ANTIBIOTICS Flashcards
goal for concentration dependent drug dosing
Cmax/MIC > or = 10-12
goal for time dependent drug dosing
time should be > MIC for 50-75% of dosing intervalEXCEPTION: Carbapenem may be 25-50% of dose interval because of rapid tidal activity
list rx based on bacterioSTATIC property
MOST protein synthesis/ribosome inhibitors–tetracyclines –phenicols–macrolides–lincosamidesSingle therapy folic acid inhibitors–sulfonamides–trimethoprim**accumulation in WBC/phagocytic cells may make them CIDAL
list rx based on bacterioCIDAL property
Cell wall inhibitors–B lactams (Penicillins, Cephalosporins, Carbapenems)–Glycopedtides (Vancomycin)DNA/RNA inhibitors–Fluorinated quinolones–Rifampin–MetronidazolePOTENTIATED folic acid sun inhibitors–TMSSOME protein synthesis inhibitors–Aminoglycosides–Macrolides–Lincosamides**accumulation in WBC/phagocytic cells may make them CIDAL
list concentration dependent drugs
–Fluorinated Quinolones–Aminoglycosides–Azithromycin (type of Macrolide)–Metronidazole
list of time dependent drugs
beta lactams (Penicillin, Cephalosporins, Carbapenems)glycopeptides (vancomycin)tetracyclinesmacrolides (EXCEPT azithromycin which is concentration dep)lincosamides
with the exception of concentration dependent drugs, which drugs have enhanced efficacy at higher doses
tetracyclinesmacrolideslincosamides
steps to avoid antimicrobial resistance
3 D’s1. de-escalate–don’t use Ab if you don’t have to2. design–make proper dosing regimes3. decontaminate–proper environmental safety and avoid exposure risks
general ways microbial resistance occurs within the bacT
inherent vs acquiredchromosomal mutations or transfer of genetic material outside of the chromosome( plasmid, bacteriophage-mediated)mechanisms:1. transposons– resistant genes that move back and forth btwn chromosome and plasmid2. conjugation–sexual transmission btwn bacT3. transduction–specific receptor transfers information via bacteriophage4. transformation–(human) naked DNA from previously lysed cell enters another bacT
Drugs that accumulate in phagocytic WBC
MacrolidesLincosamidesFluoroquinolonesRifampinSelective sulfonamidesdrug accumulation in WBC does not always = enhanced efficacy bc sometimes the drug is not released
drugs that do NOT accumulate in WBC
Beta lactamsAminoglycosidesMetronidazole
T/Flipid soluble drugs are more likely (than water soluble drugs) to move beyond extracellular fluid
TRUEand lipid soluble drugs should be used for infections that are more difficult to treat (ex. IC bacteria or tissues with barriers difficult to penetrate)
3 antimicrobial classes with good tissue penetration based on lipophilicity
FluoroquinolonesMacrolidesTMS combos
T/Fmost endotoxic release occurs with B lactams
TRUE least with amino glycosides (pg. 175)
B lactamMOA, Time vs Conc, Static vs Cidal, Spectrum
Cell wall inhibitor of PBP–transpeptidase–>perm–>lysisTIMECIDALMostly gm +Some gm - Some anaerobes(incr spectrum with incr generations of penicillins)(spectrum favors gm- with incr generation of ceph)
Types of B lactams
PenicillinsCephalosporinsCarbapenems
Mx of resistance for B lactams
- Beta lactamase production by bacT 2. Alteration in mecA gene (change in PBP)3. Efflux pumps4. Loss/Change in porins
Glycopeptide/VancomycinMOA, Time vs Conc, Static vs Cidal, Spectrum
Cell wall synthesis inhibitor and prevents elongation of cell wallTIMECIDALMostly gm + (Mainly used VRSA, VISA in humans)NO gm - Some anaerobes
AminoglycosidesMOA, Time vs Conc, Static vs Cidal, Spectrum
Inhibit binding of 30s ribosome to complete unit (70s)Concentration dependentCIDAL Mostly gm - NO anaerobes (O2 required!)some main gm + (staph not strep)do not get absorbed or penetrate well
Mx of resistance for aminoglycosides
Plasmid mediated 1. enzymatic destruction2. decreased cell entry3. altered ribosome structure
Side effects of aminoglycosides
Nephrotoxicity (tubular)OtotoxicityNM blockage
Types of anti-pseudomonal penicillins
TicarcillinPiperacillin(parenteral only)
B lactamase inhibitors added to penicillins
sulbactamclavulonic acid
characteristics of 2 newer 3rd generation cephalosporins
Convenia–Cefovecinhighly protein bound–>long half lifecats 166 hr dogs 133 hr; 3 week SQ shotSimplecef–Cefpoximelong half life for once daily dosing
1, 2, 3 generation cephalosporins
incr generation incr gm- and anaerobe spectrum but at the cost of gm + spectrum decreasing1. cefazolin, cephalexin, cefadroxil2. Cefoxitin3. Ceftiofur, Cefpodoxime, Cefovecin, Ceftazidime
tetracyclinesMOA, Time vs Conc, Static vs Cidal, Spectrum
Inhibit binding of 16s part of 30s ribosome (prevents translation) also inhibits MMPTIMEStatic (but efficacy incr with incr dose) gm +, gm - Some anaerobes, IC bacT (tick borne diseases, Lepto)
