ANTIBIOTICS Presented by Dr.Pavan kumar.G P.G.STUDENT

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ANTIBIOTICS

• Presented by
• Dr.Pavan kumar.G
• P.G.STUDENT

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CONTENTS

• TERMINOLOGY
• HISTORY OF ANTIBIOTICS
• RATIONALE OF DRUG USE
• PATTERNS OF MISUSE
• DRUG LEGISLATIONS
• CLASSIFICATION OF AMAS
• BACTERIAL GROWTH CURVE
• MODUS OPERANDI OF AMAS
• PRINCIPLES OF ANTIBIOTIC DOSING

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• PENICILLINS
• TETRACYCLINES
• METRONIDAZOLE
• ANTIBIOTIC FAILURES
• NON-EFFECTIVE CONDITIONS IN DENTISTRY
• NEWER ANTI-MICROBIAL APPROACHES
• ANTIBIOMA

• DRUG RESISTANCE
• SULFONAMIDES
• COTRIMOXAZOLE
• FLOUROQUINOLONES
• CEPHALOSPORINS
• CHLORAMPHENICOL
• AMINOGLYCOSIDES
• MACROLIDES
• MISCELLANEOUS ANTIBIOTICS
• ANTI FUNGALS ANTI VIRAL DRUGS

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BIBILOGRAPHY

• PHARMACOLOGY THERAPEUTICS FOR DENTISTRY
• ---
  Yagiela. Dowd. Neidle 5th edition
• ESSENTIALS OF MEDICAL PHARMACOLOGY
• ---
  K.D.Tripathi 5th edition
• TEXTBOOK OF MICROBIOLOGY
• ---
  R.Ananthanarayan C.K.J.Paniker
• ORAL MAXILLOFACIAL INFECTIONS
• ---
  Topazian 4th edition
• MICROBIOLOGY AN INTRODUCTION
• ---
  Tortora,Funke,Case 8th edition

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TERMINOLOGY

• DRUG Single active chemical entity present in
  medicine that is used for diagnosis,prevention,tre
  atment/cure of a disease.

• ANTIBIOTICS--Substances produced by micro
  organisms which suppress
• the growth of or kill other micro organisms at
  very low concentrations.
• ANTI MICROBIAL AGENTS Substances produced
  synthetically as well
• As naturally obtained drugs that attenuate micro
  organisms.
• CHEMOTHERAPY Treatment of systemic infections
  with specific drugs
• that selectively suppress the infecting
  microorganisms without significantly
• affecting the host.

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HISTORY

• PERIOD OF EMPIRICAL USE
• Use of mouldy curd by chinese on boils
• Chaulmoogra oil by hindus in leprosy
• Chenopodium by aztecs for intestinal worms
• Mercury by paracelsus for syphilis
• Cinchona bark for fevers

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EHRLICHS PHASE OF DYES
ORGANOMETALLICS (1890-1935)

• If dyes could selectively stain microbes,they
  could be selectively toxic also.
• Atoxyl for sleeping sickness.
• Arsphenamine norarsphenamine for syphilis
• EHRLICH also coined the term Chemotherapy.

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MODERN ERA

• It was in 1929 that ALEXANDER FLEMING by
  serendipity elaborated
• penicillin from the mould of P.notatum.
• DOMAGK in 1935 demonstrated the therapeutic
  effect of PRONTOSIL
• a sulfonamide dye.
• But it was from 1939-41when CHAIN FLOREY
  carried on the studies
• of Fleming which culminated in the use of
  penicillins.
• In 1940s WAKSMAN colleagues developed
  streptomycin from
• actinomycetes.

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THIS IS THE MOST DRUGGED GENERATION
THE MYTH A PILL TO CURE EVERY ILL
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RATIONALE OF DRUG USE

• Need
• Aim
• Knowledge
• Route dosage
• Alternatives
• Duration
• Observations
• Elimination

• Unwanted effects
• Precautions
• Contraindications
• Patients point if view
• Patient

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PATTERNS OF MISUSE

• They are used as drugs of fear to cover for
  potential errors of omission
• or commission thereby prevent a claim of
  negligence.
• In many cases they are given to prevent infection
  to ensure that was
• done to avoid later criticism.
• Inappropriate use of antibiotics in dentistry
  include
• Antibiotic therapy initiated after
  surgery to prevent infection
• Failure to use prophylactic
  antibiotics
• As analgesics in endodontics

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• Overuse in situations in which pts are not at
  risk for metastatic
• infections.
• Treatment of chronic adult periodontitis almost
  totally amenable
• to mechanical therapy.
• Administration instead of mechanical therapy for
  periodontitis.
• Long term administration in th management of
  periodontal disease.
• Antibiotic therapy instead of incision
  drainage.
• Administrations to avoid claims of negligence.
• Administrations in improper situations, dosage
  duration of therapy.

