Download Protein Synthesis Inhibitors-5

Protein Synthesis
Inhibitors
Dr. Rajendra Nath
Professor
Protein Synthesis Inhibitors
& Other Newer Antibiotics
1) Protein Synth. Inhibitors
that target the ribosome e.g.-
-Tetracyclines
- Chloramphenicol
- Macrolide antb.s (Erythromycin)
- Ketolide , Clindamycin
(Lincosamides)
Protein Synthesis Inhibitors
& Other Newer Antibiotics
Streptogramins Quinupristin / Dalfopristin
Oxazolidinones – Linezolid
2) Comps. acting on cell membrane
/cell wall : - Polymixin &
Glycopeptides – e.g.-Vancomycin & Teicoplanin
Protein Synthesis Inhibitors
Lipopeptides – e.g.
–Daptomycin.
3) Miscellaneous : Compds. acting by
direct mech. e.g.- Bacitracin
- Mupirocin
4) Newer AM : Raptamulin
Fidaxomycin
Protein Synthesis Inhibitors
Tetracyclines
HISTORY :
The development of the Tetracycline
antibiotics was the result of a systemic
screening of soil specimens collected
from many parts of the world for antibioticproducing micro-organism
Protein Synthesis Inhibitors
Tetracyclines
- 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 , Anaerobes & Chlamydia ,they are known
as Broad spectrum antibiotics .
Protein Synthesis Inhibitors
Tetracyclines
Protein Synthesis Inhibitors
Tetracyclines
Source & Chemistry :
-Oxytetracycline a natural product
isolated from Streptomyces rimosus.
-Tetracycline is semi synthetic derivative
of Chlortetracycline ( isolated from
Streptomyces aureofaciens ) .
-Others are Doxycycline & Minocycline
- Tetracyclines are close cong.s of
Protein Synthesis Inhibitors
Tetracyclines
polycyclic naphthocemecarboxamide
having fusion of four cyclohexane rad.
hence the name.
OH
O
OH
O
CO – NH2
OH
CH3
OH
N(CH3)2
Protein Synthesis Inhibitors
Tetracyclines
Susceptibility to micro-organisms
(Spectrum) :
Tetracyclines - more active against
G +ve than G -ve micro- org.s.
- G +ve: Staphylococci, Enterococi ,
& hemolytic Streptococi having variable
susceptibility
Protein Synthesis Inhibitors
Tetracyclines
G –ve:
- B. anthracis & L. monocytogenes & H.
influenzae are susceptible (Enterobacters have
acquired resistance )
- Other Sensitive G –ve org.s are
-
Brucella
,H. ducreyi ( Chancroid ) ,
V. cholerae
Legionella pnemophilla ,
Campylobacter jejuni ,
-
Helicobacter pylori
Yersinia pestis ( Plague)
Enterocolitica
Tularemia
Pasteurella multocida
Protein Synthesis Inhibitors
Tetracyclines
( strains of N. gonorrhea are no longer 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 typhus & Q – fever)
.
Protein Synthesis Inhibitors
Tetracyclines
Miscellaneous :
- 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 ) .
Protein Synthesis Inhibitors
Tetracyclines
Various Tetracyclines Used :
-Tetracycline & Oxytetracycline
-Chlortetracycline ( obsolete in US )
-Minocycline & Doxycycline
-Demeclocycline are available.
(Chlortetracyclines & Oxytetracyclines are used only
in ophthalmic solution/ oint.)
Protein Synthesis Inhibitors
Tetracyclines
- The more lipophylic drugs e.g.Doxycyclines & Minocyclines usually are
the most active followed by Tetracyclines .
- Resistance to any one can cause cross
resistance to others .
Protein Synthesis Inhibitors
Tetracyclines
Effect 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.
Protein Synthesis Inhibitors
Tetracyclines
As the fecal coliform count declines –
overgrowth of Tetracyc. resist. micro-org.s
occurs particularly-
-Yeasts (esp. Candida sp.)
- Enterococci
- Proteus &
- Pseudomonas
Protein Synthesis Inhibitors
Tetracyclines
It occasionally produce
Pseudomembranous Colitis
( caused by Clostridium difficile.)
Mechanism 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)
Protein Synthesis Inhibitors
Tetracyclines
Protein Synthesis Inhibitors
Tetracyclines
Protein Synthesis Inhibitors
Tetracyclines
Protein Synthesis Inhibitors
Tetracyclines
- 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 Tetracycline :
Plasmid mediated & is inducible .
Protein Synthesis Inhibitors
Tetracyclines
Mech. 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
occur by mutation ).
