Antibiotics action

These organelles, the sites of protein synthesis, are well-established targets for antibiotic action. 

A number of substances have been discovered in the last thirty years with a macrocyclic structure (i.e. with ten or more ring members), polar ring interior and non-polar exterior. These substances form complexes with univalent (sometimes divalent) cations, especially with alkali metal ions, with a stability that is very dependent on the individual ionic sort. They mediate transport of ions through the lipid membranes of cells and cell organelles, whence the origin of the term ion-carrier (ionophore). They ion-specifically uncouple oxidative phosphorylation in mitochondria, which led to their discovery in the 1950s. This property is also connected with their antibiotic action. Furthermore, they produce a membrane potential on both thin lipid and thick membranes. 

Ovchinnikov, Yu. A., Ivanov, V. T., Shkrob, A. M. In Molecular mechanisms of antibiotic action on protein biosynthesis and membranes (E. Munoz, F. Garcia-Femandez and D. Vasquez, eds.), p. 459. Amsterdam Elsevier 1972. 

Our job in this chapter is to nnderstand what the important antibacterials are and how they work. If yon want the whole story in all its elegant scientific detail, Christopher Walsh has bronght it together in his book Antibiotics Actions, Origins, Resistance ... 

C. Walsh, Antibiotics Actions, Origins, Resistance, ASNl Pi ess, Washington, DC, 2003. 

Threonine and a,7-diaminobutyric acid are present within the structure of these antibiotics. The distinguishing feature of the polymyxine group is in that they contain 4-5 free / amine groups of a,7-diaminobutyric acid, which gives them the property of a cationic detergent able to form complexes with phospholipids of cellular membranes. All polymyxines are similar in term of antibiotic action. 

Grell, E., Funck, Th., Eggers, F. Symposium on Molecular Mechanisms of Antibiotic Action on Protein Biosynthesis and Membranes, University of Granada, Spain, June 1—4 (1971). 

Esomeprazole (Nexium) [Gastric Acid Inhibitor/Proton Pump Inhibitor] Uses Short-term (4-8 wk) for erosive esophagitis/GERD H. pylori Infxn in combo w/ antibiotics Action Proton pump inhibitor, gastric acid Dose Adults. GERD/erosive gastritis 20 0 mg/d PO x 4-8 wk 20 0 mg IV 10-30 min inf or >3 min IV push, 10 d max Maint 20 mg/d... 

Sir Alexander Fleming first noted the ability of the mould P. notatum to produce an antibiotic substance (which he called penicillin) in 1928. However, he also noted that when penicillin was added to blood in vitro, it lost most of its antibiotic action, and Fleming consequently lost interest in his discovery. In the late 1930s, Howard Florey, Ernst Chain and Norman Heatley began to work on penicillin. They purified it and, unlike Fleming, studied its effect on live animals. They found that administration of penicillin to mice after their injection with lethal doses of streptococci protected the mice from an otherwise certain death. 

The (3-lactam antibiotics structurally resemble the terminal D-alanyl-D-alanine (o-Ala-o-Ala) in the pen-tapeptides on peptidoglycan (murein) (Fig. 45.1). Bacterial transpeptidases covalently bind the (3-lactam antibiotics at the enzyme active site, and the resultant acyl enzyme molecule is stable and inactive. The intact (3-lactam ring is required for antibiotic action. The (3-lactam ring modifies the active serine site on transpeptidases and blocks further enzyme function. 

Yoshizawa S, Fourmy D, Puglisi JD (1998) Structural origins of gentamicin antibiotic action. EMBO J 17 6437-6448... 

Di Poto, A., Sbarra, M. S., Provenza, G., Visai, L., and Speziale, P. (2009). The effect of photodjmamic treatment combined with antibiotic action or host defense mechanisms on Staphylococcus aureus biofilms. Biomaterials 30(18), 3158-3166. 

Molecular Basis of Antibiotic Action, 2nd ed. New York Wiley. 

Morris, S. L., Walsh, R. C., and Hansen, J. N. (1984). Identification and characterization of some bacterial membrane sulfhydryl groups which are targets of bacteriostatic and antibiotic action. J. Biol. Chem. 259, 13,590-13,594. 

Because peptidoglycans are unique to bacterial cell walls, with no known homologous structures in mammals, the enzymes responsible for their synthesis are ideal targets for antibiotic action. Antibiotics that hit specific bacterial targets are sometimes called magic bullets. Penicillin and its many synthetic analogs have been used to treat bacterial infections since these drugs came into wide application in World War II. 

Uses Broad-spectrum antibiotic Action Bacteriostatic protein synth Spectrum Gram(+) Staphylococcus sp, Streptococcus sp Gram(-) H. pylori Atypicals Chlamydia sp, Rickettsia sp, Mycoplasma sp Dose Adults. 250-500 mg PO bid—qid Peds > 8 y. 25-50 mg/kg/24 h PO q6-12h i w/ renal/hepatic impair, w/o food preferred Caution [D, +] Contra PRG, antacids, w/ dairy products, children <8 y Disp Caps 100, 250, 500 mg tabs 250, 500 mg PO susp 250 mg/5 mL SE Photosens, GI upset, renal failure, pseudotumor cerebri, hepatic impair Interactions T Effects OF anticoagulants, cligoxin effects W/ antacids, cimeticline, laxatives, penicillin, Fe supl, dairy products effects OF OCPs EMS T Effects of anticoagulants monitor for signs of electrolyte disturbances and hypovolemia d/t D ... 

---