The document provides an overview of antimicrobial drugs. It discusses the history of antimicrobial drugs from empirical use in ancient times to the modern era beginning in the 1930s. It then covers various topics related to antimicrobial drugs including classification based on organism targeted, mechanism of action, examples of different drug classes, and properties like spectrum of activity. Specific drugs are discussed in more detail like penicillin, its mechanism of inhibiting cell wall synthesis, examples like benzyl penicillin, and its uses and side effects. Other beta-lactam antibiotics and semisynthetic penicillins are also summarized.

1. Anti microbial drugs
Dr. L VASAVI REDDY

2. CONTENTS
• History
• Classification
• Drugs inhibiting cell wall synthesis
• Drugs affecting protein synthesis
• Drugs affecting metabolism
• Drugs acting on DNA gyrase
• Drugs interfering with DNA function
• Drugs interfering with DNA synthesis
• Drugs causing leakage of cell membrane
• Choice of antimicrobial drugs
• Problems arising with AMAs
• Applied aspects
• conclusion

3. Introduction
 Antimicrobial drugs are the greatest
contribution of the 20th century to
therapeutics.
 Their advent changed the outlook of the
physician about the power drugs can have
on diseases.
 They are one of the few curative drugs.
Their importance is magnified in the
developing countries, where infective
diseases predominate.
 As a class, they are one of the most
frequently used as well as misused drugs.

4. Terminology:
 Chemotherapy: use of drugs to treat disease.
 Antimicrobial drugs: interfere with the growth of microbes within a host.
 Antibiotics: a substance produced by microbes in small amounts which inhibits
another microbes.
 Selective toxicity: a drug that kills microbes without damaging host.

5. History
The history of chemotherapy may be divided into 3 phases.
(a) The period of empirical use: of 'mouldy curd' by Chinese on boils,
chaulmoogra oil by the Hindus in leprosy, chenopodium by Aztecs for
intestinal worms, mercury by Paracelsus (16th century) for syphilis,
cinchona bark (17th century) for fevers.
(b) Ehrlich's phase of dyes and organometallic compounds (1890-1935): He developed
the arsenicals--atoxyl for sleeping sickness, arsphenamine in 1906 and neoarsphenamine
in 1909 for syphilis. He coined the term 'chemotherapy' because he used drugs of known
chemical structure (that of most other drugs in use at that time was not known) and
showed that selective attenuation of infecting parasite was a practical proposition.
(c) The modem era of chemotherapy was ushered by Domagk in 1935
by demonstrating the therapeutic effect of Prontosil/, a sulfonamide
dye, in pyogenic infection. It was soon realized that the active
moiety was Para amino benzene sulfonamide, and the dye part was
not essential. Sulfa pyridine (M & B 693) was the first sulfonamide to
be marketed in 1938.

6. The phenomenon
of antibiosis was
demonstrated by
Pasteur in 1877:
growth of anthrax
bacilli in urine was
inhibited by air-
borne bacteria.
Fleming (1929)
found that a
diffusible
substance was
elaborated by
Penicillium
mould which
could destroy
Staphylococcus
on the culture
plate. He named
this substance
penicillin but
could not purify
it.
Chain and Florey
followed up this
observation in
1939 which
culminated in the
clinical use of
penicillin in 1941.
Because of the
great potential of
this discovery in
treating war
wounds,
commercial
manufacture of
penicillin soon
started.
In the 1940s,
Waksman and his
colleagues
undertook a
systematic search
of Actinomycetes
as source of
antibiotics and
discovered
streptomycin in
1944. Soon
tetracyclines,
chloramphenicol,
erythromycin and
many others
followed.
All three
groups of
scientists,
Domagk,
Fleming-
Chain-Florey
and Waksman
received the
Nobel Prize
for their
discoveries.

7. A. Type of organisms against which primarily active
1. Antibacterial: Penicillin, Aminoglycosides, Erythromycin, etc.
2. Antifungal: Griseofulvin, Amphotericin B, Ketoconazole, etc.
3. Antiviral: Acyclovir, Amantadine, Zidovudine, etc.
4. Antiprotozoal: Chloroquine, Pyrimethamine, Metronidazole, Diloxanide, etc.
5. Anthelmintic: Mebendazole, Pyrantel, Niclosamide, Diethylcarbamazine, etc.
CLASSIFICATION:

8. C. Mechanism of action
1. Inhibit cell wall synthesis: Penicillin, Cephalosporins, Cycloserine, Vancomycin, Bacitracin.
2. Cause leakage from cell membranes: Poly peptides-Polymyxins, Colistin, Polyenes-Amphotericin B, Nystatin,
Hamycin; Azoles-keconozole ,fluconazole,itraconozole
3. Inhibit protein synthesis: Tetracycline, Chloramphenicol, Erythromycin, Clindamycin, Linezolid.
4. Cause misreading of m-RNA code and affect permeability: Aminoglycoside, Streptomycin, Gentamicin, etc.
5.Inhibit DNA gyrase: Fluoroquinolones Ciprofloxacin and others.
6.Interfere with DNA function: Rifampicin, Metronidazole.
7.Interfere with DNA synthesis: Acyclovir, Zidovudine.
8.Interfere with intermediary metabolism: Sulfonamides, Sulfones, PAS, Trimethoprim, Pyrimethamine,
Ethambutol.

9. 1. Sulfonamides and related drugs: Sulfadiazine and others, Sulfones-Dapsone (DDS), Paraaminosalicylic acid (PAS).
2. Diaminopyrimidines: Trimethoprim, Pyrimethamine.
3. Quinolones: Nalidixic acid, Norfloxacin, Ciprofloxacin, Gatifloxacin, etc.
4. Lactam antibiotics: Penicillins, Cephalosporins, Monobactams, Carbapenems.
5. Tetracyclines: Oxytetracycline, Doxycycline, etc.
6. Nitrobenzene derivative: Chloramphenicol:
7. Aminoglycosides: Streptomycin, Gentamycin, Amikacin, Neomycin, etc.
8. Macrolide antibiotics: Erythromycin, Clanthromycin, Azithromycin, etc.
9. Lincosamide antibiotics: Lincomycin:-, Clindamycin.
10. Glycopeptide antibiotics: Vancomycin Teicoplanin.
11. Oxazolidinone: Linezolid.
12. Polypeptide antibiotics: Polymyxin-B, Colistin, Bacitracin, Tyrothricin.
13. Nitrofuran derivatives: Nitrofurantoin, Furazolidone.
14. Nitroimidazoles: Metronidazole, Tinidazole etc.
15. Nicotinic acid derivatives: Isoniazid, Pyrazinamide, Ethionamide.
16. Polyene antibiotics. Nystatin, Amphotericin-B, Hamycin.
17. Azole derivatives: Miconazole, Clotrimazole, Ketoconazole, Fluconazole.
18. Others: Rifampin, Spectinomycin, Sod fusidate, Cycloserine, Viomycin, Ethambutol, Thiacetazone, Clofazimine, Griseofulvin.
Based on chemical structure

