UNIT <0: eta Lactum Anti bioticdeet -against | agents = CAgginst life) - TAD OoeIbIOLiC 16 aMGubsEdHee produced’ by _ I micro-organisms | which has capacity oF inhibiting the growth 4 even oF destroying | oe other micro-organisms " ; AHBOR | Any substance produced by living organism [chat iS capable oF inhibiting the growth 4 __| Survival OF One OF More Species OF micro- porganisms in) low concent rat'on OR | Antibiotics are microbial metabolites Or Sunthetic analogs inspired by bhem that in smal) doses, inhibiting the growth 4 Survival OF mierd- organisms without serious toxicity Leothe host 0 Survival oF Fittest’. in which one organism destroies another to preserve Teselr * = Firsh truely effective antimicrobial agents date From mid 1930's (the sulfonamide) + the First antibiotic came in use in 1940's olthe penicillin) 2\/03(22 1 Formeconc: OF diasolved eo which eolu bility - ONE ~ e 60lUte. En equilibrium with solid _S° ghespoaYi Pre pinlogica! eFFrect 6) sEoreochemistry - ik Involve the study OF 3 \ ll dimensional nature oF molecule +. eee - Study OF chiral molecule 22/03)22 it e | Frumankind has been subject to intection by | aia micro-organisms since beFore the down of __} > recorded history { 13 i one resumes thot mONnkind oF HAS beeh © gearching For suitable theorpy as nedrly as long. This was despirately difFicute enterprises Given the. acute nature OF most inFéction 4 linearly +0401 lack oF underctanding: bout | Eheli origin thats was) Dre volont until the| Prev nue ry. S Sly Foleloric use oF plant q animal preparation» soyabean curd, motdy bread ¢ cheese where used to treat boils 4 ca but OFLOnN Eailed. = eee until the discovery oF bacteriq (300yr ago) 4 the supsquent undertaking oF their role in “iNEeckiOn About 1S50YrS- Ago. Ehejr wos no hope For rational kherapy- Zp germany during goth century Robert toch showed: that specific micro-organisms cooled always be isolated From Lhe exerka’4 tissues or people with particular inkectious disease 4-thak these Same micro-organisms USUALLY were absent in nealthy individuals they could then beengrown on culture. media ¢ peen administered +o healthy person £0 reproduce: in those healthy indidudis all the _ Classic Symptoms OF the same disease - Tn _ 1877, Lowis Ppastur reported chat when what he turned " commebh bacteria” where “inkroduced into a _pu re. culture oF anthra ere _-Haected along with it~ the bacillia died ¢ that an injectfo. cilliq into a laboratory —__ Yeommon bacteria” wacillia 7 oF deadly anthrax bac Animal was harmless iF 4 “THis did'nt always work » bub IE tec: Eo appreciation oF antibiosis, where in 2 0 iero-organisms completed with For. Survival: baue G3- The well known observation OF a ‘clear 2. “OF inhibition (lysis) In a bacterial coign — ____| surrounding Discovery oF SuIFOn Tin 1930_as an OFF shods mst om treating 1 i . 0 achievement In = ht orgno metalic 4_ his theories oF | vial gig 9 colony oF conkaminating 4 borne. penicillium mould. by Blexzdnder "Yc Eloming in england in 1920 4 subsequent ~| ourigicukion oF penicillin From it in the \gre 19306 4 Carly (940s by Florey sChdin y y tin Abraham 4 Heatley » provided important ~—— addi-ional. impetus: : 25/03/29 trp 1929 Alexander Fleming Physician 4 clnigh microbiologist was preservated a cultured | “pathogen 4 plate pecdme contaminated why ‘air borne Fungus; penicillium notatum | (or penicillium chrysoginiuny) which dt Only | grew on plate