SketchyPharm Antimicrobials FINAL

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THE!OUWB!SKETCHYPHARM!GUIDE!TO!SUCCESS!!
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ANTIMICROBIALS!!!
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By!Brian!Yuhan!and!David!Chu!!
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BLUE:!Drug!Name/Treatment!
PURPLE:!Characteristics!of!Drug!
ORANGE:!Important!Mechanism!
GREEN:!Indications!
RED:!Adverse!Reactions!
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ANTIMICROBIALS:!Cell!Wall!and!Membrane!Active!Antibiotics!
PENICILLIN!!
!(“Princess!Ellen’s!New!Hope”)!
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MECHANISM!OF!ACTION!
•! Penicillins!(PCN)!(Princess!Ellen!holding!purple!pencil!lower!right!corner)!
o! Contains!4!membered!betaAlactam!ring!(ringed!planet)!
•! Peptidoglycan!cell!wall!with!repeating!DAalanylADAalanine!oligopeptides!(Death!Coccus!wall;!repeating!DALA!
architecture)!
o! Penicillin!binding!proteins!(PBP)!forms!peptidoglycan!crossAlinks!by!removing!terminal!alanines!
(Planetary!Building!Project!worker)!
•! Penicillins!(and!other!beta!lactam!antibiotics)!inhibit!this!transpeptidation!reaction!of!the!peptidoglycan!
bacterial!cell!wall!synthesis!by!covalently!binding!the!PBPs!!!works!well!against!thick!gramApositive!
peptidoglycan!wall!
o! Bactericidal!S!Inhibits!peptidoglycan!synthesis!in!actively!growing!cells!and!the!cell!dies!!!
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PENICILLIN!V!(VSwinged!ship)!
•! Oral!form!of!PCN!is!acid!stable!(acid!nebula!behind!ship)!
•! Only!indicated!in!minor!infections!because!of!its!poor!bioavaibility,!4!times!a!day!dosing,!and!narrow!spectrum!
•! Treats:!!
o! Group!A!strep!pharyngitis!
o! Rheumatic!fever!
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PENICILLIN!G!(royal!GSshaped!hairdo!on!Princess!Ellen)!
•! IV!form!of!penicillin!(ivy!around!Princess!Ellen)!
o! Benzathine!salts!of!penicillin!G!can!also!be!given!as!IM!injections!
•! Treats:!!
o! Prophylaxis!for!Group!B!strep!due!to!Strep&agalactiae&(intrapartum)!
o! Rheumatic!fever!
o! Left!sided!endocarditis!by!Strep&viridans!and!Strep&bovis&
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INDICATIONS!
•! In!general,!PCN!has!greatest!activity!against!gram!positive!organisms,!like!Staph!and!Strep!(purple!coccoid!space!
stations!in!clusters!and!chains)!
o! Strep!infections:!
"! Oral!PCNAV!!!group!A!streptococcal!pharyngitis!(strep!throat)!(red!bandanas!around!necks!of!
VSwing!pilots)!
"! PCNAV!or!G!!!rheumatic!fever!(heartSshaped!planet!in!between!VSwing!and!Ellen)!
"! PCNAG!!!left!sided!endocarditis!(bicuspid!hat)!caused!by!Strep&viridans!and!Strep&bovis!
(Emperor!Viridans!with!dark!green!robe)!
"! Intrapartum!PCNAG!!!prophylaxis!for!Group&B&Strep&agalactiae!(A!galactic!baby)!
o! Actinomyces&israelii!(Israeli!flag)!
"! Gram!positive!rod!that!grows!in!chains!(Israeli!flag!inside!the!purple!rod!transporter)!
o! Clostridium&perfringens!(perforated!spacesuit!of!guy!on!ground!near!bike)!
o! Pasteurella&multocida!from!infected!dog!bite!wounds!(space!dog)!
"! Also!treated!with!broad!spectrum!B!lactams:!Ampicillin,!Piperacillin!
o! Secondary!Syphilis!caused!by!Treponema&pallidum,!a!type!of!spirochete!(spiral!galaxy)!
"! Presents!with!palms!and!soles!rash!(red!gloves!and!boots)!
"! Treat!with!single!dose!of!benzathine!PCN!G!!S>!provides!low!but!persistent!serum!levels!of!
penicillin!and!is!standard!therapy!for!all!types!of!syphilis!!
•! Can!also!treat!Gram!Negatives!
o! Meningococcal!meningitis!due!to!Neisseria&meningitides!(red!meningitis!Mohawk)!
"! Gram!negative!diplococcus!(red!pair!of!rocket!boosters!on!his!back)!
"! Treated!with!IV!PCN!G,!which!can!effectively!penetrate!CNS!during!active!inflammation!
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RESISTANCE!
•! Most!common!mechanism!are!betaAlactamases!–!such!as!those!produced!by!Staph&Aureus!(beta!guard!shooting!
down!VSwing!ship;!crossedSout!beta!symbol!on!turret)!
o! BetaSlactamases!expressed!by!plasmid!genes!(circular!plasmid!DNA!ring!around!beta!guard’s!gun)!
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ADRs!
•! Type!1!(IgE!mediated)!hypersensitivity!reaction!(IgE!missiles;!pilot!with!swollen!puffy!face!from!allergic!
reaction)!S>!Anaphylaxis!!
o! 10%!of!patients!have!reported!PCN!allergies!
"! 90%!of!these!individuals!will!have!negative!skin!testing!and!will!tolerate!PCN!without!an!adverse!
reaction!
o! 10%!of!patients!also!reported!to!have!some!degree!of!crossSreactivity!with!cephalosporin!
"! Cephalosporins!more!likely!to!cause!adverse!reaction!in!patients!with!a!PCN!allergy!if!they!had!
positive!skin!testing!in!the!past!to!PCN!or!if!their!previous!allergic!reaction!to!PCN!consisted!of!
definite!IgESmediated!clinical!features!and!occurred!within!10!years!
•! DrugSinduced!autoimmune!hemolytic!anemia!(exploding!asteroids!with!IgG’s!striking!them)!
o! Positive!direct!Coombs!test!(IgE!missile!on!surface)!
"! Due!to!antibodies!against!PCN!binding!to!surface!of!RBCs!
•! DrugSinduced!interstitial!nephritis!(blue!star!clusters!in!kidney!nebula)!
o! Caused!by!mononuclear!cells!entering!the!interstitium!of!the!kidney!
o! Histo:!blue!cells!throughout!interstitium!of!kidney!
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NAFCILLIN,!OXACILLIN,!METHICILLIN,!DICLOXACILLIN!
!(“The!Staphylococci!Strike!Back”)!
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GENERAL!
•! Same!as!PCN!sketch:!
o! BetaAlactam!ring!(ringed!planet)!
o! Peptidoglycan!cell!wall!with!repeating!DSalanylSDSalanine!oligopeptides!!!DAALAADAALA!pattern!(Death!
Coccus!wall)!
o! Penicillin!binding!protein!(PBP)!forms!peptidoglycan!crossAlinks!(Planetary!Building!Project!workers)!
o! BetaSlactam!antibiotics!covalently!bind!PBPs!!!halt!peptidoglycan!synthesis!!!bactericidal!(green!
ships!shooting!down!and!inactivating!PBP!worker)!
•! AntiAstaphylococcal!PCNs!more!effective!against!bacteria!with!betaAlactamase!resistance!
o! Bulky!RAgroups!on!antibiotics!prevent!betaAlactamase!binding!(protective!armor!on!ships!deflecting!
lasers!of!beta!lactamase)!
o! Narrow!spectrum!of!activity!S!Often!the!drug!of!choice!for!methicillin!sensitive,!PCN!resistant!strains!of!
staphylococci!
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DRUGS!
•! Methicillin!no!longer!used!clinically!due!to!high!rates!of!adverse!events!
•! NAFCILLIN!(purple!staff!pencil)!
•! OXACILLIN!(ox!horns)!–!also!CLOXACILLIN,!DICLOXACILLIN!!
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INDICATIONS!!!
•! Oral!drug!for!mild!to!moderate!localized!staphlococci!infections!(purple!coccoid!space!station!cluster)!
o! Empiric!treatment!for!skin!and!soft!tissue!infections!(e.g.!folliculitis,!abscesses)!(red!hump)!
•! IV!infusion:!drug!of!choice!for!serious,!systemic!staph!infections!
o! Treats!Staph!endocarditis!(tricuspid!pyramids)!
o! Treats!Staph!osteomyelitis!(fish!bones)!
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•! No!effect!against!MethicillinAresistant!Staphylococcus!aureus!(MRSA)!(golden!Merciless!dark!lord!MRSA)!
o! Produces!altered!PBPs!that!have!low!affinity!binding!with!beta!lactams!!!resistant!to!all!betaAlactam!
antibiotics!(altered!wall!builder!deflecting!lasers!shot!at!them)!
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ADRs!same!as!PCN!sketch!
•! Type!1!(IgE!mediated)!hypersensitivity!reaction!
•! DrugSinduced!autoimmune!hemolytic!anemia!
•! DrugSinduced!interstitial!nephritis!!
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AMINO!PCN:!AMOXICILLIN,!AMPICILLIN,!PIPERACILLIN,!TICARCILLIN!
BALACTAMASE!INHIBITORS:!CLAVULANIC!ACID,!SULBACTAM,!TAXOBACTAM!
!(“Amped!Up!at!the!Cantina”)!
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GENERAL!
•! BetaAlactam!ring!(ringed!planet)!
•! BetaSlactam!antibiotics!covalently!bind!PBPs!!!halt!peptidoglycan!synthesis!!!bactericidal!(green!ships!
shooting!down!and!inactivating!PBP!worker)!
o! PCNs!and!antiAstaphylococcal!PCNs!target!gram!positive!organisms!e.g.!Staph!and!Strep!(purple!coccoid!
space!stations)!
•! Amino!PCNs!(“Amino’s!Space!Cantina”)!are!broad!spectrum!(prism!hanging!from!ceiling)!
o! Retain!antibacterial!spectrum!of!PCNs!but!also!have!improved!activity!against!gram!negative!!(red!
interior)!bacteria!because!of!their!enhanced!ability!to!penetrate!the!gram!negative!outer!membrane!
o! All!amino!PCNs!treat:!
"! Streptococcal!pharyngitis!(strep!throat)!due!to!Group&A&strep!(red!bandana!around!Han!
Cillin)!in!children!
"! Pneumonia!(rusty!chest!plate!on!alien)!caused!by!Strep&pneumonia,!Haemophilus&influenza!
(H!wing!ship)!
"! Haemophilus&influenza!infection!(H!wing!ship)!
"! GI/urinary!tract!gram!negative!rods!(e.g.!E.&coli)!(GISlike!taps!behind!red!counter)!–!not!
likely!first!line!drugs!and!thus!low!yield!
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AMOXICILLIN!(ammo!box!lower!right!corner)!!
•! Better!absorbed!orally!(open!mouth!of!Han!Cillin)!
•! Indications!
o! Otitis!media!and!sinusitis!caused!by!Strep&pneumonia,!Haemophilus&influenza,!and!Moraxella&catarrhalis!
(plugged!ears!of!alien!next!to!Han!Cillin)!
o! Part!of!the!triple!therapy!(with!clarithromycin!and!a!PPI)!for!Helicobacter&pylori!infection!(helicopter!
behind!Han!Cillin)!!
o! Lyme!disease!caused!by!Borrelia&burgdorferi!transmitted!by!Ixodes!tick!(Robin!of!Ixodes!Wanted!poster)!
•! Prophylaxis!against:!
o! Encapsulated!bacteria!(e.g.!Strep&pneumonia!and!Haemophilus&influenza)!in!asplenic!patients!(spleen!
hole!in!shirt!of!punching!alien)!
o! Dental!procedures!in!patients!at!high!risk!for!endocarditis!(punched!guy!with!tooth!flying!out)!
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AMPICILLIN!(guitar!amp)!!
•! IV!administration!(ivy!cord!of!guitar)!!!treat!serious!infections!caused!by!anaerobes!(e.g.!aspiration!
pneumonia)!(gas!mask!on!guitarist)!
o! Treats!Enterococcus!infections!(Diplococcus!rock!drums)!S>!UTI!and!endocarditis!!
"! Gram!positive!diplococcus!
"! Ampicillin!resistant!enterococcus!strains!exist!due!to!betaAlactamase!(knocked!over!amp)!
o! Treats!meningitis!caused!by!Listeria&monocytogenes!(meningitis!helmet!and!“Set!List”!poster)!
"! Infants!and!elderly!
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RESISTANCE!
•! Amoxicillin!and!ampicillin!are!beta!lactamase!sensitive!(like!PCN)!(beta!bouncer!with!beta!logo)!!
o! Amino!PCNs!are!often!paired!with!beta!lactamase!inhibitor!(e.g.!amoxicillin!with!clavulanate)!to!
prevent!cleavage!!
o! Beta!lactamase!inhibitors:!
"! Clavulanate!(aka!Augmentin)!(distracting!clarinet!blocking!beta!bouncer)!
"! Tazobactam!and!sulbactam!(aka!Unasyn)!(back!to!back!tambourines)!
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PIPERACILLIN!and!TICARCILLIN!(Piper!twins!with!tiger!stripe!jumpsuits)!!
•! Not!amino!penicillins!
•! Also!paired!with!beta!lactamase!inhibitors!
o! Piperacillin!with!tazobactam!
o! Ticarcillin!with!clavulanate!