10. Based on Spectrum of activity:
Narrow-spectrum: Penicillin G, streptomycin, erythromycin
Broad-spectrum: Tetracyclines Chloramphenicol
Antibiotics are obtained from:
Fungi: Penicillin Cephalosporin
Bacteria: PolymyxinB Colistin Bacitracin
Actinomycetes: Aminoglycosides Tetracyclines Chloramphenicol GriseofulvinTyrothricin
Aztreonam Macrolides Polyenes

11. Primarily bacteriostatic: sulfonamides
Erythromycin Tetracyclines Ethambutol
Chloramphenicol Clindamycin Linezolid
Primarily bactericidal: Penicillins
Cephalosporins Aminoglycosides Vancomycin
Polypeptides Nalidixic acid Rifampin
Ciprofloxacin Isoniazid Metronidazole
Pyrazinamide Cotrimoxazole.
Based on action:

12. Drugs inhibiting cell wall synthesis:
mnemonic drug Step in cell wall
synthesis inhibited
Binds Beta lactum antibiotics transpeptidase
Bacterial Bacitracin Dephosphorylation of
bactoprenol
Cell Cycloserine Alanine racemase and
alanine ligase
Vall Vancomycin transgylcosylase
Firmly Fosfomycin Enol pyruvate
transferase

14. BETA LACTUM
ANTIBIOTCS
Beta lactam antibiotics are those drugs that contain B-
lactam ring in their structure. These drugs act by inhibiting
the cell wall svnthesis and include
 Penicillins
 Cephalosporins
 Monobactams eg aztreonam
 Carbapenems and s imipenem
All Betalactam antibiotics are bactericidal drugs

15. PENCILLINS:
 Penicillin was originally
extracted from the mould
Penicillium notatum but now it is
extracted from its related mould
Penicillium chrysogenum due to
its high yield. Penicillin consists
of thiazolidine ring fused with a
beta lactam ring which is
essential for its antibacterial
activity. These two rings forms a
nucleus named as 6-
aminopenicillanic acid.

17. Benzyl penicillin
 It is the most potent β-lactam antibiotic and inhibits the growth
of susceptible microorganism in vitro in lowest concentration and
is available in water soluble sodium and potassium salts.
 Penicillin is effective against gram positive and negative cocci and
some gram positive bacilli. Among the cocci, streptococci are
highly sensitive. Gonococci, pneumococci and meningococci are
sensitive to penicillin.
 Among the bacilli, gram positive Bacillus anthracis,
Corynebacterium diphtheriae, Clostridium species are highly
sensitive. Among the spirochetes, Treponema pallidum is highly
sensitive to penicillin.Gram negative bacilli, fungi, protozoa,
rickettsiae, chlamydiae, viruses and Mycobacterium tuberculosis
are totally insensitive to penicillin.
Pharmacokinetics
 After oral administration, benzyl penicillin is destroyed by gastric
acid. It is mainly absorbed from the duodenum.
 It is absorbed in aqueous solution rapidly after intramuscular or
subcutaneous administration. Penicillin is widely distributed in the
body after absorption and approximately 60% of plasma penicillin
is bound to albumin. The major portion is rapidly excreted by the
kidney mainly by tubular secretion and small amounts appear in
bile, saliva, and milk.

18.  Adverse Effects
 The penicillins are nontoxic and remarkably safe drug.
 The hypersensitivity reaction leading to anaphylaxis is
only major problem which is seen in approximately 5 to
10% of the patients taking penicillin. The minor adverse
effects include nausea, vomiting, pain and inflammation
at the site of injection after intramuscular
administration has been reported. After intrathecal
administration (which is a contraindication) it may lead
to convulsions, arachnoiditis and encephalopathy.
 The major side effect is allergic reactions and
anaphylaxis which is characterized by skin rash, pruritus,
serum sickness like syndrome, eosinophilia,
angioneurotic edema, asthma, haematuria, albuminuria,
haemolytic anemia, granulocytopenia and anaphylaxis.
 To avoid that, a skin test using a 10,000 U of benzyl
penicillin per ml is to be done and if any local edema or
wheal occurs within 15 minutes, it is considered to be as
a positive test and in that person penicillin should not be
used.
 Super infections and jarisch-herxheimer reaction(when
used in syphilis patients)

19. Therapeutic Uses
Penicillin G is the drug of choice for the following categories of infection:
 Dental infections: Penicillin G is effective in majority of infections caused by both
aerobic and anaerobic bacteria in dentistry. It is used in acute suppurative pulpits,
pericoronitis, oral cellulitis, necrorotizing ulcerative gingivitis etc. But due to
penicillin resistance, its use in dentistry is restricted.
 Streptococcal infections: Pharyngitis, rheumatic fever, otitis media and even for
subacute bacterial endocarditis.
 Staphylococcal infections: Penicillinase resistant penicillin can be used.
 Meningococcal infections: Meningitis & other infections caused by meningococci.
 Pneumococcal infections: Pneumonia and meningitis.
 Gonococcal infection: Procaine penicillin along with probenecid can be used.
 Sexually transmitted diseases: Penicillin is a drug of choice in the treatment of
syphilis.

20. SEMISYNTHETIC PENICILLINS
 Semisynthetic penicillins are produced by combining the specific
side chains in place of benzyl side chain. They have been
produced to overcome the shortcomings of benzyl penicillin like
poor bioavailability, susceptibility to penicillinase and narrow
spectrum of activity.
ACID RESISTANT ALTERNATIVE TO PENCILLIN G:
 PHENOXYMETHYL PENICILLIN: It has an antibacterial spectrum
similar to benzyl penicillin but is less active. It is gastric acid
stable and effective on oral administration.
 Adverse effects include urticaria, fever, rashes, angioedema,
anaphylaxis, haemolytic anemia, neutropenia, thrombocytopenia,
coagulation disorders, diarrhoea etc. It is used in tonsillitis, otitis
media, erysipelas, prophylaxis of rheumatic fever and
pneumococcal infections.

21. PENICILLINASE RESISTANT PENICILLIN
 It is resistant to degradation by penicillinase. Mainly it exhibits activity
against gram positive microorganisms and is useful against penicillinase
producing Staph. Aureus
 CLOXACILLIN It has an isoxzalyl side chain and has weaker antibacterial
activity than benzyl penicillin. It is absorbed after oral administration
partially and elimination occurs mainly by kidney and partly by liver. It is
devoid of any serious side effect but can cause hypersensitivity reaction in
some patients. Other analogs of cloxacillin are dicloxacillin and flucloxacillin.
They are relatively less protein bound, however, dicloxacillin gives
approximately double the blood level than cloxacillin
 METHICILLIN: highly penicillinase resistant but not acid resistant-must be
injected.due to emergence of MRSA these became insensitive.

22. EXTENDED SPECTRUM PENICILLINS
 They have broad antibacterial spectrum and are effective against both gram
positive and gram-negative organisms. They are hydrolysed by penicillinase.
 AMPICILLIN:
 It is a broadspectrum penicillin which is not destroyed by gastric acid but is
penicillinase susceptible.
 It is more effective than benzyl penicillin against a variety of gram negative
microorganisms. After oral administration it is readily but incompletely absorbed
and food interferes with its absorption.
 Peak plasma level are reached within two hours after oral administration and one
hour after IM administration. It is excreted in urine in unchanged form and high
amount is also present in the bile.
 Adverse effects include skin rash, nausea, epigastric distress, diarrhoea, drug
fever, urticaria etc.
 It is used in infection caused by susceptible gram positive and gram negative
organisms (respiratory tract, soft tissue, gonococcal, GI and genitourinary
infections), septicaemia, meningitis, chronic bronchitis, otitis media, sinusitis,
invasive salmonellosis and cholecystitis.

