ES
BETA-LACTAM ANTIBIOTICS AND
CELL WALL SYNTHESIS INHIBITORS
Classification and Names
v
Penicillins
Narrow spectrum
Penicillinase susceptible/
Naturally occurring
+ Penicillin G
+ Penicillin V
Very Narrow spectrum/
‘> Anti-staphylococcal drugs
(Penicillinase resistant)
Broad spectrum
(Penicillinase Susceptible)
+ Ampicillin
+ Amoxicillin
+ Piperacillin
+ Ticarcillin
> 4th Generation
+ Cefepime
Hl
*-» 5'h Generation
+ Ceftaroline
——l
(Activity against
> Methicillin resistant
staphylococci)
Cephalosporins
(Names start with prefix “Cef")
Narrow spectrum
ly 4% Generation
(Mr. Fazool a thin lorry
driver uses red lux soap)
Mr. Fazool + Cephazolin
Thin + Cephalothin
Lory + Cephaloridine
Driver + Cefadroxil
Red + Cefradine
Lux + Cefalexin
Broad spectrum
2"4 Generation
(Tall foxy met a proudy
Carbapenems.
v
Miscellaneous
+——+ Aztreonam
(Monobactam)
;—* Vancomycin
+ Daptomycin
furious actor)
Tall + Cefotetan
Foxy + Cefoxitin
Meta + Cefmetazole
+ Cefprozil
Furious + Cefuroxime
Actor + Cefaclor
3" Generation
(End mostly with “ime” or “one”)
Cefotaxime
Ceftriaxone
Ceftazidime
Ceftizoxime
Cefdinir
Cefoperazone
Cefixime BETA-LACTAM ANTIBIOTICS AND
CELL WALL SYNTHESIS INHIBITORS
Mechanism of Action
Mechanism of Resistance
Penicillins, Cephalosporins,
Carbapenems, Aztreonam
+ Bind Penicillin Binding Proteins (PBPs)
(Aztreonam binds preferentially to specific
PBP3)
+ Inhibit transpeptidase
Inhibit crosslinking of peptidoglycan
Inhibit cell wall synthesis
Cell death
Time-dependent killing, Bactericidal
Vancomycin
+ Binds D-Ala-D-Ala terminal of nascent
peptidoglycan pentapeptide side chain
+ Inhibits Trans-glycosylation
Bactericidal
Fosfomycin
+ Inhibits cytosolic enol-pyruvate transferase
+ Prevents formation of N-acetylmuramic
acid
Daptomycin
+ Binding and insertion in cell membrane
+ Oligomerization and channel formation
+ Depolarization and lon efflux
Penicillins, Cephalosporins,
Carbapenems, Aztreonam
+ Enzymatic Inactivation: B-Lactamase
hydrolyzes the cyclic amide bond of the B-
lactam ring.
Penicillinase for Penicillin.
Carbapenems and Aztreonam are less
susceptible or Resistant to B-Lactamases
Blocked Penetration
Efflux Pump
Target Modification: Modified PBPs have a
iower affinity for B-lactam antibiotics
Vancomycin
+ Replacement of D-Ala terminal by D-Lactate
Fosfomycin
* Decreased intracellular accumulations DNA SYNTHESIS INHIBITORS
——_]. JT
Antimetabolites =a Fluoroquinolones
So + Block Topoisomerase I! in G -ve
"3 Dihydropteroate + Block Topoisomerase IV in G #ve
ulfonamides Pristcing
'M.O. Resistance Dihydrofolic acid M.O. Resistance Clinical Usage
Obtain folic acid from environment Dityarofolateg g 2 EAT pumDS "aioe
+ Altered dihydropteroate synthetase, Reductase + Changes in sensitivity of | re
+ 4 Cuma pornenbOly to Graph target enzymes due to point * UTI and GIT-Ciprooxacin,
+} production of PABA. Tetrahydrofolic acid mutations in receptors Moxdfiowacin
+ + Mutationsin quinolones * Respiratory fluoroquinolones -
pectrum resistance determining region loxacin, Moxifloxacin.
