NR566 Advanced Pharmacology Care of the Family Midterm Study Guide
i i i i i i i i i
NR566 iWeek iOne iPI iSupport: iChapter i70-76
-access imedicine: iwith ichamberlain- ifor iflash icards iand ireview iof ibooks ifor ifree
Chapter i70
Table i70.1: iClassifications iof iAntimicrobial iDrugs iby iSusceptible iOrganisms:
➢ Narrow ivs. iBroad ispectrum?
o The iDifference iin iantibiotic icoverage
▪ broad: icovers imore iand ipossibly igram i– iand igram i+
▪ narrow: icovers ijust ia ifew imicroorganisms
o Which ione iis ioften iused ias iinitial itreatment iwhen itreatment iis iused ibefore itest iresults?
▪ broad i– icovers imore ibacteria iand iuse iyour iknowledge iof iwhich ibacterium iwill ibe
ilikely iat ithat isite i(UTI- ie. icoli i iuse inarrow ispectrum ibecause iyou iknow)
o Which ione iis imore ilikely ito ifacilitate iemergence iof idrug-resistant iorganisms iand
isuperinfections?
▪ broad i– iaffecting imore ibacteria
▪ secondary iinfection iwhen itreating isomething ielse
▪ more icommon iin iinappropriate idose/high idose
➢ Give iexamples iof isuperinfections?
o Ex iof isuperinfection: ivaginal icandida
➢ What iantibiotics icover igram i+ icocci iand igram i– ibacilli?
o Ex: inarrow ispectrum ipcn iG iand iV, i3rd igen icephalosporin, ibroad ispectrum ipcn
i(ampicillin), itetracyclines, itrimethoprim, isulfonamides, ifluoroquinolones i(cirpo), ivanco,
ierythromycin, iclindamycin, iCarbapenems i(imipenem)
➢ What iantibiotics icover iMycobacterium ituberculosis?
o Isoniazid, iRifampin, iEthambutol, iPyrazinamide
iAntimicrobials iMOA
➢ Aminoglycosides i(Gentamicin) ivs. iTetracyclines iMOA?
o Gentamicin icauses ilethal iinhibition iof iprotein isynthesis
▪ breaks iinto ithe icells
o Tetracycline icauses islowing i(nonlethal) iof iprotein isynthesis
➢ Bactericidal idrugs ivs. ibacteriostatic idrug?
o bactericidal: imore ilethal iat iclinically iachievable iconcentrations
o bacteriostatic: islows ibacterial igrowth iwithout ikilling
➢ Is iGentamicin ibactericidal ior ibacteriostatic?
o bactericidal
➢ Is iTetracycline ibactericidal ior ibacteriostatic?
o bacteriostatic
➢ What ihappens iwhen ia ibacteriostatic iand ibactericidal iagent iare iused iat ithe isame itime?
o antagonism iwill ioccur i- idecreased ieffects iof ibactericidal iagent ibecause ithey icannot ikill
ibacteria iunless ithey iare iactively igrowing i(bacteriostatic iagent isuppresses igrowth)
Table i70.3: iDrugs ifor iHighly iResistant iBacteria
➢ Microbes ihave i4 ibasic imechanisms ifor iresisting idrugs:
o reduction iof idrug iconcentration iat iits isite iof iaction
o alteration iof idrug itarget imolecules
o antagonist iproduction
o drug iactivation
➢ What iantibiotic ihas iresistance ito iC. idiff?
o metronidazole
➢ What iantibiotic ichoices iare ithere ito itreat iC. idiff?
, o vanco. irifaximin
o vanco iORAL i(needs ito igo ito isite iwhere igrowth iis i– igut)
iMechanisms iby iwhich iresistance iis iacquired
➢ 1. iSpontaneous imutation
➢ 2. iconjugation i(acquisition iof iDNA iR-factors ifrom ione ibacterium ito inext- ioften igram- ibacteria
iand inormal iflora)
➢ Can iantibiotics ipromote iovergrowth iof inormal iflora?
