Protein Synthesis Inhibitors Overview

Protein Synthesis Inhibitors

• This antibacterial group includes aminoglycosides, macrolides, tetracyclines, lincosamides, chloramphenicol, and linezolid.

30S Ribosomal Subunit Inhibitors

• Aminoglycosides
• Tetracyclines

50S Ribosomal Subunit Inhibitors

• Chloramphenicol
• Macrolides

Chloramphenicol

• Bacteriostatic broad-spectrum antibiotic
• Bactericidal at higher concentrations
• Mechanism: Binds reversibly to 50S ribosomal subunit, inhibiting bacterial protein synthesis.
• Clinical uses: Typhoid fever (alternative: ciprofloxacin), topical antimicrobial agent.
• Adverse reactions: Gastrointestinal disturbances, aplastic anemia (rare), gray baby syndrome, cyanosis, super-infection.

Tetracyclines

• Tetracycline, Doxycycline, Demeclocycline, Minocycline, oxytetracycline
• Mechanism: Binds to 30S ribosomal subunit, inhibiting bacterial protein synthesis.
• Therapeutic uses: Concentrated in gingival fluid, used to eradicate resistant bacteria in chronic periodontal disease. Limited usefulness in acute orodental infections, often used as a second choice after penicillin, erythromycin, and cephalosporins. Other uses include eradication of H. pylori, preventing malaria, treating amebiasis, treating acne.
• Adverse reactions: Heartburn, nausea, vomiting, alteration in the normal flora (oral candidiasis), colitis (C. difficile), discoloration and hypoplasia of teeth (in young children and during pregnancy).

Macrolides

• Erythromycin, Clarithromycin, Azithromycin
• Spectrum: Bacteriostatic, narrow-spectrum antibiotics, effective against gram-positive cocci (streptococci, gram-positive bacilli), few gram-negative bacilli, and some atypical organisms, but not effective against anaerobes.
• Kinetics: Erythromycin absorption affected by food, Clarithromycin and Azithromycin not affected. Wide distribution, concentrated in macrophages (especially azithromycin).
• Half-lives: Erythromycin (6 hours), Clarithromycin (12 hours), Azithromycin (>24 hours)
• Dose adjustment: needed for renal patients with Clarithromycin.
• Adverse reactions: Epigastric distress, nausea, vomiting, diarrhea, cholestatic hepatitis.

Aminoglycosides

• Protein synthesis inhibitors
• Mechanism: Enhance bacterial protein synthesis by cell wall synthesis inhibitors
• Bactericidal agent
• Pharmacokinetics: Poor oral absorption; given orally for local effect in GIT, adjust dosage for renal insufficiency.
• Adverse reactions: Ototoxicity (may be irreversible) and nephrotoxicity (reversible); more common in elderly patients, particularly with the presence of other ototoxic and nephrotoxic drugs (i.e. loop diuretics).

Lincosamides

• Clindamycin
• Broad-spectrum bacteriostatic antibiotic that covers both aerobic and anaerobic pathogens.
• May be prescribed in persistent infections, an excellent choice in penicillin-allergy cases.
• Adverse reactions: Vomiting, nausea, diarrhea, exanthem, jaundice, hepatitis, neutropenia, eosinophilia, agranulocytosis, blood platelet count change, pseudomembranous colitis.

Fluoroquinolones

• DNA synthesis inhibitors
• Mechanism: Inhibit DNA synthesis by inhibiting DNA gyrase.
• Categories are 1st, 2nd, 3rd, 4th generations.
• 2nd generation: Anti-pseudomonal fluoroquinolones (e.g., ciprofloxacin)
• 3rd generation: Respiratory fluoroquinolones (e.g., levofloxacin)
• 4th generation: Moxifloxacin
• Therapeutic uses: Bactericidal, used for orodental infections caused by gram-negative bacilli resistant to other antibiotics. Gatifloxacin (3rd generation) is active against Gram-positive bacteria and anaerobes. Ciprofloxacin may be combined with metronidazole in refractory or mixed infections. Moxifloxacin considered a good choice for odontogenic and periodontal infections.
• Adverse reactions: Central nervous system effects (headache, dizziness, insomnia, seizures), gastrointestinal issues (nausea, diarrhea, abnormal liver function), skin reactions (rashes, photosensitivity), musculoskeletal problems (tendonitis, tendon rupture)
• Not recommended in children or during pregnancy due to cartilage erosion.

Metronidazole

• Effective against anaerobic gram-negative and gram-positive bacteria.
• Treatment of choice for Clostridium difficle (pseudomembranous colitis). Antiprotozoal agent.
• Adverse reactions: Gastrointestinal upsets, metallic taste, seizures, and cumulative peripheral neuropathy (uncommon, but serious, avoid repeated courses).
• Drug interactions: Should be used cautiously with drugs which prolong QT interval (clarithromycin, azithromycin), inhibits cytochrome P450, and thus potentiates anticoagulant effects of warfarin.

Antifungal Drugs

• Classified as systemic or topical agents.
• Nystatin: Highly toxic, used topically (effective against Candida).
• Griseofulvin: Isolated from Penicillium griseofulvium; active against Microsporum (superficial infection/dermatophytosis).
• Amphotericin B: Poorly absorbed from the GIT and topically; widely distrubuted in tissues post IV administration. About 60% metabolized in the liver and excretion is slow (urine and bile).
• Indications: Oral candidiasis, topical treatment for oral, vaginal and cutaneous candidiasis, hospital treatment for severe systemic fungal infections.
• Adverse reactions: nausea, vomiting, headache, fever, breathlessness, thrombophlebitis (in IV administration), dose-related nephrotoxicity, and anemia (in prolonged use)..

Antiviral Drugs

• Oral viral infections (herpes simplex virus types 1 and 2, Epstein-Barr virus, varicella-zoster virus, Coxsackie virus, human papilloma virus, human immunodeficiency virus).
• Classification:
  • Drugs for herpes (Acyclovir, Ganciclovir)
  • Drugs for influenza (Amantadine, Zanamivir)
  • Drugs for HBV and HCV (Interferon, Lamivudine, Ribavirin)
  • Drugs for HIV (Zidovudine, Didanosine)
• Acyclovir: Competitive substrate for DNA polymerase; inhibits DNA polymerase, incorporated into viral DNA, premature chain termination.
• Route of administration: Oral, intravenous (IV), topical.
• Indications: Prophylaxis against herpes infections in AIDS and other immunosuppressed patients; treatment of herpes simplex virus infection; treatment of varicella (chickenpox) and herpes zoster (shingles).
• Adverse effects: Few side effects (i.e., nausea, diarrhea, headache, nephrotoxicity, hepatoxicity)

Dental Implications of Chemotherapy Agents

• Treatment of acute dental infections.
• Prophylactic use for dental procedures: Patients with congenital or history of rheumatic fever, patients with transplanted organs, patients with uncontrolled diabetes mellitus, patients with certain oro-facial traumatic wounds, and patients on immunosuppressant and/or corticosteroid therapy.
• Commonly prescribed antibiotics in dentistry: Penicillins (amoxicillin, amoxicillin and clavulanic acid), metronidazole.
• Azithromycin can be used in penicillin allergy cases as it is active against some oral anaerobes.

Ideal antibiotic duration

• ideal duration of antibiotic treatment is shortest cycle; most acute infections are resolved in 3-7 days.

Antimicrobials for dental practice

• Antimicrobials active against gram-positive cocci and oral anaerobes: amoxicillin; safe & bactericidal; chlorhexidine 0.2% also used as adjuvant to reduce bacteremia following dental extractions.