•! Broad!spectrum!of!coverage!includes!anaerobes!(e.g.!aspiration!pneumonia)(gas!masks!on!twins)!
•! MOST!IMPORTANT:!treats!Pseudomonas!infections!(Mona!Lisa)!
o! Pseudomonas!coverage!is!important!to!consider!for!nosocomial!infections!
"! HospitalAacquired!pneumonia!and!impaired!treatment!of!sepsis!
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ADVERSE!REACTIONS!
•! StevensAJohnson!syndrome!(red!mask!sloughing!off!punched!guy)!
o! Serious!rash!in!which!epidermis!separates!from!the!dermis!
•! Amoxicillin/Clavulanate:!MOST!COMMON!cause!of!drug!induced!liver!injury!(trampled!liver!spot!lower!left!
corner)!
•! AntibioticSinduced!skin!rash!in!setting!of!viral!illness!(e.g.!EBV!–!infectious!mononucleosis)!(red!lights!of!
“Ebstein’s!Bar”!in!back)!
•! Also!same!beta!lactam!side!effects!as!PCNs!
o! Type!1!(IgE!mediated)!hypersensitivity!reaction!
o! DrugSinduced!autoimmune!hemolytic!anemia!
o! DrugSinduced!interstitial!nephritis!!
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CEPHALOSPORINS!
!(“Revenge!of!the!Ceph”)!
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GENERAL!
•! Binds!PBPs!halting!peptidoglycan!wall!synthesis!(unfinished!Death!Coccus)!!!bactericidal!
•! BetaAlactamases!ineffective!against!cephalosporins!(squid)!(especially!3rd!and!4th!generations)!(ineffective!beta!
guards!with!lasers!bouncing!off!window)!
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GENERATIONS!–!grouped!by!spectrum!of!antimicrobial!activity!
Shift!spectrum!from!gram!positive!(left!purple!ships)!!!broad!spectrum!(right!red!and!purple!ships)!
•! 1st!GEN:!CEPHALEXIN!(flex)!and!CEFAZOLIN!(fez)!(1st!General!Lex)!
o! Treat!gram!positive!organisms!(e.g.!Staph!and!Strep)!(purple!coccoid!space!stations)!
"! Treats!cellulitis,!abscesses!(puffy!red!gloves!and!patches!on!uniform)!
o! Treats!Strep!pharyngitis!!due!to!Group&A&Strep&Pyogenes!(red!bandana)!
o! Treat!gram!negative!UTI!bugs!(e.g.!Proteus,!E&coli,!Klebsiella)!(red!bladder!cup!with!2!ureter!straws!–!
PEK)!
o! Cefazolin!penetrates!most!tissues!S>!surgical!prophylaxis!(surgical!instruments!behind!Lex)!
•! 2nd!GEN:!CEFUROXIN!(furious),!CEFOTETAN!(tea!cup),!CEFOXITIN!(fox)!(2nd!General!Fox)!
o! Same!coverage!as!1st!generation!with!extended!gram!negative!coverage!(some!red!space!stations!in!
front!of!Fox)!
"! Susceptible!gram!negatives:!Haemophilus&influenza,!Neisseria,!Serratia!(HENS)!(red!hens!on!
teapot)!
o! Oral:!treat!sinusitis,!otitis,!lower!respiratory!tract!infections,!mixed!anaerobic!infections!such!as!
parotitis,!diverticulitis!
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•! 3rd!GEN:!CEFTRIAXONE!(3!axes),!CEFOTAXIME!(3!axes),!CEFTAZIDIME!(3rd!General!Taz)!!!nosocomial!inf.!
o! Extended!gram!negative!coverage!beyond!2nd!generation!(mostly!red!space!stations)!
o! FIRST!LINE!drugs!for!empiric!treatment!for!meningitis!(Mohawk!helmet)!
"! Crosses!BBB!well!to!provide!excellent!coverage!for!strep&pneumo,!H&influenzae&(H!wing!ship),!
Neisseria&meningitides!
"! Vancomycin!often!added!for!extra!gram!positive!coverage!of!resistant!strep&pneumo!
"! Ampicillin!may!be!added!for!young!and!elderly!patients!to!cover!Listeria!!
o! Treats!community!and!hospital!acquired!pneumonia!(rusty!chest!plate)!
o! Ceftazidime!treats!Pseudomonas&infections!(Mona!Lisa!behind!Taz)!
o! Ceftriaxone!treats!endocarditis!caused!by!Strep&viridans!and!HACEK!(Emperor!Viridans!with!miter!hat)!
"! Treats!gram!negative!GI!bugs!(e.g.!Salmonella,!Shigella)!(intestinal!bottom!of!battle!suit)!
"! Treats!sepsis!
"! Single!dose!of!IM!ceftriaxone!is!FIRST!LINE!treatment!of!gonorrhea!(dripping!chandelier)!
"! Treats!Lyme!disease!caused!by!Borrelia&burgdorferi!transmitted!by!Ixodes!tick!(Robin!of!Ixodes!
Wanted!poster)!especially!when!it!includes!arthritis!and!neurologic!disease!
o! NOT!for!MRSA!!
•! 4th!GEN:!CEFEPIME!(4th!General!Prime)!
o! Treats!serious!systemic!infections!in!patients!at!risk!for!multiSdrug!resistant!organisms!
o! Broad!spectrum!(gram!negatives!and!positives)!(prism!necklace;!red!and!purple!space!stations)!
o! Penetrates!CNS!!!cefepime!treats!bacterial!meningitis!(Mohawk!helmet)!
o! Active!against!Pseudomonas!(Mona!Lisa!behind!3rd!and!4th!Generals)!
o! NOT!for!MRSA!!
•! 5th!GEN:!CEFTAROLINE!(5th!General!Tara)!
o! Broad!spectrum!(gram!negatives!and!positives)!(prism!necklace)!
o! Treats!MRSA!infections!(tipping!over!golden!Lord!MRSA)!–!can!bind!to!altered!PBPs!
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RESISTANCE!
•! Alter!PBPs!!
•! Producing!extended!spectrum!BetaAlactamases!
o! Can!be!counteracted!with!carbapenams!!
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ADRs!
•! Also!same!beta!lactam!side!effects!as!PCNs!
o! Type!1!(IgE!mediated)!hypersensitivity!reaction!
"! CrossSreactivity!with!PCNSallergic!patients!
o! DrugSinduced!autoimmune!hemolytic!anemia!
o! DrugSinduced!interstitial!nephritis!!
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MONOBACTAMS!and!CARBAPENEMS!
!(“The!Coverage!is!Strong!with!This!One”)!
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Ertapenem,!Imipenem!(cilastatin),!Meropenem,!Aztreonam!
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GENERAL!
•! Binds!PBPs!halting!peptidoglycan!wall!synthesis!(unfinished!Death!Coccus)!!!bactericidal!
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GENERAL!INDICATIONS!(If!see!prism!and!Mona!Lisa!–!you!have!a!big!gun!antibiotic!for!nosocomial!inf!)!
•! Pseudomonas&infections!(Mona!Lisa)!
•! Both!penetrates!CSF!!!serious!systemic!infections!with!gram!negative!pathogens!(e.g.!meningitis,!pneumonia,!
sepsis)!(red!mohawk!helmet!and!rusty!lungs)!
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MONOBACTAMS:!AZTREONAM!(one!eyed!AZS3M!bottom!right!corner)!
•! Single!betaAlactam!ring!(one!eye)!
•! Activity!against!aerobic!gram!negative!rods!(bellows!against!red!rod!shaped!R2D2)!ONLY!–!not!for!Gram!+!or!
anerobes!
•! Used!in!pts!with!history!of!PCN!allergy!(pencil!wounding!C3PO)!
o! No!immunologic!crossSreactivity!like!cephalosporins!
•! Resistant!to!beta!lactamases!(ineffective!beta!guard!getting!scared!by!junkyard!dog)!
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CARBAPENEMS:!IMIPENEM,!ERTAPENEM,!MEROPENEM,!DORIPENEM!(Hover!car!repair)!
•! Broad!spectrum!with!good!activity!against!anaerobes,!gram!positives,!and!gram!negative!rods!(broad!spectrum!
prism!on!hood!of!car)!
o! Treats!anaerobic!infections!(e.g.!Pneumonia,!intraSabdominal!infections)!(gas!mask)!
•! Used!for!bugs!resistant!to!other!available!treatments!(“when!others!fail…we!get!the!job!done!”)!
•! Resistant!to!extended!spectrum!beta!lactamases!(ineffective!rainbow!beta!guard!on!left)!
o! Carbapenems!are!the!treatment!of!choice!for!serious!infections!caused!by!extended!spectrum!beta!
lactamaseAproducing!gram!negatives!such!as!E.&coli!and!Klebsiella&&
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•! IMIPENEM!(Amy)!
o! Deactivated!by!dehydropeptidases!in!renal!tubules!(renal!tubules!engine!parts)!
"! CoSadministered!with!Cilastin!(“Keep!it!lastin!with!Cilastin”)!
•! Inhibits!dehydropeptidase!preventing!the!degradation!of!imipenem!(Cilastin!oil)!
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ADRs!
•! GI/diarrhrea!(carbepenems)!(mud!puddle!under!Amy’s!robot)!
•! Skin!rash!(carbapenems)!(rust!spots!on!Amy’s!robot)!
•! Seizures!(Imipenem)!(shaking!of!zapped!robot)!esp!in!pts!with!renal!dysfunction!
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GLYCOPEPTIDE:!VANCOMYCIN!!
!(“MRSA…why!did!it!have!to!be!MRSA?”)!
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GENERAL!
•! VANCOMYCIN!(green!van!and!professor!Indiana!Jones)!is!a!glycopeptide!antibiotic!active!only!against!gram!
positive!bacteria!(e.g.!Staph,!Strep,!Enterococcus)!(purple!coccoid!temples)!
•! Activity!against!Methicillin&resistant&Staph&aureus!(MRSA)!(golden!No!mercy!pharaoh)!
•! Vancomycin!inhibits!cell!wall!synthesis!by!directly!binding!to!DAALAADAALA!terminus!of!nascent!peptidoglycan!
oligopeptides!(Professor’s!whip!directly!bound!to!temple!wall!hieroglyphs!!!DSALA!DSALA)!
o! Bactericidal!!
o! BetaSlactams!bind!to!PBPs!responsible!for!peptidoglycan!synthesis!rather!than!directly!to!peptidoglycans!
"! Altered!PBPs!are!resistant!to!betaAlactams!(altered!wall!builder)!
"! Altered!PBPs!are!ineffective!against!vancomycin!(ineffective!altered!wall!builder)!
•! BetaAlactamases!ineffective!against!vancomycin!(ineffective!guard!bottom!left!shooting!darts)!
o! BetaSlactamases!encoded!by!plasma!genes!(ring!shaped!necklace!on!guard)!
•! Undulating!plasma!levels!of!vancomycin!(vans!on!undulating!dunes!top!right!corner)!
o! 90%!of!vancomycin!is!excreted!by!glomerular!filtration!!!plasma!level!monitoring!is!necessary!
particularly!in!patients!with!renal!dysfunction!or!on!multiple!nephrotoxic!drugs!to!ensure!
concentrations!are!therapeutic!
•! IV!administration!(ivy!whip!
•! Poorly!absorbed!in!GI!tract,!only!given!orally!to!treat!Clostridium&difficile!colitis!(temple!of!flowing!chocolate)!
o! Metronidazole!is!first!line!treatment!
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INDICATIONS!
•! Vancomycin!is!a!big!gun!antibiotic!used!to!treat!serious!systemic!infections,!especially!hospitalized!and!
immunocompromised!patients!who!are!at!higher!risk!for!multiSdrug!resistant!microbe!infections!
o! Activity!against!nosocomial!MRSA!infections!(e.g.!hospital!acquired!pneumonia)!(nurse!with!lung!stains!
on!uniform!next!to!van)!
•! CNS!penetration!!!activity!against!PenicillinGresistant&Strep&pneumo!(PRSP)!!
o! Combined!with!ceftriaxone!for!empiric!treatment!of!meningitis!(meningitis!Mohawk)!
•! Bone!penetration!!!treats!MRSA!osteomyelitis!(fish!bones!in!sand)!
•! Activity!against!Staph&epidermidis!S>!forms!biofilms!on!hospital!IV!lines!and!heart!valves&(gunky!biofilm!on!lines,!
valves,!and!repairman!under!van)!
o! FIRST!LINE!for!empiric!treatment!of!endocarditis!(heart!shaped!headpiece!of!staff)!due!to!broad!
coverage!of!Staph,!MRSA,!Strep,!and!sensitive&enterococcus!species!
!
RESISTANCE!
•! VancomycinAresistant!enterococcus!species!(diplococcus!rock!drums)!
o! Altered!peptidoglycan!structure!(DSALASDSLAC!on!different!temple)!confers!resistance!to!vancomycin!(DS
LAC!hieroglyph!block)!
!
ADRs!
•! Red!man!syndrome!(red!statue!on!right)!!!Infusion!related!flushing!caused!by!release!of!histamine!from!mast!
cells!(mast!cells!–!beehive!hanging!from!red!statue!arm)!
o! Managed!by:!
"! Prolonging!infusion!
"! Treating!with!antiShistamines!
•! Thrombophlebitis!(blue!vines!creeping!up!legs!of!red!statue)!at!injection!site!
o! Inflammation!of!the!wall!of!a!vein!with!associated!thrombosis!
