Antimicrobial Chemotherapy Flashcards
what is therapeutic index
difference between effective dose and toxic dose
what is a bacteriostatic drug
inhibit bacterial growth, but pt defense must still eliminate the microbes
what is a bactericidal drug
kill bacteria
which are bacteriostatic drugs
- Tetracyclines
- Trimethoprim
- Aminoglycosides
- macrolide
- sulfonamides
which are bactericidal drugs? (cell wall inhibitors)
- Beta lactams
- vancomycin
- fluoroquinolones
- metronidazole
which drugs are synergistic
penicillins and aminoglycosides
which drugs are antagonistic
chloramphenicol and aminoglycosides
what are 3 requirements for antimicrobials
- favorable pharmacokinetics
- minimal adverse effects (including minimal suppression of normal microbiota)
- overcome resistance
what is MIC
minimal inhibitory concentration: lowest concentration a drug prevents growth in vitro
what is MBC
minimal bactericidal concentration: lowest concentration that kills 99.9% of in assay
what are MIC and MBC measurements?
quantitative measurements
what is antimicrobial serumcidal concentration?
minimum concentration required to kill a patient’s bacterial isolate in the presence of their own serum
what is a good qualitative assay?
kirby bauer (disk diffusion) is fast
what is a good quantitative assay?
broth macro/microdilution or Etest (slowe)
what does Kirby Bauer test for
sensitivity to drugs (qualitative assay)
- sensitivity to drug
- intermediate sensitivity to drug
- resistant to drug
what does the quantitative E test
read zone of occlusion after incubation period that is microgram/m:
what do AST do
measure how sensitive bacteria are to Abx
what factors need to be considered before giving chemoprophylactics to patient?
- characteristics of patient (age, immune status, gender, pregnancy)
- risk vs benefit
- will it be short term?
is treatment of baby with erythromycin a justified chemoprophylactic?
yes
is prophylaxis against malaria justified?
yes
prophylaxis against animal or human bites justified?
yes
prophylaxis after surgeries that cross mucosal barrier justified?
yes
is giving prophylactic to patient that demands if justified?
no, unjustified
what if surgery does not cross mucosal barrier?
no prophylactic, unjustified
what factors dictate Abx efficacy?
- infection site
- pathogen and minimal inhibitory concentration
- patient’s pathophysiology (age, diseases)
which sites of infection are difficult to treat due to barriers, location, or blood flow?
CSF - csf blood barrier brain BBB prostate difficult to penetrate dead bone no blood flow kidneys does not penetrate well
what host physiological factors need to be considered before Abx?
- liver and kidney function
- weight (BMI, age, volume of distribution)
- critical illnesses
- pregnancy (because cross the placenta)
which drugs are safe in pregnancy?
- penicillins
- azithromycin
- metronidazole
- cephalosporins
- clindamycin
what circumstances limit effectiveness of antimicrobial agents?
- abscess formation
- immunosuppression
- superinfections
- drug antagonism
- foreign bodies or biofilms
mechanism of action of beta lactam drugs
binds to transpeptidase competitively inhibits (catalyze the formation of peptide bridges between NAG and NAM - crosslinkages) to disrupt cell wall synthesis
what cells are beta lactams effective against
gram + mostly, only against actively growing cells
which medication classes are cell wall synthesis inhibitors?
- penicillins
- cephalosporins
- carbapenems
- monobactums
which medication classes are protein synthesis inhibitors?
- macrolide and lincosamide
- aminoglycosides
- tetracyclines
- chloramphenicol
- oxazolidinones
which drug classes are folate synthesis inhibitors?
- sulfamethoxyzole
2. trimethoprim
which drug classes are DNA synthesis inhibitors
- quinolones
2. fluoroquinolones
which drug class if RNA synthesis inhibitor?
rifamycins
which drug class is mycolic acid synthesis inhibitor (mycobacteria)
- isoniazid
2. ethambutol
4 groups of penicillins
- natural penicillins
- anti-staphylococcal penicillins
- aminopenicillins
- extended spectrum penicillins
which is the most potent penicillin
Penicillin G
which are natural penicillins?
penicillin V and G
how is penicillin G given and why
sensitive to stomach acids so IV or IM, short acting
how is penicillin V given and wy
acid resistant, given orally
what range are natural penicillins?
narrow spectrum against gram + and few -
what bacteria do cephalosporins act against
mostly gram negative
moa of vancomycin
blocks peptidoglycan synthesis by binding to peptide side chain of NAM (blocks tetrapeptide bridge formation)
what is vancomycin effective against?
ONLY GRAM POSITIVE
general MOA of protein synthesis inhibitors
selectively bind to ribosomal subunits (30S or 50S)
MOA of cephalosporin
resistant to beta lactamases
how does bacitracin work
inhibits cell membrane, affects permeability that leads to leakage of intracellular compounds
MOA aminoglycoside
binds to 30S ribosomal protein irreversibly, blocks elongation of polypeptide chains
MOA tetracyclines
inhibit protein synthesis by blocking amino acyl transfer of tRNA to mRNA ribosome complex
MOA chloramphenicol
blocks protein synthesis by binding to 50S ribosomal subunit and prevents peptidyl transferase function
MOA of macrolides and lincosamide
binds to 50S ribosomal subunit
MOA of oxazolidinones
block formation of tRNA:mRNA:50S complex
MOA of trimethoprim and sulfamethoxyzole
inhibit different steps in synthesis of folic acid in bacteria (metabolic pathway inhibitors)
MOA fluoroquinolone and quinolones
target DNA gyrase so inhibits nucleic acid synthesis
moa rifamycins
inhibition of bacterial DNA-dependent RNA synthesis, high affinity for prokaryotic RNA polymerase
moa isoniazid
inhibits mycolic acid synthesis (targets cell wall of mycobacteria)
moa ethambutol
inhibits enzymes required for synthesis of other cell wall components of mycobacteria
