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TETRACYCLINE AND
CHLORAMPHENICOL - BROAD
SPECTRUM ANTIBIOTICS
Dr. D. K. Brahma
Associate Professor
Department of Pharmacology NEIGRIHMS, Shillong
BROAD SPECTRUM – WHY ??
 Name given as they contrasted to the existing
antibiotics – e.g., Penicillin and Streptomycin (1944)
available
1. Orally effective
2. Wider spectrum of activity
Tetracycline and Chloramphenicol
TETRACYCLINE - HISTORY
American Pharmaceutical Industry: In the 1940’s soil
actinomycetes were systematically
screened for the elaboration of antimicrobial substances
TETRACYCLINES
 A class of antibiotics named for their nucleus of four
(“tetra-”) hydrocarbon rings
 All are obtained from soil actinomycetes
 1948 first one – chlortetracycline (aureomycin) – S.
aureofaciens (Yellow coloured colony)
 Oxytetracycline from S. rimosus (1950)
 Tetracycline (1953)
TETRACYCLINES - DRUGS
 Naturally occuring:
 Tetracycline, cholrtetracycline, oxytetracycline and
demeclocycline
 Semisynthetic occurring:
 Doxycycline, minocycline, tigecycline, lymecycline,
methacycline and rolitetracycline
TETRACYCLINES – COMMON PROPERTIES
 Nucleus of 4 hydrocarbon rings
 Bitter solids and weakly water soluble – HCl salts
are more soluble
 Aqueous solutions are unstable
 Same antimicrobial activity – only minor differences
 Newer ones – high lipid solubility and greater
potency
AVAILABLE DRUGS - CHARACTERS
 Tetracycline,
oxytetracycline,
demeclocycline
 Lower potency (250-500
mg tid)
 Orally given, short acting
(t1/2 – 6-8 Hrs)
 Incompletely absorbed
from stomach (60-80%)
 Primarily excreted through
the kidneys
 Higher diarhoeal
incidence
 Phototoxicity - Low
 Minocycline,
doxycycline,
tigecycline
 Higher potency (100 - 200
mg)
 Lipid soluble, long acting
(t1/2 – 18-24 Hrs)
 Completely absorbed
from stomach (95-100%)
 Excreted through liver
 Lower diarhoeal incidence
 Phototoxicity - High
TETRACYCLINES - MOA
 Inhibition of Bacterial Protein Synthesis by binding
to 30S ribosomes – aminoacyl-t-RNA to mRNA-
ribosome complex – interfered
 Susceptible organisms: concentrating mechanism
 Energy dependent active transport – concentrates TCN
intracellularly
 By porin channels – gm-ve ones
 Passive diffusion also by lipid soluble ones
 Why do not affect host cells ? – transport (absence
of carrier) and sensitivity
TETRACYCLINES - MOA
Inhibition of Bacterial Protein
Synthesis
RESISTANCE
 Develops slowly in graded manner
1. Tetracycline concentrating mechanism lessens
2. Efflux pump
3. Plasmid mediated synthesis of “protection protein”
4. Tetracycline inactivating enzyme
Cross resistance
TETRACYCLINES – ANTIMICROBIAL SPECTRUM
 Bacteriostatic drugs: originally all types of organisms except
viruses and fungi – Both, gm+ve and gm-ve bacteria, Rickettsiae,
Chlamydia, Mycoplasma, actinomycetes and some protozoa
 Cocci: All +ve and –ve cocci
 S. pneumoniae, gonococi, meningitidis were sensitive. Resistance
developed to Staph aureus, Strep. pyrogens and enterococci
 Now also active against N. gonorrhoeae ad N. meningitidis
 Bacilli (+ve): clostridia, listeria, anthracis etc., but not
Mycobacteria
 Gm-ve bacilli: Cholerae, Y. pestis, Helicobacter, Brucella etc. but
H. Influanzae become insensitive
 Enterobacteriocae: resistant and not effective - pseudomonas,
proteus klebsiella and salmonella typhi and Bact. fragilis
 Spirochaetes (T. pallidum, Borrelia)
 All Rickettsiae (typhus), chlamydiae
 Mycoplasma and actinomycetes etc.