•! Ototoxicity!(gong!and!broken!ear!of!red!statue)!and!Nephrotoxicity!(falling!kidneySshaped!plates)!
o! Rare,!but!administration!with!another!ototoxic!or!nephrotoxic!agent!(e.g.!aminoglycosides)!increases!
risk!
•! DRESS!Syndrome!–!rare!but!potentially!life!threatening!drug!reaction!
o! Also!caused!by!antiAconvulsants,!allopurinol,!and!sulfonamides!
"! Occurs!2S8!weeks!after!exposure!
o! Eosinophilia!(EOS!slingshot!native!in!pink!dress)!and!systemic!symptoms!
o! Fever!
o! Generalized!lymphadenopathy!
o! Skin!rash!
! !
LIPOPEPTIDE:!DAPTOMYCIN!
!(“Let!My!Chickens!Go”)!
!
!
GENERAL!
•! DAPTomycin!(Police!DEPT)!
•! Activity!against!gram!positive!cell!wall!(e.g.!Staph,!Strep,!Enterococcus)!(purple!wall!of!protesters)!
•! Cyclic!lipopeptide!which!inserts!lipid!tail!into!membrane!to!depolarize!cell!(police!tasing!protester)!!!
bactericidal!
!
INDICATIONS!
•! Activity!against!vancomycin!resistant!(resisting!van!arrest)!bacterial!strains!e.g.!VRE!(diplococcus!enterococcus!
rock!drums)!
•! Activity!against!Methicillin&resistant&Staph&aureus!(MRSA)!(crossed!out!No!mercy!pharaoh!sign;!2!golden!staffs)!
o! Treats!MRSA!bacteremia!(“It’s!in!our!blood”)!
"! Associated!with!right!sided!Staph!endocarditis!(tricuspid!peaks)!
"! Skin!and!soft!tissue!infections!caused!by!MRSA!
•! Ineffective!for!pneumonia!(rusty!chest!plate!protected!from!taser)!
o! Daptomycin!is!antagonized!by!pulmonary!surfactant!
!
ADRs!
•! Myopathy!(chicken!leg!bite)!S>!rhabdomyolysis!!
o! Muscle!pains!within!1!week!of!starting!therapy!
o! Increased!creatinine!phosphokinase!(CPK)!levels!(CrisPy!chicKen)!
! !
ANTIMICROBIALS:!Inhibitors!of!Bacterial!Protein!Synthesis!
TETRACYCLINES!
(“Le!Tour!de!Cyclines”)!
!
!
MECHANISM!OF!ACTION!!
•! Tetracyclines!(bicycle)!work!by!entering!microorganisms!and!concentrating!inside!the!cell!
o! Once!inside,!they!bind!reversibly!to!the!30S!bacterial!ribsosomal!subunit!(typewriter!looks!like!
ribosome;!translator!hold!up!30s!timer)!S>!blocking!tRNA!binding!and!halting!peptide!formation!!
"! Ultimately!inhibits!translation!!
o! Bacteriostatic!–!agent!that!stops!bacteria!from!reproducing!doesn’t!kill!them!(Paper!jam)!
•! Often!given!orally!S>!absorbed!in!stomach!and!proximal!small!intestine!
•! Eliminated!fecally!(colon!shaped!sewage!pipe)!–!can!be!used!safely!in!renal!failure!pts!and!no!dosage!
adjustment!needed!
!
INDICATIONS!
•! Considered!a!broad!spectrum!antibiotic:!works!against!both!Gram!+!and!Gram!–!bacteria!(Winner!holding!up!
prism!trophy!shining!a!broad!spectrum!rainbow)!
o! Long!acting!tetracycline!i.e.!DOXYCYCLINE!or!MINOCYCLINE!works!against!MRSA:!methicillin!resistant!S.&
Aureus!(No!Mercy!Pharaoh!winner!with!Staff!Aureus!trophy)!
"! However,!empiric!treatment!is!usually!vancomycin,!daptomycin!or!linezolid!!
•! Doxycycline!works!against!tick!borne!bacteria!(ticks!jumping!from!deer)!
o! Rickettsia!(i.e.!Rocky!Mountain!Spotted!Fever)!–!pt!will!be!outdoorsy!
"! Arthropod!transmitted!diseases!presenting!with!fever,!headache,!myalgias,!and!rash!
o! Ehrlichiosis!(lone!star!tick)!
o! Tularemia!(Francisella)!
o! Early!or!disseminated!Lyme!disease!(Ixodes!tick!S>!Borrelia&burgdorferi)!
•! Doxycycline!works!against!zoonotic!diseases!!
o! Brucellosis!–!Brucella!transmitted!to!humans!through!domesticated!animals!(Bruce!the!cow)!
o! Culture!negative!endocarditis!due!to!Coxiella!Brunetii&(sheep!with!rusty!heart!bell)!S>!Q!fever!
o! The!Plague!S!Yersinia&pestis!(squirrels!with!fleas)!!
!
•! Doxycycline!+!cephalosporin!for!1!week!is!a!FIRST!line!agent!for!treating!chlamydial!cervicitis,!urethritis!and!
gonorrhea!(Female!rider!on!clam!seat)!
o! If!chlamydia!or!gonorrhea!are!left!untreated,!may!ascend!to!upper!genital!tract!and!progress!to!pelvic!
inflammatory!disease!(uterus!shape!handlebars)!
•! Oral!doxycycline!for!chlamydial!bronchitis!and!community!acquired!atypical!“walking”!pneumonia!caused!by!
atypical!bugs!i.e.!chlamydia!and!mycoplasma!(female!bicyclist!with!clam!bra!coughing;!“Cold”!walking!
snowshoer)!
•! Oral!tetracyclines!provide!some!anerobic!coverage!S>!used!for!moderate!to!severe!inflammatory!acne!caused!
by!skin!anerobes!(white!capped!mountains)!
!
ADR!
•! Known!to!chelate!metals!S>!absorption!is!decreased!with!concomitant!administration!of!multivalent!cations!i.e.!
Ca,!Fe,!and!Mg!(Metal!medals)!
o! Never!give!tetracyclines!with!milk,!antacids,!or!ferrous!sulfate!
o! Readily!bind!to!Ca!in!teeth!and!bones!of!young!children.!NOT!for!kids!<8!years!old!
"! Causes!tooth!discoloration!due!to!deposition!in!teeth!(boy!chewing!on!medal)!
"! Teratogenic!–!avoid!in!pregnancy!due!to!deposition!in!fetal!teeth!and!bones!(tarantula)!
•! GI!side!effects:!Nausea,!vomiting,!diarrhea!(fallen!cyclist!in!mud!puddle)!
•! Skin!photosensitivity!(photographers!taking!photos!of!fall)!induced!by!systemic!administration!
•! Fanconi!syndrome!caused!by!administration!of!expired!tetracyclines!(Expired!cyclist!being!dragged!by!fan!
shouting!through!a!cone)!
o! Causes!a!type!II!(proximal)!renal!tubular!acidosis!!
!
RESISTANCE!
•! Efflux!pumps!(bike!pump)!S>!moves!drug!out!of!bacterial!cell!
•! Alteration!of!ribosome!
!
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MACROLIDES!
(“The!Crow”)!
!
!
!MECHANISM!OF!ACTION!
•! Macrolides!(crow)!acts!on!the!bacterial!50S!ribosomal!subunit!(typewriter)!S>!inhibiting!translocation!and!
protein!synthesis!
!
INDICATIONS!
•! Bordetella&pertussis&(Boarded!soldier!from!sketchymicro)!
o! Give!macrolides!as!prophylaxis!for!close!contacts!(soldier!holding!family!photo)!
•! AZITHROMYCIN!and!CLARITHROMYCIN!(Keep!clear!sign)!
o! !Community!acquired!pneumonia!caused!by!Strep&pneumoniae,&Haemophilus&influenza,&Morazella&
catarrhalis&(Rusty!chest!plate!on!suit!of!armor)!
"! Used!in!pts!with!a!history!of!penicillin!allergy!(Suit!of!armor!pencil!wound)!
o! Mycobacterium&avium&(caged!mockingbird)!
•! AZITHROMYCIN!!
o! Atypical!“walking”!pneumonia!caused!by!Mycoplasma&pneumoniae&(“cold”!walking!snowshoer),!by!
Legionella&(Legion!of!ships!at!anchor),!and!by!Chlamydia&pneumoniae&(Clam!lady!statue)!
o! Urethritis!and!cervicitis!caused!by!Chlamydia&trachomatis&(Clam!lady!painting)!
o! Bartonella&henselae&i.e.!Cat!Scratch!Disease!(Bart!the!Leopard)!
o! Prophylaxis!in!pts!with!CD4!<50!(“Birds!ASZ”!and!“50”!on!graph!paper!by!cage)!
•! ERYTHROMYCIN!(Red!crow)&
o! Oral:!Neonatal!conjunctivitis!and!pneumonia!caused!by!Chlamydia&trachomatis&(baby!in!painting)&
o! Drops:!neonatal!conjunctivitis!caused!by!Neisseria&gonorrhoeae!(Dripping!wax!on!baby)&
o! Diphtheria!(Bull!statue)&
•! CLINDAMYCIN!+!ATOVAQUONE!treats!babesiosis!(Vampire!babe)&
•! CLARITHROMYCIN!+!Amoxicillin!+!Proton!Pump!Inhibitor:!Triple!therapy!for!Helicobacter&Pylori!(Helicopter)&
&
&
ADR!
•! Increased!GI!motility!(brown!puddle!on!floor)!
•! Acute!cholestatic!hepatitis!S>!jaundice!(soldier!is!yellowSskinned)!
•! Prolonged!QT!(torsades!strip!coming!out!of!typewriter)!
•! Cytochrome!PA450!inhibition!(broken!chrome!car!bumper)!
! !
CLINDAMYCIN!
(“Keeping!it!Clean!at!the!Anaerobix!Gym”)!
!
•! CLINDAMYCIN!(Keep!Clean!sign)!acts!on!the!bacterial!50S!ribosomal!subunit!(typewriter)!S>!inhibiting!
translocation!and!protein!synthesis!
•! Actively!transported!into!macrophages!and!can!achieve!excellent!penetration!into!abscesses,!esp!lung!
abscesses!caused!by!anerobes!(lung!stains!with!holes)!in!the!setting!of!aspiration!pneumonia!
!
INDICATIONS!
•! Gram!+!Staph!and!Strep!(Purple!coccoid!dumbbells)!
o! MRSA!–!Staph&Aureus!(No!Mercy!pharaoh!tattoo!on!gym!trainer)!
"! However,!empiric!treatment!is!usually!vancomycin,!daptomycin!or!linezolid!
o! Clindamycin!penetrates!well!into!tissues!S>!use!for!skin!i.e.!cellulitis!and!soft!tissue!infections!due!to!
Group&A&Strepococcus&pyogenes!(Pie!and!red!puffy!glove!on!gym!trainer)!
•! Anerobic!coverage!(Gas!mask)!
o! Treats!oral!infections!and!aspiration!pneumonia!caused!by!Bacteroides&fragilis!and!Fusobacterium(man!
choking!on!Bacteraid!–!remember!Bacteroides!in!the!back!of!your!mouth)!
"! Think!aspiration!pneumonia!when!presented!with!a!pt!with!reduced!consciousness!(alcoholics!
or!anesthetized),!upper!GI!disorders!(dysphagia!or!protracted!vomiting),!or!upper!GI!procedures!
(intubation!or!NG!tube!placement)!
o! Think!clindamycin!for!anerobes!ABOVE!diaphragm,!and!metronidazole!for!anerobes!BELOW!diaphragm!
"! Exception:!Clostridium&Perphringens!(fallen!man!with!perforated!pants)!
•! Trauma!such!as!road!rash!can!introduce!fastidious!anerobes!S>!leading!to!gas!gangrene!
and!myonecrosis!!
o! Topical:!Moderate!or!severe!inflammatory!acne!caused!by!skin!anerobes!(snow!capped!mountains)!
o! Bacterial!vaginosis!caused!by!Garderella&vaginalis!(venus!fly!trap!garden)!
!
!
!
o! Clindamycin!+!Gentamicin!(aminoglycoside!–!woman!wearing!judo!gi!with!sai!weapon)!for!broad!
spectrum!antibiotics!!
"! Treat!polymicrobial!infections!of!female!genital!tract!(uterus!machine)!due!to!constituents!of!
vaginal!flora!
•! If!chlamydia!or!gonorrhea!is!left!untreated,!may!ascend!to!upper!genital!tract!and!
progress!to!pelvic!inflammatory!disease.!!
o! At!this!point,!think!doxycycline!+!cephalosporine!
•! May!involve!Endometritis,!or!inflammation!of!the!uterine!lining,!which!is!associated!
with!retained!products!of!conception!following!delivery,!septic!abortion,!pelvic!abscess,!
or!a!foreign!body!such!as!an!IUD!
o! Antibiotics!regimens!usually!cover!anerobes!(Gently!cleaning!the!uterus)!!
!
ADR!
•! Diarrhea!–!usually!mild!and!selfSlimited!(brown!puddle)!
o! Can!occur!during!antibiotic!therapy!or!for!several!weeks!after!cessation!of!therapy!!!
•! Pseudomembranous!colitis!–!caused!by!Clostridium&difficile!(Brown!geyser)!!!
! !
CHLORAMPHENICOL!!
(“A!Splash!of!Gray”)!
!
!
•! CHLORAMPHENICOL!(chlorine!pool)!reversibly!binds!to!the!bacterial!50S!ribosomal!subunit!(typewriter)!S>!
inhibiting!translocation!and!protein!synthesis!!
