Tetracyclines bind to the 30S subunit, block tRNA binding to the A site, and thereby inhibit protein synthesis.

Oral formulations interact with orally administered cations (calcium, iron, aluminum);

Avoid in pregnancy and children < 8 years due to permanent tooth discoloration and photosensitivity.

All tetracycline are excreted primarily in the urine except doxycycline.

Doxycycline is excreted in feces and thus can be used in the presence of renal failure.

Half life of doxycycline and minocycline are longer than tetracyclines.

Tetracyclines are broad spectrum bacteriostatic drugs.

Development of resistance to tetracycline is mainly due to the development of efflux pumps.

Doxycycline is the most preferred tetracycline for most indications

due to more favorable activity, tolerability, and frequency of administration.

Minocycline is similar to doxycycline, with improved activity vs. staphylococci, Acinetobacter, and Stenotrophomonas maltophilia.

Tetracyclines are drug of choice for

lymphogranuloma venerum, granuloma inguinale,

atypical pneumonia due to chlamydia,

Cholera, brucellosis with rifampicin,

plague prophylaxis, relapsing fever, lymes disease,

rickettsial infections and chlamydial infections.

Skin and soft tissue infection (doxycycline and minocycline).

meningococcal carrier state(minocycline), malaria prophylaxis(doxycycline), Amoebiasis(doxycycline), SIADH (demeclocycline is used),

As secondary drugs for gonorrhea, syphilis and chlamydial infection,

pleurodesmosis in malignant
pleural effusion (doxycycline as a sclerosing agent), leprosy(minocycline),

peptic ulcer by H.pylori(tetracycline).

Tetracyclines may cause superinfection diarrhea and pseudomembranous colitis.

Gastrointestinal side effects are most common adverse effects.

Tetracyclines are contraindicated in pregnancy due to the risk of fetal tooth enamel dysplasia and irregularities in the fetal bone growth.

Demeclocycline(maximum) and doxycycline can result in photosensitivity.

Minocycline may lead to dose dependent vestibular toxicity.

Diabetes insipidus may be precipitated by ADH antagonistic action of demeclocycline.

They may increase intracranial pressure (pseudotumor cerebri) and cause bulged frontanelle in young infants.

Tigecycline are more resistant than tetracyclines to efflux pumps developed by the organisms.

Main indication of tigecycline is serious complicated skin and skin structures infection, intraabdominal infections and community acquired pneumonia.

It is used against MRSA, VRSA, enterococci and anaerobes.

Omadacycline is approved for the treatment of adults with acute bacterial skin and skin structure infections (ABSSSIs)

and for the treatment of adults with community-acquired bacterial pneumonia (CABP).

Eravacycline is a tetracycline class antibacterial indicated

for the treatment of complicated intra-abdominal infections in patients 18 years of age and older.

Sarecycline is a tetracycline-derived oral antibiotic, specifically designed for acne,

and is approved by the Food and Drug Administration (FDA) in 2018

for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris (AV) in patients 9 years of age and older.

The primary intracellular site of action of the aminoglycosides is the 30S ribosomal subunit.

Aminoglycosides interfere with the initiation of protein synthesis, leading to the accumulation of abnormal initiation complexes;

The drugs also can cause misreading of the mRNA template and

Incorporation of incorrect amino acids into the growing polypeptide chains.

Aminoglycosides—Inhibitors of Bacterial Protein Synthesis General: Bactericidal, no GI absorption

Oral administration used only for bowel decontamination or intestinal parasites.

Nephrotoxicity, ototoxicity (cochlear and vestibular), neuromuscular blockade are the important adverse effects of aminoglycosides.

These include streptomycin, gentamicin, kanamycin, tobramycin, amikacin, sisomicin, netilmicin, neomycin, plazomicin, paromomycin, framycetin.

Aminoglycosides exhibit CDK and have prolonged PAE.

Therefore administered as single daily dose.

Aminoglycosides are bactericidal inhibitors of protein synthesis.

Their penetration across the cell wall is dependent on the oxygen dependent transport system.

Therefore the drugs are inactive against anaerobes.

Their transport is enhanced if used along with cell wall synthesis inhibitors like penicillins.

These are not absorbed orally and donot cross the blood brain barrier.

These are excreted primarily by glomerular filtration

and their dose should be decreased in renal insufficiency.

Resistance to these drugs develops due to the formation of inactivating enzymes

which acetylate, phosphorylate or adenylate the aminoglycosides.

Gentamicin, tobramycin and amikacin are effective against gram negative organisms including pseudomonas except salmonella.

However these are not reliable for gram positive organisms if used alone.

Aminoglycosides produce synergistic effects against gram positive bacteria

when combined with beta lactams or vancomycin.

Streptomycin is the first line drug for the treatment of tuberculosis, plague and tularemia.

Amikacin is used in UTI, Lung infections, including cystic fibrosis exacerbations, Nosocomial sepsis of unknown origin.

Gentamicin is used in

UTI, Peritonitis, Endocarditis in combination with a cell wall–active agent, Plague and Tularemia.

Tobramycin is used in

UTI, Lung infections, including cystic fibrosis exacerbations, Nosocomial sepsis of unknown origin.

Plazomicin is used in UTI.

Neomycin is used in minor skin infections, Bowel preparation prior to intra-abdominal surgery, Bladder irrigation.

It has similar activity to gentamicin but only used topically, not systemically.

Paromomycin is used in cryptosporidium infection, intestinal amebiasis, and Leishmaniasis.

Spectinomycin is a drug related to aminoglycosides

which is used as single dose treatment for

penicillinase producing Neisseria gonorrhoea (PPNG) and for gonorrhoea in penicillin allergic patient.

Amikacin, kanamycin and neomycin are like to cause hearing loss whereas streptomycin and gentamicin cause predominantly vestibular dysfunction.

Nephrotoxicity maximum with neomycin> gentamicin minimum with streptomycin.

Ototoxicity maximum with amikacin(auditory) streptomycin(vestibular) minimum with netilmicin.

Neuromuscular blockade: neomycin> streptomycin least with tobramycin.