pharmacology II exam 3 aminogly, chem, misc (beuscher)

large (50S) + small (30S) = 70S ribosome

large (60S) + small (40S) = 80S ribosome

aminoacyl synthetase
checkpoints @ aminoacylation of tRNA and codon-reading by ribosome

complexation of mRNA, GTP, IF2, fMet-tRna (start codon)
complex binds to 30S
this new complex binds to 50S and begins protein synth

mupirocin

aminoglycosides, tetracyclines

chloramphenicol, macrolides, streptogramins, lincosides

linezolid

inhibit isoleucyl-tRNA-synthetase
gram + only
topical only
stap aureus elimination from nasal mucosa (scabby rash around mouth/nose)

injection only
broad spectrum (gram + and gram - )
AE: potential for nephrotoxicity or deafness!

first gen aminoglycoside
gram + usage
can cause deafness

most commonly used aminoglycoside used at present
given at high doses to destroy bacteria to the point where they can't recover
less nephrotoxicity (since no infusion over a long time), but good therapeutic effect

related to aminoglycoside, not one though
parenteral only
previously used for gonorrhea, no current usage though

targets 50S peptidyl transferase. stops peptide formation between 2 amino acids (mimics peptide bond). stops protein elongation
can cause anemia (might need bone marrow transplant) and gray baby syndrome
gram + and gram -

mixture of 2 streptogramins
bind to peptidyl transferase on 23S (large subunit)
used against vanco-resistant enterococcus faecium

similar spectrum to macrolides
for anaerobic infections and methicillin resistant staph aureus
risk for super infection of GI tract w/ clostridium difficil (can cause bloody diarrhea)

binds to 2 domains on 50S subunit
tissue concentraiton is much higher than plasma conc. high perfusion
liver toxicity

oral + parenteral
against methicillin-resistant staph aureus
inhibits ternary complex formation of fMet-tRNA, ribosome, mRNA
resistance to this drug is developing

1. ingestion of bacteria (inhale, food, etc)
2. red rod-like bacteria begin to multiply in lungs and form a ghon complex (aggregate of bacteria surrounded by fibron from inflammatory reponse
3. presence of live bacteria and immune response is what gives positive TB skin test
latent disease = not infectious, but still transmittable

10% of infected will have immune control breakdown and get a hole in their lung--this causes people to cough out sputum containing bacteria
interferon interfering drugs as therapy for autoimmune disease can also cause activation of TB since reducing immune system

susceptible to the 2 most effective TB drugs

resistant to both of the most effective TB drugs

resistant to both of the most effective TB drugs + 1,2,or 3 of the next drugs in line
50% of these patients die

isonizide, rifampin, ethambutol, pyrazinamide

aminoglycosides, polypeptides, flouroquinolones, thioamides, cycloserine, p-aminosalicylic acid

inhibits synth of mycolic acids (fatty acid cell-wall component of bacteria) by inhibiting fatty acid synthetase 2 (FAS2) enzyme.
MOST EFFECTIVE TB DRUG
can cause hepatotoxicity.

complexes w/ bacterial DNA-dependent RNA-polymerase and inhibits RNA synthesis
increases activity of INH (given concurrently)
AE: minor...rash, fever, nausea

inhibits arabinosyl transferase (prevents formation of arabinogalactan component of cell wall)
AE: optic neuritis..loss of vision (need eye exams every month)

inhibits mycolic acid synthesis (part of cell wall) at earlier step than INH
AE: arthralgia, hyperuricemia, hepatoxocity (possibly irreversible..so beware when prescribing)

structural analog of d-alanine
prevents extension of peptidoglycan by inhibiting alanine racemase
AE: frequently neurologic (seizures, psychosis, periph neuropathy)

inhibits mycolic acid formation
AE: GI problems

functionally equiv. to aminoglycosides
AE: 8th nerve toxicity (deafness), nephrotoxicity

interferes w/ folate synthesis (similar to sulfonamides)
effectiveness specific to mycobacteria (does same thing as trimethoprim)

average TB lesion contains 10^8 M. tuberculosis bacteria.
on average, 100 bacteria per lesion resistant to any one drug--treatment failure w/ monotherapy

mycobacterium avium has 3 species
+ mycobacterium intracellulare

infection w/ any one of the four subspecies or species listed qualifies as MAC disease

at least 2 agents: azithromycin or clarithromycin + ethambutol

MAC = totally resistant to INH

no regimen has proven efficacy

rifabutin (rifamprin derivative
must be continued for life

inhibit dephosphorylation of c55-isoprenyl pyrophosphate (which normally assists in bacterial cell wall production by transporting NAG and NAM. carrier recycled for next addition..but bacitracin stops recyclin)

effective only against gram +

binds guanine in bacterial DNA--interferes with DNA polymerase
used w/ rifampin + dapsone for treatment of Hansen's disease
AE: GI intolerance, skin discoleration
orphan drug

used w/ rifampin + clofazimine to treat Hansen's
inhibits folate synth.
antiinflam + immunomodulating effects
AE: dose-related hemolysis, methhemoglobinemia (interfers w/ oxygen transfer)

inserts into cell membrane and depolarizes it. loss of membrane potential leading to inhibition of protein, DNA and RNA synthesis, which results in bacterial cell death.
gram +
for skin and soft-tissue infections
AE: myalgia, myositis

effective only in organisms w/ anaerobic metabolism.
forms unstable complexes and disrupts DNA
AE: nausea, metallic taste
dont' take w/ alcohol

gram - (ex: e coli)
binds to outer and cytosolic membrane and destroys it--like a detergent
"last resort" antibiotic because of neurotoxicity and nephrotoxicity
can decrease large-intestine bacterial flora if given orally (uncommon)--normally topical use