ANTIRIBOSOMAL ANTIBIOTICS

LEARNING OBJECTIVES • To recognize the different antibiotics that inhibit ribosomal activity, their mechanism of action, spectrum, side effects and resistance Since we only want to inhibit the growth of pathogenic bacterial cells during an infection and not our own cells, we are fortunate that bacteria actually have a different type of ribosome than we do. We can use this difference by specifically inhibiting the ribosomes of bacteria, while sparing the function of our own ribosomes.

CHLORAMPHENICOL: This drug has an amazing spectrum of activity. It is one of the few drugs (like Imipenem) that kill most clinically important bacteria. Gram positive, gram negative, and even anaerobic bacteria are susceptible. Mechanism of action: It binds to 50s ribosomal subunit preventing formation of peptide bonds. Hence, preventing protein synthesis. Site of action of chloramphenicol is overlapping with site of action of Macrolides and Lincosamides, so it is antagonized by these drugs. Clinical use: 1- It is used to treat bacterial meningitis, when the organism is not yet known and the patient has severe allergies to the penicillins, including the cephalosporins. This is because is has a wide spectrum of activity and excellent penetration into CSF. 2- Rocky Mountain spotted fever in young children and pregnant females.

2. such as septic abortions. The first is reversible and often only causes an anemia. Side effects: It can cause Pseudomembranous colitis. It is also used for infections of the female genital tract. In developing countries.Alteration of the target. This is called aplastic anemia. It destroys the natural flora of the GI tract. which appears as a gray color.g. It is used to treat many gram positive and anaerobic infections.B. 3. Clinical use: It is not useful against gram negative bacteria. as there are a lot of anaerobes here.Production of inactivating enzymes by the bacteria.Gray baby syndrome: Neonates are unable to fully conjugate chloramphenicol in the liver resulting in very high blood levels. allowing Clostridium difficile to grow and secrete exotoxin. causing pseudomembranous colitis. Erythromycin. MACROLIDES They may be old generation e.N.Decreased permeability and production of efflux pump. The second type wipes out the bone marrow and is usually fatal. this drug is widely used because of its cheap price and wide spectrum of activity.g. resulting in cyanosis. This mechanism is plasmid mediated.This drug is famous for 2 types of bone marrow depression. Resistance: 1. or new generation e.Optic neuritis. Side effects: 1. 2. Surgeons use clinadamycin along with an aminoglycoside for penetrating wound infections of the abdomen. CLINDAMYCIN It has the same mechanism of action and resistance of macrolides (see later). 3. Azithromycin. .

It is inactive against most gram negatives. It is the drug of choice for community-acquired pneumonia that does not require hospitalization. aluminum hydroxide. Clinical use: 1. Mechanism of action: They bind to the 30s ribosomal subunit. Side effects: It is one of the safest antibiotics. 1. Ca++. and Mg++. Resistance: The bacteria produce enzymes that decompose the drug. When it is chelated. and Chlamydia trachomatis.Rash 4.Auditory dysfunction Azithromycin: It can be used for the treatment of (Chlamydial) non-gonococcal uretheritis.pneumonia caused by Mycoplasma pneumonia (as an alternative to erythromycin) . Doxycycline is a tetracycline that chelates cations poorly and is thus better absorbed with food.Mechanism of action: They bind to part of the 50s ribosomal subunit preventing protein synthesis.Abdominal pain (GI irritation) 2. Erythromycin: Clinical use: Gram positive organisms absorb erythromycin 100 times better than gram negative organisms.venereal diseases caused by Chlamydia trachomatis 2.Rare cholestatic hepatitis 3. It covers Streptococcus pneumoniae. TETRACYCLINES/DOXYCYCLINES Tetracycline chelates with milk and milk products. Mycoplasma pneumoniae. it will pass through the intestine without being absorbed.

It has the broadest spectrum and is good for hospital acquired (nosocomial) infections that have developed resistance to other drugs. 1.Cause misreading of mRNA Clinical use: They kill aerobic gram negative enteric organisms. Most of the aminoglycosides end with –mycin.Gentamicin: is the most commonly used of all the aminoglycosides. It is combined with penicillins to treat inhospital infections. so they are often used with penicillin.reduction of intracellular drug concentration by decrease of permeation and efflux pump 2.production of enzymes that decompose the antibiotic Side effects: 1.3.Renal and hepatic toxicity 4. AMINOGLYCOSIDES They must diffuse across the cell wall to enter the bacterial cell.Discolored teeth and depressed bone growth. 3.modification of the target (30s subunit) 3. .They bind irreversibly to 30s ribosomal subunit 2.Cause leakage of the cytoplasmic membrane 3. They are among the handful of drugs that kill Pseudomonas aeruginosa. 2. 4.Tobramycin is good against Pseudomonas aeruginosa 4.Animal and tick-borne diseases caused by Brucella and Rickettsia. Mechanism of action: 1.Streptomycin is the oldest one in the family.Amikacin: does not end with mycin.Acne Resistance: 1.GI irritation 2. Many bacteria have developed resistance to it.Phototoxic dermatitis (skin inflammation on exposure to sunlight) 3. which breaks down this wall to facilitate diffusion.

Nephrotoxicity 2.Contact dermatitis SPECTINOMYCIN: This drug has a name that sounds like an aminoglycoside. so it can only be used topically for skin infections Useful combinations with aminoglycosides include: Rifampicin+streptomycin+isoniazide for treatment of TB Streptomycin+penicillin subacute bacterial endocarditis (SABE) Streptomycin+tetracycline plague Resistance: 1.Neomycin: has very broad coverage but is too toxic.Reduction of permeability Side effects: 1. since many strains are resistant to these drugs. but it is different structurally and biologically.Neuromuscular blockade 4.Ototoxicity 3.Production of inactivating enzymes 2.5.Mutation of the target (30s subunit) 3. Clinical use: It is used to treat gonorrhea as an alternative to penicillin and tetracycline. . It is given as an IM injection. Its mechanism is similar in that it acts on the 30s ribosome to inhibit protein synthesis.

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