Tetracycline, effect

Tetracyclines are broad-spectrum antibiotics. effective against Gram-positive and Gram-negative bacteria, also against Rickettsiae (typhus fever) and certain other organisms. 

Antibiotics were used in folk medicine at least as early as 2500 years ago when the Chinese reported the medicinally beneficial effects of moldy bean curd. Evidence for some type of tetracycline antibiotic usage by the Sudanese-Nubian civilization (350 AD) was reported in 1980 (6). Fluorescent areas in human bones from this eta were observed that were identical in location and characteristics to modern bone from patients treated with tetracyclines. Identification of tetracycline in the ancient bones was further substantiated by fluorescence spectmm measurements and microbiological inhibition studies (7). 

The overall biosynthetic pathway to the tetracychnes has been reviewed (74). Studies (75—78) utilising labeled acetate and malonate and nmr analysis of the isolated oxytetracycline (2), have demonstrated the exclusive malonate origin of the tetracycline carbon skeleton, the carboxamide substituent, and the folding mode of the polyketide chain. Feeding experiments using [1- 02] acetate and analysis of the nmr isotope shift effects, led to the location of... 

It has been known for some time that tetracyclines are accumulated by bacteria and prevent bacterial protein synthesis (Fig. 4). Furthermore, inhibition of protein synthesis is responsible for the bacteriostatic effect (85). Inhibition of protein synthesis results primarily from dismption of codon-anticodon interaction between tRNA and mRNA so that binding of aminoacyl-tRNA to the ribosomal acceptor (A) site is prevented (85). The precise mechanism is not understood. However, inhibition is likely to result from interaction of the tetracyclines with the 30S ribosomal subunit because these antibiotics are known to bind strongly to a single site on the 30S subunit (85). 

Fig. 4. Comparison of the three types of tetracycline resistance where T represents the tetracycline molecule O, a tetracycline transporter and aaa/, the ribosome A shows the effect of tetracycline exposure on a sensitive cell B, the efflux of resistance where a cytoplasmic membrane protein ( D) pumps tetracycline out of the cell as fast as the tetracycline transporter takes it up C, the ribosomal protection type of resistance where the ribosome is modified by ( ) to block productive binding and D, the tetracycline modification type of resistance where t is an inactive form of tetracycline. Reproduced with...

Tetracyclines are used as alternative dnigs in a variety of circumstances when the patient is unable to take the dnig of choice, eg, in patients allergic to penicillin (88,89). Tetracyclines are widely known to cause staining of teeth (and are therefore contra-indicated in children developing permanent teeth), photosensitivity, and, in the case of minocycline, vestibular toxicity. Details of these adverse effects and others associated with administration of tetracyclines have been comprehensively reviewed (96—101). 

Resistance to Tetracyclines. The tetracyclines stiU provide inexpensive and effective treatment for several microbial infections, but the emergence of acquired resistance to this class of antibiotic has limited their clinical usehilness. Studies to define the molecular basis of resistance are underway so that derivatives having improved antibacterial spectra and less susceptibiUty to bacterial resistance may be developed. Tetracyclines are antibiotics of choice for relatively few human infections encountered in daily clinical practice (104), largely as a result of the emergence of acquired tetracycline-resistance among clinically important bacteria (88,105,106). Acquired resistance occurs when resistant strains emerge from previously sensitive bacterial populations by acquisition of resistance genes which usually reside in plasmids and/or transposons (88,106,107). Furthermore, resistance deterrninants contained in transposons spread to, and become estabUshed in, diverse bacterial species (106). 

The infection can be cured most readily with tetracycline (7), oxytetracycline (3), or chlorotetracycline (20). Metronidazole (1) and iodoquinol (2) are also effective. Additional effective dmgs include paromomycin (8), tinidazole (11), sulfadiazine (25), and carbarsone [121 -59-4] (31, -ureidobenzenearsonic acid, CyH AsN204, Ameban). 

Another subclass of proteases attacks internal peptide bonds and Hberates large peptide fragments. Bromelain, a plant protease derived from the stem of the pineapple plant, can even produce detectable semm proteolysis after oral adrninistration (180). Oral therapy with bromelain significantly reduces bmising that stems from obstetrical manipulations (181). Bromelain—pancreatin combinations have been more effective in digestive insufficiency compared to either pancreatin or placebo (182,183). Bromelain may also enhance the activity of antibiotics, especially tetracycline, when adrninistered concurrently (184). 