23. AMOXYCILLIN
 Amoxycillin is a semisynthetic penicillin, a close congener
of ampicillin and active against gram positive and negative
organisms.
 Its absorption is more complete than ampicillin. Food does
not interfere with its absorption. Its absorption after oral
administration is complete hence less incidence of
diarrhoea. It is eliminated in urine in unchanged form.
 Adverse effects: include nausea, epigastric distress,
diarrhoea, skin rash, urticaria, serum sickness,
thrombocytopenia, leucopenia, eosinophilia etc.
 It is used in respiratory, genitourinary, skin and soft tissue,
ENT infections caused by pneumococci, streptococci,
staphylococci, H. influenzae, E. coli and other susceptible
organisms.
 Also useful in Chlamydia trachomatis in pregnancy,
meningitis due to susceptible strains of gram negative
microorganisms, enteric fever, gonococcal urethritis,
bacteriaemia and septicaemia. Amoxycillin is also used in
chemoprophylaxis during dental procedures.
This Photo by Unknown Author is licensed under CC BY-NC

24.  Amoxycillin is also used in combination with
clavulanate potassium. The formulation of
amoxycillin with clavulanic acid protects
amoxycillin from degradation by beta
lactamase enzymes and effectively extends
the antibiotic spectrum of amoxycillin to
include β lactamase producing bacteria
normally resistant to amoxycillin and other
betalactam antibiotics.
 Amoxycillin along with bromhexine and
carbocisteine is used in bronchitis,
bronchopneumonia, bronchiectasis, sinusitis
and otitis media.
 Amoxycillin along with cloxacillin is used in
lower respiratory tract, skin and soft tissue,
urinary tract and postoperative infections,
osteomyelitis, gynaecological infections,
septicaemia, bacterial endocarditis and
bacterial meningitis.
 Amoxycillin along with probenecid is used in
bacterial septicaemia, skin and soft tissue
infection, acute and chronic respiratory tract
infections.

25. β-LACTAMASE INHIBITORS
CLAVULANIC ACID
 It ‘progressively’ inhibits a wide variety of β-lactamases produced by gram
positive and negative organisms and is obtained from Streptomyces
clavuligerus. It has no antibacterial activity of its own. It is used along with
amoxycillin in various infections as discussed above.
SULBACTAM
 It is another semisynthetic β-lactamase inhibitor used along with ampicillin. It
is related to clavulanic acid both chemically and in activity. Adverse effects
include diarrhoea, rash, pain at site of injection and thrombophlebitis of
injected vein. It is indicated in gynaecological, intraabdominal, skin and soft
tissue infections.

26. ANTIPSEUDOMONAL PENICILLINS
 These are indicated mainly to treat gram negative bacilli infection by pseudomonas, proteus and enterobacter.
 TICARCILLIN: It is derived from penicillin nucleus 6aminopenicillanic acid. It has broad spectrum of activity against both
gram positive and negative organisms. It is more potent than carbenicillin against Pseudomonas.
 Adverse effects include hypersensitivity, thrombocytopenia, neutropenia, leucopenia, pain at the site of injection and GI
disturbances. It is indicated in bacterial septicaemia, skin and soft tissue infections, acute and chronic respiratory tract
infections.
 CARBENICILLIN: It is a penicillinase susceptible and is principally indicated for serious infection caused by Pseudomonas
aeruginosa. It is effective against certain other gram negative bacilli including Proteus species and Bacteroides fragilis.
Adverse effects include platelet dysfunction, hypokalemia and hypersensitivity reaction.
 It is indicated in bacteriaemia, septicaemia, genitourinary and respiratory tract infections, endocarditis and
postoperative infections caused by pseudomonas or proteus
 PIPERACILLIN :The unique advantages of piperacillin are broad spectrum of antibacterial activity and excellent
antipseudomonal activity. They have a synergistic effect with aminoglycosides (e.g. gentamicin or netilmicin) and hence
should be given concomitantly in pseudomonas septicaemia. They should however, not be mixed in the same syringe.
Owing to the sodium content, high doses may lead to hypernatremia.
 Adverse effects include platelet dysfunction leading to bleeding, superinfection, local pain and thrombophlebitis. It is
indicated in systemic and local infections, gynaecological infections, UTI, RTI, neonatal and lifethreatening paediatric
infections, burns and septicaemia caused by susceptible organisms.

27. cephalosporins
oral parentral oral parentral oral parentral Fourth
generation
Fifth
genration
Cephalexin
Cephadroxil
cepharidine
cefazolin Cefaclor
Cefuroxime
loracarbef
Cefuroxime
Cefotetan
Cefoxitin
cefmetazol
e
Cefixime
Cefpodoxim
e
Cefibuten
Cefotaxime
Ceftriaxone
ceftizoxime
Cefipime
cefipirome
Ceftaroline
ceftobiprol
e
First generation Second generation Third generation

28.  First Generation These are active against positive gram cocci including
staphylococcus. MRSA is resistant to cephalosporins also. Cefazolin is the drug
of choice for surgical prophylaxis
 Second Generation group of drugs is less active against gram positive
organisms than first generation agents but has extended large negative
coverage. Cefotetan, cefmetazole and cefoxitin are against anaerobes like
Bacteroides fragilis. Cefuroxime attains higher CSF levels as compared to
other second genenation drugs.

29. Third generation
 these are active against gram negative organisms resistant to other beta
lactam antibiotics.
 They can penetrate the blood brain barrier(except cefoperazone and
cefixime),
 Ceftazidime (maximum), ceftolozane, cefoperazone are active against
P'seudomonas.
 Ceftriaxone is the first choice drug for gonorrhea, salmonellosis e coli
proteus and heamophillus.
 Loong term use of ceftraixone is associated with biliary sludging syndrome.
 Most of these drugs are reserved for serious infection.