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DRUG LEGISLATIONS

• Under the perview of CHEMICAL PETROLEUM
  MINISTRY.
• But drug controller (Dept. of health family
  welfare) possesses
• the power over the drug the manufacturer.
• Various drug acts include
• Poisons act of 1919
• Dangerous drugs act of 1930
• Drug magic remedies act of 1945
• Drugs cosmetics act of 1940
  amended in 1955,60,62,
• 64,72 1982.

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BACTERIAL GROWTH CURVE
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ANTIBIOTIC MECHANISM OF ACTION

• Inhibition of cell wall synthesis.
• Alteration of cell membrane integrity.
• Inhibition of ribosomal protein synthesis.
• Suppression of DNA synthesis.
• Inhibition of folic acid synthesis.

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PRINCIPLES OF ANTIBIOTIC DOSING

• M.I.C
• Conc. Dependent v/s time dependent antibiotics
• Post antibiotic effects (PAE)
• Microbial persistence regrowth
• Dosing resistance
• Antibiotic loading dose
• Duration antibiotic dosing

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MICROBIAL DRUG RESISTANCE

• Enzymatic inactivation
• Modification/protection of target sites
• Altered cell membrane permeability
• Active drug efflux
• Failure to activate the drug
• Use of alternate growth requirements
• Over production of target sites

• In addition drug resistance can also occur by
  MUTATION or GENE TRANSFER

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SULFONAMIDES

• First AMA effective against pyogenic infections.
• Sulfonamides still of clinical interest are
• Short acting (4-8hrs)
  sulfadiazine
• Intermediate acting (8-12hrs)
  sulfamethoxazole,etc
• Long acting (7days)
  sulfadoxine
• Special purposes
  sulfacetamide sod.,mafenide,
• silver
  sulfadiazine

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• ANTI BACTERIAL SPECTRUM
• Primarily bacteriostatic agent against many
  gramve gram_ve bacteria.
• Organisms still sensitive are St.pyogenes,H.influe
  nzae,H.ducreyi,E.coli,
• V.cholera,Chalydiae,Actinomyces,Nocardia
  Toxoplasma.

PHARMACOKINETICS

• Rapidly completely absorbed from GIT.
• PPB ranges from 10-95.
• Crosses placenta freely.
• Primarily metabolised in liver by ACETYLATION.
• Excreted by kidney through glomerular filtration
• Good penetrability into brain CSF.

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USES

• Suppressive therapy of chronic UTI.
• Streptococcal pharyngitis.
• Second drug of choice in LGV.
• In combination with Trimethoprim for many
  bacterial infections,p.carinii,etc.
• Sulfacetamide sol. (10-30) for trachoma /
  inclusion conjunctivitis.
• Topical Silver sulfadiazine or Mafenide are used
  for preventing infections
• on burn surfaces.

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ADVERSE EFFECTS

• Nausea,vomitting epigastric pain.
• Crystalluria is dose related.
• Hypersensitivity reactions in 2-5
  pts.stevens-johnson syn Exfoliative
• dermatitis are more common with long acting
  agents.
• Topical use is usually not recommended due to
  contact sensitization.

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COTRIMOXAZOLE

• Combination of TRIMETHOPRIM SULFAMETHOAZOLE in
  the ratio
• of 120.
• Both are static but the combination is cidal in
  action.
• Combination is because of similar t1/2 of
  10hrs.
• SPECTRUM
• Active against S.typhi, Serratia, Klebsiella,
  Enterobacteria, P.carinii and
• many sulfonamide resistant strains.

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USES

• UTI Specially valuable in chronic recurrent
  cases in prostitis.
• RTI like chronic bronchitis, facio maxillary
  infections otitis media.
• Second DOC in typhoid.
• Bacterial diarrheas dysentry.
• Chancroid (800mg160mg BD/7 days) is one of the
  DOC.
• Granuloma inguinale alternative to doxycycline/
  erythromycin.
• P.carinii prophylactic as well as therapeutic.

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ADVERSE EFFECTS

• Rarely folate deficiency.
• Contraindicated in pregnancy as trimethoprim
  being an antifolate has
• teratogenic risk. Neonatal hemolysis
  Methemoglobinemia can occur.
• Uremia in patients with renal diseases.
• Bone marrow hypoplasia in AIDS pt. For P.carinii
  infection.
• Cotrimoxazole Diuretics cause higher incidence
  of Thrombocytopenia.