“ oriees:
tafbereuous aaa
+ Malaria + Oral sulfadexine + pyrimethamine
Druzinterctons | [controincations Dei ineracon + Dizrness, headache, insomnia
> Theophyline + SkinRashes
~ Warfarin + Pregnancy 1 Methyvanthine + Tendon Tearing, Tendinits
+ Methotrexate 2 GOP deficient patients Abnormal Liver function tests
‘Contraindicatons + Phototoxicity
Ly Tris i SU cndizctatin Opportunistic infections (
Trimethoprim a ee
M.O. Resistance ard fpr geteputcbareary + Heart abnormalities
+ Altered dihydrofolate + Thrombocytopenia
imac LTesetr] [> Gremeetee,
IMfinty for trimethoprim Bone Leakopenia
+ Emax pumps Martow Megalblastic Anemia
+ Decreased permeability destruction + Hyperkalemia
7 . + Rash, Fever
L, Trimethoprim-sulfamethoxazole/
Co-Trimoxazole / Septran
pt (re)
Benefits |[ Resictance || Spectrum Gane
Synergism Less {Same as eee ‘sulfmethoxazole
Resistance frequent sulfonamides) Folinic Acid. and Trimethoprim) Aminoglycosides
No protein synthesis
Action on gram Negative
Nephrotoxic, Ototoxic
Streptomycin
Tobramycin Not used alone (combined with
Amikacin B-Lactams)
Neomycin (oral)
a i
cemtaeacin No Oral Absorption
Kanamycin Neomycin - Oral
(Gentamycin, Tobramycin,
Amikacin)
K - Klebsiella
E - Enterobacter
E-E Coli
P - Proteus, Pseudomonas
S-S Agalactiae
Ta - TB, Tularemia
Pled - Plague (Yersinia Pestis)
Ca - Catarrhalis
Sh - Shigella
in H. Influenza
Pur - Providentia
Se - Serratia
Neomycin, Kanamycin
Topical and Oral use only
Bowel flora
+ Skin infection
(prior to colorectal surgery)
Not used in pregnancy (teratogenic)
Mechanism of Action
1. Binds to 30S and interferes with
initiation complex
2. Misreading of codon ~ Faulty
protein synthesis ~ Misfolding -
Degeneration
3. They inhibit Translocation
> Breaking of Polysome into non-
funtional Monosomes
Bactericidal | | Post Antibiotic Effect
Conc. Dependent Killing
Mechanism of Resistance
+ Efflux pumps
+ Blocked penetration
+ Plasmid associated enzyme
inactivation (Group Transferases)
Disruption of
Ca channels in
proximal tubular cells
+ Neuromuscular Paralysis
+ Ototoxicity
(Auditory - Amikacin,
Vestibular -
Gentamycin, tobramycin)
Nephrotoxicity
Skin Reactions / Contact
dermatitis PROTEIN SYNTHESIS INHIBITORS
+ Aminoglycosides
Broad-Spectrum - Chloramphenicol All Protein synthesis
+ Tetracyclines ee aa
inhibitors are
+ Macrolides Bacteriostatic EXCEPT;
Moderate-Spectrum * Kctolides creti
Pp Ketolides (Telithromycin) enlictaesiies
+ Streptogramins
+ Lincosamides (Clindamycin) * Macrolides (at high dose only)
Narrow-Spectrum - Streptogramins
* Oxazolidinones (Linezolid)
»
Binds to 30S and interferes with
initiation complex
Mechanism of Action ._ Misreading of codon - Faulty
nN
- , protein synthesis ~ Misfolding -
‘Aminoglycosides. —————>
incerycnsid Degeneration
> Bind 30S subunit < Breaking of Polysome into non-
functional Monosomes
» Others bind 50S subunit. -
+ Macrolides
+ Common Binding site = + Telithromycin (Ketofide)|
+ Clindamycin (Lincosamide)
Inhibit transpeptidation
(Prevent charged tRNA binding)
+ Streptogramins ————————_______—> Blocks Exit site and tRNA synthetase
+ Chloramphenicol
Unique binding site —* + Linezolid (Oxazolidinones) —® Blocks formation of 70S complex ANTI-MYCOBACTERIAL DRUGS
SH 7? FF
Drugs used in Tuberculosis Drugs used Drugs used
in Leprosy for Atypical
1 line drugs Alternative drugs Mycobacteria
+ Pyrazinamide + p-Aminosalicylate + Dapsone + Azithromycin
+ Rifampin + Amikacin + Acedapsone + Clarithromycin
+ Isoniazid + Ciprofloxacin + Rifampin + Moxifloxacin
