Protein Synthesis Inhibitors Dr. Rajendra Nath Dr. Rajendra Nath Professor

Protein Synthesis Protein Synthesis InhibitorsInhibitors

Dr. Rajendra NathDr. Rajendra Nath Professor

Protein Synthesis InhibitorsProtein Synthesis Inhibitors& Other Newer Antibiotics& Other Newer Antibiotics

1) Protein Synth. InhibitorsProtein Synth. Inhibitors

that target the ribosomethat target the ribosome e.g.-

-Tetracyclines

- Chloramphenicol

- Macrolide antb.s (Erythromycin)

- Ketolide , Clindamycin (Lincosamides)

Protein Synthesis InhibitorsProtein Synthesis Inhibitors& Other Newer Antibiotics& Other Newer Antibiotics

Streptogramins -

Quinupristin / Dalfopristin

Oxazolidinones – Linezolid 2) Comps. acting on cell membrane Comps. acting on cell membrane

/cell wall /cell wall : - Polymixin &

GlycopeptidesGlycopeptides – e.g.- -Vancomycin & TeicoplaninVancomycin & Teicoplanin

Protein Synthesis InhibitorsProtein Synthesis Inhibitors

LipopeptidesLipopeptides – e.g. –Daptomycin.

3) MiscellaneousMiscellaneous : Compds. acting by

direct mech. e.g.-

- Bacitracin

- Mupirocin

4) Newer AM Newer AM : Raptamulin

Fidaxomycin

Protein Synthesis InhibitorsProtein Synthesis InhibitorsTetracyclinesTetracyclines

HISTORYHISTORY :

The development of the Tetracycline antibiotics was the result of a systemic screening of soil specimens soil specimens collected from many parts of the world for antibiotic-producing micro-organism


- Chlortetracycline (prototype) is introduced in 1948 .( by S. aureofaciens ),

followed by Oxy- tetracyclines &

Tetracyclines in 1950 & 1952 respectively

- Because of their action against G +ve ,

G- ve bact.s , Rikettsia ,Aerobes , An-

aerobes & Chlamydia ,they are known as Broad spectrum antibiotics .



Source & ChemistrySource & Chemistry :-Oxytetracycline a natural product

isolated from Streptomyces rimosus. -Tetracycline is semi synthetic derivative

of Chlortetracycline ( isolated from Streptomyces aureofaciens ) .

-Others are DoxycyclineDoxycycline & MinocyclineMinocycline - Tetracyclines are close cong.s of


polycyclic naphthocemecarboxamidepolycyclic naphthocemecarboxamide having fusion of four cyclohexane rad. hence the name. OH O OH O CO – NH2 OH CH3 OH N(CH3)2


Susceptibility to micro-organismsSusceptibility to micro-organisms (Spectrum) (Spectrum) :

Tetracyclines - more active against

G +ve than G -ve micro- org.s.

- G +ve: Staphylococci, Enterococi ,

& hemolytic Streptococi having variable susceptibility


G –ve:- B. anthracis & L. monocytogenes & H.

influenzae are susceptible (Enterobacters have Enterobacters have acquired resistance )acquired resistance )

- Other Sensitive G –ve org.s areOther Sensitive G –ve org.s are- Brucella - Helicobacter pylori

- ,H. ducreyi ( ChancroidChancroid ) , - Yersinia pestis ( Plague)

- V. cholerae - Enterocolitica

- Legionella pnemophilla , - Tularemia

- Campylobacter jejuni , - Pasteurella multocida


( strains of N. gonorrhea are no longer strains of N. gonorrhea are no longer sensitive)sensitive) .

- Various anaerobes are also susceptible (e.g. – Bacterioides species , Propiono - bacterium & Pepcococcus )

-Tetracycline is active against Actinomyces & is DOC .

-Rikettsia – All Tetracyclines are highly

effective ( It causes Rocky mountain spotted fever ,Typhus, scrub It causes Rocky mountain spotted fever ,Typhus, scrub

typhus & Q – fevertyphus & Q – fever)) .


MiscellaneousMiscellaneous : - Spirochetes including Borrelia recurrentis ,

Treponema pallidum ( Syphilis) , Chlamydia ,

- Mycoplasma

-Non T.B. strains of Mycobacterium(e.g.-M.murium) - Amoeba & some atypical mycobacteria & Plasmodium species (but not active against Fungi ) .


Various Tetracyclines Used : -Tetracycline & Oxytetracycline-Chlortetracycline ( obsolete in US )

-Minocycline & Doxycycline

-Demeclocycline are available. (Chlortetracyclines & Oxytetracyclines are used only

in ophthalmic solution/ oint.)


- The more lipophylic drugs e.g.-

DoxycyclinesDoxycyclines & MinocyclinesMinocyclines usually are the most active followed by Tetracyclines .

- Resistance to any one can cause cross resistance to others .


Effect on Intestinal FloraEffect on Intestinal Flora :

Many of the Tetracyclines are incompletely

absorbed from the GIT. & ↑ conc. in the

bowel can markedly alter enteric flora.

- Sensitive aerobic & anaerobic coliform

micro-org. & G- ve spore forming bacteria are suppressed markedly.


As the fecal coliform count declines –overgrowth of Tetracyc. resist. micro-org.s occurs particularly-

-Yeasts (esp. Candida sp.) Yeasts (esp. Candida sp.)

- Enterococci - Enterococci

- Proteus & - Proteus &

- Pseudomonas- Pseudomonas


It occasionally producePseudomembranous Colitis

( caused by Clostridium difficile.)Mechanism of ActionMechanism of Action : Tetracyclines ↓ bact. protein synth. by binding to the 30s bact. ribosomes &prevent access of aminoacyl t-RNA – ribosome complex (by ↓its attachment to ‘A’ site)





- They enter G -ve bact .by passive diff.

through the hydrophilic channels formed by Porin protein of the outer cell memb. via the active transport

energy dependent system.

Resistance to TetracyclineResistance to Tetracycline :

Plasmid mediated & is inducible .


Mech. of action of resistanceMech. of action of resistance:1.↓ Accumul. of Tetracyc. as a result of

either decreased antb. influx or acquisition

of an energy dependant efflux pathway.

2. Prod. of ribosomal protective protein that

displaces Tetracyc. from its target ( may may

occur by mutation occur by mutation ).).

3. Enzymatic inactivation of Tetracyclines


Classification Classification :

1. Incompletely absorbed ( 60-80% )

Natural- Oxytetra Oxytetra & & Demeclocyc.Demeclocyc.

Semi- synth. – TetracyclinesTetracyclines

2. Almost completely absorbed (90-100%) – Semi synthetic

DoxycyclinesDoxycyclines & & MinocyclinesMinocyclines


Pharmacokinetics Pharmacokinetics (Absorption , Distribution (Absorption , Distribution &Excretion)&Excretion)

-Abs. of most Tetracyclines is incomplete. -% of oral dose that is absorb with empty stomach is : - Lowest for Chlortetracycline

- Intermediate for Oxytetracyclines , Demeclocyclines & Tetracyclines - High for Doxycyclines (95%) & Minocyclines(100%)


Absorption of Tetracyc. is impaired by the concurrent ingestion of - Dairy prod. (milk & milk products ) - Aluminum hydroxide gel - Ca, Mg , iron & Zn salts and - Bismuth subsalicylate. ( food & dairy products do not interfere with the abs. of( food & dairy products do not interfere with the abs. of Doxy & Minocycline Doxy & Minocycline )


Half life ( t½ )Half life ( t½ ) – Oxytetracyc. & Tetracyc. -6-12 hrs. Demeclocycline – 16 hrs. Doxycyc. & Minocyc. – 16-18 hrs.


