Antibiotics protein binding effects

Methotrexate clearance can be decreased by the coadministration of NSAIDs however, this not usually a problem with the low doses of methotrexate used to treat arthritis. Methotrexate can be displaced from plasma protein binding sites by phenylbutazone, pheny-toin, sulfonylureas, and sulfonamides and certain other antibiotics. The antifolate effects of methotrexate are additive with those of other folate-inhibitory drugs, such as trimethoprim. 

Mechanism of Action An antibiotic that alters cell membrane permeability in susceptible microorganisms. Therapeutic Effect Bactericidal activity Pharmacokinetics Negligible absorption. Protein binding low. Excreted in urine. Poor removal in hemodialysis. Half-life 6 hr. 

For efficient extraction of macrolide and lincosamide residues from edible animal products, bound residues should be rendered soluble, most if not all of the proteins should be removed, and high recoveries for all analytes should be provided. Since tliese antibiotics do not strongly bind to proteins, many effective extraction methods have been reported. Sample extraction/deproteinization is usually accomplished by vortexing liquid samples or homogenizing semisolid samples with acetonitrile (136—139), acidified (136,140-142) orbasified acetonitrile (143), methanol (14, 144, 145), acidified (145-147) or basified methanol (148), chloroform (149-151), or dichloromethane under alkaline conditions (152). However, for extraction of sedecamycin, a neutral macrolide antibiotic, from swine tissues, use of ethyl acetate at acidic conditions has been suggested (153), while for lincomycin analysis in fish tissues, acidic buffer extraction followed by sodium tungstate deproteinization has been proposed (154). 

INTRAVENOUS -THIOPENTONE ANTIBIOTICS -SULPHONAMIDES t effect of thiopentone but 1 duration of action Uncertain possibly displacement from protein-binding sites Be aware that i dose may be needed... 

Although dinical microbiology laboratories report microbial susceptibility test results as sensitive or resistant to a particular antibiotic, this is not an absolute predictor of clinical response. In a given patient s infection, variables such as absorption of the drug, its penetration to the site of infection, and its activity once there (influenced, for example, by protein binding, pH, concentration of oxygen, metabolic state of the pathogen, intracellular location and concentration of microbes) profoundly alter the likelihood that effective therapy will result. 

The crucial event that initiates the antimicrobial effects of beta-lactam antibiotics is binding to and inhibition of bacterial enzymes located in the cell membrane, the so-called penicillin-binding proteins (2). This happens by... 

More directly, the effect of protein binding on antibiotic action is worth considering. 

The P-lactam antibiotics continued to be the cynosure of synthesis. Some structure-activity relationships of peni-cillins O and cephalosporins 2 v/ere discussed. Timely reports aimed primarily toward the evaluation of the newer highly serum-bound penicillins dealt with the controversial relationship of drug-serum protein binding to clinical antimicrobial effectiveness. 3,14... 

Sulfasalazine s absorption can be decreased when antibiotics are used that destroy the colonic bacteria. Sulfasalazine also binds iron supplements in the gastrointestinal tract that can lead to a decreased absorption of sulfasalazine. The administration of these two agents should be separated temporally to avoid this interaction. Sulfasalazine can potentiate warfarin s effects by displacing it from protein-binding sites. Close monitoring of the patient s International Normalized Ratio is indicated. ... 

Three patients experienced decreased INR after the administration of cloxacillin in combination with warfarin. Antistaphylococcal penicillins have been associated with decreased INR. Potential mechanisms for this include competition for protein binding and induction of CYP450 enz3unes. This is the first case series with this interaction of warfarin with cloxacillin specifically. In this case series, the INR effect was seen in 4 days, but INR remained sub-therapeutic for 3-4 weeks after cloxacillin was discontinued. Clinicians should be aware of this effect and consider choosing alternate antibiotic therapy when possible [50 ]. 

On the other hand, the antibiotic chloramphenicol binds to the bacterial ribosomes, but not the larger ribosomes of animals, thereby showing greater specificity. This inhibits peptide bond formation. Chloramphenicol is relatively nontoxic, but it still must be used with caution as side effects such as anemia can result. Other antibiotics which inhibit protein synthesis include the tetracyclines, streptomycin, and cycloheximkle. 

The desired characteristics for an antibiotic are to have a wide antibacterial spectrum, to be an effective bactericide at low concentrations, high elution from the matrix for prolonged periods, thermal stabiHty, low allergy risks as well as low influence on the properties of the biomaterial and low serum protein binding [16,19]. Additionally, it is commonly used in the powder form. The antibiotics that implement most of these conditions are the aminoglycosides and glycopeptides. 

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