o yes- iif ithey iare iresistant
➢ Normal iflora ican itransfer iresistance ito ipathogens
o Guess i# ipatients iwho iend iup iwith ihealth-care iassociated iinfections
▪ 1/20-5%
▪ This iis iproblematic iif iantibiotics iare ioverused iwhen inot ineeded, irisk iis iit imay inot
iwork iwhen ineeded i(ie. ifor iHAI)
Common iInfections iand iTreatment i(Table i70.4-70.5)
➢ What iare ithe i4 imain ikind iof ibacteria ifound iin icommunity iacquired ipneumonia i(CAP):
o streptococcus ipneumonae
o mycoplasma ipneumonae
o H iinfluenzae
o staphylococcus iaureus
➢ Main ibacteria ifound iin iCAP? istreptococcus ipneumonae i(adults)
➢ 2 imost icommon ibacteria ifound iin iUTI? ie. icoli iand iEnterobacteriaceae
➢ What iabx iis i1st ichoice ifor iuncomplicated igram i+ iUTI? iamoxicillin
➢ What ialt iabx iis iused iin iUTI icipro iresistant icaused iby ipseudomonas iaeruginosa igram-?
ilevofloxacin, ipiperacillin-tazobactam i(Zosyn), iceftazidime, icefepime, imeropenem, igentamicin,
itobramycin, iaztreonam
➢ What iabxs iis iused ito itreat imeningitis? iCefotaxime, iceftriaxone, icephalosporin
➢ What iabx iif iused ito itreat iupper iresp iinfection i(URI) ior ibronchitis i(bacterial, imost iare iviral)?
iBactrim
➢ Alternative iabx ifor iH. ipylori i(1st itreatment iineffective ior iallergy)? itetracycline i+ imetronidazole i+
isubsalicylate i+ iProtonix
Empiric iAntibiotic iTherapy iand iTests
➢ First irule: iMatch ithe idrug iwith ithe ibug
➢ Determine idrug isusceptibility iif iresistance iis icommon i(checking ifor iC. idiff; istrep isensitivity
inever idone iwhy itho?)
➢ What iis ithe iquickest, isimplest iway ito iID imicroorganisms? igram istain ito ivisualize iunder
imicroscope
, ➢ What itest ican idetect ivery ilow ititers iof ibacteria/viruses? iPCR
o PCR ican idetect ibacterial ipathogens iof iC. idiff, iS. iaureus, imycobacterium ituberculosis,
iNeisseria igonorrhoeae, ichlamydia itrachomatis, iand iH. ipylori
➢ What iviral ipathogens ican ibe idetected iby iPCR? iHIV iand iinfluenza ivirus
iHost iFactors iAffect iRx
➢ Host idefenses i(immune isystem iand iphagocytic icells)
➢ Site iof iinfection i(need iadequate iMIC- ithe iamt iof iabx iat ithe isite iof iinfection iin ia iconcentration i>
ithan ithat ito ibe ieffective)
o how imuch idrug ilevels iat ia isite ito ibe ieffective? i4-8x iMIC
➢ Why iis iminimum iinhibitory iconcentration i(MIC) iimportant iwith iabx?
➢ What iare isome iforeign i(medical) imaterials iin ibody ithat iphagocytes iattempt ito idestroy? icardiac
ipacemakers, ishuts, iheart ivalves, iprostatic ijoints
➢ Previous iallergic ireactions ito iRx iand igeneric ifactors i(avoid igiving iabx ithat ibreak iRBCs iin
ipatients iwith iG6PD ideficiency iand ido inot igive iisoniazid ito islow imetabolizers i(Asians?) ias itoxic
iaccumulation imay ioccur)
➢ Reason: iabx ipass ithru imilk i– isulfonamide ican icause ikernicterus i(neuro idamage)
➢ What: iheightened idrug isensitivity, igreater ilevels i= itoxic ilevels
Chapter i71: iDrugs ithat iWeaken ithe iBacterial iCell iWall iI
Beta-Lactams: iPenicillin
➢ Widely iprescribed id/t isafety iand iefficacy ias iNO idirect ieffects ion icells iof ithe ihost i(host icells ido
inot ihave iwalls, ibut ibacterial icells ido ihave icell iwalls)
➢ PCNs iweaken icells iwalls, iwhich iallows iwater ito ienter iand ieventually ibursts icell
➢ So iare ithey ibactericidal ior ibacteriostatic?