!
INDICATIONS!
•! IM!injections!of!long!acting!Chloramphenicol:!Empiric!treatment!for!meningitis!in!developing!countries!(e.g.!
Strep&pneumoniae,!Haemophilus&influenza,!Neisseria&meningitidis)!(Meningitis!space!helmet!kid)!
o! Used!in!developing!countries!because!it’s!cheap!–!not!widely!available!in!the!US!due!to!potential!
toxicity!(Earth!Ball)!
•! Alternative!agent!used!for!serious!rickettsial!infection!(e.g.!Rocky!Mountain!spotted!fever!caused!by!Rickettsia&
rickettsiae)!(spotted!hand!and!foot!rock!climber!swatting!away!ticks)!
o! Used!for!pregnant!women!when!doxycycline!is!contraindicated!
!
ADR!
•! Causes!dose!related!reversible!suppression!of!RBC!production!S>!anemia!(deflated!red!inner!tubes)!
•! Rare!but!possibly!fatal!aplastic!anemia!due!to!irreversible!bone!marrow!suppression!(plastic!bone!floatie)!
•! Grey!Baby!Syndrome!(Grey!baby!in!liver!floatie)!
o! Newborns!lack!an!effective!glucoronic!acid!conjugation!system!S>!liver!can’t!detoxify!and!degrade!
chloramphenicol!S>!drug!accumulates!!
o! Causes!flaccidity,!hypothermia,!grey!color,!and!shock!
o! Therefore,!use!chloramphenicol!with!caution!and!in!limited!doses!in!infants!
!
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!
LINEZOLID!
(“Do!Not!Cross”)!
!
!
MECHANISM!OF!ACTION!!
•! LINEZOLID!(police!line)!binds!to!the!bacterial!50S!ribosomal!subunit!(typewriter)!S>!prevent!formation!of!
initiation!complex,!inhibiting!translocation!and!protein!synthesis!
!
INDICATION!
•! Serious!Gram!+!infections:!Staph,!Strep,!Enterococcus!(Purple!jewels!in!clusters!and!chains)!
o! Nosocomial!MRSA!pneumoniae!(coughing!nurse!by!ambulance)!
o! Complicated!skin!and!soft!tissue!infections!due!to!MRSA!(No!Mercy!Pharaoh)!!
"! Considered!empiric!treatment!along!with!vancomycin!+!daptomycin!
o! VRE:!vancomycin!resistant!enterococcus!S!nosocomial!UTI!and!endocarditis!(Diplococcus!rock!drums;!
man!resisting!arrest!and!not!getting!into!van)!
!
ADR!
•! Thrombocytopenia!–!depressed!platelet!production!(broken!plate!exhibit)!
•! Anemia!and!neutropenia!
•! Prolonged!use!of!linezolid!S>!Optic!neuropathy!(cut!security!camera)!
o! Decreased!visual!acuity,!development!of!scotomas,!and!diminished!color!perception!
•! Peripheral!neuropathy!–!gloveAandAstocking!sensory!impairment!(investigator!with!glove!and!shoe!covers)!
•! Serotonin!syndrome!(happy!face!graffiti)!
o! Linezolid!is!a!weak!inhibitor!of!monoamine!oxidase!and!can!precipitate!serotonin!toxicity!when!
coadministered!with!MAO!inhibitors,!SSRIs,!SNRIs,!or!bupropion!
!
!
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!
AMINOGLYCOSIDES!
(“Feudal!Assassins”)!
!
!
•! Aminoglycosides!(sai)!bind!irreversibly!to!the!30S!ribosomal!subunit!(Kanji!translators!in!ribosome!booth;!
assassin!on!30s!clock),!inhibiting!formation!of!the!initiation!complex!S>!enabling!misreading!of!DNA!(smeared!
kanji)!S>!Cell!Death!!
o! Bactericidal!–!kills!bacteria!(dead!translator)!
•! Poor!oral!absorption!–!must!be!given!IV!(Ninja!swinging!from!ivy)!
•! Coupled!with!cell!wall!active!drugs!i.e.!betaSlactams,!vancomycin!(BetaSLactam!bomb!and!blown!up!wall)!to!
enhance!ability!to!penetrate!cells!!
!
GENERAL!INDICATIONS!
•! Aerobic!Gram!Negative!Bacilli!(Red!bacilli!brick!wall)!with!suspicion!of!sepsis!or!drug!resistance!
o! Aminoglycosides!are!actively!transported!via!02!dependent!process!across!the!cell!wall!to!get!inside!
aerobic!bacteria!(bellows!fanning!flames)!
o! GENTAMYCIN,!TOBRAMYCIN,!AMIKACIN!S!use!against!Pseudomonas&(Mona!Lisa)!–>!nosocomial!
infections!!
!
DRUGS!
•! NEOMYCIN!(ninjitsu!ninja!in!black!sneaking!into!underground!tunnel)!
o! When!taken!orally,!remains!active!in!GI!tract!until!secreted!into!feces!(secret!colon!tunnel)!
o! Useful!in!bowel!preparation!before!colorectal!surgery!(ninjitsu!ninja!holding!scalpel!shuriken)!
•! PAROMYCIN!(pair!of!mice!in!secret!tunnel)!
o! Luminal!agent!against!parasites!such!as!entomoeba&histolytica&
•! STREPTOMYCIN!(Sai!master!in!trees)!
o! Treats!tularemia!due!to!Francicella&tularensis&and!spread!by!tick!ridden!animals!(rabbit!hoodie)!
o! Treats!The!Plague!caused!by!Yersinia&pestis&(squirrel!with!fleas)!
!
!
•! GENTAMYCIN!(Judo!master)!
o! Treats!resistant!Gram!Negative!infections!i.e.!Enterobacter,&Serratia,&Klebsiella)!
o! Systemic!Gram!Negative!injections!i.e.!septicemia,!nosocomial!respiratory!tract!infections,!complicated!
UTI,!intraSabdominal!infection!(Red!Shogun)!
o! When!coupled!with!a!cell!wall!active!agent!i.e.!penicillin,!vancomycin!S!active!against!Enterococcus!
endocarditis!and!UTI!(double!purple!drums)!!
"! Enterococci!are!intrinsically!resistant!to!low!or!moderate!levels!of!aminoglycosides!!
•! Due!to!acetylation!enzyme!S>!inactivates!aminoglycosides!(inactivating!ninja!stars)!–!
used!by!numerous!fastidious!Gram!Negatives!i.e.!E.&faecium!against!tobramycin!
•! TOBRAMYCIN!(Cobra!ninja)!
o! Similar!spectrum!of!activity!as!Gentamicin!!
•! AMIKACIN!(Katana!master)!
o! Most!expensive,!most!broad!spectrum!and!resistant!to!inactivating!enzymes!!
!
ADRs!
•! Irreversible!Ototoxicity!–!vestibular!or!cochlear!damage!S>!manifest!as!vertigo,!disequilibrium,!light!headedness,!
nausea/vomiting,!ataxia,!tinnitus,!and!hearing!loss!(sai!striking!gong)!
•! Nephrotoxicity!(kidney!shaped!flank!armor!damaged!by!sai)!–!experienced!in!the!setting!of!renal!insufficiency!
and!concurrent!administration!of!loop!diuretics!! !
o! Due!to!acute!tubular!necrosis!(ATN)!(Rusty!raingutter!draining!muddy!water!–!tubular!necrosis!and!
brown!muddy!casts!seen!on!urinalysis)!
o! Increased!serum!creatinine!levels!and!serum!aminoglycoside!levels!!
"! Serum!drug!levels!must!be!routinely!checked!(Peaks!and!troughs!of!undulating!mountain)!
•! Neuromuscular!blockade!
o! Myasthenia!gravis!is!absolute!contraindication!(grave!outlet!with!sai!in!it)!
"! MG!affects!neuromuscular!junction!at!postSsynaptic!motor!end!plate!!
•! Teratogenic!–!may!cause!newborn!deafness!(tarantula!and!pregnant!women!near!gong)!
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ANTIMICROBIALS:!Antimycobacterials!
TUBERCULOSIS!DRUGS!
(“The!Magnificent!Four”)!
!
!
GENERAL!
•! Mycobacteria&TB!–!grow!slowly,!impermeable!lipid!rich!cell!wall,!hide!in!macrophages,!develop!resistance!
•! RIPE!therapy:!Combination!of!RIFAMPIN,!ISONIAZID,!PYRAZINAMIDE,!and!ETHAMBUTOL!used!to!prevent!
development!of!resistance!(“RIPE!Tubers”)!
•! 2!phases!of!treatment:!all!4!drugs!for!2!months!followed!by!2!drugs!(i.e.!isoniazid!and!rifampin)!for!4!months!
(“Was!$4!for!2,!now!$2!for!4”)!
!
ISONIAZID!(INH)!(The!Isolated!Ranger)!
•! Can!be!used!as!single!agent!ONLY!for!treatment!of!latent!TB!to!prevent!reactivation!(Sleeping!farmer!behind!
Isolated!Ranger)!
o! Most!other!agents,!when!used!alone,!lead!to!rapid!development!of!resistance!!
o! Primary!TB!(often!presents!as!middle!lobe!cavity)!(middle!lobe!bullet!hole!behind!Isolated!Ranger)!
•! Isoniazid!is!combined!with!the!other!agents!for!active!TB!to!prevent!development!of!resistance!
•! Mechanism:!
o! Inhibits!mycolic!acid!production!at!mycobacterial!cell!wall!(Mycobacteria!cowboy!shot!off!wall!by!
Ranger;!fuchsia!mycolic!acid!cacti!on!wall!at!right)!
o! Delivered!as!a!proAdrug,!then!activated!by!KatG!(catalase!peroxidase!produced!by!mycobacteria)!
(Aggravating!GStailed!cat!on!right)!
o! INH!metabolized!via!acetylation!by!liver!enzyme!NAacetyltransferase!–!pts!who!are!slow!acetylators!
have!higher!plasma!drug!concentrations!S>!longer!half!lives!S>!higher!risk!of!side!effects!(bandit!reaching!
for!his!acetylation!gun!in!liver!holster!but!has!already!been!hit)!
•! Resistance:!
o! Mutations!that!downreguate!the!expression!the!KatG!(silenced!G!tailed!cat!on!wall)!
•! ADRs:!
o! INH:!“Injury!to!nerves!and!hepatocytes”!
"! Peripheral!neuropathy,!ataxia,!paresthesia!
!
o! Peripheral!neuropathy!(bandit!in!white!stockings!and!gloves)!–!due!to!vit!B6!deficiency!
"! INH!promotes!excretion!of!pyridoxine!(vitamin!B6)!(pair!of!dice!–!sixes)!
"! Administration!of!B6!prevents!peripheral!neuropathy!(ungloved!hand!holding!dice!of!sixes)!
"! Decreased!acetylation!of!INH!S>!decreased!clearance!and!inc.!risk!of!neuropathy!
o! Seizures!(motion!lines!of!bandit!falling!off!wall!on!right)!
o! Hepatotoxicity!associated!with!all!RIPE!therapy!drugs!(liver!spot!cow!standing!in!center!of!sketch)!
"! So!common!!!expect!an!asymptomatic!rise!in!aminotransferases!(raised!LFT!flag)!
o! DrugSinduced!lupus!(wolf!next!to!Isolated!Ranger)!
o! Anion!gap!metabolic!acidosis!(MUD!PILES)!
o! INH!inhibits!cytochrome!P450!(broken!chrome!bumper)!!
"! Can!increase!concentrations!of!other!drugs!like!antiSepileptics!and!Warfarin!
!
RIFAMPIN!(The!Rifle)!
•! Activates!cytochrome!P450!(“reving”!and!speeding!chrome!bumper)!!
•! Mechanism:!
o! Binds!to!and!inactivates!bacterial!DNA!dependent!RNA!polymerase!(Rifle!shot!RNA!track!switch)!S>!
inhibiting!RNA!synthesis!
"! DNA!dependent!RNA!polymerase!(Double!stranded!DNA!track!junction!with!single!stranded!RNA!
track)!
•! Resistance:!
o! Mycobacteria!can!develop!resistance!through!mutations!in!their!RNA!polymerase,!making!Rifampin!
unable!to!bind!
o! Resistance!rapidly!develops!when!Rifampin!used!alone!(rarely!used!alone)!
"! However,!Rifampin!can!be!used!alone!in!prophylactic!monotherapy!in!close!contacts!exposed!
to!Haemophilus&influenza&or!Neisseria&meningitides!(carriage!driver!in!close!contact!with!
Rifampin!sharp!shooter,!clutching!onto!him)!
•! Neisseria&meningitides!(meningitis!Mohawk!from!New!Mexico!painted!on!train)!
o! Gram!negative!diploccocus!(2!red!balls!painted!also)!
•! Haemophilus&influenza!(yellow!H!plane)!
•! ADRs:!
o! Hepatitis!UNCOMMON!(liver!spot!cow!standing!in!center!of!sketch)!
"! More!common!in!patients!with!predisposing!factors!such!as!coAadministration!of!other!
hepatotoxic!agents!(e.g.!other!RIPE!therapy!drugs)!
o! OrangeARed!body!fluids!(orange!soda!spilling!out!of!Rifampin’s!carriage)!
!
ETHAMBUTOL!(Ethel!the!Horse!Whisperer)!(Ethambutol!at!the!Wall)!
