Protein Synthesis Inhibitors And Nucleic Acid Inhibitors

Protein Synthesis Inhibitors

Tetracyclines • Bacterial ribosomes – 30s subunit block access of the amino acid acyl-t RNA to mRNA – Broad spectrum – Bacteriostatic

Tetracycline • • • • •

Chlamydial infection Lyme disease Rocky mountain spotted fever Mycoplasma pneumonia Cholera

Tetracycline • E.g. – Doxycycline – Minocycline – Domeclocycline

Tetracycline • Adverse effects: – – – – – – –

Gastric discomfort Effects on calcified tissues Fatal hepatotoxicity Phototoxicity Vestibular problems Pseudotumor cerebri Superinfection

Aminoglycosides • • • • • •

Aerobic gram-negative bacilli Streptomyces - mycin Micromonospora - micin 30s B-lactams Bactericidal

Aminoglycosides • • • •

Infections due to pseudomonas aeruginosa Tularemia Chronic UTI Pneumonia

Aminoglycosides • E.g. – – – – – –

Amikacin Gentamicin Neomycin - nephrotoxic (topical) Netilmycin Streptomycin Tobramycin

Aminoglycosides • Adverse Effects: – Ototoxicity = irreversible (furosemide, bumetanide, ethacrynic acid or cisplatin) – Nephrotoxicity – Neuromuscular paralysis – Allergic reactions

Macrolides • Erythromycin – drug of choice or alternative to penicillin – 50s subunit of the bacterial ribosome – bacteriostatic and cidal in higher doses

Macrolides • Erythromycin – – – – – –

Chlamydial infection Mycoplasmal pneumonia Ureaplasma Syphilis Corynebacterium diphtheriae Legionnaires’ disease

Macrolides • Clarithromycin – similar to erythromycin – Haemophilus influenzae, chlamydia, legionella, ureaplasma

• Azithromycin – less active against staph and strep than erythromycin, far more active against respiratory infections, H. influenzae an Moraxella catarrhalis

Macrolides • Pharmacokinetics: – – – –

Oral administration Except CSF Azithromycin does not undergo metabolism Erythromycin & Azithromycin – bile

• Adverse Effects: – Epigastric distress – Cholestatic jaundice – Ototoxicity

Chloramphenicol • • • • • •

Gram-positive and gram- negative 50s ribosomal unit Inhibits protein synthesis Broad spectrum IV or Oral Adverse effects: – Anemia – Gray baby syndrome

Clindamycin • • • • • •

Same with erythromycin Anaerobic bacteria (Bacteriodes fragilis) Oral route Except CSF Bile or GF Adverse Effects – Pseudomembranous colitis (Metronidazole/Vancomycin) – Skin Rashes

Inhibitors of Nucleic acid function/synthesis Fluoroquinolones Rifampin

Quinolones and Urinary Tract Antiseptics • Fluoroquinolones – – – – –

Nalidixic acid UTI Inhibit DNA replication Bactericidal Gram – negative • Enterobacteria, Pseudomonas, Legionella, Chlamydia, H. influenzae, Moraxella

Fluoroquinolones • Ciprofloxacin – Most potent – Pseudomonas – Enterobacteria and Gram-negative

• Norfloxacin – Gram negative and gram positive – Pseudomonas and UTI

Fluoroquinolones • Ofloxacin – Prostatitis due to E. coli and STD’s with the exception of Syphilis) – Gonorrhea – Skin and lower respiratory tract infections

• Lomefloxacin – UTI and and Bronchitis – Not effective for pseudomonas

Fluoroquinolones • Adverse reactions: – CNS problems – Nephrotoxicity – Phototoxicity

• Contraindications: – Pregnancy, Nursing mothers, children 18 years old

• Interferes with caffeine, cimetidine, warfarin, cyclosporine

Quinolones • Gram negative bacteria • UTI – E.coli- most common pathogen – Staphylococcus saprolyticus – 2nd – Others: Klebsiella and Proteus mirabilis

• Methenamine • Nitrofurantoin

Quinolones • Adverse effects – – – –

Gastrointestinal disturbances Acute pneumonitis(Nitrofurantoin) Neurological problems(Nitrofurantoin) Hemolytic anemia (Nitrofurantoin)