 Enterococci: histolytica and plasmodia
TETRACYCLINES - KINETICS
 Older ones less absorbed – 60-80% (food interferes) but doxy
and mino – completely
 Chelating property – milk, antacids and iron preparations
 Distribution: wide and variable protein binding (different
members)
 Concentrated in liver, spleen and bone & teeth – minocycline in fats
 Good CSF penetration 1/4th of plasma) – no relation with inflammation
 Intracellularly binds to mitochondria
 Excretion: Primarily in urine (dose adjustment in renal failure)
 Doxycycline is exception (bile) – enterohepatic circulation
 Preparations: Oral capsules, ½ to 2 Hrs pre and post food
 No IM: painful (oxy and tetra available)
 Also cream, ointment and ocular etc. preparations – high risk of
sensitization
PREPARATION AND ADMINISTRATION
 Oral route is the most commonly used route – IM
not recommended – painful
 Local preparations - sensitization
 Oxytetracycline: Terramycin
 250/500 Caps or 50 mg/ml vial
 Also skin ointment and eye ointment
 Tetracycline:
 Hostacyclin/Restecyclin 250/500 Caps or skin and eye
ointment
 Demeclocyclin: 130/300 mg caps
 Doxycycline: 100 mg caps. and Minocycline – 50 or
100 mg caps.
ADVERSE EFFECTS
 GI disturbances: Due to Irritation
• Mild nausea and diarrhoea to severe, possibly life-
threatening colitis and Oesophageal ulcer etc.
• Thrombophlebitis
 Superinfection: Disturbances in the normal flora
(Diabetics)
• Candidiasis (oral and vaginal) – soreness and redness of
mouth black hairy tounge and inflammatory lesions in vulva,
vagina etc.
• Staphylococcal enteritis (S. aureus) – hospitalized patients –
loss of appetite, abdominal discomfort and watery diarrhoea,
• Pseudomembranous colitis - C. difficile (profuse diarrhoea
and fever) – Rare but dangerous
 Difference of diarrhoea: Pus cell or RBCs (absent in
irritation type)
(Doxycycline and Minocycline – less likely to cause
TOXICITY – CONTD.
 Liver damage: fatty infiltration – oxytetracycline safer; pregnancy –
acute hepatic necrosis
 Kidney damage: accumulates except doxycycline – enhance existing
kidney disease
 FANCONY LIKE SYNDROME – outdated tetracycline (epitetracycline,
anhydrotetracycline and anhydroepitetracycline) – glycosuria, proteinuria and
aminoaciduria etc.
 Phototoxicity: Sunburn like - Skin rashes, mainly after topical
application
 Erythema, brown black discolouration of nails and loosening etc.