Distribution Distribution : Widely distributed through out the body and into tissues & secretions including urine &

prostate .

They accumulate in RE cells of liver &

spleen, bone marrow ,dentine & enamel

of unerupted teeth .


- Penetration into most of the tissues

& fluid is excellent e.g.- CSF.

- It crosses the placenta & also secreted in milk .


ExcretionExcretion : -Except Doxycycline the primary route of elimination for most of the Tetracyclines is the kidney ,also conc. in liver & excreted in bile ( partly goes into enterohepatic circulation).

- Excretion also occurs through feces even after the parenteral administration

- Minocycline is metabolized in liver .


(Because of enterohepatic circulation these drugs may

remain in the body for a long time after cessation of

therapy).

-Doxycycline at recommended doses does not accumulate significantly in pts with renal failure & thus is one of the safest of the Tetracyclines for use in patient with renal impairment .


Dose Dose - wide variety of TetracyclinesTetracyclines are available for oral , parenteral & topical administration . Tetracycline-Tetracycline- oral – 1-2 gm /day in adult ( children -25 -

50 mg/kg daily) in two-four div. doses .

-DemeclocyclineDemeclocycline – 150 mg every 6 hrs used rarely as AM

agent because it causes photosensitivity react. &

nephrogenic diabetes insipidus .


- DoxycyclineDoxycycline- - 100 mg 12 hrly on 1st day then 100 mg

OD (Child- 4-5 mg/kg/d on 1st day then 2-2.5 mg /kg OD. )

Parenteral : - Doxycycline Doxycycline – 200 mg I.V. infusion on 1st day then 100 mg once or twice subsequently -TetracyclineTetracycline – in acute infections – 1 gm ( 2gm in severe inf.2gm in severe inf. )

div. in equal doses . (Generally Tetracyclines should be given 2 hr. before or after meals Generally Tetracyclines should be given 2 hr. before or after meals )

Tetracyclines should not be given I.M. as local irritation &Tetracyclines should not be given I.M. as local irritation &

poor absorption occurs .poor absorption occurs .


Local – except for local use in the eye topical use of Tetracycline is not recommended.


USESUSES: 1. Rikettsial inf. ( DOC is Doxy )Caused by obligate intracellular organism resembling viruses & bact.Maintained in nature by a cycle of animal reservoir & arthropod vector.They multiply in vas, endothelial cells & causes perivascular infiltr.&Leads to thrombosis , gangrene etc. Types are-Rocky mountain spotted fever-Epidemic & Scrub typhus-Q feverTetracyclines are life saving & clinical improvement occurs in 24 hrs Others effective are Chloramphenicol .


2. Mycoplasma inf. ( M. pneumonia)Mycoplasma is smallest living org. , lacks cell wall , do not synthesize

Folic acid so naturally resist. to Sulfonamides .Erythromycin also effect.

3. Chlamydia – Lymphogranuloma –venereum (Doxy.- 100 mg BD x 21 days )

-Psittacosis & Trachoma –Doxy -100 mg BD x14 d .

( Trachoma is a type of follicular conjunctivitis & cause of blindness) .

or Tetracycline in Trachoma – 250 mg QID x 14 days

( because it occurs in early childhood before complete calcification of the

permanent teeth so is C/I ) .


4. Non specific urethritisNon specific urethritis – Doxycycline – 100 mg BD. x 7 days .

5. SexuallySexually transmitted diseasestransmitted diseases (STD):

Not a DOC because of resistance.

-C. Trachomatis is often a co-existent pathogen in acute

PID including endometritisendometritis ,salpingitis & for peritonitis

Doxy – 100 mg I.V. BD. followed by oral therapy x 7 days

( usually combine with usually combine with CefoxitinCefoxitin to cover anaerobes to cover anaerobes )


-Acute Epididymitis – single inj. of Ceftriaxone + Doxy 100 mg orally BD x 10 days ( Sexual partner with any of these diseases shall also be treated )

--Primary/ Secondary Syphilis- Primary/ Secondary Syphilis-

InIn non pregnant Penicillin resist. Pts

can be treated with Tetracycline .


6. Anthrax – Doxycycline – 100 mg 12 hrly

( 2.2 mg/kg in children ) x 60 days

7. Bacillary infections – -Brucellosis -Tetracycline + Rifampicin /

Streptomycin is effective ((caused by inf. milk of goat, cow or sheep & occurs in farmers caused by inf. milk of goat, cow or sheep & occurs in farmers ).).

-Tularemia- Although Streptomycin is preferred

but Tetracyclines also are effective.


-Cholera – Doxy -300 mg single dose is effective in reducing stool volume & eradicating V. cholerae from stools with in 48 hrs ., but it is not a substitute

for I.V. electrolytes & fluid replacement .

- Shigellosis / Salmonella infection: The Tetracyclines are not effective because of

resistance.

( but can be given in Traveller’s diarrhoea by E. coli )but can be given in Traveller’s diarrhoea by E. coli )


8. UTI – no longer recommended.

9. Other- Actinomycosis , Leptospirosis

& infection by Borellia species (acute & prophylactic treatment of infections )

10. Acne – Tetracyclines have been used to treat acne by inhibiting Propioni -bact. which reside in sebaceous follicles (low doses are used -250mg orally twice a day ).


11. Amoebiasis – effective with other drugs.

12. Helicobacter pylori inf. of GIT

( peptic ulcer )

13. Malaria caused by plasmodium.


GlycylcyclinesGlycylcyclines

The Glycylcyclines are synthetic analogs of the Tetracyclines; the Glycylcycline currently approved is TigecyclineTigecycline, the 9-tert-butyl glycylamido derivative of Minocycline. -They display activity like older Tetracyc. & targets Tetracycline resistant org.s.


They are also active against - Methicillin Resist. S. aureus (MRSA) & S. epidermidis . - Penicillin resist. S. pneumoniae & - Vancomycin resist. enterococci (VRE) . (Tigecycline is not appreciably absorbed from theTigecycline is not appreciably absorbed from the Gastrointestinal (GI) tract and is only available forGastrointestinal (GI) tract and is only available for parenteral administrationparenteral administration )

Mnemonic : ( Uses) • T Tetracyclines are used for• E• T• R - Rickettsia ,Relapsing fever

• A - Atypical pneumonia• C - Cholera• Y - LYme’s disease• C - Chlamydia• L - LGV• I - Inguinale ( granuloma )• N• E - Epidemics of Plague


Side/ effectsSide/ effects:1. GIT -GI irritation most common after oral

administration

- Epigastric burning ,

- Nausea , Vomiting & Diarrhea

- Esophagitis ( give drug with food ) . - Pseudomembranous colitis

by Clostridia difficle .


2. Photosensitivity – esp. by Doxy , &

Demeclocycline

3. Hepatic toxicity :- (esp. during preg. on prolong use)

4. Renal toxicity : Tetracyc. have catabolic effect so aggravate azotemia (↑ blood urea↑ blood urea) . Doxycycline is least nephro - toxic .

(Demeclocycline often produce nephrogenic diabetes insipidus.)


