In previous lectures we talk about sterilization and ...



In previous lectures we talk about sterilization and disinfection "kill bacteria which present in innate object". Also we talk about antiseptic which used to kill bacteria on surface of skin. In this lecture we will talk about Antibacterial Agents (antibiotics).Antibacterial Agents use to treat infection inside the body and administrated in these routs :1- orally :absorb by GI .2- paternal :by injection either IV or IM .3- topically : use in skin infection .* first antibiotic reported in 17th century and it was sulfa amide .later on penicillin discovered by accident while Fleming work on cultivation of bacteria one of plates contaminated by fungi and he noticed no grow of bacteria in this plate after that he studied the fungi in detail and discover Penicillin antibiotic .Antibiotics originally are products of organism such bacteria and fungi and this table show examples: There are some definitions we should know before we going in detailPage 1 - Antibiotics: should kill bacteria and not kill human cell.- Chemotherapy: treatment for cancer by using chemicals . Don’t confuse … the Chemotherapy related to cancer but Antibiotics kill bacteria. - Antibacterial spectrum: range of activity Some of Antibiotics affect numerous types of bacteria so we called it Broad spectrum. Also some Antibiotics have narrow spectrum like Penicillin (affect only gram +ive bacteria).- Bacteriostatic :stop grow and division .Actually the bacteria kill by immune system which need 4 days to activate so bacteriostatic protect us from the bacteria until the immune system activate .- Bactericidal : kill the bacteria .. - Combination therapy : use more than one Antibiotics and that not recommended but in life threatening infection and we don’t know the organism so we should use more than one until we know the organism which cause the infection . for example patient has meningitis and we don’t know the organism cause it we start with more than one Antibiotics until we identify the organism then decide which one is the best to give it . Also we treat TB in this way we start using 3 Antibiotics then 2 then 1 But when you use combination therapy you should be attention to the effect :Synergism: Antibiotics help each other Antagonism: oppose each other for example when you give Bacteriostatic (stop the growth) and Bactericidal (work when the bacteria grow then kill it ) so Bactericidal become useless . - MIC : minimal inhibition concentration Minimal concentration of Antibiotic will inhabit the growth and division of organism.-MBC: minimal bacterial concentration Minimal concentration of Antibiotic will kill the bacteria .We use the MIC and MBC to determine sensitivity of bacteria to Antibiotic.-we will talk later about this –Page 2 We need the antibiotic injury prokaryotic cells without affect eukaryotic cells. On the other word the Antibiotic should target the specific feature for prokaryotic cells (cell wall, ribosome, nucleic acid). Mechanisms of Action:1 - Inhibition of cell wall synthesis : Beta lactams, Vancomysin, Teicoplanin, Bacitracin, Isoniazid, Ethambutol, and Cycloserine.All these Antibiotics work in cell wall synthesis and inhabit it but in different stages . 2- Alteration of cell membrane function :The cell membrane present in prokaryotic cells and eukaryotic cells .most of Antibiotics eliminate by kidney so will affect kidney and other site in body .examples Polymyxins we only use topically Amphotericin B only use in life threatening fungal infection , Imidazoles, Triazoles, Polyenes. 3- Inhibition of protein synthesis Page 3 - Chloramphenicol, Erythromycin, Lincomycins, Tetracycline, Aminoglycosides . these Antibiotics bind to ribosome unit (40s or 50s) and this binding either revisable >> Bactericidal or irreversible >> Bacteriostatic . 4- Inhibition of nucleic acid synthesisthe enzyme responsible for nucleic acid synthesis like genase is specific for prokaryotic cells so we can use them as Antibiotics - Rifampin, Quinolones, Metronidazole, Sulfonamides, Trimethoprim.NOTE: We should memorize the names of Antibiotics. ** Inhibition of cell wall synthesis All β-lactam antibiotics have β-lactam ring and the difference only in side chain Page 4 Active site of β-lactam ring is square--cell wall composed of peptidoglycon and its dynamic thing to adapt cell size so we need enzymes (proteins) to synthesis it . these proteins have ability to bind penicillin .pbp : proteins responsible to synthesis peptidoglycon and it has ability to bind penicillin . when bind to penicillin ,,the protein will not synthesis peptidoglycan so kill bacteria (β-lactam ring in penicillin bind to pbp so the protein become inactive so the cell wall will not synthsis .-penicillin G : not acid stable so we cant give it orally ,,only injection Penicillin V : acid stable and we got it by change side chain in penicillin G -- Penicillin G and V naturally produce and have narrow spectrum (gram +ive only ) because the gram –ive have outer membrane contain pores which prevent enter of penicillin so we should modify penicillin.-Ampecillin : amino acid modification lead penicillin active in both gram +ive and –ive bacteria .-Every time we change side chain we get new type of penicillin .-After we use penicillin for some time the bacteria become resistance by produce β-lactamase which breaks β-lactam ring >>>>not able to bind pbp >>> bacteria resistance.But the drug manufactures introduce new penicillin "methicillin "resistance to β-lactamase. But the bacteria due mutation change pbp so no longer binding to penicillin...at the end the bacteria become resistance to methicillin. Staphylococcus oris story :At the beginning Staphylococcus oris was week it killed by penicillin . with time it become more strong (it produce β-lactamase and become resistance ) so penicillin G , V and Ampecillin useless .but the war contentious between manufacture and Staphylococcus oris so the manufacture produce methicillin -resistance to β-lactamase- .the response of Staphylococcus oris is change pbp so again it be resistance to methicillin MRSA .Now we have Vancomycin and Teicoplanin can kill MRSA .- Vancomycin and Teicoplanin only use in hospital because wrong use make the bacteria resistance to it also .Page 5 If we have inhibitors for β-lactamase the Ampecillin will work . for examples :All have activity against staphylococci comparable to methicillin Amoxicillin + clavulanate (Augmentin)active against most respiratory tract, and some GI tract gram negative organismsAmpicillin + sulbactam (Unasyn)Very good activity against GI and respiratory tract gram negativesPiperacillin + tazobactam (Zosyn)Excellent activity against GI and respiratory tract gram negatives, including Pseudomonas aeruginosaCephalosporinsSimilar action to for β-lactame but it has 2 advantages :1-more broad spectrum 2 –less resistance to β-lactamase We have 4 generation (no need to know names of generations )When we have resistance to generation the second generation produce and so on . Page 6 ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download