 Doxycycline and demeclycline - more
 Teeth and Bones: Brown discolouration - Calcium tetracycline chelate
(orthophosphate)
 Deciduous teeth – ill formed and prone to carries teeth
 Affect the crown of permanent anterior dentition
 Pregnancy and childhood - Temporary supression of Bone growth
 Antianabolic effect: reduction in Protein synthesis
 Diabetes Insipidus: antagonizes ADH and urine conc. property
 Vestibular toxicity: Minocycline (ataxia, vertigo, nystagmus)
TOXICITY/CONTRAINDICATIONS
OF TETRACYCLINES
 Because drug is deposited in
tooth dentine and enamel,
brown bands form
 Do not give to children or
pregnant/nursing women
(bone growth, deformities, stature)
 Misc. side effects
 Thrombophlebitis
 Various WBC dystrophies
 Increased intracranial
pressure in neonates
 Hypersensitivity reactions
(superinfections)
TETRACYCLINES - USES
1. Empirical therapy: No - Mixed Infections
2. 1st choice:
i. Venereal diseases:
 Chlamydial urethritis/endocervicitis: Doxycycline – 7 days
 Lymphogranuloma venereum (Chlamydia trachomatis) – 2-3
weeks
 Granulloma inguinale (Klebsiella granulomatis) – 3 weeks
ii. Atypical pneumonia: due to mycoplasma - psittacosis
iii. Cholera: reduce stool volume
iv. Brucellosis: D 200+ R600/day X 6 weeks
v. Plague: Bubonic and Pneumonic plague
vi. Rickettsial infections: Rocky Mountain Spotted Fever, All
forms of typhus and Q fever (Coxiella burnetii)
vii. Relapsing fever due to Borrelia recurrentis
TETRACYCLINES – OTHER USES
2nd choice drugs:
 To penicillins for tetanus,anthrax,actinomycosis and
listerias
 To ceftriaxone/amoxy/azithro for gonorrhoea
 To penicillins for syphilis (allergic to penicillins)
 To pens for leptospirosis (doxy 100 mg BD 7 days)
 To azithromycin for chlamydia pneumonia
 To ceftriaxone and azithromycin for chancroid
 To streptomycin for tularemia
Other uses: UTI, Chloroquine Resistant falciparum
adjuvant to quinine, Amoebiasis, Community aquired
pneumonia, Acne vulgaris and COPD
TETRACYCLINES - PRECAUTIONS
 Pregnancy, lactation and children
 Renal and hepatic insufficiency
 Expiry Date
 With diuretics
 Intrathecal injection
CHLORAMPHENICOL
Streptomyces venezuelae
CHLORAMPHENICOL
(STREPTOMYCES VENEZUELAE)
 A natural product
(contains a nitrobenzene
moiety)
 Now, all are synthetic
products
 Yellowish white crystalline
solid
 Stable aqueous solution –
stands boiling – sunlight !
 Nitrobenzene –
antibacterial activity
 BITTER
CHLORAMPHENICOL – DIFFERENCES WITH
TETRACYCLINE
 Highly effective against S. typhi (RESISTANT
NOW)
 More effective against H. influenzae, B. pertussis,
Klebsiella, N. menigitidis and Bact. fragilis
 Less active against gm+ve cocci and spirochaetes
 Not effective against – chlamydia, entmoeba and
plasmodia
 Ineffective against Mycobacteria, Pseudomonas,
Proteus, fungi and viruses
CHLORAMPHENICOL - MOA
 Binds to 50S ribosomal
subunit
 Prevents peptide bonds from
forming and blocking proteins
synthesis
 Prevents transfer of the
elongated peptide chain to
the newly attached
aminoacyl-tRNA at the
ribosome-mRNA complex
 Bacteriostatic - Effective
against a wide variety of
organisms
 Mainly like tetracycline: +ve, -
ve, Rikettsiae and
mycoplasma
 Generally used as drug of
last resort for life-threatening
infections
RESISTANCE - CHLORAMPHENICOL
 High incidence of Resistance due to indiscriminate
use in the past – developing countries
 Resistant strains of S. typhi developed due to
transfer of R factor
 Resistance among gr-ve bacteria – by R Plasmid
encoded for acetyl- transferases acquisition -
inactivate the drug
• Acetyl – chloramphenicol does not bind to ribosomes
• Plasmid also carries resistance to – ampicillin and
tetracycline etc – multidrug resistance (S. typhi)
• Other mechnisms –