Fanconi syndrome – characterized by

nausea ,vomiting , polyuria, polydipsia, proteinuria , acidosis & glycosuria ,azotemia & kidney damage

(due to formation of toxic metabolites e.g.-due to formation of toxic metabolites e.g.-Epianhydrotetracycline & Epitetracycline which has been Epianhydrotetracycline & Epitetracycline which has been observed in pts ingesting outdated & degraded observed in pts ingesting outdated & degraded TetracyclinesTetracyclines) .


5.Effects on teeth :

Children may develop permanent brown

discoloration of teeth ( the larger is the

dose more intense the discolor.)

(Total dose is more important & risk is more when

given to neonates or babies before 1st dentition .)


the deposition of drug in teeth & bones is

due to its chelating prop. & the formation of

Tetra-calcium-orthophosphate complex .

6. Misce.Misce. : Tetracyclines are deposited in the skeleton during gestation & throughout childhood & may depress bone growth in Premature Infants .


-Thrombophlebitis following I.V. administ .

-↑ Intracranial pressure in some young infants. ( causes bulging fontanelles & pseudotumor cerebri

in adults ) -Thromcytopenic purpura ,leukocytosis


-Vestibular toxicity (especially by Minocycycline )

-Hypersens. react. may occur.

- SuperinfectionSuperinfection -caused by strains of

bacteria , fungi resistant to Tetracyclines

(vaginal , oral , systemic & intestinal inf. can occur. )


- Pseudomembranous colitis.

Characterized by fever, severe diarrhea & stools cont. shreds of mucous memb. & large no. of neutrophils . (Discontinuation of Tetracycline & administration Discontinuation of Tetracycline & administration

of Metronidazole is curativeof Metronidazole is curative ) .

Mnemonic: ( Side effects ) Mnemonic: ( Side effects ) KAPIL DEVKAPIL DEV

• K – Kidney failure ( All are contra-indicated except DoxycyclineDoxycycline )• A - Antianabolic effect• P - Photosensitivity ( maximum with DemeclocyclineDemeclocycline )• I - Insipidus ( Diabetes Insipidus : maximum with DemeclocyclineDemeclocycline )• L - Liver toxicity ( hepatic necrosis )

• D - Dentition and Bone defects ( C/I in pregnancy and children )• E - Expired drugs can cause Fanconi’s syndrome• V - Vestibular dysfunction ( maximum with MinocyclineMinocycline )


PrecautionsPrecautions : - Do not give Tetracyclines in pregnancy.

- Do not use for common infections in children younger than 8 year.

-Discard unused supply of this antibiotic .

Protein Synthesis InhibitorsProtein Synthesis InhibitorsChloramphenicolChloramphenicol

Produced by Streptomyces venezuelaeStreptomyces venezuelae

-Introduced into clinical practice in 1948

-With wide use it became evident that

Chloramphenicol (CAP) could cause

serious & fatal blood dyscrasias .

-Now CAP is reserved for Tt of life

threatening infections e.g. -


- MeningitisMeningitis

- Rikettsial inf.- Rikettsial inf. - Typhoid fever- Typhoid fever in pts who can not take safer alternative

antibiotic due to resistance or allergy.


Chemistry :Chemistry :

The antbiotic is unique among natural comp.s in that it has nitrobenzene moiety

(responsible for antibacterial actionresponsible for antibacterial action ) & is a derivative of dichloroacetic acid .Mech . of Action :Mech . of Action :

- It ↓ protein synthesis in bact. & to a lesser extent in eukaryotic cells.- It penetrates bacterial cells by facilitated


diffusion.- It acts primarily by binding reversibly to the 50S ribosomal subunit ( near the

binding site for macrolide antb.s & Clindamycin which CAP↓ competitively ).

Although binding of t-RNA at the codon recognition site on the 30S ribosomal subunit is undisturbed,


the drug prevents the transfer of elongated peptide chain to the newly attached aminoacyl-t RNA at the acceptor site of ribosome –m RNA complex ( by preventing theby preventing the

interaction between peptidyl transferase & its aminoacidinteraction between peptidyl transferase & its aminoacid substrate → ↓↓ of peptide bond formation and transfer ofsubstrate → ↓↓ of peptide bond formation and transfer of elongated peptide chain from ‘P’ to ‘A ‘site ,elongated peptide chain from ‘P’ to ‘A ‘site , thereforetherefore inhibits Transpeptidation reactioninhibits Transpeptidation reaction )

Protein Synthesis InhibitorsProtein Synthesis Inhibitors Chloramphenicol Chloramphenicol

Protein Synthesis InhibitorsProtein Synthesis Inhibitors Chloramphenicol Chloramphenicol


It can also ↓ mitochondrial protein synthesis in mammalian cells because mitochondrial ribosomes resemble bacterial ribosome (both are 70S ) more than they do the 80S cytoplasmic ribosomes of mammalian cells. ( Mammalian erythropoietic cells are particularly sensitiveMammalian erythropoietic cells are particularly sensitive

to this drugto this drug)


Anti microbial action :Anti microbial action : - Broad spectrum antibiotic . - CAP is bacteriostatic against most species although it is bactericidal against N. gonorrheae S. pneumonia H. influenzae Brucella spc. & Bordetella pertusis.


It is active against the same range of organisms as Tetracyclines but notablenotable differences differences are –

- CAP was highly active against Salmonella including S. typhi ( but now

resistant strains have developed).-It is more active than Tetracyclines against H. influenzae ( now many are resistant ) , B. pertusis Klebsiella , N. meningitidis & anaerobes e.g. Bacteria fragilis .


-It is less active against G +ve cocci , Spirochetes , some Enterobacters & Chlamydia .

- Entamoeba and Plasmodia are not

inhibitedLike Tetracyclines, it is also not effective against

Mycobacteria , many Proteus, Pseudomonas , viruses

and fungi .


Resistance to CAP:Resistance to CAP: -Caused by a plasmid encoded acetyl transferase that inactivates the drug.

- Also by ↓ permeability & from ribosomal mutation ( acetylated derivative of CAP fail to bind to

bacterial ribosome)


Pharmacokinetics Pharmacokinetics :(Absorption ,Distribution :(Absorption ,Distribution & Excretion )& Excretion )

Chloramphenicol ( Chloromycetin ) is absorbed rapidly from the GIT & peak plasma conc. occur with in 2-3 hrs after administration..


-Parenterally - water sol. , inactive prodrug CAP succinate ( prep. of

Chloramphenicol ) hydrolyzes by esterases in vivo .

It is rapidly cleared from pl. by the kidney (↓renal function in neonates & in other states

↑plasma concentration )


-Widely distributed in body tissues & fluids & readily reaches therap. conc. in CSF (values are 60 % of those in plasma ) in the presence or absence of meningitis .

-Drug may accumulate in brain , it is also present in bile , milk & placental fluid and aqueous humor after sub conj. Injection.


- Hepatic metabolism to the inactive gluco -Hepatic metabolism to the inactive gluco -

ronide is the major route of eliminationronide is the major route of elimination -This metabolite & CAP itself are excreted in the urine following filtration & secretion ( Pt with cirrhosis & impaired liverPt with cirrhosis & impaired liver

function have ↓↓ metab. clearancefunction have ↓↓ metab. clearance & therefore dosing& therefore dosing

should be adjustedshould be adjusted)


-Significant variability in the metabolism &

pharmacokinetics of CAP in neonates ,infants & children

necessitates monitoring of drug concentration in plasma .