30.  Fourth generation drugs possess activity against gram negative organisms
including Pseudomonas) resistant to 3rd generation cephalosporins.their
efficacy against gram negitive cocci is similiar to 3rd generation. however, these
are not active against anaerobes.
 Fifth Generation Ceftaroline and ceftobiprole are fith generation cephalosporins
approved for treatment of community acquired pneumonia and MRSA infections
Cetobiprole is also effective against MRSA and
 Most cephalosporins are excreted via kidney through Ceftriaxone and
cefoperazone are secreted in the bile. tubular secretion Nephrotoxicity of these
drugs is increased with diuretics.
 Toxicity: Cephalosporins can cause hypersensitivity reactions. there is complete
cross-reactivity between different cephalosporins and also 5-10% cross-
reactivity with penicillins.
 Drugs containing a methylthiotetrazole group like cefamandole, cefoperazone,
moxalactam and cefotetam may cause hypoprothrombinemia (bleeding) and
disulfiram like reaction. ceftazidime is implicated in causing neutropenia

31. Vancomycin
 Vancomycin is a bactericidal glycopeptide antibiotic that inhibits cell wall synthesis by inhibiting
transglycosylase enzyme (involved in chain elongation). It is narrow spectrum.
 Vancomycin is drug of choice for MRSA, Corynebacterium jeikeium,Serious infections in penicillin
allergic patients
 Teicoplanin is another glycopeptide with similar characteristics but can be given once daily due to
long t1/2(45-70 hours). They are administered parenterally (vancomycin by i.v route and teicoplanin
by i.v. or i.m. route) and unchanged in urine are excreted
 Rapid i.v. infusion of high dose vancomycin cause RED MAN SYNDROME (diffuse flushing due to
histamine release). It is the most common adverse reaction to vancomycin.
 Other toxic effects of vancomycin are chills, ototoxicity and nephrotoxicity. Its dose should be
decreased in renal failure. Teicoplanin does not cause red man syndrome or nephrotoxicity
 it is used orally to treat pseudomembranous colitis by Clostridium difficile because it is absorbed
from the gastrointestinal tract and higher concentration reaches the colon.
 Vancomycin resistance to enterococci and staphylococcus aureus develops because of terminal
replacement Alanine-Alanine by peptidoglycan. It decreases affinity for transglycosylase .

32. Monobactums
 Aztreonam It is a novel ß-lactam antibiotic in
bactam.
 It inhibits gram-negative enteric bacilli and
H. influenzae at very low concentrations and
Pseudomonas at moderate concentrations
 It is resistant to gram-negative B-
lactamases
 The main indications of aztreonam are
hospital acquired infections originating from
urinary, biliary, gastrointestinal, and female
genital tracts
 Lack of cross sensitivity with other beta-
lactam antibiotics appears to be the most
promising feature of aztreonam: allowing its
use in patients allergic to penicillins or
cephalosporins
 There is no specific indication of aztreonam
in dentistry It is eliminated in urine of 1.8
hours

33. Carbapenems:
 These include imipenen, doripenem, meropenem and ertapenem. These have wide
spectrum of activity including gram positive cocci, gram negative rods as well as
anaerobes.
 For the treatment of pseudomonas (meropenem is most whereas ertapenem is least)
infections, these drugs should be combined with aminoglycosides.
 Carbapenams are B-lactamase resistant and are drugs of choice for Enterobacter
Klebsiella and Acinetobacter species.
 These are the only B-lactams which are reliably efficacious against ESBL (extended
spectrum B-lactamase) producing organisms and are thus drug choice for ESBL-
producing bacteria.
 Imipenem is rapidly inactivated by renal dehydropeptidase I, it is combined with
cilastatin, an inhibitor of this enzyme Cilastatin increases the half life of imipenem and
also inhibits the formation of nephrotoxic metabolite.
 Main effects of the combination include seizures and gastrointestinal distress.
Meropenem, doripenem and ertapenen are not metabolised by renal
dehydropeptidase and are less likely to be cause seizures. Ertapenem is very long acting
and is inactive against Pseudomonas.

34.  FOSFOMYCIN: inhibits cell wall synthesis by
inhibiting enolpyruvate transferase.
Diarrhea is quite common with its use. It is
drug of choice (along with nitrofurantoin),
for uncomplicated urinary tract infections.
 BACITRACIN: It also inhibits cell wall
synthesis but of marked nephrotoxicity,
indicated only for topical use. It is
selectively active against gram positive
bacteria
 CYCLOSERINE: also inhibits cell wall
synthesis. It has potential neurotoxic
effects (tremors and seizures). It also
causes neuropsychiatric symptoms. It is
one of the second line of drugs for the
treatment of tuberculosis

35. Drugs inhibiting protein synthesis
DRUGS BINDS TO MOA
1 Aminoglycosides Several sites at 30s and 50s
subunits as well as to their
interface
Freezing of initiation
Interference with
polysome formation
2 Tetracyclines 30s ribosome Inhibit aminoacyl-tRNA
attachement to A site
3 Chloramphenicol 50s ribosome Inhibits peptidyl
transferase
4 Macrolides,
lincosamides,
streptogramins
50s ribosome Inhibits translocation of
peptide chain
5 Linezolid 23s fraction of 50s ribosome Inhibits initiation

37. CHLORAMPHENICOL:
 It is a bacteriostatic drug with wide spectrum of antimicrobial activity.
 Chloramphenicol undergoes enterohepatic circulation and is mainly inactivated by
hepatic glucuronidation.
 Earlier, it was the drug of choice for typhoid fever (interic fever) but due to the
development of resistance, ceftriaxone or ciprofloxacin are now the preferred drugs.
It is also active against anaerobes.
 Due to its wide spectrum, it may cause superinfection diarrhea. It can also cause
dependence and reversible bone marrow suppression as well as idiosyncratic
irreversible myelosuppression (can occur even after ocular administration).
 Neonates and premature infants are deficient in hepatic glucuronyl and because they
are excreted in the kidney after glucuronidation, these are very sensitive to its
toxicity. In such patients, it may lead to gray baby syndrome characterized by
decreased RBCs, cyanosis and cardiovascular collapse.

38. TETRACYCLINES
 These are classified into three groups :
 Group I: Tetracycline, chlortetracycline, oxytetracycline
 Group II: Demeclocycline, lymecycline
 Group III: Doxycycline, minocycline
 Pharmacokinetics: Oral absorption tetracyclines is impaired by food and
multivalent cations (calcium, iron, aluminum etc.). Yoghurt decreases the
absorption of tetracyclines because it contains cations like calcium and
magnesium.
 Tetracyclines cross the placenta and affect the fetus, administered to a
pregnant female All tetracyclines are excreted primarily in the urine except
doxycycline.
 Thus Half life of doxycycline and minocycline is longer than other.

39.  Tetracyclines are broad spectrum bacteriostatic drugsTetracyclines are first
choice drugs. All tetracyclines undergo enterohepatic circulation can be used
in the presence of renal failure.
 Clinical Uses: Lymphogranuloma venereum (LGV) Granuloma inguinale Atypical
pneumonia due to chlamydia (Now preferred drug is azithromycin). Cholera.
Plague prophylaxis (Drug of choice for treatment) Relapsing fever
(Doxycycline) Brucellosis (with rifampicin) streptomycin) Lyme's disease
(Doxycycline) Rickettsial infections (Doxycycline) Chlamydial infections
(Doxycycline).
 For local drug delivery in dental use it is available as tetracycline fibres and
sub antimicrobial dose doxycycline(periostat)

40. Toxicity: Tetracyclines may cause superinfection, diarrhea,
pseudomembranous colitis.
 Gastrointestinal side effects most common adverse effects.
These are contra-indicated in pregnancy due to the risk of fetal
tooth enamel dysplasia and irregularities in the fetal bone
growth.
 Treatment of young children (<8 years) with tetracyclines may
cause dentition abnormalities. Doxycycline is less likely to cause
this adverse effect.
 High dose of tetracyclines may lead to hepatic necrosis especially
in pregnant females.
 Outdated drugs may lead to lead to Fanconi's syndrome (type of
renal tubular acidosis).
 Tetracyclines may exacerbate pre-existing renal dysfunction
though these are not directly nephrotoxic.
 Demeclocycline (maximum) and doxycycline can result in
photosensitivity.
 Minocycline may lead to dose dependence vestibular toxicity.
 Diabetes insipidus may be precipitated by ADH antagonistic
action of demeclocycline.
 Tetracyclines also possess anti-anabolic effects.

