7. broad spectrum ab
TRANSCRIPT
BROAD SPECTRUM ANTIBIOTICS
TETRACYCLINES
CHLORAMPHENICOL
Tetra cyclines have four cyclic ring Produced by genus Streptomyces
Tetracycline divided into:
a) Naturally occurring:Tetracycline ChlortetracyclineOxytetracycline Demeclocycline
b) Semisynthetic occurring:Doxycycline MinocyclineMeclocycline LymecyclineMethacycline Rolitetracycline
CLASSIFICATION OF TETRACYCLINES
GROUP I : Chlortetracycline(6-10hr) Tetracycline
Oxytetracycline
GROUP II : Demeclocycline(12-13hr) Methacycline
GROUP III : Doxycycline(18-20hrs) Minocycline
Mechanism of Action BACTERIOSTATIC
1. Drug enter by : Active Transport (+Ve)
Porin channels (-Ve)
Enter into periplasmic place Protein Carrier system
Inner cytoplasmic membrane
Binds to 30s ribosome
Inhibits attach of aminoacyl t RNA to “A”site
Inhibition of protein synthesis
ANTIMICROBIAL SPECTRUM
G +ve Bacilli :
* Clostridia * Corynebacteria
* B. Anthracis * P. acnes
G –ve Bacilli :* V. Cholerae * Brucella* H. ducryi * H. pylori* Y. pestis * Y. enterocolitica
G +ve Cocci :
* Streptococci * Staphylococci
G –ve Cocci :* N. gonococci * N. meningococci
ANTIMICROBIAL SPECTRUM cont…
Rickettiae
Chlamydiae
Mycoplasma
Actinomyces
Spirochetes
Entamoeba
Plasmodia
RESISTANCE
1. Active transport Mechanism
2. Pumping Out of Drug √
3. Protective Protein – Microorganism
4. Complete Cross Resistance
5. Partial Cross Resistance
PHARMACOKINETICS
ABSORPTION :* Group I & II – Incomplete; Empty Stomach* Group III – Complete* Chelating Property
DISTRIBUTION :* Liver, Spleen, Bones & Teeth, cross Placenta
EXCRETION :* Group I & II – Kidney (70-75%)
* Group III – Bile & Faeces - Enterohepatic Circulation (Doxy)
* All Tetracycline – Milk* Mino- saliva and tears
ADVERSE EFFECTS
1. LOCAL IRRITANCY (IM)
2. HEPATOTOXICITY (preg., Inc. blood urea levels)
3. NEPHROTOXICITY (I &II)
4. TOXICITY TO TEETH & BONES
5. PHOTOSENSITIVITY –III (Sun burn, Doxy)
ADVERSE EFFECTS cont…
6. VESTIBULAR TOXICITY –III (acc.lipid cells of inner ear)
7. SUPERINFECTION
8. HYPERSENSITIVITY
9. Pseudotumor cerebri (Adults) & Bulging
fontanelles
10. DIABETES INSIPIDUS LIKE CONDITION (Mino, Anti ADH action)
THERAPEUTIC USES
FIRST CHOICE DRUG :
1. Venereal Diseases
2. Chlamydieal Infections
3. Brucellosis (with streptomycin)
4. Atypical Pneumonia
5. Plague prophylaxis
6. Cholera
7. Rickettseial Infections (Doxy)
8. Relapsing Fever (Doxy)
THERAPEUTIC USES
SEACOND CHOICE DRUG :
To Penicillin
* Tetanus * Anthrax *Actinomycosis
To Cotrimoxazole : E. coli infection
To Streptomycin : Tulaeremia
To Ciprofloxacin : Gonorrhoea &
Syphilis
Azithromycin : Chlamydial Infection
THERAPEUTIC USEScont…
MISCELLANEOUS CONDITION :1. Amoebiasis2. Malaria3. Acne4. COPD
MINOCYCLINE:
1. Meningococal meningitis
2. Community Acquired Pneumonia
3. Chronic Intestinal Amoebiasis
Glycylcyclins
Synthetic deriv. of Minocyclines Potent than Mino Effect Gm +ve, -Ve, aerobes,
Anaerobes, resistant tetracyclines Same mech, resistance
CHLORAMPHENICOL
CHLORAMPHENICOL
MECHANISM OF ACTION :
Inhibits Protein Synthesis : 50 s Ribosomes (Inhibit
formation of peptide bond)
High Doses : Inhibits Mammalian
Mitochondrial Protein Synthesis
ANTIMICROBIAL SPECTRUM
BACTERIOSTATIC
BACTERIOCIDAL – H. influenzae
BROAD SPECTRUM as TETRACYCLINES
Additional Spectrum:
HIGHLY ACTIVE– Salmonella
MORE ACTIVE - H. influenzae, B. pertusis,
Klebsiella & Anaerobes
LESS ACTIVE – G+ve cocci, Spirochetes.
INACTIVE – Entamoeba & Plasmodia
RESISTANCE
1. Transfer of R Factor
2. Formation of Acetyl Transferase
3. Decreased Permeability
4. Lowered Affinity of Bacterial
Ribosome
PHARMACOKINETICS
Oral Absorption : Complete
Distribution : CSF, Bile, Synovial Memb
Milk, Placenta.
Metabolism : Conjugation in Liver
Excretion : Unchanged in Urine
ADVERSE EFFECTS
ADVERSE EFFECTS
1. Bone Marrow Toxicity Non Dose Related (3-4g/day for 1-2week)
Inhibition of mitochondrial enzymes Dose Related Aplastic Anaemia
Thrombocytopenia Agranulocytosis
2. Gray Baby Syndrome
3. Superinfection
4. Irritative Effects
THERAPEUTIC USES
1. H. Influenza Meningitis
2. Anaerobic Infections
3. Enteric Fever
4. Intraocular Infection
5. As Second Choice Drug :
To Tetracycline : Cholera, Brucelosis, etc.
To Erythromycin: Whooping Cough
To Penicillin : Meningitis
To Cotrimoxazole : Shigella Dysentry
IMP
All undergoes enterohepatic circulation CI in pregnancy and ,8 ye.old Outdated lead to Fanconi’s syndrome
( Renal tubular acidosis) Minocyclines cause dose dependent
vestibular toxicity Tetracycline's posses anti anabolic
effects