Therapeutic UsesTherapeutic Uses : Therapy with CAP must be limited to infections for which the benefits of thebenefits of the drug outweigh the risk of the potentialdrug outweigh the risk of the potential toxicitiestoxicities . Other drugs are used if effective & less toxic instead of CAP.


1.1. Typhoid feverTyphoid fever – (Quinolones & 3Quinolones & 3rdrd gen. gen.

Cephalosp.s are DOCCephalosp.s are DOC.)

CAP can be used if senst. & above drugs are causing allergy .

(response is more rapid with oral route)

2. Bact.Bact. MeningitisMeningitis- 3rdgen. Cephalosporin have replaced CAP (but CAP remain an alternative drug for the Tt. of meningitis caused by


H. influenzae ,N. meningitis & S. pneumoniae in

patients having allergy to β –lactams ) .3. Anaerobic infAnaerobic inf. – effective against most

anaerobic bacteria including Bacteroid species & effective for Tt. of serious intra- abdominal inf. or brain diseases .


.4. Rikettsial inf.Rikettsial inf. – Preferred agents are

Tetracyclines but if pt is allergic to Tetra - cyclines with ↓ renal func.s , in pregn. or

in children younger than 8 yrs. CAP

is the DOC (50 mg/kg/day) .


5. BrucellosisBrucellosis – when Tetracyclines are resistant .Side Effects:Side Effects: CAP inhibit the synthesis of protein of mitochondrial membrane by ↓ peptidyl - transferase . Much of the toxicity can be attributed to this .


1. H/S react.H/S react. – relatively uncommon- macular or vesicular skin rash ,

fever ,angio-oedema ,Jarish - Herxheimer react. (may occur in Syphilis, may occur in Syphilis,

Brucella & Typhoid fever treatment Brucella & Typhoid fever treatment ).2. Hematological toxicityHematological toxicity – most impt. is on bone marrow & is dose related (30%)-anemia, leukopenia


or thrombocytopenia .

70% idiosyncratic – aplastic anemia →

pancytopenia. (who undergo prolonged therapy or in patients

expose to drug for more than one occasion ) .

But this does not C/I the use of CAP in

situation in which it may be life saving .


(the drug however should never be used in diseasesthe drug however should never be used in diseases

readily , safely & effectively treatable with other AMreadily , safely & effectively treatable with other AM

agentsagents .)

- Some pts who develop chronic bone

marrow suppression subsequently

develop acute myeloblastic leukemia .


3.ToxicToxic & Irritative effects& Irritative effects : - Nausea , vomiting , unpleasant taste diarrhea & perineal irritation . - Rare toxic effect – blurring of vision & digital parasthesia.

4. Neonates may develop a serious illness termed Gray Baby SyndromeGray Baby Syndrome if exposed to excessive doses of CAP,


(begin 2-9 days after Tt is started → vomiting

, refusal to suck , irregular respiration, abd. distension , cyanosis & passing of loose green stools , patient

become flaccid & hypothermic).

Two mechanism:1.) Deficiency of glucoronylDeficiency of glucoronyl -transferasetransferase ,

hepatic enzyme that metabolize CAP in first 3-4 wks of life .


2.) Inadequate renal excretion of Inadequate renal excretion of unconjugated drugunconjugated drug

(children who are younger than 2 wks of age – dose children who are younger than 2 wks of age – dose

should not exceedshould not exceed 25 mg/ kg ) .

It removed from the blood minimally by

peritoneal / hemodialysis .


D/ID/I – CAP ↓ hepatic C-P450 isozyme & prolong the half life of drugs that are metabolized by this system

e.g.- Warferin

Dicoumarol

Phenytoin

Chlorpopamide etc.


Because of serious bone marrow toxicity:Because of serious bone marrow toxicity:

1. Never use Chloramphenicol for minor infections

2. Do not use Chloramphenicol for inf.s treatable by

safe alternatives.

3. Avoid repeated courses

4. Daily dose should not exceed 2-3 gms. & duration of therapy should be less than 2 wks

Protein Synthesis InhibitorsProtein Synthesis InhibitorsMacrolidesMacrolides

It includes : Erythromycin Roxithromycin, Clarithromycin & Azithromycin.Erythromycin :Erythromycin :-Discovered in 1952 by McGuire & co- workers in the metabolic products of a

strain of Streptomyces erythruesStreptomyces erythrues.


- - ClarithromycinClarithromycin & AzithromycinAzithromycin are semi-synthetic derivative of Erythromycin (RoxithromycinRoxithromycin is also semi- synth. , long acting, acid

stable macrolide , spectrum ≡ Erythromycin & given in BD doses)

Chemistry :Chemistry : - Contain a many membered lactone ring (14 memb. ring for Erythromycin & Clarithromycin & 15 memb. ring for Azth. )


to which are attached one or more deoxy sugars .-Clarithromycin have methylation of the hydroxyl gp. at 6th position .

-Azithromycin differ in having methyl – substituted nitrogen atom into the lactone ring .


-These structural changes improves the acid stability & tissue penetration & broadens the spectrum of activity .

Anti microbial activity:Anti microbial activity:-Usually bacteriostatic but may become bactericidal in high concentration against susceptible organisms .


-Most active against aerobic G +ve cocci & bacilli e.g. S. pyogen. , S. pneumoniae & viridans .(bact. resist. is common against Streptococci & resistancebact. resist. is common against Streptococci & resistance mechanism affect all macrolide antibiotics so mechanism affect all macrolide antibiotics so cross resistcross resist.. is completeis complete .)

-Staphylococci are not reliably sensitive to Erythromycin .


-G+ve bacilli are sensitive to Erythromycin (e.g. Clostridium perfringes ,

Coryne - bacterium diphtheriae & L. monocytogenes)

-It is inactive against most aerobic inactive against most aerobic enteric G -ve bacillienteric G -ve bacilli. (but some are sensitive

e.g. -H. influenz. , N. meningitidis & N. gonorrheae .)


Active against Pasteurella multocida Pasteurella multocida

Borrelia speciesBorrelia species

Bordetella pertusis Bordetella pertusis

Campylobacter jejuni Campylobacter jejuni

M. pneumoniae .M. pneumoniae .

- Some atypical mycobact. are also senst.

e.g. M. scrofulaceum.


No activity against No activity against

- virus virus

- yeast &yeast &

- fungi .- fungi .

ClarithromycinClarithromycin: is slightly more potent

against sensitive strains of

Streptococci. ,Staphylococci. ,H. influenzae & N. gonorrhoeae .

- Good action against M. catarrhalis

Chlamydia spp. M. pneumoniae & Helicobacter pylori .


Azithromycin:Azithromycin: less sensitive against G+ve org. but more active against H. influenz.

& Campylobacter .

- very effective against M. catarrhalis , Chlamydia spp.

P. multocida , M. – pneumoniae L. pneumophilla , Fuso-bacterium spp. N. gonorrheae .


Clarithromycin & Azithromycin have enhanced activity against M. avium intracellulare Toxoplasma gondii ( protozoa ) Cryptosporidium & Plasmodium Clarithromycin have good activity against Mycobacterium leprae .


Mechanism of action :Mechanism of action : ↓ protein synthesis by binding reversibly to 50S ribosomal subunit at or very near the site that binds CAP. It does not ↓ peptide bond formation phase but rather inhibits theinhibits the translocation steptranslocation step ((wherein a newly synthesized peptidyl t-RNA molecule moves from acceptor site on the ribosome to the

peptidyl donor site) .