3. Enzymatic inactivation of Tetracyclines
Protein Synthesis Inhibitors
Tetracyclines
Classification :
1. Incompletely absorbed ( 60-80% )
Natural- Oxytetra & Demeclocyc.
Semi- synth. – Tetracyclines
2. Almost completely absorbed (90100%) – Semi synthetic
Doxycyclines & Minocyclines
Protein Synthesis Inhibitors
Tetracyclines
Pharmacokinetics (Absorption , Distribution
&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%)
Protein Synthesis Inhibitors
Tetracyclines
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
Doxy & Minocycline )
Protein Synthesis Inhibitors
Tetracyclines
Half life ( t½ ) –
Oxytetracyc. & Tetracyc. -6-12 hrs.
Demeclocycline
– 16 hrs.
Doxycyc. & Minocyc. – 16-18 hrs.
Protein Synthesis Inhibitors
Tetracyclines
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 .
Protein Synthesis Inhibitors
Tetracyclines
-
Penetration into most of the tissues
& fluid is excellent e.g.- CSF.
-
It crosses the placenta & also secreted in
milk .
Protein Synthesis Inhibitors
Tetracyclines
Excretion :
-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 .
Protein Synthesis Inhibitors
Tetracyclines
(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 .
Protein Synthesis Inhibitors
Tetracyclines
Dose wide variety of Tetracyclines are
available for oral , parenteral & topical
administration .
Tetracycline- oral – 1-2 gm /day in adult ( children -25 50 mg/kg daily) in two-four div. doses .
-Demeclocycline – 150 mg every 6 hrs used rarely as AM
agent because it causes photosensitivity react. &
nephrogenic diabetes insipidus .
Protein Synthesis Inhibitors
Tetracyclines
- Doxycycline- 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 – 200 mg I.V. infusion on 1st day then
100 mg once or twice subsequently
-Tetracycline – in acute infections – 1 gm ( 2gm in
severe inf. ) div. in equal doses .
(Generally Tetracyclines should be given 2 hr. before or after meals )
Tetracyclines should not be given I.M. as local irritation &
poor absorption occurs .
Protein Synthesis Inhibitors
Tetracyclines
Local – except for local use in the eye
topical use of Tetracycline is not
recommended.
Protein Synthesis Inhibitors
Tetracyclines
USES:
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 fever
Tetracyclines are life saving & clinical improvement occurs in 24 hrs
Others effective are Chloramphenicol .
Protein Synthesis Inhibitors
Tetracyclines
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 ) .
Protein Synthesis Inhibitors
Tetracyclines
4. Non specific urethritis –
Doxycycline – 100 mg BD. x 7 days .
5. Sexually transmitted diseases (STD):
Not a DOC because of resistance.
-C. Trachomatis is often a co-existent pathogen in acute
PID including endometritis ,salpingitis & for peritonitis
Doxy – 100 mg I.V. BD. followed by oral therapy x 7 days
( usually combine with Cefoxitin to cover anaerobes )
Protein Synthesis Inhibitors
Tetracyclines
-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 SyphilisIn non pregnant Penicillin resist. Pts
can be treated with Tetracycline .
Protein Synthesis Inhibitors
Tetracyclines
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 ).
-Tularemia- Although Streptomycin is preferred
but Tetracyclines also are effective.
Protein Synthesis Inhibitors
Tetracyclines
-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 )
Protein Synthesis Inhibitors
Tetracyclines
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 ).
Protein Synthesis Inhibitors
Tetracyclines
11. Amoebiasis – effective with other drugs.
12. Helicobacter pylori inf. of GIT
( peptic ulcer )
13. Malaria caused by plasmodium.
Protein Synthesis Inhibitors
Tetracyclines
Glycylcyclines
The Glycylcyclines are synthetic analogs of
the Tetracyclines;
the Glycylcycline currently approved is
Tigecycline, the 9-tert-butyl
glycylamido derivative of Minocycline.
-They display activity like older Tetracyc. &
targets Tetracycline resistant org.s.
Protein Synthesis Inhibitors
Tetracyclines
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 the
Gastrointestinal (GI) tract and is only available for
parenteral administration )
Mnemonic : ( Uses)
•
•
•
•
T
E
T
R
•
•
•
•
•
•
•
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A
C
Y
C
L
I
N
E
Tetracyclines are used for
- Rickettsia ,Relapsing fever
-
Atypical pneumonia
Cholera
LYme’s disease
Chlamydia
LGV
Inguinale ( granuloma )
- Epidemics of Plague
Protein Synthesis Inhibitors
Tetracyclines
Side/ 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 .