 decreased permeability (passive and facilitated diffusion)
 Lowered affinity of ribosomes to chloramphenicol
PHARMACOKINETICS
 Given orally or parenterally
 Wide distribution – serous cavities and CSF
 Present in bile, milk, and placental fluid
 Conjugated in liver (glucoronic acid)
 Cirrhotics & neonates have low conjugating ability
 Little is excreted unchanged in urine
 T1/2 = 3 - 5 hrs
 Available as capsules 250 mg – 500 mg (maximum
dose 28 gm in a course of less than 2 weeks)
 Also as inj. 0.25, 0.5 and 1 g per vial
 Eye drops 0.4% and ear drops
ADVERSE EFFECTS
 Irritative effects – Nausea, vomiting, diarrhoea and pain in
injection
 Bone marrow depression: Notorious causes aplastic anaemia,
agrannulocytosis, thrombocytopenia
1. Non dose related (idiosyncratic): genetic basis and unpredictable –
more common on repeated use - higher mortality - in long term
leukaemias
2. Dose and duration related – myelo-suppression – due to inhibition of
mitochondrial enzyme synthesis - predictable, reversible
 Hypersensitive effects – Rashes, fever, glossitis and
angioedema
 Gray Baby Syndrome: (2-9 days after dose of 100mg/kg)
 Within 24 hours, baby starts to vomit, stops eating, rapid and irregular
respiration, abdominal distension, periods of cyanosis, and pooping loose
green stool
 Baby then turns ashen gray and becomes flaccid and hypothermic
 Also can occur in adults who are cirrhotics
 Death in 40% of cases (CVS collapse)
 Due to Inability to metabolised & excrete chloramphenicol
CHLORAMPHENICOL - PRECAUTIONS
 Minor infections and undefined etiology
 Infections treatable by other AMAs
 Avoid repeated courses
 Should not use more than 2-3 gms per day, use for
less than 2 weeks and total dose should not exceed
28 gms
 Regular peripheral blood smear – reticulocyte count
 No combination with other antimicrobials
CHLORAMPHENICOL - USES
 Enteric fever: Mainstay in the past
 Pyogenic meningitis as 2nd line to 3rd generation
cefalosporins – child and allergics
 Meningcoccal meningitis and H. influenzae
 Anaerobic infections – Bact. Fragilis
 Intraocular infections – endophthalmitis
 Second choice : brucellosis & rickettsial infections,
UTI – sensitive ones ---- also topical in
conjunctivitis, external ear infections
 Conjunctivitis and external ear infection - Not to be
used on skin or other areas
REMEMBER RESISTANCE! -
PRESERVE
REMEMBER !
 Toxicities of Tetracyclines - Superinfections, gum
and teeth deposits, Fanconi like syndrome,
pseudomembranous colitis – also GI disturbance,
liver damage, kidney damage and phototoxicity
 Toxicities of chloramphenicol: Bone marrow
depression – aplastic anaemia, Gray Baby
syndrome and hypersensitivity
THANK YOU

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Broad spectrum antibiotics - drdhriti

  • 1. TETRACYCLINE AND CHLORAMPHENICOL - BROAD SPECTRUM ANTIBIOTICS Dr. D. K. Brahma Associate Professor Department of Pharmacology NEIGRIHMS, Shillong
  • 2. BROAD SPECTRUM – WHY ??  Name given as they contrasted to the existing antibiotics – e.g., Penicillin and Streptomycin (1944) available 1. Orally effective 2. Wider spectrum of activity Tetracycline and Chloramphenicol
  • 3. TETRACYCLINE - HISTORY American Pharmaceutical Industry: In the 1940’s soil actinomycetes were systematically screened for the elaboration of antimicrobial substances
  • 4. TETRACYCLINES  A class of antibiotics named for their nucleus of four (“tetra-”) hydrocarbon rings  All are obtained from soil actinomycetes  1948 first one – chlortetracycline (aureomycin) – S. aureofaciens (Yellow coloured colony)  Oxytetracycline from S. rimosus (1950)  Tetracycline (1953)