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FLOUROQUINOLONES

• FIRST GENERATION
• Cinoxacin
• Oxolinic acid
• Nalidixic acid

• SECOND GENERATION
• Lomefloxacin
• Ciprofloxcin
• Norfloxacin
• Ofloxacin
• Levofloxacin

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FLOUROQUINOLONES

• 3RD GENERATION
• Gatifloxacin
• Sparfloxacin
• Grepafloxacin
• Pazufloxacin

• 4th GENERATION
• Clinafloxacin
• Gemfloxacin
• Mofifloxacin
• Trovafloxacin

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CIPROFLOXACIN

• Inhibits the enzyme bacterial DNA gyrase which
  nicks double stranded DNA
• introduces _ve supercoils then reseals the
  nicked ends.
• FQ action is similar to Topoisomerase IV .
• This damaged DNA is phagocytosed by exonucleases.
• SPECTRUM
• Most susceptible are aerobic, gram_ve bacilli
  especially Enterobacteriaceac,
• Neisseria, E.coli, S.typhi, K.pneumoniae,
  H.influenzae, H.ducreyi,V.cholera,
• Staph.aureus, P.aeruginosa, B.anthracis,
  M.tuberculosis, etc.

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• Remarkable microbiological features of
  ciprofloxacin other FQs include
• Rapidly bactericidal highly potent.
• Relatively long PAE.
• Low freq. Of mutational resistance
• Protective streptococci anaerobes are
  spared
• Active against B- lactams
  aminoglycoside resistant bacteria
• Less active against acidic pH.
• PHARMACOKINETICS
• Rapidly absorbed orally but food delays
  absorption.
• First pass metabolism occurs.
• High tissue penetrability.
• Excreted primarily in urine.

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INTERACTIONS

• Plasma conc.of Theophylline, caffiene, warfarin
  are increased by C.floxacin.
• NSAIDs may enhance CNS toxicity.
• Antacids, Sucralfate, Fe salts if given
  concurrently reduce absorption.

USES

• UTIs
• Gonorrhoeas
• Chacroid 500mg/BD/3 days . Excellent alt. To
  Cotrimoxazole.
• .
  
  CONTD

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FIRST CHOICE DRUGS IN Typhoid
Bone, soft tissue, gynecological wound
infections Diabetic foot
In combination therapy for T.B
ADVERSE EFFECTS

• GIT symptoms like Nausea, Vomitting, Bad taste.
• CNS dizziness, headache, anxiety,
  insomnia,impairment of concentration
• and dextereit. (CAUTION WHILE DRIVING).

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CEPHALOSPORINS

• 1st generation
• Cefazolin
• Cephalexin
• Cefadroxil
• Cephradine
• Cephalothin

• 2nd generation
• Cefuroxime
• Cefaclor
• Cefoxitin

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CEPHALOSPORINS

• 3rd generation
• Cefotaxime
• Cefoperaxone
• Ceftriaxone
• Ceftazidime
• Cefixime
• Cefdinir

• 4th generation
• Cefepime
• Cefpirome

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EVOLUTION OF CEPHALOSPORINS

• 1st gen developed in 1960s have high activity
  against gramve bacteria.
• 2nd gen more active against gram_VE with some
  active against anaerobes.
• 3rd gen Introduced in 1980s, have highly
  augmented action against gram_ve
• enterobactericeac,
  B-lactamases, less active on gramve cocci.
• 4th gen developed in 1990s spectrum of action
  similar to 3rd gen. Highly
• effective in nosocomial
  pneumonia, febrile neutropenia, bacterimia,
• septicemia,etc.

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USES

• 1ST gen are used as alterntives to penicillin G.
• UTI RTIs
• Penicillinase producing staphylococcal
  infections.Cephalothin is the DOC.
• May be combined with aminoglycosides in
  septicemias.
• 1st gen cephalosporins are used in surgical
  prophylaxis.
• Ceftazidime Gentamicin for Pseudomonas
  meningitis.

• Ceftriaxone is the first DOC in gonorrhea caused
  by penicillinase producing m.o
• As alternative to FQs in typhoid, especially in
  children.
• 3rd gen cephalosporins are used in treatment of
  infections of neutropenic pts.

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ADVERSE EFECTS

• Pain after i.m is very common.
• Hypersensitivity reactions similar to
  penicillins.
• Nephrotoxicity is highest with cephaloridine.
• A ve coombs test occurs but hemolysis is rare.
• A disulfiram like reaction with alcohol has been
  reported with Cefoperaxone.

