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indications for tetracyclines
broad antibacterial spectrum, good for organisms not susceptable to cell-wall synthesis inhibitors
rickettsia, chlamydia, mycoplasma, borrelia (lyme dz), anthrax, etc
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how tetracyclines work
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
-
tetracycline side effects
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
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mechanism of action of chloramphenicol
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
-
chloramphenicol toxicity
- 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
-
macrolide abx
erythromycin, clarithromycin, azithromycin, telithromycin, etc
can be used as a substitute for penicillin in pen-sensitive patients
-
macrolide mechanism of action
erythromycin inhibits translocation step in elongation
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clindamycin especially good against...
anaerobes, esp. B. fragilis
-
common clindamycin side effect
- ulcerative colitis
- - pseudo-membranous colitis, fairly common
- - due to Clostridium difficile
- - giving with vancomycin prevents this, but the high cost of vanco is prohibitive
-
all inhibitors of bacterial protein synthesis are bacteriostatic, except for the aminoglycosides, which are bacteriocidal
very true
-
major side effects of bacterial protein synthesis inhibitors
- 1. aminoglycosides (vestibulocochlear impairment)
- 2. clindamycin (antibiotic-associated colitis)
- 3. chloramphenicol (aplastic anemia)
-
fluroquinolones are all derivatives of ...
niladixic acid
-
fluroquinolones are all...
bacteriocidal
-
fluoroquinolones are contraindicated in...
pts younger than 18yrs (due to risk of cartilage deterioration)
pregnant and nursing women
may cause tendonitis in adult patients
-
mupirocin
inhibits bacterial protein synthesis
used to treat topical (nasal) MRSA infections
-
synercid
a streptogramin
inhibits bacterial protein synthesis by binding to the ribosomal RNA of the 50s subunit (does not bind to eukaryotic rRNA)
-
linezolid
for life-threatening vancomycin resistant MRSA infections
-
daptomycin
irreversibly binds to bacterial cell membrane
rapidly depolarizes cell membrane
destroys ion concentration gradient
leads to cell death
-
metronidazole (Flagyl) uses
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
-
metronidazole precautions
"disulfiram" reaction with alcohol
potentiation of warfarin effects via interference with warfarin metabolism
stop nursing during and for 2 days after use
-
polymyxins mechanism of action
destroys selective permeability of cytoplasmic membrane
bacteriocidal
have a very low therapeutic index
-
isoniazid used to tx...
TB
-
rifampin
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
-
pyrazinamide
used to tx TB
inhibits mycolic acid synthesis
-
ethambutol
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
-
treating TB
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
-
mycobacterium avium complex (MAC)
disseminated MAC happens in up to 40% of aids patients, often limited to lungs
if only one drug is used, resistance develops quickly
-
rifambutin
rifampin derivative, more effective against MAC than rifampin
-
clarithromycin and azithromycin
excellent against many strains of MAC
-
clofamizine
initially a leprosy drug, found to be effective against MAC
-
amphotericin B
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
-
griseofulvin
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
-
ketoconazole
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
-
terbinafine (Lamisil)
inhibits squalene epoxidase
esp good for fungal infections of nails
-
tolnaftate (Tinactin)
Tx of most cutaneous fungal infections
inhibits fungal ergosterol synthesis
-
smallpox
eradicated, used to be a major problem
Group 1 in Baltimore classification
-
poliomyelitis
leads to paralysis, used to be a major problem
-
hepatitis
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
-
classification of influenza A viruses
based on hemagglutinin subtype (H1 to H16) and neuraminidase (N1 to N9)
H1N1, etc
-
zanamivir and oseltamivir (Tamiflu)
inhibitors of influenza viral neuraminidase
this enzyme needed for progeny release from infected cells
-
ribavirin mechanism of action
reduces number of guanine nucleotides that can be formed
inhibits viral RNA capping
-
ribavirin uses
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
-
acyclovir
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
-
ganciclovir
used to Tx cytomegalovirus infections
inhibits viral DNA polymerase
NOT TO BE USED IN PREGNANCY
-
interferon uses
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
-
zidovudine
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
-
nonnucleoside reverse transcriptase inhibitors
bind to a site distant from the active site in the p66 subunit of HIV-1 reverse transcriptase
induces conformational change, thus reducing activity
-
HAART = highly aggressive antiretroviral therapy
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
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