  • 5. TETRACYCLINES - DRUGS  Naturally occuring:  Tetracycline, cholrtetracycline, oxytetracycline and demeclocycline  Semisynthetic occurring:  Doxycycline, minocycline, tigecycline, lymecycline, methacycline and rolitetracycline
  • 6. TETRACYCLINES – COMMON PROPERTIES  Nucleus of 4 hydrocarbon rings  Bitter solids and weakly water soluble – HCl salts are more soluble  Aqueous solutions are unstable  Same antimicrobial activity – only minor differences  Newer ones – high lipid solubility and greater potency
  • 7. AVAILABLE DRUGS - CHARACTERS  Tetracycline, oxytetracycline, demeclocycline  Lower potency (250-500 mg tid)  Orally given, short acting (t1/2 – 6-8 Hrs)  Incompletely absorbed from stomach (60-80%)  Primarily excreted through the kidneys  Higher diarhoeal incidence  Phototoxicity - Low  Minocycline, doxycycline, tigecycline  Higher potency (100 - 200 mg)  Lipid soluble, long acting (t1/2 – 18-24 Hrs)  Completely absorbed from stomach (95-100%)  Excreted through liver  Lower diarhoeal incidence  Phototoxicity - High
  • 8. TETRACYCLINES - MOA  Inhibition of Bacterial Protein Synthesis by binding to 30S ribosomes – aminoacyl-t-RNA to mRNA- ribosome complex – interfered  Susceptible organisms: concentrating mechanism  Energy dependent active transport – concentrates TCN intracellularly  By porin channels – gm-ve ones  Passive diffusion also by lipid soluble ones  Why do not affect host cells ? – transport (absence of carrier) and sensitivity
  • 9. TETRACYCLINES - MOA Inhibition of Bacterial Protein Synthesis
  • 10. RESISTANCE  Develops slowly in graded manner 1. Tetracycline concentrating mechanism lessens 2. Efflux pump 3. Plasmid mediated synthesis of “protection protein” 4. Tetracycline inactivating enzyme Cross resistance
  • 11. TETRACYCLINES – ANTIMICROBIAL SPECTRUM  Bacteriostatic drugs: originally all types of organisms except viruses and fungi – Both, gm+ve and gm-ve bacteria, Rickettsiae, Chlamydia, Mycoplasma, actinomycetes and some protozoa  Cocci: All +ve and –ve cocci  S. pneumoniae, gonococi, meningitidis were sensitive. Resistance developed to Staph aureus, Strep. pyrogens and enterococci  Now also active against N. gonorrhoeae ad N. meningitidis  Bacilli (+ve): clostridia, listeria, anthracis etc., but not Mycobacteria  Gm-ve bacilli: Cholerae, Y. pestis, Helicobacter, Brucella etc. but H. Influanzae become insensitive  Enterobacteriocae: resistant and not effective - pseudomonas, proteus klebsiella and salmonella typhi and Bact. fragilis  Spirochaetes (T. pallidum, Borrelia)  All Rickettsiae (typhus), chlamydiae  Mycoplasma and actinomycetes etc.  Enterococci: histolytica and plasmodia
  • 12. TETRACYCLINES - KINETICS  Older ones less absorbed – 60-80% (food interferes) but doxy and mino – completely  Chelating property – milk, antacids and iron preparations  Distribution: wide and variable protein binding (different members)  Concentrated in liver, spleen and bone & teeth – minocycline in fats  Good CSF penetration 1/4th of plasma) – no relation with inflammation  Intracellularly binds to mitochondria  Excretion: Primarily in urine (dose adjustment in renal failure)  Doxycycline is exception (bile) – enterohepatic circulation  Preparations: Oral capsules, ½ to 2 Hrs pre and post food  No IM: painful (oxy and tetra available)  Also cream, ointment and ocular etc. preparations – high risk of sensitization
  • 13. PREPARATION AND ADMINISTRATION  Oral route is the most commonly used route – IM not recommended – painful  Local preparations - sensitization  Oxytetracycline: Terramycin  250/500 Caps or 50 mg/ml vial  Also skin ointment and eye ointment  Tetracycline:  Hostacyclin/Restecyclin 250/500 Caps or skin and eye ointment  Demeclocyclin: 130/300 mg caps  Doxycycline: 100 mg caps. and Minocycline – 50 or 100 mg caps.
