Pharm- antibiotics II

broad antibacterial spectrum, good for organisms not susceptable to cell-wall synthesis inhibitors

rickettsia, chlamydia, mycoplasma, borrelia (lyme dz), anthrax, etc

bind to 30s ribosomal subunit, preventing protein synthesis at ANY phase of the elongation process

selective toxicity b/c they can't penetrate into mammalian cells

GI irritation (decreased if milk taken at same time, but milk decreases the action of tetracylines)

tooth discoloration in children under 8

hepatic toxicity in pregnant women

inhibits protein synthesis by binding reversibly to 50s subunit

peptide bond can't be established

will not bind to the 80s subunit of mammaliam cells, but will bind to ribosomes derived from mammalian cell mitochondria

• the use of chloramphenicol should be limited to when there are no other drugs available, and the benefits of the drug far outweigh the risk of potential toxicities
• - salmonella, rickettsia, bacterial meningitis

• 1. Gray Syndrome (in neonates)
• 2. Leukopenia (can inhibit protein synthesis by ribosomes in mitochondria of mammalian cells, including stem cells in the marrow
• 3. Aplastic anemia

erythromycin, clarithromycin, azithromycin, telithromycin, etc

can be used as a substitute for penicillin in pen-sensitive patients

erythromycin inhibits translocation step in elongation

anaerobes, esp. B. fragilis

• ulcerative colitis
• - pseudo-membranous colitis, fairly common
• - due to Clostridium difficile
• - giving with vancomycin prevents this, but the high cost of vanco is prohibitive

very true

• 1. aminoglycosides (vestibulocochlear impairment)
• 2. clindamycin (antibiotic-associated colitis)
• 3. chloramphenicol (aplastic anemia)

niladixic acid

bacteriocidal

pts younger than 18yrs (due to risk of cartilage deterioration)

pregnant and nursing women

may cause tendonitis in adult patients

inhibits bacterial protein synthesis

used to treat topical (nasal) MRSA infections

a streptogramin

inhibits bacterial protein synthesis by binding to the ribosomal RNA of the 50s subunit (does not bind to eukaryotic rRNA)

for life-threatening vancomycin resistant MRSA infections

irreversibly binds to bacterial cell membrane

rapidly depolarizes cell membrane

destroys ion concentration gradient

leads to cell death

active against MO that carry out the phosphoroclastic reaction

blockage leads to toxic intermediates that interact with DNA, and are bacteriocidal

selective toxicity since mammalian cells do not carry out the phosphoroclastic reaction

"disulfiram" reaction with alcohol

potentiation of warfarin effects via interference with warfarin metabolism

stop nursing during and for 2 days after use

destroys selective permeability of cytoplasmic membrane

bacteriocidal

have a very low therapeutic index

TB

binds to b subunit of bacterial RNA polymerase, but not in eukaryotic cells

kills resting and intracellular tubercle bacilli

never used alone due to rapid, single step development of resistance

used to tx TB

inhibits mycolic acid synthesis

inhibits mycolic acid synthesis, but via different mechanism than isoniazid

used as first line drug if TB strains are known to be resistant to isoniazid

always use at least 2 drugs with first line drugs

2 months isoniazid (or ethambutol) + rifampin + pyrazinamide followed by 4 months isoniazid (or ethambutol) + rifampin

or

9 months isoniazid + rifampin

disseminated MAC happens in up to 40% of aids patients, often limited to lungs

if only one drug is used, resistance develops quickly

rifampin derivative, more effective against MAC than rifampin

excellent against many strains of MAC

initially a leprosy drug, found to be effective against MAC

anti fungal

binds to ergosterol in fungal membranes, leads to cell leaking

selective toxicity since mammalian cells have cholesterol instead of ergosterol

must be given IV b/c not absorbed orally

inhibits fungal mitosis by binding to microtubules of the mitotic spindle

deposited in keratin after oral dose (good to treat fungal infection of hair, nails, skin)

NOT FOR USE DURING PREGNANCY

inhibits fungal ergosterol synthesis by inhibition of sterol 14-a-demethylase

broad spectrum antifungal

its derivatives FLUCONAZOLE AND ITRACONAZOLE are better against cryptococcus neoformans (opportunistic in AIDS patients

inhibits squalene epoxidase

esp good for fungal infections of nails

Tx of most cutaneous fungal infections

inhibits fungal ergosterol synthesis

eradicated, used to be a major problem

Group 1 in Baltimore classification

leads to paralysis, used to be a major problem

virus that has been associated with many forms of cancer

Hep B is Group 7 in Baltimore classification

Hep C is Group 4 in Baltimore classification

based on hemagglutinin subtype (H1 to H16) and neuraminidase (N1 to N9)

H1N1, etc

inhibitors of influenza viral neuraminidase

this enzyme needed for progeny release from infected cells

reduces number of guanine nucleotides that can be formed

inhibits viral RNA capping

aerosol to Tx viral pheumonia and bronchiolitis caused by respiratory syncytial virus (RSV) in kids

has been used in IV to Tx Lassa virus and Hanta virus

used to Tx herpes simplex virus

selective toxicity due to the fact that the mammalian thymidine kinase will not phosphorylate the drug

Tx genital herpes, herpes zoster, etc

used to Tx cytomegalovirus infections

inhibits viral DNA polymerase

NOT TO BE USED IN PREGNANCY

used to Tx hepatitis infections

recombinant alpha interferons used clinically

interfere with viral life cycle at several stages, most importantly is inhibition of viral mRNA translation

can treat Hep B, Hep C, and HPV

inhibits viral reverse transcriptase and also causes chain termination

viral resistance can happen rapidly

DOC in AIDS treatment

may prevent the passage of AIDS virus from pregnant mother to fetus

bind to a site distant from the active site in the p66 subunit of HIV-1 reverse transcriptase

induces conformational change, thus reducing activity

can often suppress viral load to undetectable levels, but a latent viral reservoir remains that is not susceptable to HAART which can develop resistance to therapy

relies on combination therapy

need life-long treatment in most cases