-G +ve bacteria accumulates about 100 times more Erythromycin than do G –ve bacteria .

-Have ↑antimicrobial activity at alkaline pH .


Resistance :Resistance : Usually occurs from one of the four mech.1. Drug efflux by an active pump mech.

2. Ribosome protection by inducible or

constitutive prod. of methylase enzyme

, which modify the ribosomal target &

↓ drug binding .


3. Macrolide hydrolysis by esterases

produced by enterobacteriaceae.

4. Chromosomal mutation that alters a 50S ribosomal protein .


Phamacokinetics Phamacokinetics (Absorption ,Distribution & (Absorption ,Distribution & Excretion ):Excretion ):

Abs.- Erythromycin base is incompletely but adequately absorb from the upper small intestine . -It is inactivated by gastric acid therefore it is given as enteric coated tabs /capsenteric coated tabs /caps ( contain enteric coated pellets) or an ester.


-Food that ↑ acidity may delay absorption-Peak plasma conc. occurs 4 hrs after oral administration .-Ester of Erythromycin base ( e.g.- Stearate Stearate ,Estolate & Ethyl succinate,Estolate & Ethyl succinate ) have improved acid stability & less altered by food . (High conc. can be achieved by I.V. administration )


ClarithromycinClarithromycin – abs. rapidly from GI tract after oral administration.

-1st pass metabolism ↓ its bioavailability to

50 %.

(Can be given with or without food- 500mg 12 hrly or

extended release form -1gm once a day ) .


Azithromycin – Azithromycin – given orally , absorb rapidly ,distributed widely through out the body except to the brain & CSF.

(Not to be administered with food )

- Can be given I.V.


-Drug traverses the placenta & concentrated in breast milk are 50 % of those in serum.

-Clarithromycin & Azithromycin have extensive tissue distr. & reaches in most of the cells e.g. – phagocytes & greater concentration in tissues .


Elimination :Elimination : Erythromycin : Excreted in active form in the urine(also excreted in bile) .Clarithromycin - - Excreted unchanged in urine 20-40%, metabolize in liver into several metabolites .


Azithromycin-hepatic metabolism into active metabolite ( & biliary exct. is the major

route of elimination , only 12 % excreted unchanged in

urine ).Half life -40-68 hrs because of extensive

tissue sequestration & binding .


Doses :Doses : Erythromycin- 1-2 gm orally in 6

hrly div. doses. ( child – 30-50gm / kg/day )

. I.M. – not recommended because of local pain .

I.V. – for severe infection -0.5 -1 gm every 6 hrly (Erythromycin lactobionate ).

(Food should not be given simultaneously).


Clarythromycin–

250 mg BD for adult & children above 12y (500 mg BD. for severe inf. e.g. Infection with

H. influenzae . Children younger than 12 yrs- 7.5 mg/kg

BD). - With Lansoprazole (30 mg) + Amoxy - (1 gm ) BD x 14

days in H. pylori inf. to reduce incidence of duodenal ulcer .


Azithromycin -Azithromycin - Oral, suspension, powder form & I.V. injection . Loading dose – 500 mg 1st day , 1 hr before or 2 hr after meals then 250 mg OD. x 4 days . -(M. avium in AIDS -500mg daily in combination with

other agents or 1200mg once a wk.- used for STD during pregnancy when Tetracycline is C/I).


-1 gm single dose for

Nongonococcal urethritis

Chancroid &

alternative Tt. to Lymphogranuloma

venereum .

(Children – 10 mg /kg / day x 4 days )


Therapeutic Uses :Therapeutic Uses :1 Mycoplasma pneumonia – DOC

2.Legionnairs disease-DOC for pneumonia

3.Chlamydial infection - with any of the macrolides .( Single 1gm dose of AzithriomycinAzithriomycin is

recommended in uncomp. urethritis ,endocervical & epididymal inf.s(During preg. Erythromyc. 500mg QID x 7 days is the DOC.)


4.Diphtheria – Erythromycin -250mg QID x 7 days is very effect. in acute infection for eradicating the carrier state .

( Anti toxin is indicated in cases of Anti toxin is indicated in cases of

acute infectionsacute infections.)


5. PertusisPertusis – DOC for Tt & post exposure prophylaxis ( 40 mg/kg day –max. 1 gm /day x 7

days ).6. Streptococ. Inf.Streptococ. Inf. –Pharyngitis , scarlet fever , erysipelas & cellulitis – responds to macrolides (alternative to

penicillin.) -Staphylococcal inf.-Staphylococcal inf.-alternate treatment

for minor infections


7. CampylobacterCampylobacter : in Gastroenteritis- Erythromycin-250-500mg QID x 7days ( Fluoroq.s has replaced ).

8. Helicobacter pyloriHelicobacter pylori – Clarythromycin is given in comb. with Amoxycillin & Omeprazole.


9. TetanusTetanus – Erythromycin- 500mg orally 6 hrly x 10 days to eradicate Clost. tetani .( alt. to Penicillin) alt. to Penicillin) ( Debridement of wound , physiological

support ,Tetanus antitoxin & drug control of convulsions is the main stay of treatment)

10.SyphilisSyphilis- Early syphilis (alt. to Penicillin) but no longer recommended .


11. Mycobacterial inf.Mycobacterial inf. – Clarythromycin & Azithromycin for therapy & prophylaxis of Mycobacterium avium intracellulare

in AIDS pts . ( Clarythromycin 500mg BD + Ethambutol-15 mg /kg

once daily with or without Rifampicin is an effective combination regimen .)

12. Clarythromycin has been used with Minocycline for the Tt of M. leprae in Lepromatous leprosy.


Prophylactic Use :Prophylactic Use :

1. For recurrence of Rheumatic feverRheumatic fever (second choice to penicillin.) .

2. For Bacterial endocarditisBacterial endocarditis. ( in Penicillin allergic pts ) .(Uses-M-C- Chancroid , Cornebacterium , Campylobacter

L- Legionella infections A –Atypical pneumonia W- Whooping cough

Uses-Mnemonic-Erythromycin C- Chancroid , Cornebacterium , Campylobacter L- Legionella infections A –Atypical pneumonia W- Whooping cough

Uses –Mnemonic- Azithromycin & Clarithromycin

C- Chlamydia

H- H. influenzae

A- MAAC

T- Toxoplasma


Side Effect :Side Effect : Serious S/E are rarely present .- Fever , Eosinophilia & skin eruption (disappear after stoppage of therapy)- Cholestatic hepatitisCholestatic hepatitis ,most sig. S/E (by

Erythromyc. estolate ,rarely by ethyl-succinate or

stearate develop after 10-20 days of drug Tt., starts with nausea, vomiting & abdominal cramps → jaundice –

↑ transaminase level , eosinophilia & leukocytosis.)