  • 14. ADVERSE EFFECTS  GI disturbances: Due to Irritation • Mild nausea and diarrhoea to severe, possibly life- threatening colitis and Oesophageal ulcer etc. • Thrombophlebitis  Superinfection: Disturbances in the normal flora (Diabetics) • Candidiasis (oral and vaginal) – soreness and redness of mouth black hairy tounge and inflammatory lesions in vulva, vagina etc. • Staphylococcal enteritis (S. aureus) – hospitalized patients – loss of appetite, abdominal discomfort and watery diarrhoea, • Pseudomembranous colitis - C. difficile (profuse diarrhoea and fever) – Rare but dangerous  Difference of diarrhoea: Pus cell or RBCs (absent in irritation type) (Doxycycline and Minocycline – less likely to cause
  • 15. TOXICITY – CONTD.  Liver damage: fatty infiltration – oxytetracycline safer; pregnancy – acute hepatic necrosis  Kidney damage: accumulates except doxycycline – enhance existing kidney disease  FANCONY LIKE SYNDROME – outdated tetracycline (epitetracycline, anhydrotetracycline and anhydroepitetracycline) – glycosuria, proteinuria and aminoaciduria etc.  Phototoxicity: Sunburn like - Skin rashes, mainly after topical application  Erythema, brown black discolouration of nails and loosening etc.  Doxycycline and demeclycline - more  Teeth and Bones: Brown discolouration - Calcium tetracycline chelate (orthophosphate)  Deciduous teeth – ill formed and prone to carries teeth  Affect the crown of permanent anterior dentition  Pregnancy and childhood - Temporary supression of Bone growth  Antianabolic effect: reduction in Protein synthesis  Diabetes Insipidus: antagonizes ADH and urine conc. property  Vestibular toxicity: Minocycline (ataxia, vertigo, nystagmus)
  • 16. TOXICITY/CONTRAINDICATIONS OF TETRACYCLINES  Because drug is deposited in tooth dentine and enamel, brown bands form  Do not give to children or pregnant/nursing women (bone growth, deformities, stature)  Misc. side effects  Thrombophlebitis  Various WBC dystrophies  Increased intracranial pressure in neonates  Hypersensitivity reactions (superinfections)
  • 17. TETRACYCLINES - USES 1. Empirical therapy: No - Mixed Infections 2. 1st choice: i. Venereal diseases:  Chlamydial urethritis/endocervicitis: Doxycycline – 7 days  Lymphogranuloma venereum (Chlamydia trachomatis) – 2-3 weeks  Granulloma inguinale (Klebsiella granulomatis) – 3 weeks ii. Atypical pneumonia: due to mycoplasma - psittacosis iii. Cholera: reduce stool volume iv. Brucellosis: D 200+ R600/day X 6 weeks v. Plague: Bubonic and Pneumonic plague vi. Rickettsial infections: Rocky Mountain Spotted Fever, All forms of typhus and Q fever (Coxiella burnetii) vii. Relapsing fever due to Borrelia recurrentis
  • 18. TETRACYCLINES – OTHER USES 2nd choice drugs:  To penicillins for tetanus,anthrax,actinomycosis and listerias  To ceftriaxone/amoxy/azithro for gonorrhoea  To penicillins for syphilis (allergic to penicillins)  To pens for leptospirosis (doxy 100 mg BD 7 days)  To azithromycin for chlamydia pneumonia  To ceftriaxone and azithromycin for chancroid  To streptomycin for tularemia Other uses: UTI, Chloroquine Resistant falciparum adjuvant to quinine, Amoebiasis, Community aquired pneumonia, Acne vulgaris and COPD
  • 19. TETRACYCLINES - PRECAUTIONS  Pregnancy, lactation and children  Renal and hepatic insufficiency  Expiry Date  With diuretics  Intrathecal injection
  • 21. CHLORAMPHENICOL (STREPTOMYCES VENEZUELAE)  A natural product (contains a nitrobenzene moiety)  Now, all are synthetic products  Yellowish white crystalline solid  Stable aqueous solution – stands boiling – sunlight !  Nitrobenzene – antibacterial activity  BITTER