Protein Synthesis Inhibitors
Tetracyclines
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) .
Doxycycline is least nephro - toxic .
(Demeclocycline often produce nephrogenic diabetes insipidus.)
Protein Synthesis Inhibitors
Tetracyclines
Fanconi syndrome – characterized by nausea
,vomiting , polyuria, polydipsia, proteinuria ,
acidosis & glycosuria ,azotemia & kidney damage
(due to formation of toxic metabolites e.g.Epianhydrotetracycline & Epitetracycline which has been
observed in pts ingesting outdated & degraded
Tetracyclines) .
Protein Synthesis Inhibitors
Tetracyclines
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 .)
Protein Synthesis Inhibitors
Tetracyclines
the deposition of drug in teeth & bones is
due to its chelating prop. & the formation of
Tetra-calcium-orthophosphate complex .
6. Misce. :
Tetracyclines are deposited in the skeleton
during gestation & throughout childhood &
may depress bone growth in Premature
Infants .
Protein Synthesis Inhibitors
Tetracyclines
-Thrombophlebitis following I.V. administ .
-↑ Intracranial pressure in some young
infants.
( causes bulging fontanelles & pseudotumor cerebri
in adults )
-Thromcytopenic purpura ,leukocytosis
Protein Synthesis Inhibitors
Tetracyclines
-Vestibular toxicity (especially by Minocycycline )
-Hypersens. react. may occur.
- Superinfection -caused by strains of
bacteria , fungi resistant to Tetracyclines
(vaginal , oral , systemic & intestinal
inf. can occur.
)
Protein Synthesis Inhibitors
Tetracyclines
-
Pseudomembranous colitis.
Characterized by fever, severe diarrhea
& stools cont. shreds of mucous memb.
& large no. of neutrophils .
(Discontinuation of Tetracycline & administration
of Metronidazole is curative ) .
Mnemonic: ( Side effects ) KAPIL DEV
•
•
•
•
•
K – Kidney failure ( All are contra-indicated except Doxycycline )
A - Antianabolic effect
P - Photosensitivity ( maximum with Demeclocycline )
I - Insipidus ( Diabetes Insipidus : maximum with Demeclocycline )
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 Minocycline )
Protein Synthesis Inhibitors
Tetracyclines
Precautions :
- 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 Inhibitors
Chloramphenicol
Produced by Streptomyces 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. -
Protein Synthesis Inhibitors
Chloramphenicol
- Meningitis
- Rikettsial inf.
- Typhoid fever
in pts who can not take safer alternative
antibiotic due to resistance or allergy.
Protein Synthesis Inhibitors
Chloramphenicol
Chemistry :
The antbiotic is unique among natural
comp.s in that it has nitrobenzene moiety
(responsible for antibacterial action ) & is a
derivative of dichloroacetic acid .
Mech . of Action :
- It ↓ protein synthesis in bact. & to a lesser
extent in eukaryotic cells.
- It penetrates bacterial cells by facilitated
Protein Synthesis Inhibitors
Chloramphenicol
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,
Protein Synthesis Inhibitors
Chloramphenicol
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 the
interaction between peptidyl transferase & its aminoacid
substrate → ↓↓ of peptide bond formation and transfer of
elongated peptide chain from ‘P’ to ‘A ‘site , therefore
inhibits Transpeptidation reaction )
Protein Synthesis Inhibitors
Chloramphenicol
Protein Synthesis Inhibitors
Chloramphenicol
Protein Synthesis Inhibitors
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 sensitive
to this drug)
Protein Synthesis Inhibitors
Chloramphenicol
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.
Protein Synthesis Inhibitors
Chloramphenicol
It is active against the same range of
organisms as Tetracyclines but notable
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 .
Protein Synthesis Inhibitors
Chloramphenicol
-It is less active against G +ve cocci ,
Spirochetes , some Enterobacters &
Chlamydia .
- Entamoeba and Plasmodia are not
inhibited
Like Tetracyclines, it is also not effective against
Mycobacteria , many Proteus, Pseudomonas , viruses
and fungi .
Protein Synthesis Inhibitors
Chloramphenicol
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)
Protein Synthesis Inhibitors
Chloramphenicol
Pharmacokinetics :(Absorption ,Distribution
& Excretion )
Chloramphenicol ( Chloromycetin ) is
absorbed rapidly from the GIT & peak
plasma conc. occur with in 2-3 hrs after
administration.
.