➢ Inhibit itranspeptidases iand iactivated iautolysins iby ibinding ito ithose ienzymes i(PCP)
iMechanisms iof iBacterial iResistance ito iPCN
➢ Inability iof iPCN ito ireach itheir itargets i(PBP)
o Gram- ibacteria iwalls ihave i3 ilayers i(outer imembrane idifficult ito ipenetrate ito iget ito ithin
iwall)
o Gram+ ibacteria iwalls ithat ihave i2 ilayers i(no iouter imembrane, ibut ithicker iwall) iof
ienvelope iaround itheir icells
o Which ione iis imore idifficult ito ipenetrate iand iwhy?
➢ Inactivation iof iPCN iby ibacterial ienzymes
o Some ibacteria iproduce ib-lactamases; iProduction iof iPBPs ihave ilow iaffinity ifor iPCN
i(MRSA)
▪ What iare ibeta-lactamases/how ido ithey iinactivate iPCN?
, Penicillin
➢ Absorption: iPCN isalts idissociate ito irelease iPCN iG, iwith iK iand iNa iPCN iG iabsorbs ifaster ithan
iprocaine iand ibenzathine isalts
➢ Distribution: iwell ito imost itissues iand ibody ifluids, imay ipenetrate imeninges iif iinflammation
ipresent
➢ Metabolism: iminimal
➢ Elimination: iexcreted ithrough ikidneys imostly iby iactive itubular isecretion ias iunchanged idrug
➢ May ineed ito imonitor ikidney ifunction ior ireduce idosage iif irenal iimpairment ipresent ias iit ican
iincrease ihalf-life iand ilead ito ineurotoxicity i(seizures, iconfusion, ihallucinations)
➢ 1% iof ipatients iwith iPCN iallergies ihave icross isensitivity ito icephalosporins i(avoid iif iPCN iallergy
isevere)
➢ An iallergy ito iPCN ican idecrease iovertime iso iimportant ito iknow iwhat iprior ireaction iwas i(if imild
iORAL icephalosporin ican ibe igiven)
➢ What iare isafe ialt ifor iPCN iallergy?
➢ What ihappens iif iinadvertent iarterial iinjection?
➢ What ihappens iif iaccidental iinjection iinto iperipheral inerve?
➢ How iis iPCN igiven iin i“desensitization iprocedure” iif inecessary ito iPCN iallergic ipatient iif ialt
itreatments ito iPCN iare iineffective i(i.e.. ienterococcal iendocarditis)
Cephalosporin iPharmacokinetics
i i i i i i i i i
NR566 iWeek iOne iPI iSupport: iChapter i70-76
-access imedicine: iwith ichamberlain- ifor iflash icards iand ireview iof ibooks ifor ifree
Chapter i70
Table i70.1: iClassifications iof iAntimicrobial iDrugs iby iSusceptible iOrganisms:
➢ Narrow ivs. iBroad ispectrum?
o The iDifference iin iantibiotic icoverage
▪ broad: icovers imore iand ipossibly igram i– iand igram i+
▪ narrow: icovers ijust ia ifew imicroorganisms
o Which ione iis ioften iused ias iinitial itreatment iwhen itreatment iis iused ibefore itest iresults?
▪ broad i– icovers imore ibacteria iand iuse iyour iknowledge iof iwhich ibacterium iwill ibe
ilikely iat ithat isite i(UTI- ie. icoli i iuse inarrow ispectrum ibecause iyou iknow)
o Which ione iis imore ilikely ito ifacilitate iemergence iof idrug-resistant iorganisms iand
isuperinfections?
▪ broad i– iaffecting imore ibacteria
▪ secondary iinfection iwhen itreating isomething ielse
▪ more icommon iin iinappropriate idose/high idose
➢ Give iexamples iof isuperinfections?
o Ex iof isuperinfection: ivaginal icandida
➢ What iantibiotics icover igram i+ icocci iand igram i– ibacilli?
o Ex: inarrow ispectrum ipcn iG iand iV, i3rd igen icephalosporin, ibroad ispectrum ipcn
i(ampicillin), itetracyclines, itrimethoprim, isulfonamides, ifluoroquinolones i(cirpo), ivanco,
ierythromycin, iclindamycin, iCarbapenems i(imipenem)
➢ What iantibiotics icover iMycobacterium ituberculosis?
o Isoniazid, iRifampin, iEthambutol, iPyrazinamide
iAntimicrobials iMOA
➢ Aminoglycosides i(Gentamicin) ivs. iTetracyclines iMOA?