41. MACROLIDES:
 These antibiotics large cyclic lactone ring
structure with attached sugars. The drugs included
in this group are erythromycin, azithromycin,
roxithromycin and clarithromycin. An
immunosuppressant drug, tacrolimus also a
macrolide. antibiotic
 Pharmacokinetics: These drugs are well absorbed
orally. Erythromycin is excreted by biliary route
and clarithromycin by both renal and biliary
routes. Excretion of azithromycin is slow (longest
half life) and mainly in the urine. Erythromycin
administered four times a day whereas
azithromycin is administered as a single daily
dose.

43.  Clinical Uses: Macrolides are the drug of choice for Chancroid (Azithromycin single dose),
Corynebacterium. Legionella infections Atypical pneumonia Whooping cough. It is also used for
diphtheria and the infections caused by chlamydia and gram positive organisms (as second choice
drugs to penicillins).
 Azithromycin has similar spectrum but is more active. against H. influenza and Neisseria. Because of
its long t1 / 2, a single dose is effective in the treatment of urogenital infections and trachoma
caused by chlamydia. It can be used once weekly in the prophylaxis of MAC infections.
 Roxithromycin has similar spectrum that azithromycin
 Clarithromycin is approved for the prophylaxis and treatment of Mycobacterium avium complex and
in the treatment of peptic ulcer caused by H. pylori.
 Macrolides have anti-inflammatory action due to their effect on neutrophils and inflammatory
cytokines. This action is responsible for the use of macrolides in the prevention of cystic fibrosis
exacerbation Spiramycin is another macrolide antibiotic that is the drug of choice for the treatment
of toxoplasmosis in pregnancy. Fidaxomycin is a non-absorbed macrolide approved for treatment of
C. difficile infection.
 Erythromycin, roxithromycin and clarithromycin inhibit CYP3A4. If you are taking ciprofloxacin
(CYP3A4 substrates), these drugs may cause prolonged QT interval and serious polymorphic
ventricular tachycardia (torsades de pointes).
 Azithromycin is not an enzyme inhibitor and is free from these drugs. Intravenous erythromycin (not
oral) can cause dose dependent reversible ototoxicity. Erythromycin also increases plasma
concentration of theophylline by inhibiting CYP1A2. Mnemonic Adverse Effect of Macrolides M
Motilin receptor agonists A Allergy c Cholestasis R Reversible Ototoxicity

44. LINCOSAMIDES
 This group includes clindamycin and lincomycin. These have same mechanism of action
as macrolides.
 Main use of clindamycin is against anaerobes like bacteroides and propionbacterium
(responsible for acne).
 It is also a drug of choice for treatment of severe, invasive group A streptococcal
infections along with penicillin. It was also active against Pneumocystis jiroveci
(previously called P. carnii) and Toxoplasma gondii.
 It is used as an alternative to amoxycillin or ampicillin for prophylaxis against
endocarditis following dental procedures.
 It was the most common antibiotic implicated causing pseudomembranous colitis but
now second and third generation cephalosporins (particularly cefotaxime, cefuroxime,
ceftriaxone and ceftazidime) are most frequently responsible.
 It can also cause hepatic dysfunction.

45. AMINOGLYCOSIDES
 These include streptomycin, gentamicin, kanamycin, tobramycin,
amikacin, sisomicin, netilmicin, neomycin drugs exhibit CDK and have
prolonged PAE, therefore are administered as single daily dose.
 Pharmacokinetics: These are not absorbed orally and do not cross blood
brain barrier. These are excreted primarily by glomerular filtration and
the dose should be decreased in renal insufficiency.

46. Clinical Uses.
 Gentamicin, tobramycin and amikacin are effective against gram negative organisms
including pseudomonas (except salmonella). However, these are not reliable for gram
positive organisms.
 Aminoglycosides produces synergistic effects against gram positive bacteria when
combined with beta-lactums or vancomycin.
 Streptomycin is the first line drug for the treatment of tuberculosis,plague and
tularemia.
 Amikacin is a second line drug for the treatment of tuberculosis and is also used in MDR
tuberculosis.
 Netilmicin is used for serious infections .Neomycin and framycetin are used only
topically because of their high toxic potential.
 Neomycin can also be used orally for gut sterilization in hepatic encephalopathy.
 Spectinomycin is a drug related to aminoglycosides, which is used as a single dose
treatment for penicillinase producing Neisseria gonorrhea (PPNG) and for gonorrhea in
penicillin -allergic patients

47. Toxicity
 Ototoxicity: It can occur due to damage to hair cells. This
adverse effect is more likely with prolonged use, high serum
concentrations (especially with renal impairment),
hyopovolemia and other ototoxic medications.
 Nephrotoxicity: It results from toxicity to proximal tubular
cells and is almost always reversible. Risk factors for
nephrotoxicity include hypokalemia, pre-existing renal
disease and concomitant nephrotoxic medications (like AMB,
vancomycin etc.).
 Neuromuscular blockade: This adverse effect can lead to rare
but severe respiratory depression. It can occur due to
inhibition of pre-synaptic release of ACh and partly by
decreased sensitivity of post-synaptic receptors and
hypocalcemia, peritoneal administration, use of
neuromuscular blockers and pre-existing respiratory
depression of risk factors.
 This complication can be avoided by slow i.v. infusion (over
30 min.) by i.m. route. If respiratory depression occurs, it is
reversed by i.v, administration of calcium.

48. maximum minimum
nephrotoxicity Neomycin>gentamicin streptomycin
ototoxicity Amikacin(auditory) netilmicin
Streptomycin(vestibular)
Neuromuscular
blockade
Neomycin>streptomycin tobramycin

49. ANTIMETABOLITES
 The drugs that are able to interfere with the role of
an endogenous compound cellular metabolism are
called antimetabolites
 This includes sulfonamides, trimethoprim,
pyrimethamine proguanil and methotrexate

50. SULFONAMIDES
 Function: These drugs are bacteriostatic agents and act by inhibiting folate synthase
competitively
 The selective toxicity to bacterium is due to the reason that mammalian cells do not
synthesize folic acid and utilize preformed folic acid in the diet
 Sulfonamides are not effective in the presence of pus because it contains a large
amount of PABA.
 These drugs undergo hepatic metabolism by ACETYLATION) and can cause SLE which
may result in precipitation of the drug causing crystalluria .
 Risk is minimum with soluble drugs like sulfisoxazole
 Sulfadoxine is longest acting while sulfacytine is shortest acting sulfonamide.