Protein Synthesis Inhibitors
Chloramphenicol
-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 )
Protein Synthesis Inhibitors
Chloramphenicol
-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.
Protein Synthesis Inhibitors
Chloramphenicol
- Hepatic metabolism to the inactive gluco ronide is the major route of elimination
-This metabolite & CAP itself are
excreted in the urine following filtration
& secretion ( Pt with cirrhosis & impaired liver
function have ↓↓ metab. clearance & therefore dosing
should be adjusted)
Protein Synthesis Inhibitors
Chloramphenicol
-Significant variability in the metabolism &
pharmacokinetics of CAP in neonates ,infants & children
necessitates monitoring of drug concentration in plasma
.
Protein Synthesis Inhibitors
Chloramphenicol
Therapeutic Uses :
Therapy with CAP must be limited to
infections for which the benefits of the
drug outweigh the risk of the potential
toxicities .
Other drugs are used if effective & less
toxic instead of CAP.
Protein Synthesis Inhibitors
Chloramphenicol
1. Typhoid fever – (Quinolones & 3rd gen.
Cephalosp.s are DOC.)
CAP can be used if senst. & above drugs
are causing allergy .
(response is more rapid with oral
route)
2. Bact. Meningitis- 3rdgen. Cephalosporin
have replaced CAP (but CAP remain an
alternative drug for the Tt. of meningitis caused by
Protein Synthesis Inhibitors
Chloramphenicol
H. influenzae ,N. meningitis & S. pneumoniae in
patients having allergy to β –lactams
).
3. Anaerobic inf. – effective against most
anaerobic bacteria including Bacteroid
species & effective for Tt. of serious intraabdominal inf. or brain diseases .
Protein Synthesis Inhibitors
Chloramphenicol
.
4. 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) .
Protein Synthesis Inhibitors
Chloramphenicol
5. Brucellosis – when Tetracyclines are
resistant .
Side Effects:
CAP inhibit the synthesis of protein of
mitochondrial membrane by ↓ peptidyl transferase . Much of the toxicity can be
attributed to this .
Protein Synthesis Inhibitors
Chloramphenicol
1. H/S react. – relatively uncommonmacular or vesicular skin rash , fever
,angio-oedema ,Jarish - Herxheimer
react. (may occur in Syphilis, Brucella & Typhoid
fever treatment ).
2. Hematological toxicity –
most impt. is on bone marrow & is
dose related (30%)-anemia, leukopenia
Protein Synthesis Inhibitors
Chloramphenicol
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 .
Protein Synthesis Inhibitors
Chloramphenicol
(the drug however should
never be used in diseases
readily , safely & effectively treatable with other AM
agents .)
- Some pts who develop chronic bone
marrow suppression subsequently
develop acute myeloblastic leukemia .
Protein Synthesis Inhibitors
Chloramphenicol
3.Toxic & 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 Syndrome if exposed
to excessive doses of CAP,
Protein Synthesis Inhibitors
Chloramphenicol
(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 glucoronyl -transferase ,
hepatic enzyme that metabolize CAP in
first 3-4 wks of life .
Protein Synthesis Inhibitors
Chloramphenicol
2.) Inadequate renal excretion of
unconjugated drug
(children who are younger than 2 wks of age – dose
should not exceed 25 mg/ kg ) .
It removed from the blood minimally by
peritoneal / hemodialysis .
Protein Synthesis Inhibitors
Chloramphenicol
D/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.
Protein Synthesis Inhibitors
Chloramphenicol
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 Inhibitors
Macrolides
It includes : Erythromycin
Roxithromycin,
Clarithromycin &
Azithromycin.
Erythromycin :
-Discovered in 1952 by McGuire & coworkers in the metabolic products of a
strain of Streptomyces erythrues.
Protein Synthesis Inhibitors
Macrolides
- Clarithromycin & Azithromycin are
semi-synthetic derivative of Erythromycin
(Roxithromycin is also semi- synth. , long acting, acid
stable macrolide , spectrum ≡ Erythromycin & given in
BD doses)
Chemistry :
- Contain a many membered lactone ring
(14 memb. ring for Erythromycin &
Clarithromycin & 15 memb. ring for Azth. )
Protein Synthesis Inhibitors
Macrolides
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 .
Protein Synthesis Inhibitors
Macrolides
-These structural changes improves the acid
stability & tissue penetration & broadens
the spectrum of activity .
Anti microbial activity:
-Usually bacteriostatic but may become
bactericidal in high concentration against
susceptible organisms .