•! Blocks!arabinosyl!transferase,!inhibiting!carbohydrate!polymerization!at!the!cell!wall!(Arabian!horse!knocking!
over!carbohydrate!wall)!!
•! Bacteriostatic!(Ethel!holding!hand!out!–!halt!)!
•! ADRs:!
o! Optic!neuritis!(loss!of!visual!acuity,!redAgreen!color!blindness)!(redSgreen!blinders!on!horse)!
o! Hepatotoxicity!(liver!spot!cow!standing!in!center!of!sketch)!
!
PYRAZINAMIDE!(The!Knitting!Pyro,!bottom!left!corner)!
•! Only!used!for!treating!TB!
•! ADRs:!
o! Hyperuricemia!and!needleSshaped!uric!acid!crystal!formation!(needles)!
"! !!Precipitate!gout!attacks!(yellow!yarn!ball!on!toe)!
o! Hepatotoxic!!!may!even!lead!to!liver!necrosis!(liver!spot!cow!standing!in!center!of!sketch)!
!
! !
LEPROSY!DRUGS!
(“For!a!Few!Mycobacteria!More”)!
!
!
MYCOBACTERIUM!AVIUM!COMPLEX!(MAC)!
•! Mycobacterium!avium!complex!(MAC)!includes!both!Mycobacterium&avium&and&Mycobacterium&intracellulare!
(caged!mockingbird)!
o! It!is!much!less!susceptible!to!the!usual!tuberculosis!drugs,!so!a!combination!is!used!
•! MAC!is!a!common!cause!of!disseminated!disease!in!AIDS!patients!(immunocompromised!cane)!
o! Especially!in!late!stages!when!CD4!count!<!50!
o! Give!macrolide!prophylaxis!for!MAC!when!CD4!<!50!(speed!limit!50;!crow!on!sign)!
•! Give!a!Macrolide!(e.g.!AZITHROMYCIN!or!CLARITHROMYCIN)!combined!with!ETHAMBUTOL!(crow;!Sheriff!Ethel)!
•! RIFAMBUTIN!may!be!added!as!a!third!agent!in!treatment!of!MAC!infection!(Billboard!Buttes)!
o! Related!to!Rifampin!and!has!similar!activity!!
o! Rifampin!and!rifabutin!activate!cytochrome!P450!(speeding!chrome!bumper)!
"! Rifabutin!is!a!less!potent!activator!than!rifampin!(driver!pulling!back!on!reins)!
•! Therefore!indicated!in!treatment!of!TB!in!patients!with!HIV!infection!!
o! These!patients!are!usually!on!antiSretroviral!medications!which!are!metabolized!
by!CP450!system!
!
MYCOBACTERIUM!LEPRAE!(leaping!armadillo)!
•! DAPSONE!(deputy!zone)!adverse!effects:!
o! Agranulocytosis!(multiSlobed!sand!timer)!
o! Hemolytic!anemia!in!patients!with!G6PD!deficiency!(broken!G6PDSfree!fruit)!!
"! Includes!bite!cells!and!Heinz!bodies!seen!in!RBCs!(watermelon!bite!and!seeds)!
•! CLOFAZIMINE!treats!lepromatous!leprosy!(cloth)!
o! Leonine!facies!seen!in!lepromatous!leprosy!(lion!bandana)!
•! Rifampin!also!treats!leprosy!caused!by!Mycobacterium!leprae!(rifle)!
! !
ANTIMICROBIALS:!Other!Antibiotics!!
TRIMETHOPRIM/SULFAMETHOXAZOLE,!PYRAMETHAMINE/SULFADIAZINE!
(“Trick!or!Treat,!Smell!my!Sulfa!Drugs”)!
!
!
GENERAL!
•! Sulfonamides!are!antiAfolate!drugs!!
•! Mammals!obtain!folate!exogenously!through!our!diet!
o! SulfaSsusceptible!organisms!must!synthesize!folate!from!PAamino!benzoic!acid!(PABA)!intermediate!
(Panda)!
"! PABA!is!the!beginning!of!the!folate!pathway!that!leads!to!synthesis!of!purines!(Panda!passing!
out!purine!shaped!cookies)!
o! PABA!S>!dihydrofolic!acid!(2!leaves!on!first!step)!S>!tetrahydrofolic!acid!(4!leaves!on!second!step)!
(bamboo!costumes!=!folate!foliage!found!in!leafy!greens)!
!
•! SULFAMEXAZOLE!(SMX!twin!with!rotten!eggs)!
o! PABA!analog!that!blocks!1st!enzymatic!step!A!dihydropteroate!synthase!(Panda!“drops”!cookies!from!
high!as!sulfa!eggs!hit!him)!
•! TRIMETHOPRIM!(TMP!twin!with!toilet!paper)!
o! Blocks!dihydrofolate!reductase!(2!leaves!“ducking”!toilet!paper)!
•! Combination!of!both!leads!to!synergistic!block!of!folate!synthesis!(both!toilet!paper!and!sulfa!eggs)!
•! Bacteriostatic!when!separate!
•! Bactericidal!when!used!together!
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INDICATIONS!
•! Gram!Negative!GI!and!urinary!tract!bacteria!in!men!and!women!(red!unisex!portSaSpottie)!
o! FIRST!line!treatment!for!UTI!in!men!and!women!(red!costumed!man!holding!bladder!cup)!
o! Acute!prostatitis!in!men!(egg!down!pants!of!man!waiting!for!bathroom)!
•! Gram!Positives!(purple!fence)!
o! Staph&Aureus!and!MRSA!(No!Mercy!Pharaoh!graffiti)!
"! However,!empiric!treatment!is!usually!vancomycin,!daptomycin!or!linezolid!
o! Nocardia!(cardSdealing!cowboy!spraypainting!long!chains!of!nocardia!branching!colonies)!!
•! Pneumocystis&jirovecii!pneumonia!(PJP)!(Old!ping!pong!man!in!PJs)!–!affects!immunocompromised!
•! Used!as!prophylaxis!for!HIV!pts!with!CD4!count!<200!(Address!200!sulfa!egg!filled!mailbox)!
o! For!CD4<100,!TMP/SMX!used!for!toxoplasmosis!prophylaxis!(Address!100!egg!filled!mailbox)!
"! Pyrimethamine!(pyramid!witch!hat)!+!Sulfadiazine!(dyed!sulfur!eggs)!treats!toxoplasmosis!
caused!by!Toxoplasma&gondii!(Ghandi!cat)!
!
ADRs!
•! Pancytopenia!(Panda!holding!empty!pan)!which!may!manifest!as!megaloblastic!anemia!(red!fireworks)!
•! Teratogenic!if!used!in!first!trimester!S>!antifolate!effects!S>!neural!tube!defects!(tarantula)!
•! Sulfa!drug!ADRs!(all!found!on!sidewalk)!
o! Sulfa!allergies!(Sweaty,!itchy!red!devil)!
"! 2nd!most!common!cause!of!allergic!drug!reactions!after!betaSlactams!
"! Fever,!urticaria,!rash!
"! Hemolytic!anemia!in!pts!with!G6PD!deficiency!(Smashed!G6PDSfree!fruit)!
•! Bite!cells!and!Heinz!bodies!seen!in!RBCs!(bite!in!watermelon!and!seeds)!
o! StevenAJohnson’s!syndrome!!
"! Uncommon!but!serious!skin/mucous!membrane!eruption!and!sloughing!(red!mask!falling!off)!
"! Toxic!epidermal!necrolysis!(TEN)!(“ten”gu!mask)!
o! Type!IV!renal!tubular!acidosis!(RTA)!(Mad!scientist!with!4!tubes!of!acid)!
"! Leads!to!hyperkalemia!(tubes!in!K!shape)!
o! Interstitial!nephritis!(Kidney!bag!with!little!blue!candies)!with!monocytic!infiltrate!in!interstitium!seen!in!
histology!
o! Photosensitivity!(flash!photo)!
o! Kernicterus!in!neonate!(Yellow!candy!corn!baby)!
"! Sulfonamide!is!used!in!the!last!month!of!pregnancy!displaces!bilirubin!bound!to!albumin,!
increasing!freeSunconjugated!bilirubin!levels!!
•! Displaces!other!drugs!from!albumin!i.e.!Warfarin!(Displaced!photos!from!album)!
o! Causes!overAanticoagulation!and!bleeding!(Bloody!mom)!
o! Inhibit!metabolism!by!cytochrome!P450!(vandalized!chrome!bumper!on!car)!
o! Drug!induced!Lupus!(werewolf!mask)!
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FLUOROQUINOLONES!
(“A!Nordic!Spring”)!!
!
!
•! Fluoroquinolones!(flowers)!inhibit!bacterial!topoisomerases!i.e.!DNA!gyrase!–!relieves!strain!as!dsDNA!is!
unwound!(Maid!unwinding!braid)!
o! Inhibits!normal!transcription!and!replication!
o! Bactericidal!–!kills!bacteria!!
•! Well!absorbed!when!taken!orally!
o! Absorption!is!decreased!with!concomitant!administration!of!multivalent!cations!i.e.!Ca,!Fe,!and!Mg!
(Metal!medals!for!Springtime!games)!
"! Never!give!fluoroquinolones!with!milk,!antacids,!or!ferrous!sulfate!
INDICATIONS!
•! Mainly!indicated!in!Gram!Negative!infections!(mostly!red!flowers)!
o! UTIs!due!to!E.&Coli,!Proteus!(Red!bladder!cup)!
"! Uncomplicated:!treat!with!Bactrim,!Fosfomycin,!or!nitrofurantoin!
"! Complicated!–!history!of!diabetes!or!urinary!tract!obstruction:!Fluoroquinolones!
•! Levofloxacin!and!Ciprofloxacin!for!UTI!caused!by!Pseudomonas!(Mona!Lisa!sipping!
bladder!cup)!
o! Pts!in!hospital!settings,!those!who!are!immunocompromised,!or!have!received!
urinary!tract!instrumentation!are!at!increased!risk!
o! Levofloxacin!or!Ciprofloxacin!for!empiric!treatment!for!complicated!and!uncomplicated!pyelonephritis!S
>!pyelouria!(milky!kidney!flask)!
o! Acute!prostatitis!in!men!(boy!putting!flower!bulb!down!pants)!
o! Gastroenteritis!caused!by!GI!Pathogens!Shigella,!Salmonella!(salmon),!E.&Coli,!Campylobacter!
(Gastrointestinal!feast)!
o! Osteomyelitis!–!fluoroquinolones!penetrate!well!into!bone!(fish!bones)!
"! Sickle!cell!pts!are!at!increased!risk!of!Salmonella!osteomyelitis!(Sickle!for!fish)!
!
!
•! Some!Gram!Positive!coverage!
o! Anthrax!due!to!Bacillus&anthracis!(bloody!lung!axe)!
o! LEVOFLOXACIN!or!MOXIFLOXACIN!treat!community!acquired!pneumoniae!due!to!Strep&Pneumoniae,!
Haemophilus&influenza,&and!others&!(Rusty!chest!plate)!
"! Also!treats!atypical!“walking”!pneumoniae!from!Mycoplasma&pneumoniae!(“Cold”!walking!
snowshoer),!Legionella!(legion!of!ships),!etc!!
!!
ADRs!
•! Prolonged!QT!interval!(torsades!strip!tug!of!war)!!
•! GI!side!effects:!Nausea,!Vomiting,!Diarrhea!(sick!Viking)!
•! Risk!of!tendon!and!cartilage!damage!in!the!elderly!(old!king!knowing!on!tendon)!and!chronic!steroid!use!(moon!
faced!shield)!S>!arthropathy!
•! Teratogenic!–!damage!to!growing!cartilage!(tarantula!shield)!)!S>!arthropathy!
o! Fluroquinolones!not!recommended!for!children!<!10!years!old!(child!gnawing!on!cartilage)!
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METRONIDAZOLE!
(“Murder!on!the!Metro!Express”)!
!
GENERAL!!
•! METRONIDAZOLE!(metro)!S!coverage!of!polymicrobial!anaerobic!infections!(e.g.!intraAabdominal!infections)!
(Mr.!Fragilis!stabbed!in!the!abdomen)!
•! Forms!Free!radical!metabolites!that!disrupt!bacterial!DNA!(bactericidal)!(broken!helix!outside!metro)!
•! Bactericidal!!
!
INDICATIONS!
•! Entamoeba&histolytica!(“Do!not!enter”!sign)!
o! Intestinal!protozoa!that!causes!amoebic!dysentery!and!liver!abscess!
•! Giardia!(Colonel!Giardia!with!the!protozoan!shield)!!
o! Carried!by!international!travelers,!causing!acute!watery!diarrhea!
•! Vaginitis!and!cervicitis!caused!by!Trichomonas!(Mr.!Trichomonas!pulling!strawberry!out!of!hat)!
o! Greenish!discharge!and!strawberry!cervix!of!vaginitis!
o! Metronidazole!is!administered!to!both!patient!and!partner!(Mrs.!Trichomonas!next!to!him)!
•! Bacterial!vaginosis!caused!by!Gardnerella!(Ms.!Gardner!with!the!venus!fly!trap)!
o! Fishy!odor!
•! Substitute!for!amoxicillin!in!the!triple!therapy!for!Helicobacter&pylori!infection!in!penicillinAallergic!patients!
(Helicopter!outside)!
o! Triple!therapy:!PPI,!amoxicillin,!clarithromycin!
•! Anaerobic!bacteria!(e.g.!Bacterioides,!Prevotella,!Fusobacterium,!Clostridium)!(Mlle.!Clostridium!with!the!gas!
mask)!
o! Treating!anaerobes:!clindamycin!above!the!diaphragm,!metronidazole!below!