Fig. 29. Effect of the extent of crosslinking of sulfonated cation exchangers (quantity of cross-linking agent) on diffusion coefficient of tetracycline in sorbent grains 1) SDMDMA, 2) SHMDMA, i) SEDMA, 4) Dowex-50W...

The tetracyclines exert their effect by inhibiting bacterial protein syndiesis, which is a process necessary for reproduction of die microorganism. The ultimate effect of diis action is tiiat the bacteria are either destroyed or dieir multiplication rate is slowed. The tetracyclines are bacteriostatic (capable of slowing or retarding die multiplication of bacteria), whereas die macrolides and lincosamides may be bacteriostatic or bactericidal (capable of destroying bacteria). 

These antibiotics are effective in die treatment of infections caused by a wide range of gram-negative and gram-positive microorganisms. The tetracyclines are used in infections caused by Rickettsiae (Rocky Mountain spotted fever, typhus fever, and tick fevers). Tetracyclines are also used in situations in which penicillin is contraindicated, in the treatment of intestinal amebiasis, and in some skin and soft tissue infections. Oral... 

The tetracyclines are contraindicated if the patient is known to be hypersensitive to any of the tetracyclines. Tetracyclines also are contraindicated during pregnancy because of die possibility of toxic effects to the developing fetus. The tetracyclines are classified Pregnancy Category D drag. These drug also are contraindicated... 

There is an increased risk of toxicity of MTX when administered with the NSAIDs, salicylates, oral antidiabetic drugs, phenytoin, tetracycline, and probenecid. There is an additive bone marrow depressant effect when administered with other drug known to depress the bone marrow or with radiation therapy. There is an increased risk for nephrotoxicity when MTX is administered with other drug that cause nephrotoxicity. When penicillamine is administered with digoxin, decreased blood levels of digoxin may occur. There is a decreased absorption of penicillamine when the dmg is administered with food, iron preparations, and antacids. 

The effects of warfarin may increase when administered with acetaminophen, NSAIDs, beta blockers, disulfiram, isoniazid, chloral hydrate, loop diuretics, aminoglycosides, cimetidine, tetracyclines, and cephalosporins. Oral contraceptives, ascorbic acid, barbiturates, diuretics, and vitamin K decrease the effects of warfarin. Because die effects of warfarin are influenced by many drugp, die patient must notify die nurse or die primary healdi care provider when taking a new drug or discontinuing... 

The absorption of oral iron is decreased when tlie agent is administered with antacids, tetracyclines, penicillamine, and the fluoroquinolones. When iron is administered with levothyroxine, there may be a decrease in tlie effectiveness of levothyroxine When administered orally, iron deceases the absoqition of lev-odopa. Ascorbic acid increases tlie absoqition of oral iron. Iron dextran administered concurrently with chloramphenicol increases serum iron levels. 

The following drugp have a decreased pharmacologic effect when administered with an antacid corticosteroids, digoxin, chlorpromazine, oral iron products, isoniazid, phenothiazines, ranitidine, phenytoin, valproic acid, and the tetracyclines. 

The effects of metoclopramide are antagonized by concurrent administration of anticholinergics or narcotic analgesics. Metoclopramide may decrease the absorption of digoxin and cimetidine and increase absorption of acetaminophen, tetracyclines, and levodopa Metoclopramide may alter die body s insulin requirements. 

The effects of the progestins are decreased when administered with anticonvulsants, barbiturates, or rifampin. Administration of the penicillins or tetracyclines with the oral contraceptives decreases the effects of the oral contraceptives. 

Oral administration of bicarbonate may decrease the absorption of ketoconazole. Increased blood levels of quinidine, flecainide, or sympatiiomimetics may occur when these agents are administered with bicarbonate There is an increased risk of crystalluria when bicarbonate is administered with the fluoroquinolones. Fbssible decreased effects of lithium, methotrexate, chlorpropamide, salicylates, and tetracyclines may occur when these drag s are administered with sodium bicarbonate. Sodium bicarbonate is not administered within 2 hours of enteric-coated drugs the protective enteric coating may disintegrate before the drug reaches the intestine. 

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