but gisd produced a clear zore| oF inhibition around its colony. on _returing From a vacatron 4 Finding this: | he recognized the potential siqniticance | — + with 48t successful clinjeol criaLoF crude J -penicillin on Feb (2) (quay 4 OF 7 Or khis antibiotic effect Se he preserve te-—— Fungus 4 tried to identity its active ~~ —7— [consistituents. [war times 4 explosion oF gut ces I Homycin, bacitracin pol 4MOrs I Comphotericin =B) oF Re | 7 || Y aoa 6 | . Cf tphibit Protein Synthesis | eq. Tetracycline, sinpgaing = 7 : Clindamycin, linezoline r i : ct cule Q: | Cause: misreading or RNA 4 Fock porneasl : ; 24. “6minagiyoosides “streptomycin, Qentomg:| —e: E- || Inhibit “pnp gyrase’ fal } 3 €9- Fluoroquiolones, ciprotloxacn |e | I | E | Interfere with ONA Function 7 a ey reg: Rifampin, Metronidazole | ] c 1 &: I unterFere with BNA Synthosig $ B | eg. Acyclovir, zidavudine - | SUIFOHeS,” THmet hop 7 : — _ | InterFer Lnhtermediar lism — '- 1 eg- SUIFonamides, eae ee _ e+ham buto}° | classiticakion based on Source A Bungi eq pepleiip, eephaleporty, Griseo! Furl B®. Backeria Keg polymy CimB , Clos colistim, backracin » I Tyrokbrichn, Qe whe ronan Co ACkiMomycekes Hier . eg: aminoglycosides , Tekracy yelimes.s. polyornes Semi - sunt hekic B Backeri Sakabic ‘anbibi ble cy eg. Chiordmphenicol, erythromycin, lincomycin “Backerfocidal antibiotic eq: i eg: Cephalosporin, penicillin, eryEhromycin, _ I aminoglycosides, cObrim oxqzolea hfyekowards ge _ Fh he 6 S oop spake Spockrutm (oer a “systat ogee bacteria 36 well as Si o-SU Ste ositive Pac negotve bacteria L 4 utr causing Le Sulronomides eg aminoglycosides. 288 active agains grim» ~~. [Narrows soard San my [positive 4 gram negative ~ eg. B-tackum chive against gram poet © Brot Se aga: except Seu comon| | cpbacteria) Sea eae ehenicol , tetracycline Ee. | Antimycobacterial antibiotics _ | eg. ethambutol, Rigompicin, sonore | pyrdzinamide- ile e [ classiFicat ion basis On rouke.oF administra, A. | orale “apEibiobse. (avid Skoble antibiobie) — | eg: Penicillin v | | v 8. | Parentral route Gov. administration) eg: Penicillin &t= CASH s 14 snag fans UEP nes Bin P49 9 LR-C-NH3— $9 ac CN3 REC -NH ET SNCHD FAN TESS CHS ay SOs icles tHO 0 3) || Penam ; Sy fu thia -I- azobieyclo heptane-7- Oni fy nee a 0 “le ESS = f4-thig-1- ozobicyele hep-2~ene= Sn One} uy) _coroa penene ‘ 6. e—Y¥ + -2 -ene -7- pF ye a (= azabicyclo-hep pS tt one)Ficalion Acc: to mechanism Ac Stake orl AnlibibLic [process | tate or} Ankibidtic “oid —Action | (rnbernip cell wal!_| Bacikracin- mucopoptide 7 |_| cephalosporin|_cross= linking; —— —____|_|cycloserine_ synthesis oF cQllt || pentciliin [eet wolt_cr0ss link! | vincomycin | irnucopepeide link — cell |_| Amphokericin| membrane tunck? membronel_nystetin iS — Polymyyins aie —Proteim | chloramphen; Protein ‘Bactericidal y - —~Syntho gis ical synthosis rele: ; 50's erythromycin Protein eee Bactericidg) i= | Se Subunit! | Lin comycin | y 30's Aminoglyco- erokein synthe Bactoricid| © 3 _ Subunit sides Sig. i Sclinimnyein ove. 4 waka —[<~Ponida | oe E. acid synthesis fut “ona 4__[micromycin | ua synthesis _ “Pancidal—| RNA | Rifampin MRNA Synthesis BactericidalA: [a. “used. _Fopitally ~ bacikraéin; novobiecin | classification Acc: bo antimicrobial activity Drugs mainty eFFecHve against gram. positive bacteria - - FOr St ype hesis » ink ecHon-t penicillin, dincomye macrolides Drugs. Mainly eFFeckive against. gram | negative bacteriq- |: For Sunthesis inFecHon - aminoglycosides, cyclosering 1. used lacaly in the intestine = Paro moMycir a orugs oFFOCkive against both gram positive. 