Protein Synthesis Inhibitors
Macrolides
-Most active against aerobic G +ve cocci
& bacilli e.g. S. pyogen. , S. pneumoniae
& viridans .
(bact. resist. is common against Streptococci & resistance
mechanism affect all macrolide antibiotics so cross resist.
is complete .)
-Staphylococci are not reliably sensitive
to Erythromycin .
Protein Synthesis Inhibitors
Macrolides
-G+ve bacilli are sensitive to Erythromycin
(e.g. Clostridium perfringes ,
Coryne - bacterium diphtheriae &
L. monocytogenes)
-It is inactive against most aerobic
enteric G -ve bacilli. (but some are sensitive
e.g. -H. influenz. ,
N. meningitidis &
N. gonorrheae .)
Protein Synthesis Inhibitors
Macrolides
Active against
Pasteurella multocida
Borrelia species
Bordetella pertusis
Campylobacter jejuni
M. pneumoniae .
-
Some atypical mycobact. are also senst.
e.g. M. scrofulaceum.
Protein Synthesis Inhibitors
Macrolides
No activity against
- virus
- yeast &
- fungi .
Clarithromycin: 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 .
Protein Synthesis Inhibitors
Macrolides
Azithromycin:
less sensitive against G+ve org. but more
active against H. influenz.
& Campylobacter .
- very effective against
M. catarrhalis ,
P. multocida ,
L. pneumophilla ,
N. gonorrheae .
Chlamydia spp.
M. – pneumoniae
Fuso-bacterium spp.
Protein Synthesis Inhibitors
Macrolides
Clarithromycin & Azithromycin
have enhanced activity against
M. avium intra- cellulare
Toxoplasma gondii ( protozoa )
Cryptosporidium &
Plasmodium
Clarithromycin have good activity
against Mycobacterium leprae .
Protein Synthesis Inhibitors
Macrolides
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 the translocation step
(wherein a newly synthesized peptidyl t-RNA molecule
moves from acceptor site on the ribosome to the
peptidyl donor site) .
Protein Synthesis Inhibitors
Macrolides
Protein Synthesis Inhibitors
Macrolides
Protein Synthesis Inhibitors
Macrolides
-G +ve bacteria accumulates about 100
times more Erythromycin than do
G –ve bacteria .
-Have ↑antimicrobial activity at alkaline
pH .
Protein Synthesis Inhibitors
Macrolides
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 .
Protein Synthesis Inhibitors
Macrolides
3. Macrolide hydrolysis by esterases
produced by enterobacteriaceae.
4. Chromosomal mutation that alters a 50S
ribosomal protein .
Protein Synthesis Inhibitors
Macrolides
Phamacokinetics (Absorption ,Distribution &
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 /caps
( contain enteric coated pellets) or an
ester.
Protein Synthesis Inhibitors
Macrolides
-Food that ↑ acidity may delay absorption
-Peak plasma conc. occurs 4 hrs after oral
administration .
-Ester of Erythromycin base ( e.g.- Stearate
,Estolate & Ethyl succinate ) have improved
acid stability & less altered by food .
(High conc. can be achieved by I.V. administration )
Protein Synthesis Inhibitors
Macrolides
Clarithromycin – 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 ) .
Protein Synthesis Inhibitors
Macrolides
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.
Protein Synthesis Inhibitors
Macrolides
-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 .
Protein Synthesis Inhibitors
Macrolides
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 .
Protein Synthesis Inhibitors
Macrolides
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 .
Protein Synthesis Inhibitors
Macrolides
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).
Protein Synthesis Inhibitors
Macrolides
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 .
Protein Synthesis Inhibitors
Macrolides
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).
Protein Synthesis Inhibitors
Macrolides
-1 gm single dose for
Nongonococcal urethritis
Chancroid &
alternative Tt. to Lymphogranuloma
venereum .
(Children – 10 mg /kg / day x 4 days )
Protein Synthesis Inhibitors
Macrolides
Therapeutic Uses :
1 Mycoplasma pneumonia – DOC
2.Legionnairs disease-DOC for pneumonia
3.Chlamydial infection - with any of the
macrolides .( Single 1gm dose of Azithriomycin is
recommended in uncomp. urethritis ,endocervical &
epididymal inf.s(During preg. Erythromyc. 500mg QID x 7 days is the DOC.)
Protein Synthesis Inhibitors
Macrolides
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
acute infections.)
Protein Synthesis Inhibitors
Macrolides
5. Pertusis – DOC for Tt & post exposure
prophylaxis ( 40 mg/kg day –max. 1 gm /day x 7
days ).
