energy of these radiations are considered important to diagnose medical problems such as cancer, infection, thrombosis, kidney and liver abnormalities, cardiological and neurological disorders.
Tcm possess ideal properties due to which it occupies an important position in nuclear medicine. In a desirable radiometal, some important features should be considered including the half-life of radioisotope, mode of decay, cost and availability of the radioisotope. Tcm has a half-life of about 6 hours; long enough to carry out the desired chemistry to synthesize the radiopharmaceuticals and also long enough to allow accumulation in the target tissue, whilst allowing quick clearance through nontarget organs.
Another important factor is its cost and availability, for this purpose radionuclide generators are considered the best, having a long-lived parent isotope that decays to a short-lived daughter radionuclide which is easily separated by simple methods like ion exchange chromatography and solvent extraction. How should this medicine be used? Other uses for this medicine What special precautions should I follow? What special dietary instructions should I follow? What should I do if I forget a dose?
What side effects can this medication cause? What should I know about storage and disposal of this medication? Brand names. Other uses for this medicine. What special precautions should I follow? Before taking tetracycline, tell your doctor and pharmacist if you are allergic to tetracycline, minocycline, doxycycline, demeclocycline, any other medications, or any of the ingredients in the tetracycline capsule.
Ask your pharmacist for a list of the ingredients. Be sure to mention any of the following: anticoagulants 'blood thinners' such as warfarin Coumadin, Jantoven , and penicillin.
Take tetracycline 2 hours before or 6 hours after antacids, calcium supplements, zinc products, and laxatives containing magnesium. Take tetracycline 2 hours before or 4 hours after iron preparations and vitamin products that contain iron.
Take tetracycline 2 hours before or after zinc containing products. If you become pregnant while taking tetracycline, call your doctor immediately. Tetracycline can harm the fetus. Tetracycline may make your skin sensitive to sunlight. Tell your doctor right away if you get a sunburn.
Tetracycline should not be used in children under age 8 unless your doctor decides it is needed. Unless your doctor tells you otherwise, continue your normal diet. Tetracycline may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: nausea vomiting diarrhea itching of the rectum or vagina swollen tongue black or hairy tongue sore or irritated throat Some side effects can be serious.
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