  • 22. CHLORAMPHENICOL – DIFFERENCES WITH TETRACYCLINE  Highly effective against S. typhi (RESISTANT NOW)  More effective against H. influenzae, B. pertussis, Klebsiella, N. menigitidis and Bact. fragilis  Less active against gm+ve cocci and spirochaetes  Not effective against – chlamydia, entmoeba and plasmodia  Ineffective against Mycobacteria, Pseudomonas, Proteus, fungi and viruses
  • 23. CHLORAMPHENICOL - MOA  Binds to 50S ribosomal subunit  Prevents peptide bonds from forming and blocking proteins synthesis  Prevents transfer of the elongated peptide chain to the newly attached aminoacyl-tRNA at the ribosome-mRNA complex  Bacteriostatic - Effective against a wide variety of organisms  Mainly like tetracycline: +ve, - ve, Rikettsiae and mycoplasma  Generally used as drug of last resort for life-threatening infections
  • 24. RESISTANCE - CHLORAMPHENICOL  High incidence of Resistance due to indiscriminate use in the past – developing countries  Resistant strains of S. typhi developed due to transfer of R factor  Resistance among gr-ve bacteria – by R Plasmid encoded for acetyl- transferases acquisition - inactivate the drug • Acetyl – chloramphenicol does not bind to ribosomes • Plasmid also carries resistance to – ampicillin and tetracycline etc – multidrug resistance (S. typhi) • Other mechnisms –  decreased permeability (passive and facilitated diffusion)  Lowered affinity of ribosomes to chloramphenicol
  • 25. PHARMACOKINETICS  Given orally or parenterally  Wide distribution – serous cavities and CSF  Present in bile, milk, and placental fluid  Conjugated in liver (glucoronic acid)  Cirrhotics & neonates have low conjugating ability  Little is excreted unchanged in urine  T1/2 = 3 - 5 hrs  Available as capsules 250 mg – 500 mg (maximum dose 28 gm in a course of less than 2 weeks)  Also as inj. 0.25, 0.5 and 1 g per vial  Eye drops 0.4% and ear drops
  • 26. ADVERSE EFFECTS  Irritative effects – Nausea, vomiting, diarrhoea and pain in injection  Bone marrow depression: Notorious causes aplastic anaemia, agrannulocytosis, thrombocytopenia 1. Non dose related (idiosyncratic): genetic basis and unpredictable – more common on repeated use - higher mortality - in long term leukaemias 2. Dose and duration related – myelo-suppression – due to inhibition of mitochondrial enzyme synthesis - predictable, reversible  Hypersensitive effects – Rashes, fever, glossitis and angioedema  Gray Baby Syndrome: (2-9 days after dose of 100mg/kg)  Within 24 hours, baby starts to vomit, stops eating, rapid and irregular respiration, abdominal distension, periods of cyanosis, and pooping loose green stool  Baby then turns ashen gray and becomes flaccid and hypothermic  Also can occur in adults who are cirrhotics  Death in 40% of cases (CVS collapse)  Due to Inability to metabolised & excrete chloramphenicol
  • 27. CHLORAMPHENICOL - PRECAUTIONS  Minor infections and undefined etiology  Infections treatable by other AMAs  Avoid repeated courses  Should not use more than 2-3 gms per day, use for less than 2 weeks and total dose should not exceed 28 gms  Regular peripheral blood smear – reticulocyte count  No combination with other antimicrobials
  • 28. CHLORAMPHENICOL - USES  Enteric fever: Mainstay in the past  Pyogenic meningitis as 2nd line to 3rd generation cefalosporins – child and allergics  Meningcoccal meningitis and H. influenzae  Anaerobic infections – Bact. Fragilis  Intraocular infections – endophthalmitis  Second choice : brucellosis & rickettsial infections, UTI – sensitive ones ---- also topical in conjunctivitis, external ear infections  Conjunctivitis and external ear infection - Not to be used on skin or other areas
  • 30. REMEMBER !  Toxicities of Tetracyclines - Superinfections, gum and teeth deposits, Fanconi like syndrome, pseudomembranous colitis – also GI disturbance, liver damage, kidney damage and phototoxicity  Toxicities of chloramphenicol: Bone marrow depression – aplastic anaemia, Gray Baby syndrome and hypersensitivity