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CHLORAMPHENICOL

• Initially obtained from St.venezuelae in 1947.
• Has a nitrobenzene substitution.
• Inhibits bacterial protein synthesis by binding
  to 50s.

SPECTRUM

• Primarily static but cidal at high conc.
  against H.influenzae.
• A broad spectrum AMA.

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PHARMACOKINETICS

• Rapidly completely absorbed orally.
• 50-60 PPB t1/2 of 3-5 hrs.
• Crosses placenta secreted in bile milk.
• Undergoes glucoronic acid conjugation in liver
  excreted in urine.

INTERACTIONS

• Inhibits metabolism of Tolbutamide,
  Chlorpropamide, Warfarin, Phenytoin
• and Cyclophosphamide.
• Phenobarbitone, Phenytoin, Rifampin enhance the
  metabolism.

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USES

• Second choice drug in enteric fever.
• H.influenzae meningitis 50-75mg/kg/day/2weeks.
• Prefferred drug for intraocular infections like
  endopthalmitis.
• Topically effective in conjunctivitis, external
  ear infections.
• AS SECOND CHOICE DRUG
• TO TETRACYCLINES in brucellosis,
  cholera, ricketssial chlamydial
• infections in children below 6yrs
  in pregnant women.
• TO ERYTHROMYCIN for whooping cough
• TO PENICILLIN for meningococal
  pneumococcal meningitis
• TO COTRIMAZOLE for shigella,
  dysentry,enteritis.

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ADVERSE EFFECTS

• Bone marrow depression causing aplastic anemia,
  agrnulocytosis,
• thrombocytopenia pancytopenia.
• GRAYBABY SYNDROME
• Occurred when high doses (100mg/kg) were given.
• Baby stopped feeding, vomited, became hypotonic,
  hypothermic, abdomen
• distended, irregular respiration,ashen gray
  cyanosis, CV collapse death.
• Increase in blood lactic acid.At higher conc. It
  blocks e- transport in liver
• myocardium skeletal muscle.
• Avoided in neonates. If given lt25mg/kg/day.

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AMINOGLYCOSIDES

• Bactericidal effective against gram_ve
  bacteria.
• Streptomycin binds to 30s whereas others bind to
  30s-50s interface.
• Various aminoglycosides include streptomycin,
  gentamicin, kanamycin,
• tobramycin, amikacin, etc.
• SHARED TOXICITY
• OTOTOXICITY
• NEPHROTOXICITY
• NEURO MUSCULAR
  BLOCKADE

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PRECAUTIONS INTERACTIONS

• Avoid during pregnancy risk of fetal
  ototoxicity.
• Avoid using with other ototoxic drugs like high
  ceiling diuretics minocycline
• Avoid concurrent use of other nephrotoxic drugs
  like AMB, vancomycin,
• cyclosporine, etc.
• Cautious use in renal pts.
• Cautious use of muscle relaxants.
• Do not mix aminoglycoside with any drug in same
  syringe / infusion bottle.

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STREPTOMYCIN

• Obtained from St.griseus.
• Narrow antibacterial spectrum.
• Practically restricte to use of T.B.

PHARMACOKINETICS

• Highly ionised not metabolised.
• Neither absorbed nor destroyed in GIT.
• Absorption from site of inj. Is rapid.
• Only extracellular distribution with t1/2 of 2-4
  hrs.
• Excreted unchanged in urine.

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USES

• Tuberculosis
• May be used with penicillin in SABE.
• In plague (tetracyclines in epidemics).
• Drug of first choice in tularemia.

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MACROLIDES

• Bacteriostatic at low conc. But cidal at high
  conc.
• Various macrolides include erythromycin,
  roxithromycin, clarithromycin,
• and azithromycin.

ERYTHROMYCIN

• Isolated from St.erythreus.
• Acid labile
• Widely distributed, crosses serous membrane
  placenta but not BBB.
• PPB is 70-80 with t1/2 of 1.5hrs.
• Excreted primarily in BILE.

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SPECTRUM

• Narrow spectrum.
• Mostly gramve organisms.
• Highly active against Str.pyogenes,
  Str.pneumoniae, gonococci, clostridia,
• C.diptheria, listeria, etc.
• INTERACTIONS
• Inhibits hepatic oxidation causes rise in
  plasma levels of drugs like
• theophylline, carbamazepine, valproate,
  ergotamine, warfarin, terfanadine,
• astemizole cisapride.

