OIA1015 30S INHIBITORS

30s inhibitors

Antibiotics that target the 30S ribosomal subunit, interfering with bacterial protein synthesis; includes aminoglycosides and tetracyclines.

Aminoglycoside mechanism of action

Binds irreversibly to the 30S subunit, causing misreading of mRNA and inhibition of protein synthesis; bactericidal and concentration-dependent.

Examples of aminoglycosides

Streptomycin, gentamicin, tobramycin, amikacin, kanamycin, neomycin.

Post-antibiotic effect (PAE) (Aminoglycosides)

Continued suppression of bacterial growth even after drug levels fall below MIC; enables once-daily dosing.

Concentration-dependent killing (Aminoglycosides)

Efficacy correlates with peak concentration (Cmax); target Cmax = 8–10× MIC.

Indications for aminoglycosides

Serious aerobic Gram-negative infections; often used in combination with β-lactams for synergy.

Synergistic use (Aminoglycosides)

Combined with β-lactams against Enterococcus faecalis and E. faecium.

Route of administration (Aminoglycosides)

Given IV due to poor oral absorption (high polarity); neomycin used orally for GI decontamination only.

CSF penetration (Aminoglycosides)

Inadequate, even with inflamed meninges; intrathecal (IT) route required for CNS infections.

Placental crossing (Aminoglycosides)

All aminoglycosides cross the placenta; risk of fetal ototoxicity.

Excretion (Aminoglycosides)

90% excreted unchanged in urine via glomerular filtration; dose adjustment needed in renal impairment.

Nephrotoxicity (Aminoglycosides)

10–20% incidence; due to accumulation in proximal tubule; reversible on discontinuation.

Potentiating nephrotoxicity (Aminoglycosides)

Drugs like vancomycin, amphotericin B, NSAIDs increase renal toxicity risk.

Ototoxicity (Aminoglycosides)

Affects vestibular and cochlear function—causes vertigo, tinnitus, hearing loss; irreversible and dose-dependent.

Ototoxicity risk factors (Aminoglycosides)

High peak plasma levels, prolonged treatment, and concomitant ototoxic drugs.

Neuromuscular blockade (Aminoglycosides)

Can cause paralysis; contraindicated in myasthenia gravis.

Myasthenia gravis Contraindications (Aminoglycosides)

Due to enhanced risk of fatal respiratory muscle paralysis.

Tetracycline structure

Contain four fused hydrocarbon rings (tetra = four); bacteriostatic class.

Tetracycline mechanism of action

Binds reversibly to 30S subunit, blocking aminoacyl-tRNA from accessing the acceptor site → halts protein synthesis.

Examples of tetracyclines

Tetracycline, doxycycline, minocycline; newer derivative: tigecycline (IV only).

Spectrum of tetracyclines

Broad-spectrum; active against Gram-positives, Gram-negatives, atypicals, and spirochetes.

Absorption (Tetracyclines)

Orally absorbed from upper small intestine; reduced by multivalent cations (Ca²⁺, Mg²⁺, Fe²⁺, Al³⁺).

Chelation effect (Tetracyclines)

Cations form non-absorbable complexes with tetracyclines—avoid antacids, dairy, iron supplements.

Distribution (Tetracyclines)

Bind 40–80% to plasma proteins; cross placenta; excreted in breast milk.

CSF penetration (Tetracyclines)

Only doxycycline and minocycline reach therapeutic CSF levels.

Excretion pathways (Tetracyclines)

Most are renally excreted; doxycycline excreted via feces—safer in renal failure.

Minocycline advantage

High saliva levels—useful in meningococcal carrier eradication.

GI irritation (Tetracyclines)

Common side effects: nausea, vomiting, diarrhea; take on empty stomach with full glass of water.

Tooth discoloration (Tetracyclines)

Binds Ca²⁺ in developing teeth; causes yellow/brown staining and enamel hypoplasia.

Skeletal effects (Tetracyclines)

Deposits in growing bone; stunts growth in children under 8 years old.

Pregnancy risk (Tetracyclines)

Crosses placenta → affects fetal teeth and bones; contraindicated, especially in 2nd–3rd trimester.

Photosensitivity (Tetracyclines)

Especially with doxycycline; causes sunburn reactions—advise sun protection.

Hepatotoxicity (Tetracyclines)

High doses may cause liver damage; risk higher in pregnancy and renal impairment.

Vestibular toxicity (Tetracyclines)

Minocycline can cause vertigo and dizziness; reversible after discontinuation.

Pseudotumor cerebri (Tetracyclines)

Increased intracranial pressure causing headache, visual disturbances; reversible with drug cessation.

Antacids and supplements (Tetracyclines)

Chelation with calcium, magnesium, aluminum, iron reduces absorption—separate administration by 2 hours.

Bactericidal antibiotics

Tetracyclines may antagonize effect—avoid concurrent use with β-lactams.

Digoxin

Tetracyclines may increase bioavailability of digoxin—monitor for toxicity.

Anticoagulants

Tetracyclines reduce prothrombin levels—may require warfarin dose adjustment.

Lithium

Tetracyclines can potentiate lithium toxicity—use cautiously.