52. clinical Uses: Sulfacetamide is used for ocular infections whereas mafenide and silver
sulfadiazine are used in patients as topical agents.
 Sulfadiazine can be used for nocardiosis and sulfisoxazole for urinary tract
infections.
 Sulfasalazine and olsalazine are used for the treatment of ulcerative colitis.
Sulfadoxine plus pyrimethamine is used for malaria.
 Sulfadiazine and pyrimethamine combination can be used for the treatment of
toxoplasmosis and prophylaxis Pneumocystis jiroveci pneumonia in AIDS patients.
 Silver sulfadiazine is also used for fungal keratomycosis.
Toxicity: rash due to hypersensitivity is the most common adverse effect. These can also
cause granulocytopenia, thrombocytopenia and aplastic anemia (more common in HIV-
infected patients).
Sulfonamides can cause acute hemolysis in patients with G-6 PD deficiency These can
precipitate in the urine at acidic and may displace bilirubin from plasma protein binding
resulting in crystalluria and hematuria.
Causes kernicterus in the new born (if given in third trimester of pregnancy)

53. COTRIMOXAZOLE  This is a fixed dose combination of sulfamethoxazale
trimethoprim in a ratio of 5: 1 / Commercially available double
strength septran contains 800 mg sulfamethoxazole an 160 mg
trimethoprim.
 Both drugs have similar half life and the combination is
bactericidal to most pathogens.
 Due to different bioavailability (more for sulfamethoxazole),
plasma concentration of the two drugs attained is 20: 1.
 The bactericidal activity is due to sequential blockade at two
steps in the DNA synthesis (sulphamethoxazole inhibits folate
synthase and trimethoprim inhibits DHFRase).
 Cotrimoxazole is effective UTI, respiratory tract infections,
MRSA, middle ear and sinus infections caused by hemophilus
and moraxella.
 It is the drug of choice for pneumocystosis and nocardiosis.
Adverse effects are similar to sulfonamides and trimethoprim.
Indications of Cotrimoxazole - STD's (Chancroid, LGV) ts) .E-
Enteritis (E.coli, Shigella) Typhoid RTI Acute uncomplicated UTI .

54. Drugs inhibiting DNA gyrase:
FLUOROQUINOLONES:
 These drugs have long PAE.
 Important drugs in this group include norfloxacin, lomefloxacin, ciprofloxacin, ofloxacin,
levofloxacin, gatifloxacin, pefloxacin, sparfloxacin, moxifloxacin, fleroxacin, garenoxacin,
gemifloxacin and trovafloxacin
 Pharmacokinetics: These have good oral bioavailability (except norfloxacin) but like
tetracycline multivalent cations, interfere with absorption, and they have no excretion.
 Pefloxacin is excreted by both renal and hepatic route
 All other drugs (ciprofloxacin, gatifloxacin, levofloxacin, lomefloxacin, norfloxacin and
ofloxacin) are excreted by tubular secretion in the kidneys
 Probenecid inhibits tubular secretion of these drugs
 Dose adjustment is required in renal disease for all fluoroquinolones except pefloxacin,
and trovafloxacin .
 Sparfloxacin (followed by moxifloxacin) has longest half-life among fluoroquinolones

56. Clinical Uses
 Quinolones are the oral agents with greatest activity pseudomonas (maximum with
ciprofloxacin)
 First generation drugs like norfloxacin have narrow spectrum.
 The concentration of norfloxacin reached in urine bactericidal, thus it can be used for
UTI but it is effective for systemic use.
 Second generation drugs like ciprofloxacin and ofloxacin are effective against
gonorrhea and other gram negative organisms including pseudomonas.
 Ciprofloxacin is the drug of choice for prophylaxis and treatment of anthrax and for
prophylaxis of meningococcal meningitis.
 Ciprofloxacin and levofloxacin are the only fluoroquinolones effective against
Pseudomonas.
 Levofloxacin is l-isomer of ofloxacin and is effective against infections caused by
atypical microorganisms like mycoplasma.

57.  Sparfloxacin has greater activity against gram positive organisms but is not effective
against pseudomonas
 Levofloxacin, gatifloxacin, gemifloxacin and moxifloxacin are called respiratory
fluoroquinolones due to the enhanced activity against gram positive and atypical
organisms (like chlamydia, mycoplasma and legionella).
 Moxifloxacin and trovafloxacin have widest spectrum including gram negative and
gram positive micro- and organisms as well as anaerobes.
 Fluoroquinolones (ciprofloxacin, levofloxacin and moxifloxacin) are also effective in
tuberculosis and can be used for the prophylaxis of neutropenic patient

58. Toxicity:
 GI distress is the most common side effect followed by CNS ffects (headache and
dizziness; rarely seizures also).
 These may also cause cartilage problems, so they are not advocated in children less than
18 years old and in pregnancy. However, when outweighs risks, these can be indicated
e.g. in adolescent patients with cystic fibrosis who have pulmonary exacerbations Which
is maximum with lomefloxacin and sparfloxacin Tendinitis resulting in tendon rupture can
be seen rarely
 These drugs can also cause phototoxicity.
 Gatifloxacin has recently been withdrawn from India due to its dysglycemic effects.
 Moxifloxacin can also cause hypoglycemia.
 Sparfloxacin and gatifloxacin prolonged QTc interval (grepafloxacin was withdrawn
because of arrhythmias caused due to prolongation of QT interval).
 Gatifloxacin can also result in hypo or hyperglycemia.
 Trovafloxacin has hepatotoxic potential.

59. Drugs inhibiting DNA function
RIFAMPICIN:
 Rifampicin It is a derivative of rifamycin (other derivatives are rifabutin and rifapentine).
 Metabolites are colored and can cause orange discolouration of the urine and secretions. It can
also cause orange staining of contact lens. It is mainly in the feces and can be used safely in
renal dysfunction
 It is the only bactericidal drug active against dormant bacteria in solid caseous lesions Apart
from tuberculosis, it is also used in leprosy (to delay resistance to dapsone). It is the most
effective and fastest acting drug in leprosy.
 It can also be used as a prophylactic drug for meningococcal and staphylococcal carrier states.
It is also hepatotoxic and may cause skin rash, flu like syndrome (more intermittent regimen)
and anemia.
 Rifampicin is an inducer of drug metabolizing enzymes and improves the metabolism of many
drugs like anticonvulsants, oral contraceptives, oral anticoagulants antiretroviral drugs etc.
 Rifabutin has little chances of drug interactions and is equally effective, it is used in the
treatment of tuberculosis in AIDS patients (getting antiretroviral drugs)

60. Metronidazole:
 It is a nitroimidazole. It has broad spectrum protozoal and antimicrobial
activity.
 Active against anerobe infections, c. difficile, h. pylori, bacterial vaginosis,
trichomonas vaginalis, amoeabiasis, giardiasis.
 Side effects include epigastric distress, seizures, mettalic taste, darkening of
urine, peripheral neuropathy, pancreatitis, hepatitis, fever and reversible
netropenia
 Not indicated in pregnancy and lactation
drug Interaction
alcohol Disulfuram like reaction
Anticoagulants Prolonged prothrombin time
Cimetidine Prolonged half life and decreases
clearance
Phenytoin and phenobarbitone Increases metabolism of
metronidazole and decreases serum
concentration

61. Drugs interfering with DNA synthesis:
 Antiviral drugs:Acyclovir and its Congeners is a guanosine
analogue active against herpes simplex virus (HSV-I and 2) and
varicella zoster virus (VZV) Acyclovir is not active against CMV
infections.
 It is activated first by a specific virus kinase (thymidine kinase) to
form acyclovir monophosphate (virus develops resistance due to
mutation of this kinase) and then by host kinases to form
acyclovir triphosphate.
 This product competitively inhibits the action of DNA
polymerase (by competing with CTP) and also gets incorporated
into the DNA and causes chain termination.
 It can be used topically orally or intravenously. It has very short
and requires multiple daily dosing.