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USES

• As alternative to penicillins in
• streptococcal infections
• diptheria
• tetanus
• syphilis
• As a first choice drug in
• atypical pneumonia caused by
  m.pneumoniae
• whooping cough
• chancroid (2gm/day/7days)
• As a second choice drug in
• campylobacter enteritis (next to
  FQ)
• legionnaires pneumonia
• chlamydia trachomitis
  (500/6hrs/7days)
• penicillin resistant
  staphylococcal infections

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ADVERSE EFFECTS

• Remarkably safer drug.
• GIT symptoms include mild to severe epigastric
  pain ocassional diarrhea.
• Very high doses have caused reversible hearing
  impairment.

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MISCELLANEOUS ANTIBIOTICS
CLINDAMYCIN

• Lincosamide antibiotic with mechanism of action
  spectrum of activity
• similar to erythromycin.
• Inhibits most gramve cocci including
  penicillinase producing staph.,
• C.diptheria, nocardia, Actinomyces
  Toxoplasma.
• Highly active against anaerobes especially
  Bact.fragilis.
• Good oral absorption does not cross BBB.
• Accumulates in neutrophils macrophages.
• Metabolised in liver excreted in urine and
  bile.
• T1/2 3hrs

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• Major adverse effect is diarrhea
  pseudomembranous enterocolitis
• caused by C.difficle super infection.
• Employed for prophylaxis in colorectal/pelvic
  surgeries.
• In AIDS pt., with pyrimethamine for
  toxoplasmosis, with primaquine
• for P.carinii pneumonia.
• Topically used for infected acne vulgaris.
• Clindamycin, Erythromycin Chloramphenicol
  exhibit mutual antagonism.
• Potential neuromuscular blockers.

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VANCOMYCIN

• Glycopeptide antibiotic discovered in 1956 as a
  penicillin substitute due
• to efficacy against MRSA, Str.viridans,
  Enterococcus, Cl.difficle.
• Bactericidal.
• Acts by inhibiting bacterial cell wall synthesis
  by binding to terminal
• D-ala-D-ala sequence.
• Not absorbed orally.
• After i.v, it is widely distributed ,penetrates
  serous cavities, inflammed
• meninges is excreted by urine.

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• T1/2 of 6hrs.

• Toxicity cuses plasma conc. Dependent permanent
  deafness.kidney
• damage is also dose related.
• Rapid i.v injection causes chills, fever,
  urticaria, intense flushing
• this is REDMAN SYNDROME.

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ANTI FUNGAL DRUGS

• Used for superficial deep fungal infections.
• Two important antifungals are
• AMB to deal with systemic
  mycosis
• GRISEOFULVIN to supplement attack on
  dermatophytes
• Advancement of antifungals included development
  of imidazoles in 70s
• triazoles in 80s.
• Imidazoles include clotrimazole, miconazole, etc.
• Triazoles are fluconazole, itraconazole.

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AMPHOTERICIN B (AMB)

• From St.nodosus. It is a polyene with a
  macrocyclic ring.
• One of the most toxic systemically used
  antibiotic least toxic polyene.
• Antifungal spectrum include many yeasts fungi
  like C.albicans,
• H.capsulatum, C.neoformans, B.dermatidis,
  Apergillosis, Sporothrix, etc.
• Fungicidal at high conc.
• Have high affinity for ergosterol present in
  fungal cell membrane.
• Resistance is rarely noted.
• Not effective against Dermatophytes.

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PHARMACOKINETICS

• Not absorbed can be given orally for intestinal
  candidiasis.
• Widely distributed with poor CSF penetration.
• Metabolized in liver with t1/2 of 15days
  excreted by urine bile.
• USES
• Gold standard of antifungal therapy.
• Used topically for oral, vaginal cutaneous
  candidiasis otomycosis
• Most effective for systemic mycoses.
• Reserve drug for resistant cases of kala azar.

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ADVERSE EFFECTS

• Acute reactions like chills, fever, aches,nausea,
  dyspnoea,etc.
• Thrombophlebitis of injected vein can occur.
• Nephrotoxicity is the most important long term
  effect.
• INTERACTIONS
• Flucytosine has supra-additive action with AMB.
• Rifampin minocycline potentiate AMB.
• Aminoglycosides, vancomycin, cyclosporine enhance
  the renal
• impairment caused by AMB.

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GRISEOFULVIN

• Heterocyclic Benzofuran from P.griseofulvam.
• Active against most most Dermatophytes but not
  candida.
• Interferes with mitosis causing multinucleated
  stunted fungal hyphae.
• Irregular absorption improved by taking it with
  fats.
• Gets deposited in keratin forming cells of
  skin,hair nails
• Ineffective topically.
• Induces warfarin metabolism reduces efficacy of
  OCP. Phenobarbitone
• reduces oral absorption induces metabolism of
  the drug.