+ Streptomycin + Ethionamide + Clofazimine
+ Ethambutol ANTI-MALARIAL DRUGS
| Pina Quen ett many eh) Plasmodium
9 Pn
: Sine bend
* Chioroauine Tizue Schizontcide Blood Sehzonticde | + malariae
apiece + Primanlne 2 onan Ee
(Have Hepatic dormant
|. _stage: Responsible for
7 5 recurrent infections and
Mechanism of Actions relapses)
Chloroquine Clinical Uses Adverse Effects (Toxicity)
+ Accumulate ood vacuole of plasma 5 5
+ Preventpoimetaston of eneitoremoren Chloroquine Chloroquine
Accumulation of Heme stoi tothe parasite
Quinine
+ Complexes with double stranded ONA
+ Prevent strand separation of DNA
+ Prevent Repiestion and Transcription
Mefloquine
+ ts Mechanism of Action f not known,
Primaquine
+ Converted to Electrophies
+ Generates Reactive oxygen species (ROS)
+ Intereres with oxygen transport
Also act as Gametocie that prevents
rari ansmision
+ Non-faeizarum and Sensitive faleparum Maas
tweatment
Quinine
+ Chloroquine resistant facparum Malai treatment
* Used with danyycine and clindamycin to shorten
toxiy duration and limit toxicity)
+ Should be used for prophyans to delay
resistance emergence]
Mefloquine
+ Chloroquine resistant Malaria prophylaxis
+ Alternative to Quinine in acute attacks
+ Uncomplicated infection of. faliparam
Primaquine
+ Eraticate liver tages of P vivax and P. ovale
+ Used in conjugation with Bod scizenticides
Anti-Folates PABA : ment afte cloroquine:
+ Sueramides ——v@J, Pmdeptrote < Rtsmatvetor pany preven
+ Proguanil Dinydropteroic acid Anti-Folates
(Chloroguanide) 4 Dihyrotlte "Blood shone agains P.facparum
synthase + Eersidar(Pyimethamine + Sulfadcxne
} art voate Slot resnt crun tresrent
rofoate + Malaone (Proguanl + Aowaquone) Coroquine
yecoguani 1 Prcaicee fest pram ons
«+ Pyimetharine -! Tevahvérfoli acd
Mechanism of Resistance Traveler's Malaria
Chloroquine
+ pert (Plasmodium falciparum Chloroquine
tesistance transporter
Anti-Folates
+ Target enzyme modification
+ Chioroquine = Prophylaxis
+ Mefloguine - Chloroguine resistant
+ Doxyeyeline & Malarone ~ Multidrug resistant
+ Primaquine ~ Terminal prophyans of P vivax
&Povale
Clinitation Retinal damage, Auditory damage,
"Neuropaties, tack of porphyria, Skin ash & lesions
uinine
‘Black water fever (Hematotoncity)
‘+ Clnchonism (GI dsturbances, headache, ints, blurred
vision
Mefloquine
Payette diseases, CVS disorders, Headache, Skin rash Gl
disturbances, Dzness
Primaquine
Glastrbances, Prius, Headache. Methemoglobinemi,
Mil anemia, Cyanoss Hemelyis in GSPD patients.
Not given inPregnaney ad G6PO patients
Anti-Folates
(HINGE)
emotss ru interactions Neproti damage, GIT
stest
OTHER ANTI-MALARIAL DRUGS
+ Doxyoytine -Tetracytne - Chemoprophyactic
2 amodiaquine (Low Cost) CHorequmne resistant
falciparum
+ Atovaquone - Disrupt mitochondrial electron
transport
+ Hnlofantrine (HITE Active aginst,
roeybe 2356 of ald forms of malaria,
+ Artemisinins = Reliable against quinine resistant ANTI-FUNGAL DRUGS
Systemic
drugs for
Alter Membrane Disrupt Mucocutaneous
Permeability Microtubule | tnfections
1 hes Block B-Glucan |, Functions
2 etna thesis caer eee
ei] niet) Acid Synthesis Peprceh Drs
+ angen ee Nystatin
en ons Anpten
Drugs for Systemic Systemic drugs for Topical Drugs |:
Fungal Infections Mucocutaneous «nian Eni
i nr Foxe neues ci
+ pen 8 Infections Conran Sirens Creare
= "aan + Griscoftvin|
+ foie + Testing
‘Amphotericin B Flucytosine
MOA MOA | 5 Fc'Ousice! Te
is pte - rf ‘ aa]
reer celimonivare Sane] scons SauleneEeste |
fermebity [cit + + Taian
; Lenore
Decree o/s fete!