•! Pseudomembranous!colitis!caused!by!Clostridium!(chocolate!fondu!fountain)!S>!diarrhea!!
!
ADRs!
•! Concurrent!ingestion!of!alcohol!results!in!a!disulfiramAlike!reaction!(metallic!taste,!flushing,!tachycardia,!
palpitations,!nausea,!vomiting)!(“No!Drinking!on!Metro”)!
ANTIMICROBIALS:!Antifungals!!
AMPHOTERICIN,!FLUCYTOSINE!
(“Bio!101!meets!Music!101”)!
!
!
GENERAL!
•! AMPHOTERICIN!(amphibian)!binds!to!ergosterol!and!forms!pores!in!the!cell!membrane,!allowing!leakage!of!
electrolytes!and!macromolecules!S>!cell!death!(water!leaking!through!holes!in!glass!of!terrarium)!
o! Fungal!cell!membrane!is!composed!of!ergosterol,!not!cholesterol!like!in!human!or!bacterial!cells!(Non!
“sterol”!sign)!
•! Resistance!to!amphotericin!due!to!change!of!molecular!components!of!fungal!cell!membrane!!
o! Decreased!amount!of!ergosterol!=!no!amphotericin!effect!!
!
AMPHOTERICIN!B!
•! Antifungal!with!the!broadest!spectrum!of!action!!
•! Given!IV!(Ivy!in!terrarium)!
•! Due!to!severe!toxicities,!liposomal!drug!formulations!have!been!developed!(frog!with!round!expanded!throat!
from!croaking!S>!round!liposome)!
o! Permits!packaging!of!the!drug!and!lipid!delivery!vehicles!S>!decreases!binding!to!human!cholesterol!
membranes!S>!lowering!toxicity!!
•! Use!for!severe!systemic!or!life!threatening!fungal!infections!(anatomical!organ!model!by!terrarium)!
o! Candida,!Cryptococcus,!Endemic!mycoses:!Histo,!Blasto,!Coccidio,!Molds:!Aspergillosis,!Mucor!
"! Severe!fungal!pneumonia,!cryptococcal!meningitis,!disseminated!infection!
"! !
•! ADRs!
o! All!ADRs!due!to!amphotericin!nonAselectively!binding!to!human!cell!membranes!(frogs!clinging!to!
cholesterol!tie)!
o! Infusion!related!immediate!reactions!–!universal!
"! Hypotension!and!headache!(fainting!teacher!with!tie)!
"! Fevers!and!chills!(Knocked!over!Bunson!burner!onto!burning!frog)!
"! Also!muscle!spasms!and!vomiting!
"! When!used!to!treat!fungal!CNS!infections,!must!be!administered!intrathecally!(frog!with!tongue!
latched!onto!anatomical!brain)!S>!CNS!side!effects:!Seizures!(motion!lines!on!tongue!and!model)!
"! Thrombophlebitis!at!injection!site!(blue!veiny!pattern!on!frog!with!tongue)!
o! Slow!cumulative!toxicity!!
"! Renal!damage!is!the!most!significant!toxic!reaction!–!seen!in!all!pts!!
•! Reversible!preArenal!azotemia!
•! Irreversible!renal!tubular!injury!S>!Type!I!Renal!Tubular!Acidosis!(1!shaped!graduated!
cylinder!of!acid)!
o! Hypokalemia!(banana!peel!underneath!foot!of!man!with!cylinder)!
•! Renal!Magnesium!wasting!(red!magnet!used!to!stir!kidney!beaker!in!sink)!
•! Give!IV!normal!saline!before!drug!administration!for!volume!expansion!which!
ameliorates!initial!decline!in!GFR!and!prevent!renal!damage!(emergency!saline!shower!
wash)!
"! Anemia!due!to!decreased!EPO!production!by!kidney!(drained!cracked!bleeding!kidney!and!
white!frog)!
•! Damaged!renal!tubular!cells!(not!just!bone!marrow!)!may!lead!to!anemia!(test!tubes!
tipping!over)!
!
FLUCYTOSINE!(flute!player!in!music!classroom;!F!and!C!on!sheet!music)!
•! Used!in!combination!with!amphotericin!B!to!treat!cryoptococcal!meningitis!(The!Crypt:!The!Musical)!
o! Will!rapidly!sterilize!the!CSF!
•! Cytosine!deaminase!converts!flucytosine!(a!fluorinated!cytosine)!into!5AFluorouracil!(5SFU)!(F!and!C!sheet!music!
turns!into!F!and!U)!!
•! Halts!fungal!DNA!and!RNA!synthesis!(smeared!double!helix!and!single!stranded!DNA!on!chalkboard)!
o! Inhibits!fungal!DNA!replication!and!protein!synthesis!!
!
NYSTATIN!(Be!Nyce!to!Lab!animals)!
•! Same!mechanism!of!action!as!amphotericin!(frog!on!poster)!
o! Binds!to!ergosterol!and!forms!pores!in!the!cell!membrane,!allowing!leakage!of!electrolytes!and!
macromolecules!A>!cell!death!
•! Active!against!Candida!(Canada!flag!outside!with!snow)!
o! Used!topically!for!mucocutaneous!candidiasis!i.e.!vaginal!candidiasis!(snow!on!crotch!of!girl!outside)!
o! Used!as!a!rinse!for!oropharyngeal!candidiasis!(drinking!fountain!by!window)!
"! Esophageal!candidiasis!must!be!treated!systemically!
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AZOLES!!
(“We’re!Not!in!Candida!Anymore”)!
!
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GENERAL!
•! Conazoles!(pine!cones)!!
o! Fungal!cell!membrane!is!composed!of!ergosterol,!not!cholesterol!like!in!human!or!bacterial!cells!
(emerald!perimeter!of!castle)!
•! Mechanism:!
o! Inhibition!of!ergosterol!synthesis!from!lanosterol!(house!crushing!emerald!builder)!
o! Inhibit!conversion!of!lanosterol!to!ergosterol!(“Lane!Closed”!sign)!by!inhibiting!cytochrome!PA450!
(broken!chrome!bumper)!
"! While!azoles!exhibit!higher!affinity!for!fungal!CYPS450s!than!for!mammalian!CYPS450s,!there!is!
still!some!azole!effect!on!mammalian!CYPS450s!!!drugAdrug!interactions!
!
VORICONAZOLE!(vortex)!
•! Inhibition!of!mammalian!CYPA450!(car!crushing!vortex)!
o! Must!reduce!dose!of!concurrent!meds,!including!CYP450!substrates!–!cyclosporins,!tacrolimus,!statins!
•! ADRs:!
o! Blurry!vision!or!flashes!of!light!(blurry!flashes!in!vortex)!
o! Changes!in!color!vision!(vortex!traveling!through!sepia!tone!landscape)!
•! Indications:!
o! Invasive!(systemic)!aspergillosis!(aspirating!scarecrow!with!lung!hyphae!next!to!vortex;!systemic!–!hay!
bursting!from!scarecrow’s!lungs)!
o! Candida!infections!(e.g.!Candida!esophagitis)!(Canada!flag!top!left)!
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FLUCONAZOLE!(flying!monkey!top!right)!indications:!
•! Candida!infections!(e.g.!mucocutaneous!candidiasis)!(Canada!flag!under!monkey)!
o! Easily!scraped!off!patches!of!mucocutaneous!candidiasis!(white!patches!of!snow)!
o! Vaginal!candidiasis!with!oneAtime!oral!dose!of!fluconazole!(flying!monkey!getting!hit!in!crotch!by!snow)!
o! IV!fluconazole!treats!candida!stomatitis!and!esophagitis!(snow!in!esophagitisSlike!gutters!of!crypt!on!
right)!in!AIDs!pts!
"! Esophagitis!requires!systemic!antifungal!therapy!–!should!never!use!oral!agents!
•! Cryptococcal!meningitis!(“CRYPT”!written!on!crypt!on!right)!
o! Fluconazole!has!high!levels!of!CNS!penetration!(meningitis!Mohawk!helmets!on!flying!monkeys)!!!can!
be!used!for!lifelong!maintenance!therapy!of!cryptococcal!meningitis!
!
ITRACONAZOLE!(good!pink!witch!bottom!left)!!
•! Systemic!infections!with!dimorphic!fungi!(e.g.!histoplasmosis,!blastomycosis,!coccidioidomycosis,!sporothrix)!
(dimorphic!butterflies!around!pink!witch)!
•! Onychomycosis!and!dermatophytosis!(witch’s!wand!touching!tarnished!ruby!slippers!of!Dorothy)!
o! Onychomycosis:!nail!fungal!infection!
o! Dermatophytosis:!tinea!infections!(Tin!man!with!tinea!spots)!
!
TOPICAL!CLOTRIMAZOLE!(close!trim!of!lion!behind!tin!man)!and!MICONAZOLE!(lion!clutching!pine!cone!saying!“it’s!my!
cone!!”)!indications:!
•! Tinea!infections!(Tin!man!with!tinea!spots)!
•! Vaginal!candidiasis!(snow!on!crotch!of!green!barber)!
!
TOPICAL!KETOCONAZOLE!(Tinman’s!key!with!pine!cone!keychain)!
•! Indications:!
o! Dermatophytosis,!such!as!tinea&corporis!
o! Inhibits!overproduction!of!cortisol!in!Cushing’s!disease!(moon!face!in!witch’s!recipe!book)!
•! ADRs:!
o! Not!usually!used!as!a!systemic!agent!because!other!azoles!have!a!better!safety!profile!
"! Ketoconazole!has!greater!propensity!to!inhibit!mammalian!CYPA450!
o! Inhibits!adrenal!steroid!production!by!inhibiting!17,20Adesmolase,!the!first!step!of!steroid!synthesis!
from!cholesterol!(ketoconazole!key!locking!the!adrenal!gland)!
"! Inhibits!gonadal!synthesis!of!androgens!and!estrogens!(male!and!female!symbols!in!recipe!book!
next!to!witch!synthesizing!steroid!structures)!
"! AntiAandrogenic!side!effects,!including!gynecomastia!(breasts!on!tin!man)!
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GRISEOFULVIN,!TERBINAFINE,!ECHINOCANDINS!
(“There’s!No!Place!Like!Canada”)!
!
!
GRISEOFULVIN!(grease!in!mouth!of!tin!man)!
•! Oral!fungostatic!drug!binds!to!fungal!cell!microtubules!S>!halting!mitosis!(broken!spindly!vines)!
•! Accumulates!in!keratin!forming!tissues!S>!best!at!treating!tinea!infections!of!scalp!and!skin!
•! FIRST!LINE!treatment!for!dermatophytic!infections!(rust!tinia!tin!man):!tinea&corporis,!tinea&pedis,!tinea&cruris&&
o! FIRST!LINE!treatment!for!tinea&capitis!in!children!(nearby!tin!man!cap!on!kid)!
•! With!prolonged!treatment,!griseofulvin!can!also!be!used!to!treat!dermatophytic!infection!of!the!nails,!though!
relapse!is!common!(farmhand’s!greasy!and!unsightly!nails)!
•! ADRs!
o! GI!distress,!headache,!rash!
o! Serious:!Hepatotoxicity,!granulocytopenia!
o! Most!important:!Activates!CYP!450!in!liver!(adding!greasy!oil!to!car!with!shiny!chrome!bumper)!
•! Not!used!that!much!anymore!
!
TERBINAFINE!(Turban)!
•! Terbinafine!works!by!inhibiting!squalene!epoxidase!S>!leads!to!accumulation!of!the!sterol!squalene!S>!toxic!to!
cell!(squealing!pig!pen)!
o! Fungal!cell!membrane!is!composed!of!ergosterol,!not!cholesterol!like!in!human!or!bacterial!cells!(Non!
“sterol”!sign)!
•! Like!griseofulvin,!deposits!in!keratin!forming!tissues!!
•! Used!topically!to!treat!dematophytosis!(tin!man!in!crystal!ball)!
o! FIRST!LINE!treatment!for!tinea&capitis!in!children!(nearby!tin!man!cap!on!kid)!
•! When!given!orally,!treats!onchomycosis!(biting!nails)!
•! ADRs!rare!
o! GI!side!effects!(mud!puddles!in!pig!pen)!
o! Hepatotoxicity!(liver!spot!on!pigs)!
!
!
ECHINOCANDINS!(CASPOFUNGIN,!MYCOFUNGIN,!ANIDULAFUNGIN)!(EchinoSCanadian!fur!cap!S>!Caspofungin)!
•! Act!at!fungal!cell!wall!(crumbling!brick!wall)!by!inhibiting!synthesis!of!BetaA1A3Aglucan!(polysaccharide!shaped!
sides!of!truck)!
o! Does!NOT!act!on!fungal!cell!membrane!S>!acts!on!CELL!WALL!!
o! Does!NOT!inhibit!ergosterol!synthesis!S>!inhibits!POLYSACCHARIDE!synthesis!
•! Given!IV!for!systemic!Candida!infections!(Ivy!around!Canadian!flag!and!patches!of!white!snow)!
o! Used!for!mucocutaneous!candidiasis,!candidemia,!and!prophylaxis!for!candida!infections!in!transplant!
pts!
o! Treatment!of!esophageal!candidiasis!in!HIV!pts!(Exhaust!pipe!with!snow)!
"! Requires!systemic,!NOT!topical!fungal!agents!–!echinocandins!are!systemic!
•! Caspofungin!
o! Used!to!treat!invasive!aspergillosis!in!pts!who!have!failed!to!respond!to!amphotericin!(aspergillosis!
scarecrow!with!lung!hyphae)!
•! ADRs!
o! Well!tolerated!with!minor!GI!side!effects!(friendy!canadians)!
o! Anidulafungin!may!cause!histamine!release!during!infusion!
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ANTIMICROBIALS:!Antivirals!S!HIV!!
NRTIs!
(“Le!Morte!d’HIV”)!
!
!
GENERAL!
•! Nucleoside/Nucleotide!Reverse!Transcriptase!Inhibitors!A!NRTIs!(Knights!of!the!Round!Table)!
o! Act!by!competitive!inhibition!of!HIV!reverse!transcriptase!(Reverso!transcriptum!book)!
o! NRTIs!are!nucleotides!or!nucleosides!(nucleosideSshaped!mace)!!
"! Can!completely!incorporate!into!viral!DNA!strands!
"! However,!they!lack!the!hydroxyl!at!3’!end!(broken!spike)!!!premature!chain!termination!
(broken!double!helix!bookmark)!
o! Inhibition!of!3’!to!5’!phosphodiester!bond!formation!(page!3!and!5!in!book)!
•! Nucleosides!need!phosphorylation!by!cellular!enzymes!in!order!to!be!activated!(activating!“P”!scroll)!
•! General!Adverse!Reactions!
o! Mitochondrial!toxicity!(woodgrain!cisternae)!
o! Lactic!acidosis!(sour!milk)!
•! Adine!suffix!(feast)!
!
LAMIVUDINE!(Sir!Lancelot)!
•! Lamivudine,!stavudine,!and!didanosine!may!cause!peripheral!neuropathy!(stockings!and!gloves)!
•! Lamivudine!and!tenofovir!treat!hepatitis!B!infection!(Lancelot!next!to!hippie!hippo!sigil)!
•! Because!lamivudine!inhibits!DNA!replication,!if!patients!are!coSinfected!with!HIV!and!HPV,!discontinuing!this!
agent!can!result!in!a!flare!of!hepatitis!
!
TENOFOVIR!(Sir!Tristan)!
•! Starts!with!T!!!this!is!a!nucleotide,!NOT!a!nucleoside!!!!does!not!need!to!be!phosphorylated!to!become!
activate!(Tristan!already!actively!sailing!the!tide!outside)!
•! Lamivudine!and!tenofovir!treat!hepatitis!B!infection!(Tristan!next!to!hippie!hippo!sigil)!
!
! !
!
ZIDOVUDINE!(Princess!Izolde!and!dove!sigil)!
•! Used!during!pregnancy!and!postSpartum!breastfeeding!to!reduce!vertical!transmission!(pregnant!woman)!
o! Infants!receive!several!weeks!of!prophylaxis!!
o! ALL!pregnant!women!should!take!antiSretroviral!therapy!regardless!of!viral!load!and!CD4!count!
•! Adverse!effects:!
o! Myelosuppression!(devoured!marrow)!
o! Anemia!(white!dress)!
o! Neutropenia!&!Granulocytopenia!(multilobed!sand!timer)!
o! Lipodystrophy!–!redistribution!of!fat!from!extremities!to!trunk!(central!adiposity!of!horse)!
"! Also!caused!by!stavudine!!
!
STAVUDINE!(Sir!Steve)!adverse!effects:!
•! Lipodystrophy!(central!adiposity!of!horse)!
•! Peripheral!neuropathy!(stockings!and!gloves)!
o! Also!caused!by!lamivudine!and!didanosine!
!
DIDANOSINE!(Sir!Dan)!adverse!effects:!
•! Pancreatitis!(squeezed!sponge)!
•! Peripheral!neuropathy!(stockings!and!gloves)!
o! Also!caused!by!lamivudine!and!stavudine!
!
ABACAVIR!(Abracadabra)!adverse!effects:!
•! Delayed!type!4!hypersensitivity!reaction!(distracted,!delayed!reaction!to!rash)!
o! Associated!with!the!HLAAB!57:01!allele!(HLASB!spell!on!p.!57!line!01)!
!
EMTRICITABINE!(Excalibur)!adverse!effects:!
o! Hyperpigmentation!of!palms!and!soles!(dark!gloves)!
! !
NNRTIs!
(“The!Council!of!Elfavir”)!
!
!
GENERAL!
•! NonAnucleoside!reverse!transcriptase!inhibitors!(NNRTIs)!(outside!Camelot!–!not!Knights!of!the!Round!Table)!!!
NNRTIs!are!not!phosphorylated!by!intracellular!enzymes!(fleeing!“P”!signal)!
o! Direct!binding!and!allosteric!inhibition!of!HIV!reverse!transcriptase!(arrow!in!Reverso!Transcriptum)!
"! Halts!DNA!polymerase!activity!(broken!double!helix!bookmark)!
!
AGENTS!
•! NEVIRAPINE!(Elven!pine!forest)!
•! EFAVIRENZ!(Queen!Elfavirez)!
•! DELAVIRDINE!(Princess!Delavir)!
!
ADVERSE!EFFECTS!
•! Liver!failure!can!occur!within!6!weeks!of!starting!therapy!(jaundiced!yellow!glow!and!liver!spot)!
•! EFAVIRENZ!may!cause!CNS!symptoms!(e.g.!dizziness,!drowsiness,!headache,!psychosis)!(mesmerized!by!
hallucinations)!
o! Insomnia!and!nightmares!(dark!moon)!
•! EFAVIRENZ!and!DELAVIRDINE!may!be!Teratogenic!(pregnant!Princess!Delavir!running!from!tarantula)!
•! Varying!effects!on!the!cytochrome!P450!system!(chrome!bumper)!
o! NEVIRAPINE:!moderate!inducer!
o! EFAVIRENZ!and!DELAVIRDINE!activate!and!inhibit!CP450!system;!these!drugs!also!are!metabolized!by!
CP450!system!
•! StevensAJohnson!syndrome!(SJSSTEN)!(sloughed!off!mask)! !
PROTEASE!INHIBITORS!
(“Lady!Guinevere!and!the!Sword!in!the!Stone”)!
!
!
GENERAL!
•! Protease!inhibitor!(sword!in!stone;!protease!is!normally!sword!cutting!a!protein)!
o! !“Anavir”!suffix!of!protease!inhibitors!(Guinevere)!
o! Are!not!NRTIs!(outside!Camelot)!!!not!phosphorylated!by!intracellular!enzymes!(fleeing!“P”!signal)!
•! Pol!gene!codes!for!production!of!HIV!enzymes!(e.g.!protease)!(Paul’s!Smithy)!
o! Pol!gene!mutations!lead!to!HIV!protease!virions!that!are!resistant!to!standard!protease!inhibitors!!
"! Therefore,!protease!inhibitors!are!never!used!as!monotherapy!
!
MECHANISM!
•! Before!HIV!can!assemble!mature!viruses,!its!gene!products!are!translated!into!long!polyproteins;!then!HIV!
proteases!must!cleave!these!precursor!molecules!in!order!to!form!the!mature!virion!
•! With!protease!inhibitors,!HIV!virions!remain!immature!(immature!knight)!
!
ADVERSE!EFFECTS!
•! Hyperglycemia!due!to!insulin!resistance!(elevated!candy!jar)!which!may!lead!to!diabetes!
•! Dyslipidemia!(elevated!butter)!
•! Lipodystrophy!A!redistribution!of!fat!from!extremities!to!trunk!(central!adiposity)!
•! INDINAVIR!(indigo!princess)!may!cause!nephrolithiasis!(stones!in!kidney!fountain)!due!to!urinary!crystalization!
o! Adequate!hydration!helps!to!prevent!nephrolithiasis!(kid!drinking!fountain!water)!
•! Inhibition!of!cytochrome!P450!(broken!chrome!bumper)!
o! RITONAVIR!has!greatest!cytochrome!P450!inhibitory!effect!and!increases!concentration!of!other!
protease!inhibitors!(Right!on!!High!five!)!!!can!be!used!as!a!clinical!advantage!
•! Remember,!Rifampin!activates!cytochrome!P450!and!decreases!the!concentration!of!protease!inhibitors!
(speeding!rifle)!
o! Therefore!contraindicated!with!protease!inhibitors!–!use!rifambutin!instead!
! !
MARAVIROC,!FUSION!INHIBITORS,!INTEGRASE!INHIBITORS!
(“Chapter!IV:!How!HIV!was!Thwarted!at!the!Gates!of!Camelot”)!
!
!
GENERAL!
•! HIV!infects!CD4+!T!cells,!macrophages,!and!dendritic!cells!(seized!castle!with!T!shaped!crosses)!
o! Once!incorporated!into!host!DNA,!it!uses!the!host’s!machinery!to!transcribe!viral!genes!
o! Budding!virion!then!invades!next!cell!(invading!ship)!
!
GENES!
•! Gag!structural!gene!codes!for!virion!core!proteins!(e.g.!p24,!p7)!(gagged!prisoners!in!the!core!of!the!ship;!24!
hour/7!days!a!week!sundial)!
•! Env!structural!gene!encodes!viral!envelope!proteins!for!infiltration!(e.g.!gp41,!gp120)!(envoy!coming!ashore!
unloading!gp120!and!gp41)!
o! Env!encoded!surface!proteins!are!first!sent!to!the!host’s!endoplasmic!reticulum!(endoplasmic!reef)!!!
eventually!sent!to!cell!membrane!and!incorporated!into!surface!of!budding!virion!
o! Surface!glycoprotein!gp120!allows!HIV!to!gain!entry!(120!battering!ram)!
"! gp120!binds!to!the!host!cell!CD4!molecule!and!chemokine!receptor!(CXCR4!or!CCR5)!(helper!
squire!and!CCR5!banner)!
•! The!entry!inhibitor!MARAVIROC!binds!CCR5!(mare!with!CCR5!banner)!
o! Maraviroc!binds!specifically!to!CCR5,!NOT!CXCR4!!!strain!of!virus!should!be!
determined!before!starting!therapy!
o! Surface!glycoprotein!gp41!facilitates!HIV!fusion!(41!grappling!hook)!
"! Fusion!inhibitor!ENFUVIRTIDE!binds!gp41!(fusion!hook!deflector)!
o! Resistance!may!be!due!to!mutations!in!the!Env!gene!which!alters!CCR5!and!gp41!
!
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•! Pol!gene!encodes!for!protease,!reverse!transcriptase,!and!integrase!(Paul!the!blacksmith!producing!swords,!
spell!books,!and!keys)!
o! Reverse!transcriptase!(Reverso!Transcriptum!spell)!transcribes!viral!RNA!into!double!stranded!DNA!
(doubling!army)!
"! NRTIs!and!NNRTIs!inhibit!reverse!transcriptase!(King!Arthur!and!elf!queen!Elfavir)!
o! Integrase!allows!viral!DNA!to!integrate!with!host!cell!DNA!(double!helix!staircase!behind!keyhole)!
"! Integrase!inhibitor!RALTEGRAVIR!binds!viral!integrase!(key!deflector)!!!prevents!transcription!
of!HIV!mRNA!!
•! If!the!viral!DNA!had!integrated,!it!would!then!use!host!cell!RNA!polymerase!to!produce!
viral!mRNAs!to!code!for!protein!production!
"! May!cause!rhabdomyolysis!(shield!man!eating!crispy!chicken!with!bite)!
o! Pol!gene!mutation!!!resistance!to!NRTIs,!NNRTIs,!protease!inhibitors,!and!integrase!inhibitors!
! !
ANTIMICROBIALS:!Antivirals!S!Hepatitis!
INTERFERON!α,!β,!γ!
(“Insert!Cytocoin!to!Continue”)!
!
GENERAL!
•! Interferons!are!host!cytokines!released!from!virusAinfected!cells!(infected!manager!releasing!cytoScoins)!!
o! Exert!antiviral,!immunomodulatory,!and!antiSproliferative!effects!by!modulating!tScells,!activating!
macrophages,!and!buffing!up!host!cells!against!further!infection!
•! Interleukins!upregulate!interferon!synthesis!in!infected!cells!(Manager!Luke)!
INTERFERON!ALPHA!(alpha!symbol!in!pachtdermSman)!
•! Indications:!
o! Hepatitis!B!and!C!infections!(yellow!pacShippo)!though!not!often!used!due!to!severe!adverse!effects!
"! PEGylated!–!preparations!that!allow!for!longer!halfSlife!=!less!frequent!dosing!
o! Hairy!cell!leukemia!(hairy!creature)!
o! Malignant!melanoma!(melanotic!ghost)!
o! Kaposi!sarcoma!associated!with!AIDS!and!caused!by!HHV8!(posies!design)!
o! Condyloma!accuminata!caused!by!HPV!(accumulated!pillSbug!like!tokens!in!a!jar)!
o! Renal!cell!carcinoma!(plush!cancer!crab!in!kidney!machine)!
•! Adverse!Reactions:!
o! FluAlike!syndrome!including!headaches,!fevers,!malaise,!myalgias!!
o! Chronic!therapy!may!lead!to!neurotoxicity,!fatigue,!tinnitus,!retinopathy,!pneumonitis!(red!fainted!kid)!
o! Myelosuppression!(devouring!marrow!in!arcade!game)!
o! DrugAinduced!lupus!(plush!wolf!prize)!
!
INTERFERON!BETA!(beta!invaders)!
•! Treats!relapsing!multiple!sclerosis!(MS)!(“Time!and!space”)!!!lesions!separated!by!time!and!space!
