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