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ANTIVIRAL DRUGS

• Therapy has to be started in the incubation
  period,i.e, has to be prophylactic.
• Anti herpes include acyclovir, ganciclovir,idoxuri
  dine etc.
• Anti-retroviral are NRTIs zidovudine,didanosine,e
  tcNNRTIs like
• nevirapine,efavirenz,etcprotease inhibitors
  like ritonavir,indinavir,etc.
• Idoxuridine is used only for H.simplex
  keratoconjunctivitis.
• Acyclovir acts by inhibiting DNA synthesis
  viral replication.
• Effective in genital herpes simplex,mucocutaneous
  H.simplex,H.simplex
• encephelatitis,H.simplex keratitis,herpes
  zoster,chicken pox (DOC).

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HIV TREATMENT GUIDELINES

• Treatment of HIV is complex, prolonged, needs
  expertise, strong motivation,
• commitment of the pt., resources is very
  expensive.
• Therapy is usually HAART.
• Guidelines according to international AIDS
  society-USA 2002 are
• CD4 cell count is the major
  determinant
• all cases of symptomatic HIV
• asymptomatic HIV with CD4lt 200/ul.
• THERAPEUTIC REGIMENS
• Should be aggressive HAART
• 2-NRTIS 1-PI
• 2-NRTIS 1-NNRTI
• 3-NRTIS

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HIV PROPHYLAXIS

• Accidental exposure to HIV AZT or other drugs
  administered soon after
• the exposure.
• Pregnant HIV ve women treatment of the mother
  with AZT continued
• in the neonate for 6wks substantially reduces
  the risk.

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TO BE CONTD....
TO BE CONTD...
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B-LACTAM ANTIBIOTICS

• Has 5 different groups with B-lactam nucleus as
  the common feature.
• They include the following
• Penicillins
• Cephalosporin
• Carbapenems
• Monobactams
• Carbacephems
• B-lactams as a group has action ranging from
  extremely narrow spectrum
• to a very wide spectrum.

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PENICILLINS

• Originally obtained from P.notatum but the
  present source is P.chrysogenum
• Nucleus consists of fused thiazolidine B-lactam
  rings to which side chains
• are attached through an amide linkage.
• Natural penicillins are F, G, X K.
• UNITAGE
• 1 U of crystalline sod. Benzyl penicillin
  0.6 ug of standard prep.
• 1gm 1.6 million units or 1MU 0.6 gm.
• PnG is also thermo labile acid labile.

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Mechanism of action

• Classic example of Paul Ehrlichs magic
  bullet.
• Interfere with the bacterial cell wall synthesis.
  
• Bacteria dividing in the presence of a B-lactams
  produce CWD forms.
• Certain organisms produce bizarre or filamentous
  forms which are
• incapable of multiplying known as PROTOPLASTS.
• Bactericidal in action.
• Peptidoglycan cell wall is unique to bacteria.
• Blood, pus tissue fluids do not interfere with
  the action.

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PENICILLIN-- G

• Benzyl penicillin
• Narrow spectrum antibiotic mainly against gram
  ve.
• Bacterial resistance is acquired mainly by
  production of penicillinase.
• PHARMACOKINETICS
• Acid labile.
• Less than 1/3 of an oral dose is absorbed in
  active form.
• Distributed mainly extracellularly.
• Little metabolized because of rapid excretion.
• T1/2 is 30min.

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USES

• Streptococcal infections like pharyngitis,otitis
  media, scarlet fever, RF,etc.
• Pneumococcal infections
• Meningococcal infections
• Syphilis
• Diphtheria
• Tetanus gas gangrene
• DOC for rare infections like anthrax,
  actinomycosis, trench mouth,etc.
• For prophylactic uses of RF, gonorrhea, BE,
  Agranulocytosis pts for
• surgical infections.

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ADVERSE EFFECTS

• One of the most nontoxic antibiotics.
• Local irritancy direct toxicity.
• Hypersensitivity. Most common drug implicated in
  drug allergy. Features
• include rash, itching, urticaria, fever.
  Wheezing, angioneurotic oedema,
• serum sickness, exfoliative dermatitis are
  less common.
• Anaphylaxis is rare but fatal.
• Topical use of penicillin is highly sensitizing.
• Super infections.
• Jarisch-Herxheimer reaction.

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SEMISYNTHETIC PENICILLINS

• Produced to overcome the shortcomings of PnG like
• Poor oral efficacy.
• Susceptibility to penicillinase.
• Narrow spectrum of activity.
• Hypersensitivity.
• B-lactamase inhibitors.