4 gram negative bacteria - 7 ‘For synthesist intoction = broad Spectrum. _ pen icillin, cephdlosporine, hifampicin _ a | a. used: Eopieatly = neomycin; “iyroknricin ’ - Dig. Feckive jorug_eFfestivelagaingt « orug aFFoctive against acid Fast bacilli - _viFampilcn, “streptomycin mycin, umagilliin an Fung! | orug_efre eFFective | _agains\1 | Gram_ave packeria—— 4 Violet stain during Gram _Positive —|— ri cer raresauor NRE vekain the crystal —[ sang gram — i iu 1G pram —v2bACkerig my gram staining: y Lo 2 Appear in purple App oor in ee e under she ae t —| calc rb nder the d | taieroscape 3. | outer membrane is | outér sombraneg~ ; present Qbsont au 4- | Pept idogiyenn layer is S-} colt wall is around * |coll wall ts around | Peptidog hyct.s layer is To 20-80 mm 5@-i10 nm Ly @-lce wall is amanth 7 | Mipid’ + lipoprotein | content is low in the ‘cOll wall 1S wavy | | lipid 4 lipoprobein Conte — is high inthe: cali wil — i cell waltGram Posi itive __| Gran wegabive \) cet wall __ “singlezlayerod,. | doubler layered. J + vp ea smooth |___ wavy —__ ‘cell Wal 30-80nm | 8 =fo nm thickness Sa ettei | a uct [PeptlBiogycon thick layered / thin. layered ae foyer multi 0 yorod. Sing! reichdic acid Present abciont —LNipop bly sachh- absent "J Present + arias t] 2 orosond ost ;_ = —| outer mem brane dbsont » Present ontent avery: [pip ) | s ohign"{ 20-307) | resistance +ol_very susceptible | very resistant to | antibiotic [+o antibiotics otibioti t| | rug metabolism method = ___ i Phase + I- converts a parent drug to polar active _ metdbolikes - — oxidation , veductio dlysis_, cyclization, decyclization _ _Phase 2 = converts a parent drug drug £0 Polar ing; ~ _meta boHtes 7 Se | _Gleurdnide conjug ations acetylation, | — methylation , Sulfate | Glycine age —— _ Ghitathione conjugation. a — | nucleotide synthedgis- —— .= Gram posizve bacteria: |= Filamentous branching bacteria ) i= andgerobic organism j | = non- motile “organism | = not Form spore |-non-sporing -organis — intermediate into bacteria 4 Fungi - causes actinomycosis disease i) chronic granulomatous disease ii) endogenous infection ii) immuno comeremisgod i 9 \ , + va wadePencillin Structure- : =e? r Te ay : EE Ro CN pc - _ N—)-OH 3 a 6=Aminopenicillin: Acid (6- APA) Penicillin G (Benzyl penicillim) - Ct f “Oy Cole He! i SF SEP 6a phony} acens)) artine = (343. pimethyl- 7=0x0 -6-(2- phenyl deet amido} “Ty U--thia--b azn bicyctol = Da-COr ic acid‘) = 2) Penicillin v_[ Phenoxy benzyl penicillin) a : (DS 0=CH2= e-NH Seek ui) rN oH HW) Grainoe © 3,3- Dimethy)771-0x0 ~ 6-( 2 Phenoxijacetomid [.-G- thia-1- azabicycloheptane~2 - carboxylic6- (a4 ~omino- 2 (a= “hig phonyl ace] ~ Ominoy - 3,3~ =~] -0x0-4~ Lig aza bi€ycloho pane - 2.- carboxylic “acid methicillin an OCHa i ~ A Sv_cHa Sa - ona 0H SO 6- ae =dimeLhoxyjbone amiga): =3,3, >dimethi_ Is O* Lp-'thig- ; Cyclo heptane-2-~ eorboivic nad S204eycla heptane 2_6- [(aethoxy-1— napthoy) amin6) ~3,3~dimethyk ‘T+ OKO- Y= khi0 -1-azabicyclo hepkane- “2- carboxylic acid 7) oxacillin 4 I5 mn 1 CH 4 = Cc - NH Pres" NgstHe 8 77-OH 6 - (C5- methy!