side effects of tetracyclines
Gastrointestinalesophageal stricture/esophagitis in catscollapse if rapid IVnephrotoxicity (high dose)enamel hypoplasia, bone growth problemsAVOID IN PREGNANT ANIMALS
Types of tetracyclines
tetracylineoxytetracyclinedoxycyclineminocycline
Advantages of doxy and minocyclin
TETRACYLINE GROUP–inhibitors of protein sunmost lipophilic of group and biliary excretionbetter penetrating hard to reach areas
Mx of resistance for tetracyclines
Plasmid Mediated/Induced;-interfer w influx and efflux-enzymatic destruction-change binding to ribosome
Spectrum of activity gentamicin vs amikacin aminoglycosides
gentamicin STAPH sppamikacin PSEUDOMONAS
PhenicolsMOA, Time vs Conc, Static vs Cidal, Spectrum
Inhibit Protein Synthesis – Binds 50s (peptidyl transferase)TIMESTATICGm +, -, anaerobes NOT pseudomonas
Which phenicol drug is more resistant to bacterial destruction
Florfenicol is more resistant than chloramphenicol
Side effects of phenicol drugs
Anemia (Non-Regen in animals and Aplastic in People) prolong barbituates (potent cyp inhib)affect active immunization procedures
Mx of resistance for phenicol drugs
Plasmid Mediated–inactivation by transacetylase action on drug **florfenicol is more resistant to destruction by bacT
MacrolidesMOA, Time vs Conc, Static vs Cidal, Spectrum
Inhibit Protein Synthesis – Binds 50s at 2 sites (peptidyl transferase and translocation)TIME (Concen del at high doses)STATIC (cidal at high doses)very lipid soluble; can accumulate in WBC (azithromycin)Gm + Azithromycin/Clarithromycin may have incr spectrum for gm - bacT
additional activity of erythromycin macrolide
GI prokineticMimics motilin and stimulates gastric, pyloric, and duodenal contractions
list macrolides
- erythromycin, tylosin, tilmicosyn2. azithromycin, clarithromycin
LincosamidesMOA, Time vs Conc, Static vs Cidal, Spectrum
Inhibit Protein Synthesis – Binds 50s (translocation)TIME STATIC (*cidal at high doses)can accumulate in WBC Gm + , anaerobes
list types of lincosamides
clindamycin, lincomycin
Main side effect of clindamycin
clostridial overgrowth and diarrhea
mx of resistance for lincosamides
Plasmid MediatedMutation in 50s ribosome that prevents drug binding
mx of resistance for macrolides
Plasmid Mediated–increased efflux from cells–mutation in 50 S ribosome that prevents drug binding
RifampinMOA, Time vs Conc, Static vs Cidal, Spectrum
inhibits RNA SYNTHESIS (DNAdep RNA pol inhibitor)CIDAL but used in COMBO THERAPY ONLY because incr risk resistanceonly gm +can cause incr ALP and red/orange urine
mx of resistance for rifampin
Single mutation in bindingoccurs quicklyonly use in combo therapy
NitroimidazolesMOA, Time vs Conc, Static vs Cidal, Spectrum
METRONIDAZOLEinhibits BOTH RNA and DNA synthesisCIDALCONCENTRATION DEPANAEROBES ONLY
side effects metronidazole
GI upsetdose related neurotoxicity (cerebellum most sensitive)Teratogenic–DO NOT GIVE DURING PREGNANCY
T/F metronidazole is “re-generated” on death of the microbe increasing and facilitating its efficacy
TRUEmetronidazole is “re-generated” on death of the microbe increasing and facilitating its efficacy
FluoroquinolonesMOA, Time vs Conc, Static vs Cidal, Spectrum
Inhibit DNA synthesis (DNA gyrase/topoisomerase II AND topoisomerase IV inhibition)CIDALConcentration dependentGM +, GM -lipid soluble, into WBC!
side effects fluoroquinolones
GI signsanaphylactoid reactionsseizuresDose dep retinal degeneration in cats ( less risk w marbofloxacin)cartilage damage in young animalsinduction of bacteriophage supergenes
Mx of resistance for fluoroquinolones
CHROMOSOMALLY mediated;-Dec cell wall permeability (decr expression of porins)-Efflux pump activation-Mutation of topoisomerasesGM + bacT resist topoisomerase IVGM - bacT resist topoisomerase II/DNA gyrase
Sulfonamides ALONEMOA, Time vs Conc, Static vs Cidal, Spectrum
inhibit folic acid pathway (folic acid synthetase)Static TimeGM + , Gm -, anaerobes(should be given potentiated)
POTENTIATED SulfonamideMOA, Time vs Conc, Static vs Cidal, Spectrum
inhibit folic acid pathway (folic acid synthetase AND reductase)CIDAL TimeGM + , Gm -, anaerobes(should be given potentiated–TMS)
Why are sulfonamides/TMS specific for bacterial folic acid pathways
mammal cells are not dependent on making own folic acid and they can get it from their dietbacT depend in FA synthesis for purine and nucleic acid synthesis
side effects of sulfonamides/TMS
KCSHypersensitivity (polyarthritis, fever, thrombocytopenia, hepatitis)Doberman’s predisposed to reactions (AVOID)thyroid suppression w chronic use?
mx of resistance for sulfonamides/TMS
Plasmid and chromosomal mediated–Decr drug penetration–decr affinity for substrate