o Gentamicin icauses ilethal iinhibition iof iprotein isynthesis
▪ breaks iinto ithe icells
o Tetracycline icauses islowing i(nonlethal) iof iprotein isynthesis
➢ Bactericidal idrugs ivs. ibacteriostatic idrug?
o bactericidal: imore ilethal iat iclinically iachievable iconcentrations
o bacteriostatic: islows ibacterial igrowth iwithout ikilling
➢ Is iGentamicin ibactericidal ior ibacteriostatic?
o bactericidal
➢ Is iTetracycline ibactericidal ior ibacteriostatic?
o bacteriostatic
➢ What ihappens iwhen ia ibacteriostatic iand ibactericidal iagent iare iused iat ithe isame itime?
o antagonism iwill ioccur i- idecreased ieffects iof ibactericidal iagent ibecause ithey icannot ikill
ibacteria iunless ithey iare iactively igrowing i(bacteriostatic iagent isuppresses igrowth)
Table i70.3: iDrugs ifor iHighly iResistant iBacteria
➢ Microbes ihave i4 ibasic imechanisms ifor iresisting idrugs:
o reduction iof idrug iconcentration iat iits isite iof iaction
o alteration iof idrug itarget imolecules
o antagonist iproduction
o drug iactivation
➢ What iantibiotic ihas iresistance ito iC. idiff?
o metronidazole
➢ What iantibiotic ichoices iare ithere ito itreat iC. idiff?
, o vanco. irifaximin
o vanco iORAL i(needs ito igo ito isite iwhere igrowth iis i– igut)
iMechanisms iby iwhich iresistance iis iacquired
➢ 1. iSpontaneous imutation
➢ 2. iconjugation i(acquisition iof iDNA iR-factors ifrom ione ibacterium ito inext- ioften igram- ibacteria
iand inormal iflora)
➢ Can iantibiotics ipromote iovergrowth iof inormal iflora?
o yes- iif ithey iare iresistant
➢ Normal iflora ican itransfer iresistance ito ipathogens
o Guess i# ipatients iwho iend iup iwith ihealth-care iassociated iinfections
▪ 1/20-5%
▪ This iis iproblematic iif iantibiotics iare ioverused iwhen inot ineeded, irisk iis iit imay inot
iwork iwhen ineeded i(ie. ifor iHAI)
Common iInfections iand iTreatment i(Table i70.4-70.5)
➢ What iare ithe i4 imain ikind iof ibacteria ifound iin icommunity iacquired ipneumonia i(CAP):
o streptococcus ipneumonae
o mycoplasma ipneumonae
o H iinfluenzae
o staphylococcus iaureus
➢ Main ibacteria ifound iin iCAP? istreptococcus ipneumonae i(adults)
➢ 2 imost icommon ibacteria ifound iin iUTI? ie. icoli iand iEnterobacteriaceae
➢ What iabx iis i1st ichoice ifor iuncomplicated igram i+ iUTI? iamoxicillin
➢ What ialt iabx iis iused iin iUTI icipro iresistant icaused iby ipseudomonas iaeruginosa igram-?
ilevofloxacin, ipiperacillin-tazobactam i(Zosyn), iceftazidime, icefepime, imeropenem, igentamicin,
itobramycin, iaztreonam
➢ What iabxs iis iused ito itreat imeningitis? iCefotaxime, iceftriaxone, icephalosporin
➢ What iabx iif iused ito itreat iupper iresp iinfection i(URI) ior ibronchitis i(bacterial, imost iare iviral)?
iBactrim
➢ Alternative iabx ifor iH. ipylori i(1st itreatment iineffective ior iallergy)? itetracycline i+ imetronidazole i+
isubsalicylate i+ iProtonix
Empiric iAntibiotic iTherapy iand iTests
➢ First irule: iMatch ithe idrug iwith ithe ibug
➢ Determine idrug isusceptibility iif iresistance iis icommon i(checking ifor iC. idiff; istrep isensitivity
inever idone iwhy itho?)