-3- phenyl — 112 -oxazole -Y = carb ony!) cimino}-"3.)3~'\dimethy |-7-ox0- 4~thia- \=aza@ bicyclo- heptona ats = Carb Caylie” acid 8)/_ cloxacillin a 1 rs ; iu ee fe 7 OH 6- § C3- ce SaaeEona S- methyl - oxazole-g- Fcarbony)} aminog- 3,5= dimethyl -7-Ox¢-U-thia-I- I Cycle heptone- 2- Carboxylic actdor S-methu- [3 (a- Chloropheny/) 4 -iSoxazoy) Penicillin a. 9) Oicloxacin = 8-{ [3( 3,6 dichlorophenyll=5-meihy—~ - “oxazole ¥ 4 = carbonyl: | Carboxylic acid r 1Oy | cuclociliin itiggag TN, ! cH a 1 — i C-NFS Ss ae 7 ; | el AH i 7— OH } é in) = fF [i ominocycishexiyncarbony!) ammo sia dim ethyl- T=oxoey'—thig=) = Gealoieylinn! ptane- 2 -carboxylic acid 17 Il Ticarcillin Sm ye ! an SSH -CHNA Toe “oC J-N 5 My, CO2H ZN oH oO ti i 6-{ (2R)-9-corbory - 9. (3 = thionyl) acetyl] Amino y ~ 313- dimethyl -7-oxo- 4 Eh ign 1- | azabicytlo heptane - o~ carboxylioicid\ . 7 W602 opr \qurakyon | ciocewise> consigurasis 12) | corbenicilin ~ xy CPhengi. acetyr} amino§ 13:3- | dimethy | T0%0- WY-khia= | pheptane- = COMOX Yi acid: - 5 = “4 6 | joulaa _ o riochemistru! 7" oy E _ 7 | i Eney mediate —.0 Funcha «ll L BTA jocisia ats Troup | a ws (Act \eft|iside@ (2,)3 ui Bi L 6h i WIGHt Sid eldimentS Tih C Enc CODE, Cay eleEmen H CN = 6- AcylamMinoT:212-dimethyl= 710 X0- ls icyclo | (3 20) heptane- 3- carboxyiie acid To = Tower Lhe plane (S- conFiguration) L Be - upper labove the plane (R- CONF) descending LE [AN Bicyclo ring.analog (eA). = 8-9-0 [si hae Chir), => 3C, SC) 6C (GIFF§4 Functions | | group) LN al abSoulke ackual COnFiguration(Ane | | 6 _ $5, SR, ER : i 1) (A) : onFiguration (R|. group are trans £0 each OLher, with 0 as Ey chiral a penicillin molecule ix ome 1 ee ae . i ; s E eur Ss nt etic PenNCilling i 0 all notu ral 4s yf thetic pencilli a ms uy \— [3 contres ig the same: The 6tN oa, 13 by atom bearing the acy! amino grou bag h— L=congiguratign, whereds the Carbon wigp <— arboxy! 9a group NaS D* conFiguration. ~—— Thus, the acyl amino group + Cardo, Former in a ade 4 the lokter in) B Orientation relative +0 penam ring. I- The absolute stereochemistry oF Pench was designated as 8S:S5R:6R- tho atoms —— | constituting 6 - aminopenicillanic? acid are —— biosynthetitaly derived From L cysteine ¢ —— D- valine amino acids. }+— Pen bacteria) Chr ume colle the Crone poptidace enzynre which iS involved in the synthesis OF khe -backerial | cell wall: Lar The B= lackum ving is iniiced Ip mechani —_ | oF inhibition linkes ——#—Penciliin_beco, HeOA 3 — entyme's Active’ site leadina 40. irreversible ivthibition "gq a~ covalent bond Formed to transpeotidase enzyme ; ~ irreversible inhibition “rdechanism oF Action - Bacterial cell wall | Sunthesisa ¢ popidaserisnal 4 1 penicillin 2 TYaNSP ot i Ie, | vindily {01/9 _o | ome” 2 . - the v te _ D - ebay ante ree, — Foateoe Fem exist potorocuclic SYSECM_E Sen ED — he chemical abstract SY: system CCAS); the numbering “with Sulphur atom ass [ nat 4 position Thy S ving _hitro gel ke J are named as LU-thig, |~9% __penicilin Tbicyclo (2-2-0) heptanes 1 acc: 0 Bhig __| system: Z the numbering System adpoted by Usp yeverse OF chemica) obStrack procedure assig Ning no: t0mas N Atom 4 no- 4 ty Sulphur atom. 3 simplify Forms OF penicillin nomenon adpted For genera use The First uses the noOme “penam” For unsubstituted bicyclic system . ind) uding e oe coe gr0up with one of the r n pumbering syste to described, i] MOS just Trus.eenicillin_generaiiy designation ace. & chemical ObStract System as _ 6- acylaming > 2,0 — — carboxylic cea dimethy penom=- 3. phen ip Pe emi, —[Paeid” to desoing the ns ri (| oupstituents tho ae ene INQ system WIEN ‘hot are g enerany y present | ItCO = | (ve) Nucleophile - electron yich - donate | Crue) electyophile - eleckron pop =[Aceept Dat 2. 