i e {Gee Resistance
Spectrum Ek
aspeaias mn@s— acomeumie
+ ions :
+ Gyros css Avion | Resistance Classification
: sasiaicnian oF — Drug Interactions
Cran xine fr Fal irisie — (ere20 Rd
‘up eatment with Azle) Spectrum accra ata Poth repr
Toxicity Inception wih Ampere Bor [Trois J obras at Catt
Gina erptocccs > Farle |___ten pm inhibitors
Geeemeeee Geet Matec! cos
Infusion Related Dose limiting Toxicity + itraconazole - DOC tor BHS—> > Fyrcoccose
Seg te ine nsdn wena 1 Socamer
5 Mie spasm * bey donee 1 Re rein * CODE rhe peg
2 Ramee 1 eet * Rew he dstnon ‘city | Yor#ine lates, ash
2 Vermin «LATEST su. cx anutaces| TOXiCity |. Semin
OC fr Oropharygea.
‘Gtanecus, VuWoragnal
Griseofulvin uneitatic.
+ MOA tinkibits mitt spine formation.
+ MOA: nhs Squene epoxide
Toul ct Osturonces Rates,
“Toxic lia ke reaction with
tavol
Interaction CYP450 nce. erase
Resistance: Target ene odifeation
‘Spec: Dematophyts, Candids
Headache, Vu and taste dturances
+ Gontandcation Nursing mothers Rena
“erhepatedystuncion
Echinocandins
MOA
+i the sythess of 1.3) duran
+ Prevents Yung el wal yess
Resistance
edition of RY dpc stse
Drug Interactions
creas daly dose of Gspotunin
Isrenied with CVP450 aces
+ Echinocandns th spore
raise hepa Wansainass
Spectrum
Paracoccidiodomyces. Up boven coment
Toxicity
‘caspatungn
§ resistant cadiass
* Deine gor imasieasperiss
cstran
ucacitneous candids
5 Prophis focondls
Joist
Testy 6 Unconann
+ Fevers pcb
{Hite ie renetion ting)
tented oo ath ANTI-VIRAL DRUGS
Anti-Herpes Drugs Drugs used for HIV Drugs used in Influenza Drugs used in Hepatitis
(Gerseneee) 1. Nucleoside RT M2 Inhibitors Hepatitis B Hepatitis C
2 ene ace inhibitors 2. Anecmnne | Rabin Cia
Vea RST Aaewenzarsen # ctr * fi ~ pee
Acyclovir — ss on 1 Eiereovane oni
on Sse: ‘ Bieieatitoee — : Ee
vorepnte > Age Toxicity IFN (Interferon) Alpha Ribavirin
{ {iti 2. Non-Nucleoside Tsiiaton MOA MOA
Dbhozonate RT inhibitors Rion Rat tivough AK-STAT pathway and + Nudecde Resemblonce
¥ om + Slurred Speech ‘form antiviral proteins “+ Incorporated into RNA
Incorporation in¢~ Triphosphate + Delavindne i + Activates host cell ribonuclease that = Cause mutation and death
vr A + Frain NA Inhibitors + mots eration of tral Ker
+ Competitively inhibits + 1 co Cells that kill infected liver cells Use
Gain NA polymerase: + a this used adjunctivety with
Saasen y 3 Protease * wibionetrewminines — [Uses reenact
saioelgiueat SES oer.
Inhibitors Seaomswdimcrts — temssec Toxicity
Clinical Uses (Ruan Ure) Fol la demide ES ie 5 vcaepaend alec
socpameasareatanes + « BStmcenemime — tgantegatnns |” Sips
+ ost in ais : HRS feats + Hen Aria
: ame am a
1 ivforencephatis Toxicity Toxicity Contraindication
Toxicity ee emt 2 re
” ‘Bronchospasm in Asthma ‘GIT initation | © (RBC Hema)
Lae _, ome eran
{poten 4. CCR-5 antagonist * Ssmens : Woes! + few
Tenor Merwe 2 Fatque Poste Syndrome Pregnancy
1 Regretsty 5. Fusion inhibitor 2 hyd onetion + Congr and
Datu > enh 1 Bone Marow Fonty Bronchial ration
Nobels redueotaevco)
(Contrainte in Pregnancy)
+ Hemolytic Aner