➢ What iis ithe iquickest, isimplest iway ito iID imicroorganisms? igram istain ito ivisualize iunder
imicroscope
, ➢ What itest ican idetect ivery ilow ititers iof ibacteria/viruses? iPCR
o PCR ican idetect ibacterial ipathogens iof iC. idiff, iS. iaureus, imycobacterium ituberculosis,
iNeisseria igonorrhoeae, ichlamydia itrachomatis, iand iH. ipylori
➢ What iviral ipathogens ican ibe idetected iby iPCR? iHIV iand iinfluenza ivirus
iHost iFactors iAffect iRx
➢ Host idefenses i(immune isystem iand iphagocytic icells)
➢ Site iof iinfection i(need iadequate iMIC- ithe iamt iof iabx iat ithe isite iof iinfection iin ia iconcentration i>
ithan ithat ito ibe ieffective)
o how imuch idrug ilevels iat ia isite ito ibe ieffective? i4-8x iMIC
➢ Why iis iminimum iinhibitory iconcentration i(MIC) iimportant iwith iabx?
➢ What iare isome iforeign i(medical) imaterials iin ibody ithat iphagocytes iattempt ito idestroy? icardiac
ipacemakers, ishuts, iheart ivalves, iprostatic ijoints
➢ Previous iallergic ireactions ito iRx iand igeneric ifactors i(avoid igiving iabx ithat ibreak iRBCs iin
ipatients iwith iG6PD ideficiency iand ido inot igive iisoniazid ito islow imetabolizers i(Asians?) ias itoxic
iaccumulation imay ioccur)
➢ Reason: iabx ipass ithru imilk i– isulfonamide ican icause ikernicterus i(neuro idamage)
➢ What: iheightened idrug isensitivity, igreater ilevels i= itoxic ilevels
Chapter i71: iDrugs ithat iWeaken ithe iBacterial iCell iWall iI
Beta-Lactams: iPenicillin
➢ Widely iprescribed id/t isafety iand iefficacy ias iNO idirect ieffects ion icells iof ithe ihost i(host icells ido
inot ihave iwalls, ibut ibacterial icells ido ihave icell iwalls)
➢ PCNs iweaken icells iwalls, iwhich iallows iwater ito ienter iand ieventually ibursts icell
➢ So iare ithey ibactericidal ior ibacteriostatic?
➢ Inhibit itranspeptidases iand iactivated iautolysins iby ibinding ito ithose ienzymes i(PCP)
iMechanisms iof iBacterial iResistance ito iPCN
➢ Inability iof iPCN ito ireach itheir itargets i(PBP)
o Gram- ibacteria iwalls ihave i3 ilayers i(outer imembrane idifficult ito ipenetrate ito iget ito ithin
iwall)
o Gram+ ibacteria iwalls ithat ihave i2 ilayers i(no iouter imembrane, ibut ithicker iwall) iof
ienvelope iaround itheir icells
o Which ione iis imore idifficult ito ipenetrate iand iwhy?
➢ Inactivation iof iPCN iby ibacterial ienzymes
o Some ibacteria iproduce ib-lactamases; iProduction iof iPBPs ihave ilow iaffinity ifor iPCN
i(MRSA)
▪ What iare ibeta-lactamases/how ido ithey iinactivate iPCN?
, Penicillin
➢ Absorption: iPCN isalts idissociate ito irelease iPCN iG, iwith iK iand iNa iPCN iG iabsorbs ifaster ithan
iprocaine iand ibenzathine isalts
➢ Distribution: iwell ito imost itissues iand ibody ifluids, imay ipenetrate imeninges iif iinflammation
ipresent
➢ Metabolism: iminimal
➢ Elimination: iexcreted ithrough ikidneys imostly iby iactive itubular isecretion ias iunchanged idrug
➢ May ineed ito imonitor ikidney ifunction ior ireduce idosage iif irenal iimpairment ipresent ias iit ican
iincrease ihalf-life iand ilead ito ineurotoxicity i(seizures, iconfusion, ihallucinations)
➢ 1% iof ipatients iwith iPCN iallergies ihave icross isensitivity ito icephalosporins i(avoid iif iPCN iallergy
isevere)
➢ An iallergy ito iPCN ican idecrease iovertime iso iimportant ito iknow iwhat iprior ireaction iwas i(if imild
iORAL icephalosporin ican ibe igiven)
➢ What iare isafe ialt ifor iPCN iallergy?
➢ What ihappens iif iinadvertent iarterial iinjection?
➢ What ihappens iif iaccidental iinjection iinto iperipheral inerve?
➢ How iis iPCN igiven iin i“desensitization iprocedure” iif inecessary ito iPCN iallergic ipatient iif ialt
itreatments ito iPCN iare iineffective i(i.e.. ienterococcal iendocarditis)
Cephalosporin iPharmacokinetics