22 2dimethylg. 3 carboxy) 8 The 3d Form, Followed inthis chapter _ uses trivia} pon ture to 2 name tre _6~ carbony! amino penicillin portion _ _ oF the molecule penicillin ¢ then distinguis- __bes the compound From the basis of R group OF Gey) portion,of the molecule. ~* This penicillin @ is tamed, ag benzy J penicitin 4 penicillin vis Ppenoxy penicillin [2 | methicillin is 216 diethory phenyi penicillin 4 7 | .S00n- i > . For the most park. the jator 2 System _ | serve well For naming 4 comparing closely ; _selrrer similar penicillin structure » but | they are too restrictive to applied 2 compounds __ unusual Substituents or £o ring modified | derivatives i iw y {2-04-20 ifvalency= bDeFined aS the Combining capacity oF [an element to Form a chemical bond either |_-by sharing, donating or qdining of electrons. Element | valency) Atomic __ Atomic po number mass. j H s i 4 0 Zi- | 8(aey 16 No 3 ~ 1(25) 4 Cc Y 6(24) | 2 Los 216 16 (28,6) 20“Sorat: “penicilloic gis rd ORF I 4 ~ Penile) aw ERIE Bap a acid) R= CaN po Te Sets Tae [ iE | OH coocHs NA Log, { : Pees: Niethyy penicilline q par } acid: Ls LO ju- J | acey] amine B-l azol chair Ockim Ko Zoli i | |- | SPR - PHarmcophore ame 7 Stevi gchemistry pr: - Rvariables ott drug] Pee@rpietcy | uf yLtl j Sid@ eFFeck | | at resistance! | i Dimethyl: FBuUp i 5 wembered nitrogen __ | Sue Saturated ring ».veplace thot Axackivity gf S21) also essential For:bi O/OgiCa).ACkivitxy = Carboxylicacid ;. usually ionized ¢ administered as sodium'/ potassium salt. + Carboxylate ions bind to charged nitrogen oF aslysine residue in the bindihg site+ Activity reduces when. modified-to alcoh ester: aad ead os vdin activity retain, vetdensity ye withdrawing ‘ group t 4 3 “ie Bicyclic system conkers Further strain Bp olackuimJring- bait Wits a jhe greater tho activity, the greater the Styain., the greater the instability oF the § | ls omolecule to. obher Factors: I carbony)) group» Lone pair electron located | 4 on _Hitrogen “dtom not Red: bo 'carbony/ group | [£9 Form oO. Stabilized resonance Structure _ Fhus, more electrophilic For nucleophilic aap yep Waal t99 yebd 9 aye = “acylamino side chain electro withdrawing group render amide oxygen \ese nucleophilic. | Bulle group provides steric hindrance 0EE * (in| Cry LION OF Pola L 5 co) ipord [r _B- ieee je more bydrophilic. = group ma yb 19 Jou jaa ae pe _Resis pe oF panilings C j yepol Se E — The St tity qkure re 190. This phenome: S where PulbliS 1 Oe Ih eee ra qt zhat time ¢ Cause pot [_ alayn- Resistance 2OF B=lockue, | turperl increasink 1 paras or! required - uptake oF drug © _aFfinity £0 the PBP'S + This is particularly “the case with MRSA | Cmethicillin resistance. stephatocotus O url vc emirsp. produce mutate PRP -2 thot? doe | | not “ereiciently bind - methici in’ any T fonger- nore common however; Is the “r| elboration oF @- B- Igckuimase. B-lackumase are enzymes elborate by —— | miero - organism that ccatalayse hydrolysis — bor lactum: wone 4 inactive’ p-factum — A antibioH top enicilolic acid: beFore they — ot) cam reach EWE PRPs. They somewhat —— “resemble the ceil wali pransanpicdl ase. ib which is the usual, eargot 4| CWilison) i 3 Th ee biochemically distinct mechmnism oF esistance:-£o: penicillin. (B= tactun antibiotic) naa been. desciibe in | iQ - |B eFBlux mediated by. trangmombrand= 7 Spanning « active transport protein Epa — _ Yeduces intraceliuiae penicillin in concentration © gibosoman protein nwhich the bacterial Protein Synthesis: apparatus is. rendered resistant +o the action of Letracydlins by t Qn indusibte. CRU Nsnie protein. ) f | O- enzy matic oxidation Lin 20/04 [22 penicillin ikse is active against sterptococc! s Listeria, clostridium, » peptococcus 4 peptostreptococcus.. Pnoumonia A i Scarlet Fever > ett 5 ne ENT infection thety Pharyo gitis ment gitis > Ways Oo spLospirosis yt Tea moguas UNS OD oda hor 2 Gonorrhea Dwpiyadt Wo _ =H byte dy TS a=ee Hous penicilling ~— J teqckions +o-Va sy ae in coverity Frnm a_varieky o¢ rang So nicouS > membranes Cashes | Sing : __--Feve g apapnglanis within Seeing Sy wads Fl enone Bally "a = SET Swe + Hives Cred bumps on Skin ¢ might be ip brug induced Cinema «low: real Siang | ceilo>eban .normal = Hrednessii herb ook | £00 Fast’ or Slow +t ee ae syndrome es IL (Toxie epidermal necro(y sis.) L Nephritis (inflam ed kidney) - ‘blood in Coneusion , Swelling atl over body— ~cortioan En Antibit amine wel reduce qilergu __| skin. ¢ 0 FFOCL = ! : iclliD OIEFICULEY UlEY breathing. Sweeling FACE Jing congue or throae m = Darrhea thot is bloody | = Fever, chillc, bod hog fl |S: ius | = easy bruising or bleedi i |= urinating 1ecs usual or Bok ab all ——t = Severe Skin rash, itching or 1Pe Ling (me |= agitation, Confusion Hous): houg hs | | | | | | {I OF behavidr east enibag. Staak pain — FE a fYea Swollen, black tonal I - headache _ - vaginal itching Ahrush Cuhite patches, inside mouth or _ throat) | Stop. Ed eing Penicillin. (side er ect) -fast 4 irregular breathing F every i | = joink prin = lightheadedness of Fainting (sudden) Bey ~ purriness OF SwoeIling Oround pone Face - red, Scaly Skin i we Ghortness10F breath” = skin-vash » jeching Ben yl Penicillin (anjection Wa MEQeAlembie Ltd. 0 ®.| Fortified procain Sone (ay ec 7 Meg: ‘Alenmbieltd:) .° 7 3° pentids (capsule:/ Fablet) ] NEQ. Nicholas Pinames sndig ited aT podeeitin (injection) peng 7 INTEg: Hinduskons Antibiotic\2> - ae oleh" | cephalosporin’ Ss | penicillin baat | EN = ior - it TP eoimoga Oe 1S0lbed rom cephatseei 9 BT RDS HL ORR Bao a T- Aminocephalosp orinic Acid A { Tgnbiblokic eo! ko = These dre 8 lackum ane From cepha)csporiurs Species Or prepreg | Semisyntnotic — T most of the antibiotics introduced singg-— | 1965 have been semi sdnkhetic esha lsporig— I Interest in eephalosporia um Fungi beqay — | ip tdus with Criuseppe Rrokzu's discovay— ae! that cultures OF cephalosporium I | acrim onium: inhibited the growth of | wide variety 0F Gram +ve 4-qram.-ver | backerig set iD 1 jis} + Abtoham 4 Newton in Oxtord » having been Supplided cultures oF Fungus in. | (948 Isolated: 3 principal antibiotic fomponents- NE) ut moe bcehalosporin pt (cpt) = asteroid wilh - minimal antibacterial octivtt t- J) cephalosparin N (CN). idon ed) witb —}- —____—— L Sa 3fet ephalosporin ce. (cc) = contain dihychothio- | ne rig inskead oF thiazolinide ving of _| HOWBAN a Somplex than penicillin peca ie oF double bond in_dihydrothi zine ringia. 7 cepharm porivatives : copham i is the unsubstituted bicyclic iactum 1 chemical abstracts; cephalothin is B3=( acetoxy methyl) + 2 - oxd-7+ (2-chi acetomido - 5 ~thia - |-aza- bicyclo -ock~ 2. ene- 2 carboxylic’ acid- 3 i A.