6. Streptococ. Inf. –Pharyngitis , scarlet
fever , erysipelas & cellulitis –
responds to macrolides (alternative to
penicillin.)
-Staphylococcal inf.-alternate treatment
for minor infections
Protein Synthesis Inhibitors
Macrolides
7. Campylobacter : in GastroenteritisErythromycin-250-500mg QID x 7days
( Fluoroq.s has replaced ).
8. Helicobacter pylori – Clarythromycin
is given in comb. with Amoxycillin &
Omeprazole.
Protein Synthesis Inhibitors
Macrolides
9. Tetanus – Erythromycin- 500mg orally
6 hrly x 10 days to eradicate Clost.
tetani .( alt. to Penicillin)
( Debridement of wound , physiological support
,Tetanus antitoxin & drug control of convulsions is the
main stay of treatment)
10.Syphilis- Early syphilis (alt. to Penicillin)
but no longer recommended .
Protein Synthesis Inhibitors
Macrolides
11. 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.
Protein Synthesis Inhibitors
Macrolides
Prophylactic Use :
1. For recurrence of Rheumatic fever
(second choice to penicillin.) .
2. For Bacterial 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- MAC
T- Toxoplasma
Protein Synthesis Inhibitors
Macrolides
Side Effect :
Serious S/E are rarely present .
- Fever , Eosinophilia & skin eruption
(disappear after stoppage of therapy)
- Cholestatic 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.)
Protein Synthesis Inhibitors
Macrolides
-Large doses orally associated with
epigastric pain .
-Cardiac arrhythmia ( ↑QT interval with
ventricular tachycardia ) .
-Transient auditory impairment ( by I.V.
large doses ).
(↑ GI motility by acting on Motilin recpt. to ↑ motilin secretion a harmone
present in GI-tract & therefore used post operatively to ↑ peristalsis
& also to improve gastric emptying in gastric paresis in diabetes )
Protein Synthesis Inhibitors
Macrolides
-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 – Erythromycin & Clarythromycin→
↓CYP3A4 microsomal enzyme &
therefore potentiate the effect of Carbamazepine
Cyclosporin
Corticosteroid
Digoxin
Theophylline
& Warferin
when given simultaneously
Valproate
Ergot alkaloids
Protein Synthesis Inhibitors
Macrolides
(Azithromycin is free of these D/I ).
Adverse Effects- Mnemonic
M- Motilin receptor agonists
A - Allergy
C- Choleastasis
R - Reversible
O- Ototoxicity
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 Antibiotics
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
macrolide resistant organisms )
-Approved for multidrug resist. Resp. tract infections.
-It is also an enzyme inhibitor so prone for similar D/I
like Erythromycin .
Miscellaneous & Newer Antibiotics
Clindamycin :
-It is a chlorinated derivative of 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.- B. fragilis,
Fusobacterium, Peptostreptococci & Clostridium perfringes .
( All aerobic G -ve organisms are resistant )
Miscellaneous & Newer Antibiotics
-Good penetration in bone but does not
cross BBB.
S/E - Antibiotic assos.colitis (pseudom. col.)
Skin rashes
Neuromuscular blockade.
Indication- Anaerobic infections e.g.–
abscess,
bacteremias,
empyma ,
pneumonia & prostatitis (reaches prostatic fluid)
- Pneumocystis jiroveci
- Toxoplasma encephalitis & Malaria
Miscellaneous & Newer Antibiotics
GLYCOPEPTIDES :
Vancomycin ( 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 to
the D- Ala –D-Ala terminus of nascent peptidoglycan
pentapeptide . This ↓ the Transglycolase
Miscellaneous & Newer Antibiotics
, preventing further elongation of peptidoglycan &
cross linking & thus cell become susceptible to
lysis.)
-Poor oral abs. so given as I.V. infusion
used orally only for local effect in GIT
-More than 90% excreted by kidney.
Miscellaneous & Newer Antibiotics
S/E :
-Fever , chills ,phlebitis.
- Extreme flushing (
RMS- red man/red neck
syndrome ,due to massive release of histamine by rapid
infusion , other histamine liberators are –Morphine ,
Tubocurarine , Polymixin B )
-Nephrotoxicity
-H/S reactions.
-Ototoxicity
Miscellaneous & Newer Antibiotics
Indications:
-Methicillin resist. staphylococci inf. (MRSA)
-Antibiotic associated colitis.
- Enterococcus endocarditis
-Penicillin resist. Pneumococcal infections.
(dose-1 gm IV 12 hrly, orally 500 mg 6 hrly in pseudm. col.)