!
INTERFERON!GAMMA!(gammaga)!
•! Treats!chronic!granulomatous!disease!(CGD)!(destroyed!granulomatous!asteroids)!
o! Interferon!gamma!activates!macrophages!that!are!not!otherwise!able!to!form!the!superoxide!species!
necessary!for!oxidative!burst!
RIBAVIRIN,!SOFOSBUVIR,!SIMEPREVIR!
(“Dr.!LiverSstone,!I!Presume?”)!
!
!
GENERAL!
•! Hepatitis!C!(sea!hippo)!can!cause!both!acute!and!chronic!hepatitis!!
o! The!acute!process!is!usually!selfSlimited,!but!commonly!leads!to!chronic!infection!!
o! Must!first!identify!the!HCV!genotype!to!select!treatment!regimen!(“Genotype??”)!
o! Liver!fibrosis!is!assessed!before!beginning!treatment!(stony!liver!under!microscope)!
•! All!patients!with!virologic!evidence!of!chronic!HCV!infection,!except!those!with!limited!life!expectancy,!should!be!
considered!for!treatment!(photographic!evidence)!!
o! A!cured!hepatitis!C!infection!results!in!improved!survival,!reduced!morbidity,!and!higher!quality!of!life!
•! The!goal!of!treatment!is!to!eliminate!Hepatitis!C!virus!RNA!
o! Predicted!by!the!achievement!of!a!Sustained!Virologic!Response!(SVR)!!
"! Means!that!an!HCV!RNA!is!not!detected!by!PCR!for!6!months!after!stopping!treatment!
(sustained!search!for!6!months!on!calendar)!
"! Achieving!SVR!means!the!patient!has!99%!of!being!HCV!RNA!negative!at!longSterm!follow!up!
•! New!investigational!drugs!include!second!generation!NS3/NS4A!protease!inhibitors!and!NS5A!inhibitors!(North!
Sea!under!investigation)!
!
RIBAVIRIN!(rack!of!ribs)!
•! Give!daily!oral!ribavirin!with!once!weekly!pegylatedAinterferon!alpha!(alpha!shaped!antenna)!
o! However,!interferon!therapy!has!a!number!of!severe!side!effects!S>!protease!and!polymerase!inhibitors!
are!being!studied!!
•! RIBAVIRIN!is!a!guanosine!nucleoside!analog!(purine!shaped!stakes!at!the!end!of!the!tent!ropes)!
o! Must!be!phosphorylated!3!times!by!intracellular!enzymes!into!its!active!nucleotide!form!(3!pepper!
shakers)!
!
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!
!
o! Dose!dependent!hemolytic!anemia!(bursting!fruits)!in!10S30%!of!patients!
o! Teratogenic!(tarantula)!–!do!NOT!use!in!both!men!and!women!who!refuse!contraception!
•! FIRST!LINE!for!respiratory!syncytial!virus!(RSV)!(RSV!tombstone)!
SOFOSBUVIR!(sofa)!
•! A!nucleoside!analog!NS5B!polymerase!inhibitor!(sofa!with!nucleoside!pattern)!
•! Directly!inhibits!NS5B!RNA!dependent!RNA!polymerase!(disrupted!RNA!rope)!in!patients!infected!with!
genotypes!1,2,3!or!4!
•! Can!be!used!as!a!regimen!that!includes!Ribavirin!and!InterferonSalpha!
o! Fatigue!and!nausea!(fatigued!explorer)!
!
SIMEPREVIR!(simmering!fire!in!background)!
•! An!NS3/4A!protease!inhibitor!(stuck!machete)!!
•! Directly!binds!to!the!polymerase!that!cleaves!HCV!encoded!polyproteins!
o! Photosensitivity!and!rash!(flash!photo)!
o! Inhibits!cytochrome!P450!(broken!chrome!bumper)! !
ANTIMICROBIALS:!Antivirals!S!Other!
ACYCLOVIR,!VALACYCLOVIR,!FAMCICLOVIR!
!(“You!are!Now!Free!to!Move!About!the!Ganglia”)!
!
GENERAL!
•! Herpes!simplex!virus!(HSV)!(Hermes)!
•! General!Adverse!Reactions!
o! Uncommon!CNS!side!effects:!delirium,!confusion,!vertigo,!hallucinations!(disoriented!kid!bottom!left)!
especially!with!high!doses!and!IV!administration!
!
ACYCLOVIR!(recycling!bin)!
•! Guanosine!nucleoside!analog!(purine!shaped!luggage)!which!must!be!phosphorylated!to!become!active!
o! First!converted!to!acyclovir!monophosphate!via!VIRALAencoded!thymidineAkinase!(hermes!worker!with!
“P”!luggage!tag)!
"! This!occurs!selectively!in!virusSinfected!cells!and!not!in!uninfected!cells!! !
•! Acyclovir!is!ineffective!against!CMV!and!EBV!because!the!first!phosphorylation!step!
requires!a!specific!herpes!virusAencoded!thymidine!kinase!!!the!rate!determining!
activation!step!(“Rate!limit”)!
o! Absence!of!thymidineAkinase!confers!resistance!(closed!baggage!check)!
o! Then!converted!to!acyclovir!triphosphate!by!2!CELLULAR!kinases!(bag!checkers!with!“P”!tags)!
"! As!a!triphosphate,!it!can!readily!compete!with!deoxySguanosine!triphosphate!for!Viral!DNA!
dependent!DNA!polymerase!(branching!double!helix!conveyer!belts)!
•! Acyclovir!triphosphate!incorporates!into!replicating!viral!DNA,!halting!synthesis!(baggage!jam)!
•! IV!acyclovir!treats!serious!HSV!and!VZV!infections!(ivy)!like!HSV!encephalitis!(red!winged!helmet)!and!neonatal!
HSV!(baby!Hermes!helmet)!
•! Used!for!Varicella!zoster!virus!(Zeus)!
o! Shingles!hemidermatomal!vesicular!rash!–!due!to!reactivated!VZV!(shingles!on!roof)!
o! Ability!to!prevent!postSherpetic!neuralgia!is!unclear!
o! Famcyclovir/valacyclovir!are!preferred!due!to!superior!activity!and!less!frequent!dosing!(family!value)!
"! Most!effective!if!given!within!3!days!of!onset!of!symptoms!(3Sday!vacation!package)!
!
!
•! Adverse!Reactions:!Interstitial!nephritis!or!crystalline!nephropathy!(sharps!in!kidney!bin)!
o! Adequate!hydration!prevents!renal!side!effects!(guy!drinking!water)!
!
CIDOFOVIR!(security!officer!Cid)!
•! Does!not!require!phosphorylation!by!the!viral!kinase!!!active!against!acyclovir!or!ganciclovir!resistant!HSV,!
CMV,!VZV!(“P”!access!badge)!
o! Phosphorylated!and!activated!solely!by!cellular!kinases!!!important!in!immunocompromised!patients!
o! For!example,!thymidine!deficient!strains!of!VZV!are!almost!exclusively!found!in!patients!with!AIDS!and!
can!be!treated!with!cidofovir!
•! Directly!inhibit!viral!DNA!polymerase!(conveyer!belt!stop!switch)!
!
FOSCARNET!(luggage!car!net)!
•! A!pyrophosphate!analog!that!selectively!inhibits!the!pyrophosphate!binding!site!on!viral!DNA!polymerases!
(conveyer!belt!stop!switch)!
•! Does!not!require!intracellular!activation!at!all!!!active!against!acyclovir!or!ganciclovir!resistant!HSV,!CMV,!
VZV!(luggage!car!net)!
!
VALACYCLOVIR!(VALet!parking;!great!VALue)!
•! An!acyclovir!prodrug!with!improved!oral!bioavailability!(open!mouth;!available!booth)!
•! Daily!valacyclovir!suppressive!therapy!for!multiple!yearly!episodes!of!recurrence!(daily!rate!for!frequent!flyers)!
o! Acyclovir!and!famcyclovir!reduces!the!rate!of!viral!shedding,!time!for!leasing!healing,!and!local!pain!but!
does!NOT!affect!recurrence!rates!
!
HSV!PROPHYLAXIS!(“Prepare!for!your!flight”)!
•! Important!in!immunocompromised!states!(Hermes!worker!with!cane)!
•! Agents!such!as!acyclovir!and!valacyclovir!can!be!used!to!prevent!reactivation!of!herpes!viruses!after!
hematopoetic!stem!cell!transplantation!(organs!on!display)!
•! Important!in!pregnant!women!with!active!recurrent!genital!herpes!(pregnant)!
o! Recommended!to!start!suppressive!acyclovir!therapy!beginning!at!week!36!to!reduce!the!risk!of!viral!
shedding!at!delivery!and!the!need!for!a!CSsection! !
GANCICLOVIR,!VALGANCICLOVIR,!FOSCARNET,!CIDOFOVIR!
(“Clean!Up!on!Aisle!HHVS5”)!
!
GENERAL!
•! Cytomegalovirus!(CMV)!(MegaSLo!Market)!infections!occur!in!the!setting!of!advanced!immunosuppression!
typically!due!to!reactivation!of!latent!infection!after!organ!transplantation!
o! Involves!hemorrhages!and!infiltrates!of!CMV!retinitis!(pizza),!esophagitis,!and!CNS!involvement!
•! CMV!infections!are!more!common!with!a!CD4+!count!<!50!(50!items!or!less)!
!
GANCICLOVIR!(green!can!recycling)!
•! Mechanism!similar!to!acyclovir:!
o! Guanosine!nucleoside!analog!(G’s!on!cans)!
"! Must!be!phosphorylated!3!times!before!incorporated!into!viral!DNA!!
o! First!converted!to!ganciclovir!monophosphate!by!a!CMVAencoded!protein!kinase!(UL97)!(market!
worker!with!“P”!label!gun)!!
"! This!occurs!selectively!in!CMVSinfected!cells!and!not!in!uninfected!cells!
"! CMV!can!gain!resistance!from!mutations!in!its!protein!kinase,!resulting!in!decreased!levels!of!
the!active!form!of!ganciclovir!!!use!foscarnet!or!cidofovir!
o! Subsequent!phosphorylation!steps!are!then!taken!over!by!cellular!enzymes!
"! Converted!to!ganciclovir!triphosphate!by!cellular!kinases!(customers!with!“P”!label)!!
•! As!a!triphosphate,!it!can!readily!compete!with!deoxySguanosine!triphosphate!for!viral!
DNA!dependent!DNA!polymerase!(branching!double!helix!conveyor!belts)!
"! As!a!nucleotide!analog,!it!can!be!incorporated!into!replicating!viral!DNA,!halting!synthesis!
(grocery!jam)!
•! Given!IV!for!CMV!retinitis!or!in!organ!and!bone!marrow!transplant!recipients!(organs!on!ice)!
•! Adverse!Reactions!
o! Bone!marrow!suppression!(bone!sample!tray!with!marrow!being!eaten),!especially!leukemia!
"! Can!be!managed!with!hematopoietic!growth!factors!
"! Myelosuppression!may!be!additive!in!patients!receiving!concurrant!zidovudine!(NRTI!Princess!
Izolde!used!for!HIV)!
!
VALGANCICLOVIR!(VALue)!
•! ProAdrug!of!ganciclovir!with!better!oral!bioavailability!(open!mouth;!available!sample!tray)!
•! As!effective!as!gancyclovir!for!CMV!retinitis!!
•! Use!in!highSrisk!solid!organ!and!bone!marrow!transplant!recipients!(organs!on!ice)!
•! Adverse!reactions!same!as!ganciclovir!
!
FOSCARNET!(fast!car!net)!
•! Does!not!require!phosphorylation!by!the!viral!kinase!!!active!against!ganciclovir!or!acyclovir!resistant!HSV,!
CMV,!VZV!(bypassed!“P”!labeler)!
•! Directly!inhibits!viral!DNA!polymerase!(fast!car!directly!slamming!into!conveyer!belt)!
o! Foscarnet!is!a!pyrophosphate!analog!that!selectively!inhibits!the!pyrophosphate!binding!site!on!viral!
DNA!polymerases!
o! Reversible!renal!insufficiency!(spilled!kidney!beans)!due!to!renal!tubule!cell!toxicity!!
o! Hypocalcemia!(broken!milk!bottles)!due!to!complex!formation!with!free!Ca2+!
o! Hypomagnesemia!(falling!magnets)!
o! Hypokalemia!(banana!peel)!
o! Seizures!(shaking!foscarnet!kid)!
!
CIDOFOVIR!(security!officer!Cid)!
•! Does!not!require!phosphorylation!by!the!viral!kinase!!!active!against!ganciclovir!or!acyclovir!resistant!HSV,!
CMV,!VZV!(“P”!access!badge)!
•! Directly!inhibits!viral!DNA!polymerase!(Security!officer!pulling!conveyer!belt!stop!switch)!
o! CMV!strains!can!gain!resistance!with!mutations!in!viral!DNA!polymerase!
o! Nephrotoxicity!(broken!kidney!merchandise)!
"! Leads!to!proteinuria,!azotemia,!metabolic!acidosis!!
"! Give!PROBENICID!to!blocks!the!active!tubular!secretion!of!cidofovir!(probation!officer!Cid!
preventing!display!from!toppling!over)!
•! Prevents!the!excretion!and!increases!plasma!concentrations!of!many!different!drugs!
e.g.!penicillins,!methotrexate,!NSAIDs!(cashier’s!DRUGS!tattoo)!

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