| First Generation - highly active against gram _t+ve bacteria eg. cephaloridine, cephalothin. cephapirin, cephasexin, cépha|oglycine , ceFadroxil cephradinie,, corazolin.. Lephradine 8. eecand Generation =m more active agains Gram ve bacterig ) : (eq. ceFamandole, cefoxitin, cefuroxime, 4 ceraclor. cefonicid: * aE hird_( Generation a Q: coFtizoxime, corotaxime. cert azidimTm copeniaxone » coEmenoxime — st jon - “exkende 6 “Fourth Generation — aq Pe Antibiotics — ___ eg: corepimes cer pi S a Ew) Fifth Ger Generqtion ~ = : ie eg. certaraline, certo biprol : 2a = ¢ eased Lon! Roto OF administration 1 A. | oral cephalosporin | op eq: cephalexin £ coradroxil eeenerixing 150. 2eph 3 E 8. Poraontrat Géphalosporin: i= | eg. coFoxithin 7 | 7 . : > 7 j MODS i t/ear —~ : { cephal exin - i i = A, a io ma Bey 3 8sy oe i oan 2 ACH ; sporso Sie oo Ss ee i OH. (2am 2 phon yl acety!) amino] -3- meh DpH +B 0X0 = B=thiae fe ‘Aza bi | x icY¥clo oct -2-e%| — [ 2 carboxylic (olathe Le a f at 2" 0) _ —{ Brand sain fa caipauie Phoxin. a6 mp ee Pex | S0mMq » 500m |as/ou|22 to 3 meEerEaIRS with bacterial cell walt SUNkhHeSiS >) Bacteria Ssynthes urvamic' acid 4 Mid e- a These Beptidogucan residue sare linked cegethér forming Jong strand 4 UDP iS Split oFF. ~.PReptidoglucans layer is spongy, gel Forming \dyer. ‘consisting ‘Sories OF | alterndting sugars (NAG:4 NB MA) linked in org chain = Final stage is “cleavage oF D-analin | epti rans peptidase the energy soirelensed is: utilized: OF establishment oF -Cross.-linkage between peptide chain. oF neighbouring “etrand which > provides: Stability 4. rigidity +0 cell wall. — cephalosporins TAHbIES “he ‘erizume transpeptidase ,s0 cross. linking dose art: -acerul glucosa— not take place _ Le also inhibit, Stage oF | protein synthesis . ont G nistrained R-lactum ised 6 membered __ o:ess ential For anti i “arnide- side chain cor oxylic. aa _nekerd iato Ting \ackivits i position nacberial act ~ the. picyclic | gotta Any_structura moiety leads’ #01 carboxylic Acio tbe present at cy e fo rlely mck be_erecone = Acyl amino moiety noust be’ preseng ivity— — 3OnN ying IS vital For, an RS Oct, | jal modit ication in ony £O inactivatio (d_group is eSSengi [=the substitution of Ce: positio io|e s methoxy group has stability. ‘Be lactdmase + ‘ ~ the dlic- cco Oxy. group ae ca iS-n wtp — TN Diby, — Sig necessary For antibiatle Octivity = palneatter injeceion > ial = Digrrhnoea, Hypersensitivity reothion ‘USkin-rashes: asthma, anaphiyoxs) -nephrotoxicity - bleedin 4 _ = Thrmbocytopenia, 9 | uses: i=Olternative to penicillin. Gri in potions f developin | reaction ng-ekin ashes 4 other allergic —|— js used in’ theatment on Respixatony —rinesction.._urinan trace -inFection +” , SEL tan “pacteng * oeetkin ned bye a aveCoral) cephalexin _ — oO __&y- cn = E = NH aa : WH noOZ>CcHs — oO | =8-0x0-S- thia -\ - azabicyclo -oct- 2-ene - I 2-CA ay | cephradine t | @ cu ~ Uy SH 1 ae | éHo SRN cHS | : ° oN oy o | a le-amino- 2-cyclonexa —-1,4 dien -\-acetyl Lamino) 3- methy) -8-0x0 -S-thia -1- azabicy [clo~ oct -2ene- 2- carboxylic acid 1 3) ceFadroxil . || AL 0H CH = EoNH ~ | NH2 NACH H C~OH _ o — — | [2-amino- 2-(G- hydroxy phenyl) acetyl) amino) 3-methy] - 3- x0 -5 -thig- \-aza__ | wicyclo -oct- 2 ene -2- carboxylic acid7 [2= amino-2 pheny| acetyl) aming=g ——~— “chiovo - 8- oxo- 5 tia |-aZOBICUCIO- oS 2-ene- 2 -carboxylic aci 5) | ceFprozil | g onal CAT ENH TE Lc ectig I NH2 6 _ j 7-0 oe | 1 (2= amino-2 -(U-budraxy phenyl) 3-pig¢— _€nyl- $~ Oxo - S- thid- razabicyclo- oct. | 2-ene- 2 - carboxylic acid 6) | Loracarber o Ul 1 SY —ean = SH OH vs a C-NH Tt ) 2 7 it i ee oO en | 1 (2- aming-2- henuyl ACetamido) a - cnNOr0 = R= OKO \~ Gz op) ! jgdnen ie = -2- Qne-}- __2= carbox Hie acig PT O=0C8 2-8 ;| cefuroxime axeti| cS Te — Rogan __NHOCH3 TL a —CH2-0C NH 9 . 