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CLASSIFICATION

• Acid resistant alternate to PnG Phenoxy methyl
  penicillin
• Penicillinase resistant Methicillin, Oxacillin,
  Cloxacillin, Nafcillin
• Extended spectrum
• A) AminopenicillinsAmpicillin,
  Amoxicillin, Becampicillin
• B) Caboxypenicillins Carbenicillin,
  Ticarcillin
• C) Ureidopenicillins Mezlocillin,
  Piperacillin
• D) Mecillinam
• B-lactamase inhibitors Clavulanic acid,
  Sulbactam

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AMPICILLIN

• Active against all organisms sensitive to PnG in
  addition to gram_ve bacilli.
• Not acid labile.
• Oral absorption is incomplete but adequate. Food
  interferes with absorption.
• Mainly excreted by kidney partly by bile but
  reabsorbed.
• Plasma t1/2 is 1hr.
• USES
• UTI, RTI.
• Meningitis, Gonorrhoea, Typhoid, Bacillary
  dysentry, Cholecystitis, SABE,
• Septicemias, etc.

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ADVERSE EFFECTS

• Diarrhoea is frequent after oral administration.
• Produces a high incidence of rashes. Concurrent
  administration of
• Allopurinol increases the incidence.
• INTERACTIONS
• Hydrocortisone inactivates ampicillin if mixed in
  the i.v. sol.
• Failure of OCP.
• Probenecid retards renal excretion of ampicillin.

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TETRACYCLINES

• Broad spectrum antibiotics.
• Obtained from soil actinomycetes.
• Bitter solids weakly water soluble with
  unstable aqueous sol.
• Subsequently developed members have high lipid
  solubility, greater
• potency,etc.
• Antibiotics having a nucleus of 4 cyclic rings.

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GROUP 1 GROUP 2
GROUP 3 Chlortetracycline
Democycline
Doxycycline Oxytetracycline
Methacycline
Minocycline Tetracycline
Lymecycline
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Mechanism of action

• Primarily bacteriostatic.
• Inhibit protein synthesis by binding to 30S
  ribosomes thereby preventing
• attachment of aminoacyl-t-RNA to the m-RNA. As a
  result the polypeptide
• chain fails to grow.
• Group 3 drugs enter by passive diffusion also.
• Safer drug to host cells because
• Carrier involving in active transport of
  drug is absent in host cells.
• Protein synthesizing apparatus of host
  cells is less sensitive.

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• Antimicrobial spectrum
• Many gramve gram_ve cocci especially
  Neisseria.
• Most gramve bacilli except Mycobacteria.
• Sensitive gram_ve bacilli include H.ducreyi,
  V.cholera, Yersinia, H.pylori
• Brucella, Campylobacter,etc.
• All chlamudiae Rickettsiae are highly
  sensitive.
• Spirochetes Borrelia are quite sensitive.
• Enterobacteriaceae are now largely resistant.

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PHARMACOKINETICS

• Incompletely absorbed from g.i.t. Better if taken
  on an empty stomach.
• Group 3 drugs are completely absorbed
  irrespective of food.
• Tetracyclines have chelating property.
• Widely distributed in the body
• Concentrated in liver, spleen bind to
  connective tissue in bone teeth.
• Primarily excreted in urine. Dose has to be
  reduced in renal failure.
• Significant amount enters bile secreted in
  milk.
• Enzyme inducers like Phenobarbitone Phenytoin
  enhance metabolism.

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• ADVERSE EFFECTS
• Irritative effects like epigastric pain, nausea,
  diarrhoea, esophageal ulceration.
• DOSE RELATED
• Liver damage acute hepatic necrosis in pregnant
  women.
• Kidney damage Fancony syndrome is produced by
  outdated tetracyclines
• due to proximal tubular damage.
• Phototoxicity more with Demeclocycline
  Doxycycline.
• Teeth bones.
• Superinfection.

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• PRECAUTIONS
• Should not be used in pregnancy, lactation in
  children.
• Avoided in pts on diuretics as blood urea may
  rise.
• Used cautiously in renal or hepatic
  insufficiency.
• Inactivation if mixed with penicillins.
• May reduce insulin requirements.
• Addition of tetracyclines with the anticoagulants
  may lead to serious
• bleeding episodes.