Miscellaneous & Newer Antibiotics
Teicoplanin :
Similar to Vancomycin but safe by I.M. route
(very expensive like Vancomycin used only in Vancomycin
allergy)
Cycloserine: ( produced by Streptomyces orchidaceus )
It inhibits cell wall synthesis, effective
orally.
-Used as a second line drug for E. coli
& Tuberculosis .
Miscellaneous & Newer Antibiotics
S/EHeadache (The effects aggravated by alcohol )
Drowsiness
Convulsions
Psychosis
Miscellaneous & Newer Antibiotics
Fusidic 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 .
Miscellaneous & Newer Antibiotics
-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.
Miscellaneous & Newer Antibiotics
Polypeptide Antibiotics:
-They are peptides but lack antigenecity.
( molecular wt. is low).
- They are- Polymixin B
Polymixin E (Colistin )
Bacitracin
Capreomycin
Miscellaneous & Newer Antibiotics
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 .
Miscellaneous & Newer Antibiotics
- 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.
Indication – Local infections of skin , eyes
ears & mucous membrane.
Miscellaneous & Newer Antibiotics
-Colistin is used orally for infective
diarrhea in a child or to alter gut flora in
hepatic failure.
Bacitracin:
-It is bactericidal by inhibiting cell wall
synthesis - It is highly nephrotoxic hence
used locally in combination with Neomycin
and/or Polymixin.( Nebasulf – Neomycin + Bacitracin +
Sulfacetamide , powder / ointment )
Miscellaneous & Newer Antibiotics
Capreomycin: -
-Bacteriostatic
- Second line drug for Tuberculosis
- High risk of nephrotoxicity
& vestibular toxicity
Miscellaneous & Newer Antibiotics
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.
Miscellaneous & Newer Antibiotics
Quinupristin & 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 .
Miscellaneous & Newer Antibiotics
-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,
streptococcus & pneumococcus infections .
Miscellaneous & Newer Antibiotics
Linezolid :
It is a synthetic oxazolidinone with a
unique site of action i.e.- 23S
ribosomal subunit of 50S ribosome &
its inhibition prevents formation of
70S ribosome complexes & therefore
inhibits the early assembly step in protein
synthesis
Miscellaneous & Newer Antibiotics
-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 but
not against G –ve org.s.
-Indicated as a last resort for MDR Staphylococcal,
Streptococcal & Pneumococcal infections .
Miscellaneous & Newer Antibiotics
( Other latest ones are- Radezolid & Torezolid both are in phase III cl.
trial . 4-6 times more active against- staphyl. , enterococ.& anaerobes.)
S/EGI upset
Skin rashes
Headache
↓platelet count hence ↑risk of bleeding
Week MAO ↓ that may lead to the cheese
reaction .
Miscellaneous & Newer Antibiotics
Fosfomycin:
-It ↓ cell wall synthesis & transported by
G6PD transport system .
-Used for selective cases of UTI .
-It is safe in pregnancy .
Miscellaneous & Newer Antibiotics
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.
Miscellaneous & Newer Antibiotics
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 &
Streptococcal infections .
Miscellaneous & Newer Antibiotics
Other Glycopeptides:
Oritavancin & Dalbavancin
-For GISA (glycopeptide intermediate susp.
staphylococcus aureus ) &
-MRSA (methicillin resistant S. aureus ).
Miscellaneous & Newer Antibiotics
Oritavancin is an analog of Vancomycin
also effective against vancomycin resistant
enterococci ( VRE ).
Long t½ permits once a day administration.
Dalbavancin is similar but not effective
against VRE .It has a prolonged retention in
organisms so once a week administration is
sufficient .
Miscellaneous & Newer Antibiotics
Platensimycin :
- It ↓ fab F enzyme , which is required for
fatty acid biosynthesis which is essential
to construct cell membrane .
- Effective for MRSA & VRE.
Miscellaneous & Newer Antibiotics
Pleuromutilins :
Newer class of antibiotic
MOA:
Bind to 50S subunit of ribosomes inhibiting
protein synthesis
Approved Drug:
Retapamulin: Approved in 2007
-Topical antibiotic
-Treatment of skin infections such as impetigo by S. aureus
(methicillin-susceptible only) or S. pyogenes
Miscellaneous & Newer Antibiotics
Macrocyclic antibiotic drugs :
Fidaxomicin ( Dificid*) -2011
-Narrow spectrum bactericidal agent
-Demonstrated selective eradication of
pathogenic Clostridium difficile
-MOA:
Inhibit bacterial enzyme RNA polymerase
Awaiting FDA approval
ANTIMICROBIAL THERAPY
Disease
( Pathogen)
Drugs of First
Choice
Alternative Drugs
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 g
G –ve rods ( aer.)
