Macrolides protein binding

The macrolides are orally absorbed but they are acid-labile. They therefore need to be administered in acid-resistant capsules or as acid-resistant esters. The macrolides are widely distributed into all fluids except the CNS. Protein binding is about 90%. They are eliminated via biliary excretion with extensive enterohepatic circulation. Elimination half-lives vary from 1.4 h for erythromycin to 40-60 h for azithromycin. 

Mechanism of Action A macrolide that binds to ribosomal receptor sites of susceptible organisms, inhibiting protein synthesis of the bacterial cell wall. Therapeutic Effect Bacteriostatic maybe bactericidal with high dosages or very susceptible microorganisms. 

Mecfianism of Action A macrolide that reversiblybindstobacterial ribosomes, inhibiting bacterial protein synthesis. Therapeutic Effect Bacteriostatic. Pharmacokinetics Variably absorbed from the GI tract (depending on dosage form used). Protein binding 70%-90%. Widely distributed. Metabolized in the liver. Primarily eliminated in feces by bile. Not removed by hemodialysis. Half-life 1.4-2 hr (increased in impaired renal function). 

Although there is no evidence that neuropsychiatric complications of macrolides develop more readily in uremic patients, several factors may predispose toward these adverse effects, such as reduced drug clearance, altered plasma protein binding, different penetration of drug across the blood-brain barrier, and an increased propensity for drug interactions. 

The macrolides distribute well and tissue concentrations may be higher than serum concentrations. Erythromycin concentrates and is active in leukocytes because of its high lipid solubility and ion trapping. The of erythromycin is 3.7-7.21/kg in adult horses and foals. The protein binding is low. The hepatic clearance of the macrolides may be slower in animals of up to 1 month of age than in adult animals. 

Menninger and Otto [101] proposed a major inhibitory mechanism common to probably all macrolide antibiotics. In E. coli mutants with temperature-sensitive peptidyl-tRNA hydrolase (aminoacyl-tRNA hydrolase EC 3.1.1.29), they observed that peptidyl-tRNA accumulates at a nonpermissive temperature (40°C) and that the cells die. The accumulation at a high temperature was enhanced when the cells were pretreated with erythromycin, carbomycin, or spiramycin at doses sufficient to inhibit protein synthesis in wild-type cells but not sufficient to kill either mutant or wild-type cells at the permissive temperature (30°C). Based on their observations, they suggested that stimulated dissociation of peptidyl-tRNA from ribosomes is the major mechanism of action of macrolide antibiotics. Their observations agree with recent results showing that a macrolide antibiotic binds to peptidyltransferase in ribosome. 

Macrolide antibiotics bind to the 50 S ribosomal subunit, inhibiting bacterial protein synthesis. This results in a decrease in bacterial cellular function and replication. 

In contrast to macrolides, the targets of (3-lactams, the penicillin binding proteins (PBPs) require several mutations in order to become resistant while simultaneously maintaining their viable function as cell wall transpeptidases/transglycosidases. Thus, in order to achieve clinically relevant resistance Streptococcus pneumoniae uses a unique strategy to rapidly accumulate several point mutations. Due to its natural competence for transformation during respiratory tract... 

The macrolides are bacteriostatic or bactericidal in susceptible bacteria The drugs act by binding to cell membranes and causing changes in protein function. 

The macrolide erythromycin inhibits protein synthesis and resistance is induced by N -dimethyl-ation of adenine within the 23S rRNA, which results in reduced affinity of ribosomes for antibiotics related to erythromcin (Skinner et al. 1983). Sulfonamides function by binding tightly to chromosomal dihydropteroate synthetase and resistance to sulfonamides is developed in the resistance plasmid through a form of the enzyme that is resistant to the effect of sulfonamides. 

Macrolides Erythromycin Inhibits protein synthesis by binding Gram-positive cocci, mycoplasma,... 

Newer and more generally usefnl macrolide antibiotics include azithromycin (Zithromax) and clarithromycin (Biaxin). These too are wide-spectrum antibiotics and both are semisynthetic derivatives of erythromycin. Like the tetracyclines, the macrolide antibiotics act as protein synthesis inhibitors and also do so by binding specifically to the bacterial ribosome, thongh at a site distinct from that of the tetracyclines. 

Macrolides, lincosamides and streptogramins are protein biosynthesis inhibitors that bind to 50S subunit of the ribosome and inhibit peptidyl tRNA translocation from the A-site to the P-site." Macrolides have a glycosylated 14-, 15- or 16-membered lactone ring structure and are produced by several species of Streptomyces. Lincosamide antibiotics were isolated initially from Streptomyces lincolnensis but later isolated from different species of Streptomcyces. Streptogramins were also isolated from Streptomycesgraminofaciens and subsequently from several different Streptomyces species. There are two structurally different streptogramins, A and B they are bacteriostatic individually and can be bactericidal when combined. 

Pharmacology Macrolide antibiotics reversibly bind to the P site of the SOS ribosomal subunit of susceptible organisms and inhibit RNA-dependent protein synthesis. They may be bacteriostatic or bactericidal, depending on such factors as drug concentration. 

Pharmacology Telithromycin belongs to the ketolide class of antibacterials and is structurally related to the macrolide family of antibiotics. Telithromycin blocks protein synthesis by binding to domains II and V of 23S rRNA of the 508 ribosomal subunit. Pharmacokinetics ... 

Pharmacology Sirolimus, a macrolide immunosuppressive agent, inhibits both T-lymphocyte activation and proliferation that occurs in response to antigenic and cytokine (interleukin-2, -4, and -15) stimulation and also inhibits antibody production. In cells, sirolimus binds to the immunophilin, FK binding protein-12 (FKBP-12), to generate an immunosuppressive complex. 

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