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• USES
• First DOC in
• LGV
• Granuloma inguinale
• Chalmydial infections
• Atypical pneumonia
• Cholera
• Brucellosis
• Rickettsial infections
• Second DOC to
• penicillins for anthrax,
  actinomycosis, etc
• ciprofloxacin for
  gonorrhoea
• cotrimoxazole for
  chancroid
• streptomycin for tularemia

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METRONIDAZOLE

• Prototype Nitroimidazole with broad spectrum
  cidal activity.
• A tissue amoebicide highly active against
  anaerobic bacteria.
• Probably acts by damaging DNA cause
  cytotoxicity.
• Selectively high activity against anaerobic
  organisms has suggested
• interference with e- transport from NADPH.
• Found to inhibit cell mediated immunity, to
  induce mutagenesis to cause
• radiosensitization.

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PHARMACOKINETICS

• Completely absorbed from small intestine.
• Widely distributed in the body various body
  fluids.
• Metabolized in liver primarily by oxidation
  Glucuronide conjugation.
• Excreted in urine.
• CONTRAINDICATIONS
• In neurological diseases, blood dyscrasias, 1st
  trimester of pregnancy and
• chronic alcoholism.

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• ADVERSE EFFECTS
• Relatively frequent but non serious.
• Anorexia, Nausea, Metallic taste Abdominal
  cramps are the most common.
• Headache, Glossitis, Dryness of mouth transient
  neutropenia are less
• frequent side effects.
• Thrombophlebitis of injected vein.
• INTERACTIONS
• A disulfiram like intolerance to alcohol.
• Enzyme inducers like phenobarbitone rifampin
  may reduce its therapeutics.
• Cimetidine can reduce its metabolism. So dose to
  be decreased.

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• USES
• Amoebiasis
• Giardiasis
• Trichomonas vaginitis
• Many anaerobic infections
• Pseudomembranous enterocolitis
• Ulcerative gingivitis trench mouth
• H.pylori infections
• Guinea worm infestations

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ANTIBIOTIC FAILURE

• Failure to surgically eradicate the source of
  infection.
• Too low a blood antibiotic conc.
• Inability to penetrate the site of infection.
• Patient failure to take the antibiotic.
• Emergence of antibiotic resistance.
• Impaired/inadequate host defenses.
• Delayed incorrect diagnosis.
• Antibiotic antagonism.
• Inappropriate choice slow microbial growth.

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NON EFFECTIVE CONDITIONS IN DENTISTRY

• Irreversible purpitis with moderate to severe
  symptoms with (or) without
• apical periodontitis.
• Asymptomatic necrotic pulps with chronic apical
  periodontitis but no
• swelling.
• Necrotic pulps with acute apical periodontitis,
  no swelling moderate
• to severe symptoms.
• Asymptomatic necrotic pulps with chronic apical
  periodontitis with (or)
• without a sinus tract.

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NEWER ANTIMICROBIAL APPROACHES

• Inhibiting species-specific enzymes.
• Employing bacteriophages.
• Using our natural cationic peptide antibiotics.
• Inhibiting glycosyltransferases that control
  bacterial membrane
• lipopolysaccharide synthesis.
• Using antisense RNA inhibitors.

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• Sequestering the iron necessary for microbial
  survival.
• Sequencing the bacterial genome to identify
  unique antibiotic targets

• Improving the immune systems ability to
  recognize destroy microbial
• pathogens.
• Developing highly specific narrow-spectrum
  antibiotics to target specific
• microbes identified by real-time polymerase
  chain reaction.
• Developing chemicals that inhibit microbial
  surface adhesion.
• Interfering with microbial quorum sensing so that
  bacteria misread signals
• for virulence, adherence, growth.

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COMBINATION ANTIBIOTIC THERAPY

• The objectives of using antimicrobial
  combinations are
• To achieve synergism
• To reduce severity or incidence
  of adverse effects
• To prevent emergence of
  resistance
• To broaden the spectrum of
  action

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DISADVANTAGES

• The more drugs are present, the greater the
  likelihood of adverse
• reactions.
• Antibiotic antagonism.
• Increased financial costs.
• Greater microbial resistance.
• Greater environmental spread of resistance genes.
• Increased risk of superinfections.

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ANTIBIOTIC SYNERGISM

• 11 gt 2
• Combinations that are proven to be synergistic
  are
• Cell wall inhibitors
  aminoglycosides.
• Beta-lactams with beta-lactamase
  inhibitors.
• Beta-lactams that act on different
  PBPs.
• Streptogramim combinations.
• Sulfonamides trimethoprim.

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ANTIBIOTIC ANTAGONISM

• Decrease in efficacy of two or more AMAs in
  combination.
• Not well documented clinically.
• Examples include
• Penicillins macrolides in
  S.pneumoniae.
• B-lactam induction of
  B-lactamase in enteric bacilli.
• Macrolide Lincosamide against
  Staph.aureus
• resulting in MLS resistance.

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