Antibiotics 1 and 2 Flashcards
how was penicillin discovered
1928- dr felming notices that the mold penicillium prevented normal growth of saphylococci
1941- alternative strain of penicillium chyrosogeium which yielded 200x amount of penicilin
first pt treated w/ peniccilin
1942- anne miller treated w/ penicillin
ideal antibiotics
target one or more bacterial species w/ no toxicity or allergy
effective concentration at sites of infection, absorption, distribution, metabolism, excretion
persist long enough to destroy target
overcome bacterial resistance
pharmacokinetics
what the body does to the drug
pharmacodynamics
toxicity and therapeutic index (Lethal Dose/Effective Dose)
two major mechanisms of antibiotic action
bacertiostatic- prevents growth but does not kill bacteria. removal of drug results in resumed growth
bacteriacidal- kills bacteria. drug is removed when bacteria is dead
large therapeutic index
over 10
indicates a large window where the drug can be safely used
methods for determining the efficacy of antibiotics in vitro
kirby bauer disc diffusion essay- testing multuple antibiotics ability to kill a pathogen. culture a plate of bacteria and add antibiotics to plate. incubate overnight. measure the diamater of the zone of inhibition. only tests for inhibitory concentrations
MIC- minimal inhibitory concentration (minimal amount of antibiotic required to inhibit growth). done by diluting the amount of antibiotic in a bacterial culture to find minimum necessary amount. alternatively, can use e-test as a quick version w/ antibiotic gradient
MBC- minimal bactericidal concentration (minimal amount of antibiotic to kill the bacteria). done by plating MIC results to see if they grow.
describe the MBC/MIC ratio in bacteriostatic and bactericidal drug
static- high
cidal- low
properties of antibiotics that must be considered before use
bacteriostatic vs bacteriocidial
therapautic range (low can e toxic)
resistance
drug penetration at infected sites
factors that affect drug distribution (absorption, distributoin, metabolism, and excretion)
toxicity
characterisitics of the patient that are important when considering antibiotics
route of administration
duration of treatment
age, sex, general health, concurrent medication and disease, allergies, immunological status
what are the mechanisms of antibiotics?
- inhibition of cell membrane synthesis
- inhibition of cell wall synthesis
3 inhibition of bacterial protein synthesis
4 inhibition of nuclei acid synthesis
drugs that affect cell membrane synthesis
lincomycins
daptomycin
polymixin
drugs that affect bacterial protein synthesis
aminoglycosides- 30S ribosome
tetracyclines- 30S ribosome
chloramphenicol- 50S ribosome
macrolides- 50S ribosome
clindamycin- 50S ribosome
mupirocin- tRNA
antimetabolites
analogs that interfere w/ synthesis or function involved in cell metabolism
sulfonamide- group of compounds w/ structure to PABA that interferes w/ folic acid metabolism (prevents production of dihydropteric acid, an intermediate of THF) (static)
trimethoprim- prevents last step in folic acid metabolism, used in conjuction w/ sulfonamide (inhibits DHF reductase, which binds 1000x more strongly to bacterial DHF) (cidial)
isoniazid- bactericidal drug that destroys integral component of mycobacterial cell wall (cidial)
are antimetabolites static or cidal?
static- interfere w/ folic acid metabolism which inhibits DNA synthesis
bactrim
antimetabolite which is the combination of sulfamethoxazome and trimethoprim
used for UTIs
B- lactam antibiotics
anti-cell wall antibiotics
penicillin- uses its b-lactam ring to bind the penicillin binding protein necessary for the transpepitdation rxn that creates the cross linking in cell walls
synthetic penicillins- methicillin, oxacillin, cephalosporins
more effective in combination w/ b-lactamase inhibitors (augmentin)
when is penicillin effective?
cells must be growing and dividing for penicillin to be effective
penicillin g vs v vs vk vs ampicillin
K- sensitive to acid hydrolysis- only for IV or IM
sensitive to B-lactamases
active against Gram+, not gram
V and VK- resist acid hydrolysis- taken orally
ampicillin/amoxicillin- amino penicillin- resists acid hydrolysis, has a broader spectrum (w/ some Gram - efficacy)
synthetic penicillins
sensitive to penicllinase, broader spectrum
- ampicilin- acid stable
- amoxicillin (higher serum levels) acid stable
sensitive to penicillinase, extended spectrum
- tricarcillin
- piperacillin - most effective against G- entero bacilli
resistant to penicllinase, less active against G+, no G-
- methicllin (acid labile)
- oxacillin- acid resistant
carboxypenicillins
tricarcillin, pipeacillin, carbenicillin
extended spectrum into Gm -, but decreased Gm+ efficacy
cephalosporins
similar to structure w/ B-lactam ring, bacteriocidal, but w/ a different R group (has dihydrothiazine)
broader spectrum
greater acid stability
resistant to B-lacamases
cross rxn w/ penicillin allergy
monobactams
aztereonam
monocyclic b-lactam
b-lactamase resitant
active against aerobic Gm- bacteria
generally inactive against Gm + or anerobes
carbapenems
imipenem or meropenem
resistant to b-lactamases
broadest spectrum, most effective against gram - bacteria
b-lactamse inhibitors
used in combination w/ b-lactam antibiotics
clavulonic acid- in combination with amoxicillin (augmentin- oral)
sulbactam - in combination w/ ampicillin (unasyn- parenteral)
tazobactam- in combination w/ piperacillin (zosyn IV)
glycopeptide cell wall synthesis inhibitors
vancomysin
talvancin
teicoplanin
vancomysin
binds to D-ala-D-ala, restricted to gram +
nephrotoxicity
inhibits peptidoglycan precursor transfer
vancomysin is the drug of choice for which infections?
multiple resistant enterococcus
methicllin resistant staph aureus (MRSA)
cycloserine
inhibits cell wall synthesis
d-ala analogue, inhibits d-ala-d-ala cross link
TB secondary dr8gug
bacitracin
inhibits cell wall synthesis
inhibits lipid carriers step. can only be used topically
gram + only
drugs that inhibit cell wall synthesis
penicllins vancomycin telavancin cephalosporin monobactam carbapenem
drugs that inihibit nucleic acid synthesis
sulphonamides trimethoprim- folic acid metabolism metronidazole quinolones- inhibit DNA gyrase rifampacin- inhibit RNA polymerase
cephalospore generatoins
1st- effective against Gm+ and some -. not PA
cephazolin
2nd- effective against Gm + and -, not PA
cefuroxime
3rd- increased B-lactamse resistance, Gm + and -, effective against Pa
ceftriaxone, ceftazidime