62.  It is primarily excreted by kidneys. It is used for the treatment of
mucocutaneous and genital herpes and also for the prophylaxis
of herpes infections in AIDS and immunocompromised patients.
 Parenteral administration for serious herpes infections cause
nephrotoxicity and neurotoxicity (altered sensorium, tremor,
myoclonus, delirium, seizures, etc.) as main dose limiting
toxicities but it does not cause bone marrow suppression.
 Mycophenolate (immunosuppressant) potentiates antiherpes
activity of acyclovir and related drugs depleting intracellular GIP.
It is essential to maintain hydration while the patient is on
acyclovir therapy because dehydration increases its nephrotoxic
potential. Valacyclovir has long half life and is converted to
acyclovir by hepatic metabolism. Famciclovir is a prodrug that
gets converted penciclouir (also developed as a separate drug)
and acts via similar mechanism.

63. Drugs causing leakage of cell membranes
Antifungals:
According to the mechanism of action these can be classified as:
 Drugs altering membrane permeability:
Azoles Triazoles eg. Fluconazole, itraconazole voriconazole, terconazole, posaconazole.
Imidazoles e.g. Ketoconazole, miconazole, clotrimazole, econazole, butoconazole,
oxiconazole, sertaconazole, sulconazole.
Terbinafine, butenafine, naftifine
Polyenes e.g. Amphotericin B, nystatin, hamycin
 Drugs blocking nucleic acid synthesis eg. Flucytosine Drugs disrupting microtubule
function e.g. Griseofulvin
 Drugs inhibiting cell wall synthesis eg. Caspofungin, nikkomycin

64. Amphotericin B
 It the widest antifungal spectrum (except Pseudoallescheria boydit (also called
Scedosporium apiospernmum) and Fusariom] and is the drug of choice or drug of
choice for most systemic fungal infections.
 It can be used intrathecally in fungal meningitis and locally for corneal ulcers and
keratitis.
 Infusion related reactions are seen with this drug and require premedication with
antihistaminics glucocorticoids
 Dose limiting toxicity is nephrotoxicity manifested by renal tubular acidosis,
hypokalemia and hypomagnesemia.
 Infusion of normal saline before giving AMB decreases nephrotoxicity but solution
of AMB should not be made in normal saline (lt is made in dextrose)
 Saline loading Itracona (IL of normal saline infusion before therapy) may decrease
nephrotoxicity It may also result in anemia (due to decreased erythropoietin)
Intrathecal administration may cause seizures and neurological damage. .
Liposomal AMB, colloidal dispersion (ABCD) and lipid complex (ABLC) are lipid
preparations of amphotericin B (costlier than conventional preparations). These
formulations resulted in decreased accumulation of the drug in tissues like kidney,
thus nephrotoxicity is decreased. Some formulations also show decrease incidence
related reactions. However, these new preparations have similar efficacy and
antifungal spectrum as possessed by infusion of conventional preparations

65.  Fluconazole has maximum penetration bi oral bioavailability and CNS g this
group of drugs and kidney as compared to other metabolized by liver. It is t
candidiasis, coccidioidal and cr (co-drug of choice with AMB). It azoles which
are the drug of choice for yp tococcal meningitis
 Itraconazole is the drug of choice (non-meningeal), histoplasmosis, coccidio
for used for sporotrichosis) infections. Its entry in the for biastomycosis
coccidioidomycosis and sporotrichosis (previously KI was is limited, for CNS
fungal infections
 Fluconezole is antifungal DOC for prophylaxis of febrile neutropenia whereas
voriconazole is DOC for treatment Voriconazole has the widest spectrum
among azoles except Mucor and Sporotrichosis) and is the drug of choice
invasive aspergillosis, Fusarium and Scedosporiam
 Adverse reactions of azoles include diarrhea, rash hepatotoxicity in
preexisting liver dysfunction. It is fusionimplicated in prolonging QT interval.
Voriconazole causes visual disturbances like blurred vision, altered color
byperception and photophobia. Long-term use is associated with multistep
phototoxic process followed by actinic keratosis, then squamous cell
carcinoma. Posaconazole is the only azole active against mucormycosis
Isavuconazole is an orphan drug for treatment of aspergillosis and
mucormycosis

66. Griseofulvin
 It is used orally and its oral absorption is increased by fatty meal. It gets
distributed to stratum corneum and acts by interfering the microtubule
function in dematophytes.
 It may also inhibit svnthesis and polymerization of nucleic acids. It is used for
dematophytosis of skin and hair (tinea infections) because it gets
concentrated in keratin.
 It causes gastrointestinal disturbances, photosensitivity and liver dysfunction.
It can use disulfiram like reaction with alcohol.
 Its metabolism induced by phenobarbitone.
Allylamines butenafine.
These are fungicidal agents that act by inhibitin squalene epoxidase resulting in
the decreased ergosterol synthesis.
Inhibition of this enzyme can lead to accumulation
The drugs in this group terbinafine, naftifine and of squalene that is toxic to the
fungus. Main adverse effect of terbinafine is rash and gastrointestinal upset.
Allylamines terbinafine are oral fungicidal drugs.

67. Nystatin
 Obtained from S. noursei, it is similar to AMB antifungal
action and other properties.
 However, because of the higher toxicity, it is used only in
dentistry, topically applied.
 It is 2nd choice drug to clotrimazole for oral thrush, is the
denture stomatitis, antibiotic associated stomatitis,
corticosteroid associated oral candidiasis and
mucocutaneous candidiasis of lips, etc. .
 The 1 lac U (1 mg 2,000 U) tablet is placed in the mouth
dissolve slowly 4 times a day, or it can be crushed and
suspended in glycerine for application on the lesions.
 A bitter foul taste and nausea are the side effects. Given
orally, it is not absorbed; can be used for monilial diarrhea.
 It is effective (but less than azoles) in monilial vaginitis-1 lac
U tab inserted twice daily. Similarly, it is used for corneal,
conjunctival and cutaneous candidiasis in the form of an
ointment.
 No irritation or other side effect is ordinarily. Candidal
resistance to nystatin is not a clinical problem. It is
ineffective in dermatophytosis. MYCOSTATIN 5 lac U tab, 1
lac U vaginal tab,

68. Choice of an antimicrobial agent:
 Age:
Chloramphenicol in new born baby may cause grey baby syndrome and
sulphonamides may cause kernicterus.
Half life of aminoglycosides is prolonged in elderly.
Tetracyclines are contraindicated in children below 6 years as it accumulates in
developing bone and teeth
 Pregnancy:
All antibiotics pose risk to the fetus in pregnancy. Pencillins, most cephalosporins
and macrolides appear safe
 Impaired host defenses:
Bactericidal drugs are must in immunocompromised patients
 Liver function:
contraindicated Required dose reduction
erythromycin chloramphenicol
tetracyclines isoniazid
pyrazinamide rifampicin
pefloxacin clindamycin

