Lecture 19 - Chemical Methods - Inhibit Protein Synthesis and Inhibit Nucleic Acid Synthesis

Aminoglcyosides
Glycosides are common in the plant world, and are used to make some chemicals water-soluble by adding a sugar molecule to it. Aminoglycosides are ototoxic (ears) and nephrotoxic (kidneys), so are only used for severe infections.

Streptomycin
Streptomycin is used as a DOC for severe TB infections and Yersinia pestis. It is injected to ensure administration. Tuberculosis is also known as the white plague, and Yersinia pestis causes the black plague.

Neomycin
Neomycin is a broad spectrum drug that is found in triple antibiotic ointments. It is not recommended to be used for large wounds because it can get into the blood stream and cause hearing loss.

Gentamycin
Gentamycin is replacing streptomycin for treating Gram-negative infections, especially if it is hospital-acquired. This is used as a DOC for Pseudonomas other infections. It is used in combination with ticarcillin.

**Capreomycin, Kanamycin, Amikacin
If a strain of tuberculosis is resistant to one of these drugs by injection, it is classified as XDR TB.

Tetracycline (Doxycycline)
Doxycycline is the most commonly used tetracycline in the US. It is used as a penicillin substitute for Gram-positive infections such as Borrelia (lyme disease), Chlamydia (UTI), Mycoplasma pneumoniae (CAP), and Rickettsia (Rocky Mountain fever). Treats both diseases caused by ticks.

Nitrobenzene Derivatives
Nitrobenzene derivatives are highly toxic; they cause aplastic anemia, preventing bone marrow from producing white blood cells and red blood cells. In fact, they are so toxic that they are only used as a last resort, and are in the process of being removed from use. Chloramphenicol is used as a last resort for vancomycin resistant enterococci (VRE), which grows in feces. It is also used to treat salmonella typhi (typhoid fever) and meningitis (haemophilus influenzae).

Macrolide
The macrolides are a group of drugs (typically antibiotics) whose activity stems from the presence of a macrolide ring.

Azithromycin
Azithromycin (brand name Zithromax or Z-Pak), is used as a DOC for many infections. They are very commonly prescribed to adults for Neisseria gonorrhea, chlamydia, mycoplasma, and Bordetella pertussis.

Azithromycin is also used as a beta-lactam substitute for pregnant women who are allergic.

Erythromycin
Erythromycin is used for the same uses as azithromycin, but in babies, for ophthalmia neonatorum.

Linezolid (Zyvox)
Linezolid is a DOC for VRE, and an alternate for systemic MRSA.

Structural Analogues (DNA)
Structural analogues are things that look like DNA. They fit into the DNA and cause mutations that kill the organism. These drugs are toxic to anything that make DNA, but some organisms are more sensitive than others.

Acyclovir
Acyclovir is a purine (A+G) analogue that is used for Herpes virus, chicken pox, and shingles.

AZT (Azidothymidine)
AZT is a Thymine analogue. It was the primary drug for treatment of AIDS. Nowadays, they give it to pregnant women before birth to prevent transfer of the AIDS virus to the baby.

Metronidazole (Flagyl)
Flagyl gets reduced in anaerobic cells, and turns into a DNA analogue that interferes with the synthesis of DNA. It is used for anaerobic infections, and has little effect on humans and aerobic bacteria. It is used to treat amoebic dysentery, trichomonas vaginalis (very common protozoan STD), and antibiotic-associated colitis, which is caused by Clostridium difficile, a very resistant strain.

Cytoskeleton Inhibitors
Cytoskeleton inhibitors attack the microtubules in any eukaryotic organism (fungi, humans, protists, but not bacteria). They prevent mitosis from occurring.

Griseofulvin
Griseofulvin is also produced by the penicillium mold. It is used as a DOC for athlete's foot caused by Trichophyton.

Mebendazole
Mebendazole is an anthelmintic, used to treat worm infections. It binds to microtubules and interferes with ATP synthesis.

Fluoroquinolones
Fluoroquinolones are a broad-spectrum, synthetic antibiotic that has many side effects. They target the gyrase in Gram-negative bacteria. Fluoroquinolones are used to treat MDR TB. Ciprofloxacin, specifically, is used for Pseudomonas aeruginosa UTIs and Bacillus anthracis.

Rifampin
Rifampin blocks RNA polymerase, and is a DOC for Mycobacterium TB.

Ethambutol
Ethambutol is also a DOC for TB. The mechanism of this drug is has something to do with RNA.