Manga, Marjuleane L.

2F Pharmacy

Chapter 11 ANTIBIOTICS AND SYNTHETIC ANTIMICROBIAL AGENTS; THEIR PROPERTIES AND USES 1. ANTIBIOTIC DEVELOPMENT -originally defined in the 1940s as a substance produced by a microorganism which inhibited the growth of other organism -but the definition has changed as the increasing number of synthetics derivatives come on to market -sulphonamides in the 1930s were the first significant antibiotics and predated penicillin by about 10 years -onset of World War 2, the production of Benzylpenicillin joined by other penicillins -tetracyclines, macrolides, aminoglycosides-true antibiotics in traditional sense kasi extracted from streptomyces bacteria /fungi [kung penicillin] sila so natural ung source pero during 1960s naman nag start itong mga semi synthetic-from naturally occurring substance galing sila pero na modify na ung structure nila kaya aun. -noon pa man recognize na ung prob about bacterial resistance kaya continous ung studies para ma remedyohan pero na something ung mga assumptions na to kasi nagging bongga na ung resistance ng mga bacteria as years passed by katulad ng hospital superbugs like MRSA (meticillin resistant Staph. Aureus) and Clostridium difficile so naging nahirapan talaga ung industry. -during 1970-2000 structural modifications lang din kasi ng mga existing ones pero sa pag start ng new millennium ..dandaran!!! Linezolid and Quinupristin/dalfopristin ayan nagsilabasan sila.

-although need naman na ma cure itong mga MRSA VRE chu chu gamit ung antibiotics hindi masyadong masomethingan kasi nga maiksi lang naman ung theraphy , mabilis magkaroon ng resistance at may possibility na malugi or di ba mapeperahan ung pag gawa compare sa pag focus ng mga studies sa obesity and all. Antibiotic Usage -kahit konti lng ung bagong labas na mga antibiotic marami namang class na currently being used pa din naman. -B-Lactam ung pinaka mabili -mukhng di na lalabas sa quiz ung ibang facts tignan m pa sa page 171. Haha 2. B-LACTAM ANTIBIOTICS -these antibiotics all have the same mechanism of anibaterial action at lahat sila may B-lactam ring baby pero different syempre sila sa characteristics. Penicillin

Ito ung sinasabi ni sir na bahay na may garahe pero sa pic na ito na earthquake ata kaya bumaliktad pero ito pa din un. Ung B lactam ring baby. -naturally occurring sila. Pwedeng galing sila sa fermentation ng moulds such as Penicillium notatum at saka P. Chrysogenum . example din... penicillin G-benzylpenicillin, penicillin Vphenoxymethylpenicillin.

-pwede ding semi synthetic. Katulad nung sa Beecham research lab, na isolate daw ung nucleus sa 6-aminopenicillanic acid(6APA). Kasi once upon a time during the commercial production ng benzylpenicillin may inaadd na phenyl acetic acid dun sa medium kung saan ung penicillium mould nag gogrow..precursor kasi ito para sa side chain ng benzylpenicillin. Kapag may tumubo na walang phenylacetic acid maiisolate na ung 6APA, getz? May different Rf value ito kaya madedetect chromatographically. -ung another method naman sa pag produce ng 6APA is from the thingy na may ilang microorganism kasi na nag proproduce ng penicillin amylases<-enzymes yan okie?...so catalysis sila sa pag remove ng side chain ng benzylpenicillin katulad kanina... -acylation naman ng 6APA results in new penicillins, different only in the nature of the side chains, Some of these have considerable activity against gram and +bacteria. May broad spectrum at pwedeng i-alter ung Pharmacokinetics nila baby. Sodrium and Potassium salts are soluble in water. So? They are hydrolysed in sol at room temp-dependent. So? ...kasi lahat to corresponding sa PENICILLOIC ACID which is not antibacterial. Na creacreate to at alkaline pH or at neutral pH . ay degradation product pala to ng benzylpenicillin in solution, penicilloic, penicilinoic acid at saka penillic acid(pag acidic pH ) -Kaya susceptibility to hydrolysis means that penicillins cannot be formulated as aqueous product -okay medyo change topic, maraming bacteria ung nag proproduce nito B lactamase/penicillinase- nakaka inactivate ito ng penicillin kung ma open nya ung B lactam ring. Ung may clinical significance lang is ung sa S. Aureus (gram +). Gram negative kasi konti

lng kaya wala masyadong clinical significance daaw. -pero may mga penicillin na more enzyme resistant kaya pwede sila ditto sa bacteria na nag proproduce ng B lactamase. Benzylpenicillin and phenoxymethlylpenicillin, both active yan against Gram positive bacteria./at saka mga B lactamase sensitive din [4 paragraphs remaining page 174-175] Cephalosporins First ones- cephalothin and cephaloridine. -consists of 6 membered dihydrothiazine ring na fused to a B lactam ring . -mas maraming structural modification ito kayssa sa penicillindahil may dalawang side chain to. -act as good inducers for B lactamase -ang general trend ditto is increase in activity againsy gram negative species and inc resistance to B lactamase -may disturb the gut flora and give rise to diarrhoea [study ung sa per generation di mo pa masyado getz ] Structure activity Relationships -ung activity ng cepha nay an naka depende sa penicillin sensitive enzymes (PSEs) so ung resistance na to pwede ma alter ung B lactamase at saka nga pala ung activity agains t gram nega naka depende un sa penetration sa B lactams through the outer membrane. -ung pag modify sa nucleus ng cephalosporins sa pamamagitan ng pag add sa methoxy grp nakakaincrease un ng B lactamase stability pero na dedecrease nya namn ung activity against gram positive dahil na babawasan din un affinity for PBPs.

-ung mga molecules na nag poposses ng 7alpha methoxy grp katulad ng cefoxitin are termed cephamycin. -ung mga side chains naman na may 2 aminothiaxoyl grp sa R1 katulad ng cefoxatime ceftriaxone at ceftazidime , yield Cephalosporin WITH enhanced AFFINITY FOR PBPs of gram bacteria at sa streptococci. -ang iminomethoxy grp naman eg cefuroxime nag proprovide un ng B lactamase stability against common plasmid B lactamase. -propylcarboxyl grp eg ceftazidime increases B aeriginosa while at some time reducing B lactamase induction capabilities