69. Renal function: drugs that are secretd in bile need not require dose adjustment as they
can be excreted in feaces. They include pencillins,
rifampicin,lincosamides,doxycycline,erythromycin,ceftriaxone and cefperazone.
Genetic factors:
Antimicrobials producing heamolysis in G-6PD deficient patients are primaquine,
chloroquine, chloramphenicol, nitrofurantoin, fluoroquinolones, dapsone and
sulphonamides.
contraindicated Require dose adjstment
Cephalothin Aminoglycosides
Cephaloridine Amphotericin B
Nitrofurantoin Vancomycin
Nalidixic acid Ethambutol
Tetracyclines( except doxycycline)

70. COMBINED USE OF ANTIBIOTICS: Although
every combination is unique but the general
guidelines are that:
 Two bacteriostatic agents often show
additive effect. Two bactericidal agents
are additive if the organism is sensitive to
both e.g. isoniazid and rifampicin in
tuberculosis.
 Combination of a bactericidal with a
bacteriostatic drug is additive if the
organism has low sensitivity to the cidal
drug e.g. streptomycin + tetracycline for
brucellosis.
 Combination of bactericidal with
bacteriostatic agent is antagonistic if the
organism has high sensitivity to cidal
drug e.g. penicillin + tetracycline (or
chloramphenicol) for pneumococci

71. Problems that arise with AMAs:
 Toxicity
a)Local irritancy. This is exerted at the abscess formation at the site of i.m. Practically all AMAs, especially at site of
administration. Gastric irritation, pain on injection ,thromboflebitis of the injected vein are the erythromycin, tetracyclines,
certain cephalosporins and chloramphenicol are irritants.
b) Systemic toxicity: Practically all AMAs produce dose related and predictable organ toxicities. Characteristic toxicities are
exhibited by different AMAs. Some have a high therapeutic index- doses up to 100-fold range may be given without
apparent damage to host cells. These include penicillins, some cephalosporins and erythromycin.
 Others have a lower therapeutic index-doses have to be individualized and toxicity watched for, e.g. aminoglycosides
8th cranial nerve and kidney toxicity.
a)Tetracyclines: liver and kidney damage, antianabolic effect.
b)Chloramphenicol bone marrow depression.
Still others have a very low therapeutic index-use is highly restricted to conditions where no suitable alternative is available,
e.g
Polymyxin B :neurological and renal toxicity
Vancomycin :hearing loss, kidney damage
Amphotericin B: kidney, bone marrow and neurological toxicity.

72. Hypersensitivity reactions:
Practically all AMAs are capable of causing hypersensitivity reactions.
These are unpredictable and unrelated to dose. The whole range reactions
from rashes to anaphylactic shock can be produced. The most commonly
involved AMAs are-penicillins, cephalosporins,
sulfonamides,fluoroquinolones.
SUPERINFECTION It refers to the appearance of a new infection as a result
of antimicrobial therapy. Superinfection, intestine, respiratory and
genitourinary tracts are common sites for the development of new
infection. The organisms frequently involved are Candida albicans,
Clostridium difficile, Staphylococci, Proteus and Pseudomonas. Clostridium
difficile superinfection may result in pseudomembranous colitis (recently,
monoclonal antibody cephalosporins) for against C. difficile toxin B
(Bezlotoxumab) has been approved reduce the recurrence of C. difficile
infection. Further, due to the loss of commensal flora, there may be
decreased formation K leading to enhanced anticoagulant effects of
warfarin

73. Drug resistance:
 Drug resistance It refers to an
unresponsiveness of microorganism or AMA
and is akin to the phenomenon, tolerance
seen in nomenon higher organisms,
microbes have always been resistant to
certain AMAs.
Natural resistance Acquired resistance
They lack metabolic process or the
target which affected by the particular
drug. This is a group or species
characteristic, e.g. gram-negative
bacilli are normally unaffected by
penicillin G, or M. tuberculosis is
insensitive to tetracyclines. This type of
resistance does not pose a significant
clinical problem
Acquired resistance It is the
development resistance by an organism
(which is sensitive earlier) the use of an
AMA over a period of time. This can
happen with any microbe and is a major
clinical problem

74. DRUG RESISTANCE
It may be developed due to single step mutation (as seen with
streptomycin and rifampicin) or multi step mutation (erythromycin,
tetracycline and chloramphenicol) drug resistance can be transferred
from gene transfer (also called infectious resistance) via conjugation,
transduction or transformation.
 Conjugation: It is due to the physical contact between bacteria and
is responsible for multidrug resistance. This is a very important
mechanism for the development of resistance against
chloramphenicol and streptomycin and microorganism.
 Transduction: It is the transfer of resistance gene through
bacteriophage e.g. penicillin, erythromycin and chloramphenicol
 Transformation: It is the transfer of resistance through the
environment and is not clinically significant e.g. penicillin G.
Resistance once acquired becomes prevalent due to selection of a
widely used antimicrobial agent i.e. antimicrobials allow resistant
organisms to grow preferentiall

75. Mechanism of resistance Drug
Decrease affinity for target MRSA,Vancomycin
Inactivating enzymes Aminoglycosides, Beta lactams, Chloramphenicol
Alternative metabolic pathway Sulfonamides
Decrease permeability Aminoglycosides, Tetracyclines
Efflux pumps Tetracyclines, Erythromycin, Fluoroquinolones

76. Applied aspects:
Periodontal abcess

77. Combination therapy:
 Valuable antibiotic therapies
are amoxicillin and
metronidazole( 250 gms
each , 3 times daily for 8
days) for young and middle
aged patients and
ciprofloxacin-
metronidazole(500 mg of
each twice daily for 8 days)
who frequently harbor
enteric rods subgingivally.
 Metronidazole of 250mg thrice daily was
effective (loesche et al 1982)
 Clindamycin is used for gram negative
anerobic pathogens when allergic to
pencillin
 Ciprofloxocin: At present, it is the only
antibiotic in periodontal therapy to
which all strains of A.
actinomycetemcomitans are susceptible.
 Azithromycin after 7 days of therapy
have shown in Gingival Crevicular Fluid,
above the MIC for A.
actinomycetemcomitans, P. gingivalis
and P. intermediaSlots J. Perio2000,2012

78. Local drug delivery:

79. Antifungals :

80. Antivirals:

81. Antibiotic prophylaxis

82. Conclusion:
 Target definitive therapy to known pathogens.
 Know the contraindications and interactions of drugs.
 Excess use of antimicrobial drugs can develop resistance,
hence important to understand when to use and when not
to.

83. References
 K.D. Tripathi on pharmacology.
 Review of pharmacology by gobind garg and sparsh gupta
 Surender singh on pharmacology.
 Goodman and son. Essentials of pharmacology
 PALLASCH, T. J. (2002). Antifungal and antiviral chemotherapy. Periodontology
2000, 28(1), 240–255.
 Slots J.Selection of antimicrobial agents in periodontal therapy. J Periodontal
Res. 2002 Oct;37(5):389-98.

84. This Photo by Unknown Author is licensed under CC BY