E.Coli , Proteus ,
Cephsp. I / II g., TMPQuinol.s & Aminog.s
Klebsiella
SMZ .
ANTIMICROBIAL THERAPY
Enterobacter, Serrt.
Shigella
Salmonella
Campyl. jejuni
Brucella sp.
Helico. pylori
Vibrio sp.
TMP-SMZ ,Quinol.s
Imipenem/ Meropen.
Quinol.s
TMP-SMZ , Quinol.s
Cephsp. III g.
Quinol.s , Eryth.
Doxy + Rifamp./ Aminog.
Bismuth + Metronid.+
Tetracyc.or Amoxicil.
Tetracyc . , TMP-SMZ
Antipseud. Penicil.,
Aminog., Cefepime
TMP-SMZ ,Ampicil.
Cefixime, Ceftriaxon.
Chloramph., Ampicil.
Tetracyc., Furazolid.
Chloramph.+ Aminog
or TMP-SMZ
Omepraz. + Amoxicil
or Clarith.
Quinol.s
ANTIMICROBIAL THERAPY
P.aeruginosa
Legionella sp.
Antipseudomonal Penicil. Antipseud. Penicil. +
+ Aminogl.
Quinol.s ,Ceftazidime
Imipenem / Meropenem
or Aztreonam + Aminog.
Erythromycin ( + Rifamp.) Quinol.s ( + Rifamp.) ,
Clarithromycin .
G+ve cocci (aer.)
Strep. pneum.
Penicil.
S.pyog.( gp -A)
Penicil., Clindamy.
S. agalact. (gp. B) Penicil.( + Aminog. )
Viridans Strept.
Penicil.
Ceftriaxone , Cefotax.,
Vancomy., TMP-SMZ,
Eryth., Imipenem/ Mero.
Eryth., Cephsp.( I g )
Vancomycin
Vancomy., Cephsp.
ANTIMICROBIAL THERAPY
Staphyl. aureus
(Beta- lactamase - ve)
Beta-lactamase +ve
Methicil. – resist.
Enterococ. sp.
G-+ve bacilli( aer.)
Bacil.sp. ( non anth)
Listeria sp.
Nocardia sp.
Penicil.
Vancomy., Cephsp.( I g )
Penicillinase resist. Vancomy., Cephsp.( I g )
Penicil.
Vancomycin
TMP-SMZ , Minocyc.
Penicil. + Aminog. Vancomy.+ Aminogl.
Vancomycin
Imipenem / Meropenem,
Quinol.s, Clindamycin
Ampicil.+ Aminogl. TMP-SMZ
Sulfadiazine,
Minocyc. , Imipenem or
TMP-SMZ
Meropenem, Amikacin
ANTIMICROBIAL THERAPY
Anaerobic bact.:
G +ve ( Clostridia
Penicil , Clindamyc.
Peptococ., Actinomyc.
Peptostreptococ.)
Clostr. Difficile
Bacteroides fragilis
Fusobacterium
Mycobacteria:
Mycobact . tubercul.
Vancomycin , Amikacin
Imipenem / Meropenem
Metronidazole
Metronidazole
Clindamyc
Vancomycin , Bacitracin
Chloramph Imipenem/
Meropenem, beta-lactum
beta-lactamase inh.comb
Metronid, Clindamyc. As above
Penicil.
Isoniazid + Rifampin
Streptomyc. , Quinol.s
ANTIMICROBIAL THERAPY
+ Ethambutol
+ Pyrazinamide
Mycobact. Leprae
Multibacillary
Dapsone +Rifampin
+ Clofazimine
Paucibacillary
Dapsone +Rifampin
Mycoplasma pneu. Tetracyc., Eryth.
Chlamydia :
trachomatis
Tetracyc., Eryth.
pneumoniae
Tetracyc., Eryth.
Amikacin , Cycloser.
Ethionamide, PAS .
Azithromyc. , Clarith.
Azithromyc., Ofloxac.
Clindamyc.
Clarythromyc. &
Azithromyc.
ANTIMICROBIAL THERAPY
Spirochetes :
Borellia recur.
Leptospira sp.
Treponema sp.
Doxy. , Penicil.
Penicil.
Penicil.
Eryth. , Chloramph.
Tetracyc.
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
•
•
•
•
•
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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
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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
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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)
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