-Large doses orally associated with

epigastric pain ..-Cardiac arrhythmiaCardiac arrhythmia ( ↑QT interval with ventricular tachycardia ) .-Transient auditory impairmentTransient auditory impairment ( by I.V. large doses ).((↑ GI motility by acting on Motilin recpt. to ↑ motilin secretion a harmone↑ GI motility by acting on Motilin recpt. to ↑ motilin secretion a harmonepresent in GI-tract & therefore used post operatively to ↑ peristalsispresent in GI-tract & therefore used post operatively to ↑ peristalsis & also to improve gastric emptying in gastric paresis in diabetes ) & also to improve gastric emptying in gastric paresis in diabetes )


-Other non chemotherapeut. role is its anti-infl. effect by↓ pro-infl. Cytokine release from the phagocytes -- may be useful in Rheumatoid arthritis ,cystic fibrosis , chronic sinusitis & asthma

D/I –D/I – Erythromycin & Clarythromycin→ ↓CYP3A4 microsomal enzyme &

therefore potentiate the effect of - Carbamazepine Cyclosporin Valproate Corticosteroid Digoxin Ergot alkaloids

Theophylline & Warferin

when given simultaneously


(Azithromycin is free of these D/I ).Adverse Effects- Mnemonic M- Motilin receptor agonists

A - Allergy

C- Choleastasis

R - Reversible

O- Ototoxicity

Spiramycin :Spiramycin : A macrolide antib.& has been employed only sporadically

-It resembles Erythromycin in spectrum . It has been found to limit risk

of transplacental transmission of Toxoplasma gondii infection ..

(Its specific utility is for Toxoplasmosis & recurrent abortion in

pregnant womens) .

Miscellaneous & Newer AntibioticsMiscellaneous & Newer Antibiotics

Ketolides:Ketolides: Telithromycin -It is a macrolide with keto gp. that binds with ribosome with greater affinity & resists efflux mediated & methylase mediated resistance . (Thus it is effective against many Thus it is effective against many

macrolide resistant organismsmacrolide resistant organisms ) -Approved for multidrug resist. Resp. tract infections.

-It is also an enzyme inhibitor so prone for similar D/I like Erythromycin .


Clindamycin :Clindamycin : -It is a chlorinated derivative of Lincomycin,Lincomycin, more effective & more safer than Lincomycin-It acts on 50S ribosomal subunit ≡ Erythromycin .-It is bacteriostatic with similar AM spectrum.-Better effectiveness against anaerobic organisms e.g.- Better effectiveness against anaerobic organisms e.g.- B. fragilis,B. fragilis,

Fusobacterium, Peptostreptococci & Clostridium perfringes .Fusobacterium, Peptostreptococci & Clostridium perfringes . ( All aerobic G -ve organisms are resistant )


-Good penetration in bone but does not cross BBB.S/E S/E - - Antibiotic assos.colitis (pseudom. col.)

Skin rashes Neuromuscular blockade.IndicationIndication- Anaerobic infections e.g.– abscess, bacteremias, empyma , pneumonia & prostatitis (reaches prostatic fluidreaches prostatic fluid)

- Pneumocystis jiroveci - Toxoplasma encephalitis & Malaria


GLYCOPEPTIDES :GLYCOPEPTIDES :Vancomycin (Vancomycin ( produced by Streptococcus Orientalis produced by Streptococcus Orientalis )) -Effective against Staphylococci (second choice due to toxicity ) , Streptococci & Clostridium. - It is bactericidal by ↓cell wall synthesis (It inhibits cell wall synthesis by binding firmly toIt inhibits cell wall synthesis by binding firmly to the D- Ala –D-Ala terminus of nascent peptidoglycanthe D- Ala –D-Ala terminus of nascent peptidoglycan pentapeptide . This ↓ thepentapeptide . This ↓ the TransglycolaseTransglycolase


, preventing further elongation of peptidoglycan &, preventing further elongation of peptidoglycan &

cross linking & thus cell become susceptible tocross linking & thus cell become susceptible to

lysislysis.)

-Poor oral abs. so given as I.V. infusion

used orally only for local effect in GIT

-More than 90% excreted by kidney.


S/E S/E :

-Fever , chills ,phlebitis.

- Extreme flushing ( RMS- RMS- red red man/red neck man/red neck

syndromesyndrome , ,due to massive release of histamine by rapid due to massive release of histamine by rapid

infusion infusion , other histamine liberators are –, other histamine liberators are –Morphine , Morphine , Tubocurarine , Polymixin BTubocurarine , Polymixin B )

-Nephrotoxicity -Ototoxicity

-H/S reactions.


Indications:Indications: -Methicillin resist. staphylococci inf. (MRSAMRSA)

-Antibiotic associated colitis.

- Enterococcus endocarditis

-Penicillin resist. Pneumococcal infections.(dose-1 gm IV 12 hrly, orally 500 mg 6 hrly in pseudm. coldose-1 gm IV 12 hrly, orally 500 mg 6 hrly in pseudm. col..)


Teicoplanin :Teicoplanin :

Similar to Vancomycin but safe by I.M. route(very expensive like Vancomycin used only in Vancomycin very expensive like Vancomycin used only in Vancomycin

allergyallergy)

Cycloserine: Cycloserine: ( produced by Streptomyces orchidaceus )( produced by Streptomyces orchidaceus )

It inhibits cell wall synthesis, effective orally.-Used as a second line drug for E. coli & Tuberculosis .


S/ES/E- Headache (The effects aggravated by alcoholThe effects aggravated by alcohol )

Drowsiness Convulsions Psychosis


Fusidic AcidFusidic Acid:- It is a steroidal antibiotic.- Does not actually bind to ribosomes but ↓

protein synthesis by ↓a factor necessary for elongation of peptide chain .

- Effective against penicillinase producing Staphylococci .


-Dual interaction with penicillin i.e. in sensitive org.s there is antagonistic effect while in resistant org.s it enhances the penicillin action. -Penetration in bone is good so used as a reserved drug for osteomyelitis.reserved drug for osteomyelitis.


Polypeptide Antibiotics:Polypeptide Antibiotics:-They are peptides but lack antigenecity. ( molecular wt. is low).- They are- Polymixin B Polymixin E (Colistin ) Bacitracin

Capreomycin


Polymixin B & E:Polymixin B & E: - Narrow spectrum bactericidal antibiotic - Effective against G- ve org.s (e.g.

Pseudomonas except Proteus & Neisseria). - Not absorb orally. - Systemically they are nephrotoxic

therefore used only locally .


- They are surface active , cationic detergents. - They interact with phospholipid of bacterial cell membrane & alters its permeability so that vital substances leak out & cell dies.

IndicationIndication – Local infections of skin , eyes ears & mucous membrane.


-ColistinColistin is used orally for infective diarrhea in a child or to alter gut flora in hepatic failure.

Bacitracin:Bacitracin:

-It is bactericidal by inhibiting cell wall

synthesis - It is highly nephrotoxic hence

used locally in combination with Neomycin

and/or Polymixin.( NebasulfNebasulf – Neomycin + Bacitracin + Sulfacetamide , powder / ointment )


Capreomycin:Capreomycin: -

-Bacteriostatic

- Second line drug for Tuberculosis

- High risk of nephrotoxicity

& vestibular toxicity


Mupirocin ( Pseudomonic acid ):Mupirocin ( Pseudomonic acid ): -Rapidly inactivated after absorption therefore used just topically. -Staphylococci is highly sensitive so it is effective against impetigo . -Can become resistant if applied to a large surface area.


Quinupristin & DalfopristinQuinupristin & Dalfopristin : It is a combination of Streptogramin A (Dalfopristin) & Streptogramin B (Quinopristin ) in the ratio of 70 : 30. The Dalfopristin ↑ sensitivity of 50S ribosome to

enhance the binding with the Quinopristin, which ↓ polypeptide elongation & terminates protein synthesis by ↓ 50S ribosome .