7” “O= CHOLCHR ——— tr — cH3 \= Acetoxyethyl (6R,7R)-aCcarbomoy oxy) _methy - 7 (2)-2 (2 -fury!)-2 = (methoxyimius)| acetyl] amino) -8- ox0-5-thig-1- anabicyclo = OCt~ 2~ene- 2- carboxylic acid 8)| cefpodoxime proxetil ° S ut — CHecoaNH ao y nen ® uo i J hens ocr NectH oO ca O=CHOCOCH ° y tcHe), CHa 5 (2- (2- amino-4- éniazolyl)~2 methoxy — imino) acetamido]-3- methoxymethyl) Z- 0xo- 5 -thida -| ~azabicyclo.-oct -2- ene a-carb oxylic acid: - “@\| ceFixime 7 | s g a > it — NaN S mi \ enero 7 NOcH2CO2H fan Cc _f son —i, —eniazolu) Gc are OR TG qmine- so cot!) AMrdo) J Lee ing Perio n) =cdzo 3 _cerazol pene ae a Derenyl = 8=-2%2-carborylic Acid ¢ d eae o-ene- = XYli¢ I acid. | 2) | cephapirin |] Q t f JT § - CH2=C -NH PA TaN, 3( acetyloxymethy! ) - 32 ORO T= =Ca-pyridit: a =yisulFany)| cetyl) Amino) Ss -thia- | - ea Ott = 2-eho = 2- carboJ?) . .) ee ose C\oH CH3, oO | 3 3CUS-methyl-1,3,4-thiadlazol- 2-yi)thio} | _Mmethyl% - 8-0x9-7-L(\ -tetrazol-|-y1acetil] | amino]= 5 - Ehia-| -aza bicyclo L426) ock- | 2-ene-2 = carboxylic acid cefamandole oO o 7 “CH -C-NH S NEN: f +5 SN CHaSX yy OH 6} F-$ Ufa gy 2 -hudroxy- 2 =phenylaceéyi]amn aoa C Li-methyltetrazol- 5-Y)) Sufanymethy): -$8-ox0- 5- thid- 1-azabicyclo -Ock-2-ene- = 2- carboxylic acid Ha S- NU-N et be 2S03H—sayiiromy=2-PhEnylacetyy amino] -8-0x0-3- -L1- (sulFomethy) Z Letrazol - $-y!] SulFanylme WG Spe \- azabicyclo ~Oct-2- ene- 2 ~ CArboy lies L acid ee 6) | ceForanide ¢ r _— Va) 42 = C= NH Kou ay CHaNH2 é 1-§ (a= C2-Caminomethys) pheny/)acey > — “amino? - 3- $ [i- Lcarboxymethyl) £2biaey — _=5- yl} SulFany| methyl % - 8 Ox0-5 ~thiq. -— Ozapicyllo- oct -2~-ehoe~ 2 — Carboxylic 1 | acid. T— mY cefaraxing I Li L I Qa AcGrecN wey 5 9 | NocHa 4 NYS CHA0CNHa Cc Oo OH 3 §[CAminocarbonyiy oxy] methyig=1- 301 22)-2 -(2-Furyi)~2- Umeth oxyimino) acetyl’ amino ?~& -ox9-5- Ehig- I~ azabicyel | ock-2-ene- - Carboxylic acid _—|3- (Acetoxymethyl)-7- (2 -(2-aminothiazok | u-y)- 2- Cmethoxyimino) acetamido)-6- [ oxo-S-thiag-I- arabicyclo- oct- 2-ene— 2+ carboxylic acid piorrheea due +0 alterotion oF gut ecology — or irritative eFfect commonly occurs on Ora administration of copemnalite 4 parental — administration oF ceFoperozone._____ - cephalosporins cause hypersensitivity reactions — 4—| ‘ust like penicillin, but to O lesser extent: It riding causes nephrotoxicity , thus is ephalori Sea -epore_in use + Cephaloxhin 4 other cephalo- oo “iby. tasiins iipot SUL ombocutopenia. [Ft al egg | aba a gimilor Substitution at C-3 causes bleeding |_due. to eee ———+ “Zimpottant Producks~ — Sas | “) cephalexin semi synthetic ankimicigy eohalexin - semi sunt! aby » | cepnalosporin = rt is_ LOE Enea -_ Ik 1s_active againsk— gram_p i) ) _as_gram negative bi ____ [uses = cephalexin - | rook i val by Strepto ____| pneumoniae ¢ skreptococe a Likis media coused by Hd emo lig inFlugns.oe.skreplocoecuspneumoning Streptococcus pyajands.- CO-NH CH3 Ha N 3 Na TNA oak 7 1 z ee CHa-COOH a | | (a G- (2- amino-1, 8- thiazo] -4- yi)-2-(2,2~ —___| dimethy!- 4-0xo- 1= Sultoxy azetidine -3-yl) —__|_ amino) 2- oxo- ethylidene) amino) oxy acetic acid.