-The combination has rapid bactericidal effect which remains for longer time period.-They are soluble semi-synthetic derivative of Pristinamycins .- Used as I.V. infusion in 5% dextrose solution for an hour. (Inj. may lead to pain -arthralgia, myalgia & phlebitis)- They are indicated for serious MDR staphylococcus,indicated for serious MDR staphylococcus, streptococcus & pneumococcus infectionsstreptococcus & pneumococcus infections . .


Linezolid :Linezolid :

It is a synthetic oxazolidinone with a unique site of action i.e.- 23S23S ribosomal subunit of 50S ribosomeribosomal subunit of 50S ribosome & its inhibition prevents formation of 70S ribosome complexes & therefore inhibits the early assembly step in protein synthesis


-Due to its unique site of action there is no cross resistance.

-Its oral bioavailability is 100% so the oral & I.V. doses are the same.-Active against G +ve aerobic & anaerobic organisms butActive against G +ve aerobic & anaerobic organisms but

not against G –ve org.snot against G –ve org.s..-Indicated as a last resort for MDR Staphylococcal,last resort for MDR Staphylococcal, Streptococcal & Pneumococcal infectionsStreptococcal & Pneumococcal infections . .


(( Other latest ones are- Other latest ones are- RadezolidRadezolid & & TorezolidTorezolid both are in phase III cl. both are in phase III cl. trial . 4-6 times more active against- staphyl. , enterococ.& trial . 4-6 times more active against- staphyl. , enterococ.&

anaerobes.)anaerobes.)

S/ES/E- GI upset Skin rashes Headache ↓platelet count hence ↑risk of bleeding Week MAO ↓ that may lead to the cheese reaction .


Fosfomycin:Fosfomycin:

-It ↓ cell wall synthesis & transported by G6PD transport system .-Used for selective cases of UTI .-It is safe in pregnancy .


Spectinomycin:Spectinomycin: -It is similar to Aminoglycosides , binds to 30S subunit of ribosome in G- ve bacteria . - It is not bactericidal. -It is a reserve drug for resist. gonorrh. used as a single dose by deep I.M. inj.


Lipopeptide :Lipopeptide :- Daptomycin -Binds to bacterial membrane leading to depolarization & cell death .-Has a concentration dependent bactericidal effect.-There is no known resistance or cross resistance.-Indicated for resistant Staphylococcal &resistant Staphylococcal & Streptococcal infectionsStreptococcal infections .


Other GlycopeptidesOther Glycopeptides: Oritavancin & Dalbavancin -For GISA (glycopeptide intermediate susp. staphylococcus aureus ) &-MRSA (methicillin resistant S. aureus ).


OritavancinOritavancin is an analog of Vancomycin also effective against vancomycin resistanteffective against vancomycin resistant enterococci ( VREenterococci ( VRE )).. Long t½ permits once a day administration.

DalbavancinDalbavancin is similar but not effective against VRE .It has a prolonged retention in organisms so once a week administration is sufficient .


Platensimycin :Platensimycin :

- It ↓ fab F enzyme , which is required for

fatty acid biosynthesis which is essential

to construct cell membrane .

- Effective for MRSA & VRE.


Pleuromutilins :Pleuromutilins :

Newer class of antibiotic

MOA: MOA:

Bind to 50S subunit of ribosomes inhibiting

protein synthesis Approved DrugApproved Drug:

Retapamulin: Retapamulin: Approved in 2007

-Topical antibiotic

-Treatment of skin infections such as impetigo by S. aureus (methicillin-susceptible only) or S. pyogenes


Macrocyclic antibiotic drugs :Macrocyclic antibiotic drugs :Fidaxomicin ( Dificid*) -2011Fidaxomicin ( Dificid*) -2011

-Narrow spectrum bactericidal agent

-Demonstrated selective eradication of pathogenic Clostridium difficile

-MOA:

Inhibit bacterial enzyme RNA polymerase

Awaiting FDA approvalAwaiting FDA approval

ANTIMICROBIAL THERAPYANTIMICROBIAL THERAPY

DiseaseDisease Drugs ofDrugs of FirstFirst Alternative DrugsAlternative Drugs( ( PathogenPathogen)) ChoiceChoiceG –ve cocci (aer.)G –ve cocci (aer.) Moraxella catarrh. TMP-SMZ ,cephalosp Eryth., Quinol.s, Clarith. ( II / III g.) Azith. N. gonorrhoeae Ceftriaxone , Cefexime Spectinomy.& Cefoxitin Quinol.s N. Meningitidis Penicil. G Chloramph., Cephsp.III gN. Meningitidis Penicil. G Chloramph., Cephsp.III gG –ve rods ( aer.)G –ve rods ( aer.) E.Coli , Proteus , Cephsp. I / II g., TMP- Quinol.s & Aminog.s Klebsiella SMZ .


Enterobacter, Serrt. TMP-SMZ ,Quinol.s Antipseud. Penicil., Imipenem/ Meropen. Aminog., CefepimeShigella Quinol.s TMP-SMZ ,Ampicil. Cefixime, Ceftriaxon.Salmonella TMP-SMZ , Quinol.s Chloramph., Ampicil.Salmonella TMP-SMZ , Quinol.s Chloramph., Ampicil. Cephsp. III g.Cephsp. III g.Campyl. jejuni Quinol.s , Eryth. Tetracyc., Furazolid.Brucella sp. Doxy + Rifamp./ Aminog. Chloramph.+ Aminog or TMP-SMZHelico. pylori Bismuth + Metronid.+ Omepraz. + AmoxicilHelico. pylori Bismuth + Metronid.+ Omepraz. + Amoxicil Tetracyc.or Amoxicil. or Clarith.Tetracyc.or Amoxicil. or Clarith.Vibrio sp. Tetracyc . , TMP-SMZ Quinol.s


P.aeruginosa P.aeruginosa Antipseudomonal Penicil. Antipseud. Penicil. + + Aminogl. Quinol.s ,Ceftazidime

Imipenem / Meropenem

or Aztreonam + Aminog.Legionella sp. Erythromycin ( + Rifamp.) Quinol.s ( + Rifamp.) , Clarithromycin .G+ve cocci (aer.)G+ve cocci (aer.)Strep. pneum. Penicil. Ceftriaxone , Cefotax.,Strep. pneum. Penicil. Ceftriaxone , Cefotax., Vancomy., TMP-SMZ,Vancomy., TMP-SMZ, Eryth., Imipenem/ MeroEryth., Imipenem/ Mero.S.pyog.( gp -A) Penicil., Clindamy.Penicil., Clindamy. Eryth., Cephsp.( I g )S. agalact. (gp. B) Penicil.( + Aminog. ) Vancomycin Viridans Strept. Penicil. Vancomy., Cephsp.Viridans Strept. Penicil. Vancomy., Cephsp.


Staphyl. aureus Penicil. Vancomy., Penicil. Vancomy., Cephsp.( I g )(Beta- lactamase - ve)Beta-lactamase +ve Penicillinase resist. Vancomy., Cephsp.( I g ) Penicil.Methicil. – resist. Vancomycin TMP-SMZ , Minocyc.Methicil. – resist. Vancomycin TMP-SMZ , Minocyc.Enterococ. sp. Penicil. + Aminog. Vancomy.+ Aminogl.Vancomy.+ Aminogl.G-+ve bacilli( aer.)G-+ve bacilli( aer.) Bacil.sp. ( non anth) Vancomycin Imipenem / Meropenem, Quinol.s, ClindamycinListeria sp. Ampicil.+ Aminogl. TMP-SMZListeria sp. Ampicil.+ Aminogl. TMP-SMZNocardia sp. Sulfadiazine, Minocyc. , Imipenem or

TMP-SMZ Meropenem, Amikacin


Anaerobic bact.:Anaerobic bact.:G +ve ( Clostridia Penicil , Clindamyc. Vancomycin , AmikacinPeptococ., Actinomyc. Imipenem / Meropenem Peptostreptococ.)

Clostr. Difficile Metronidazole Vancomycin , BacitracinClostr. Difficile Metronidazole Vancomycin , BacitracinBacteroides fragilis Metronidazole Chloramph Imipenem/ Clindamyc Meropenem, beta-lactum beta-lactamase inh.combFusobacterium Metronid, Clindamyc. As above Penicil.Mycobacteria:Mycobacteria:Mycobact . tubercul.Mycobact . tubercul. Isoniazid + Rifampin Streptomyc. , Quinol.sIsoniazid + Rifampin Streptomyc. , Quinol.s


+ Ethambutol + Ethambutol Amikacin , Amikacin , Cycloser.Cycloser.

+ Pyrazinamide + Pyrazinamide Ethionamide, PAS . Ethionamide, PAS .Mycobact. LepraeMycobact. Leprae Multibacillary Dapsone +RifampinMultibacillary Dapsone +Rifampin + Clofazimine+ ClofaziminePaucibacillary Dapsone +Rifampin Paucibacillary Dapsone +Rifampin Mycoplasma pneu. Tetracyc., Eryth. Azithromyc. , ClarithMycoplasma pneu. Tetracyc., Eryth. Azithromyc. , Clarith..Chlamydia :Chlamydia : trachomatis Tetracyc., Eryth. Azithromyc., Ofloxac.trachomatis Tetracyc., Eryth. Azithromyc., Ofloxac. Clindamyc.Clindamyc. pneumoniae Tetracyc., Eryth. Clarythromyc. &pneumoniae Tetracyc., Eryth. Clarythromyc. & Azithromyc.Azithromyc.


Spirochetes :Spirochetes :

Borellia recur. Doxy. , Penicil. Eryth. , Chloramph.Borellia recur. Doxy. , Penicil. Eryth. , Chloramph.

Leptospira sp. Penicil. Tetracyc.Leptospira sp. Penicil. Tetracyc.

Treponema sp. Penicil. Tetracyc. & Eryth.Treponema sp. Penicil. Tetracyc. & Eryth.

MCQs• 1. All of the following antibiotics are macrolides, EXCEPT:

• a) Erythromycin

• b) Clarithromycin

• c) Lincomycin

• d) Roxythromycin

• 2. Tetracyclins have following unwanted effects:

• a) Irritation of gastrointestinal mucosa, phototoxicity

• b) Hepatotoxicity, anti-anabolic effect

• c) Dental hypoplasia, bone deformities

• d) All of the above

• 3. Chloramphenicol has the following unwanted effects:

• a) Nephrotoxicity

• b) Pancytopenia

• c) Hepatotoxicity

• d) Ototoxicity

MCQs 4. Lincosamides have the following unwanted effect:• a) Nephrotoxicity• b) Cancerogenity• c) Pseudomembranous colitis• d) Irritation of respiratory organs

5. Choose the characteristics of Vancomicin:• a) It is a glycopeptide, inhibits cell wall synthesis active only against Gram-negative• bacteria• b) It is a glycopeptide, that alters permeability of cell membrane and is active against• anaerobic bacteria• c) It is a beta- lactam antibiotic, inhibits cell wall synthesis active only against• Pseudomonas aeruginosa• d) It is a glycopeptide, inhibits cell wall synthesis and is active only against• Gram-positive bacteria.

MCQs

• 6. The additional anti-inflammatory & immunomodulatory activities are found in which• of the following group of antibiotics :• a) Fluoroquinolones• b) Macrolides• c) Polypeptide antibiotics• d) Tetracyclines • • 7. Mechanism of action of Tetracyclines is by :• a) Binding to 30 S subunit and inhibiting the binding of aminoacyl -t-RNA to A

site• b) Inhibiting peptidyl transferase activity• c) Inhibiting translocation• d) Inhibition of initiation and misreading of mRNA

MCQs• 8. Tetracyclines are avoided in pregnancy because they can :

• (a) Cause abortions

• (b) Cause excessive postpartum hemorrhage

• (c) Affect the bones and teeth of the fetus

• (d) Cause excessive vomiting in the mother

• 9. Erythromycin is the drug of choice in :

• (a) Pertussis

• (b) Gonococcal urethritis

• (c) Prophylaxis of bacterial endocarditis

• (d) Chlamydial infections

• 10. Which of the following agents is not a broad spectrum antibiotic ?

• (a) Ampicillin

• (b) Tetracycline

• (c) Chloremphenicol

• (d) Gentamicin

MCQs 11. Vancomycin has the following unwanted effects:

• a) Pseudomembranous colitis

• b) Hepatotoxicity

• c) “Red neck” syndrome, phlebitis

• d) All of the above

12. Chloramphenicol is the drug of choice in :

• (a) Staphylococcal infection

• (b) Salmonella infection

• (c) Viral infection

• (d) Amoebic dysentery

13. In renal failure safest tetracycline is :

• (a) Oxytetracycline

• (b) Chlortetracycline

• (c) Doxycycline

• (d) Demethyl chlortetracycline

MCQs• 14.Which of the following preparation of Erythromycin causes hepatitis with• cholestatic Jaundice as an adverse effect ?• a) Erythromycin ethyl succinate• b) Erythromycin base• c) Erythromycin stearate• d) Erythromycin estolate• • 15. Which of the following drug interfere with translocation of protein synthesis?• a) Tetracycline• b) Chloramphenicol• c) Penicillins• d) Gentamicin• e) Erythromycin•

MCQs• 16.Mechanism of action of Chloramphenicol is through :

• a) Nucleus

• b) 30S ribosome

• c) Mitochondria

• d) 50S ribosome

• e) Cell wall

• 17.Best indication of Linezolid is :

• a) VRSA

• b) K.pneumoniae

• c) MRSA

• d) E.coli

• e) Pseudomonas

• 18.Which of the following antibiotic is effective in a single dose therapy in Trachoma?

• a) Azithromycin

• b) Clarithromycin

• c) Erythromycin

• d) Doxycycline

• e) Chloramphenicol

MCQs 19. The choice of drug in Lymphogranuloma venereum is:• a) Ciprofloxacin• b) Tetracycline• c) Penicillin• d) Erythromycin • e) Gentamicin• • 20.Which of the following is drug of choice in Mycoplasma pneumoniae infection?• a) Cefotaxime• b) Azithromycin• c) Tetracycline• d) Amoxycillin• e) Gentamicin

Answer Key:

1-c , 2-d, 3-b, 4-c, 5-d , 6-b ,7-a , 8-c, 9-a

10-d, 11-c, 12-b, 13-c, 14-d, 15-e ,16-d, 17-a

18-a, 19-b , 20-b.

Bibliography

1.Goodman & Gilman’s ,The Pharmacological Basis of Therapeutics (12th Edition).

2. Principles of Pharmacology by

H. L. Sharma & K K Sharma ( Latest Edition)

4. Essentials of Medical Pharmacology by K. D. Tripathi

(7th edition)


THANK YOUTHANK YOU

Documents

Protein Synthesis Inhibitors Dr. Rajendra Nath Dr. Rajendra Nath Professor