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106 Cards in this Set
- Front
- Back
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Draw the sturcture of Sulfonamides
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YES
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Modification to SO2 group results in
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increased competive inhibtion of PABA, increases antimicrobbal activity
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Free NH2 at carbon 4 results in
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increased antimicorbal activity
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Modificaiton of 4-amino group results in
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decreases GI absoprtion
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What is necuessary for PURINE synthesis in mamals and bacteria
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folic acid
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Bacterica CANNOT use exogenous folic, but human can, so sulfa selectively
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inhibit bacterial growth
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Sulfonamides are sturctual analogues of PABA and compete with
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PABA in synthesis of dihydropteroic acid
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Where do sulfonamids bind
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ENZYME dihydropeteroate synthase and inhibits folic acid production
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What type of killing does sulfonamides do
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bacteroSTATIC
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Sulfonamids have good absoprtion and variable protein binding what is penetration into tiisue
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ALL TISSUES (everyone)
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For is the MOST responbile organ for elmination of sulfonamides
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KIDNEY
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Metabolism of Slfonamides occurs primarly in
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LIVER via N4 acetlyayion
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N4-acetalayed sulfas do NOT possess
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antibacterial acitivity
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N-4 acetlayed sulfas are excreted and concentrated in the urine, and have LMINTED solubility at
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neurtal or acidic pH resulting in cyrsalluria and renal toxicity
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What is metabolism at N1 sulfonamide nitrogen
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glucurondiation
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What metabolism is important in forming the haptenated structure which the body recognizes as foriegn
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hydoxylation at the N4 position bt CYP 2C9
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What are the 4 classes of Sulfonamides
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1. Short to medium acting
2. Long acting 3. Poorly absorbed 4. Topical |
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What are the short-medium acting sulfonamides
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sulfamethoxazole
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The long-acting sulfonamides are NOT used often why
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assoication with Steven Jongn syndrome
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The Poorly absorbed sulfonmaides are used to
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cleanse the bowel and treat ulcerative colitits
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What are the major averse effects of sulfonamides
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Vasculitic
Anemia/Agranulocytosis Crysallurai Hemolytic anemia Rash (SJS) |
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What are the 2 types of resistance with Sulfas
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Intrinsic resistance or
Acquired resistance |
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What is intrinsic resistance
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use a different pathway for folic acid production
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What are examples of pathogens with intrinsic resistance
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Etneroccouc facalis and lactobaccilli
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Acquired resistance comes from chromomal mutation or plasmid mediation, what are 3
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Alteration in dihydropeteroate synthases
overproduction of PABA Reduced uptake or efflux |
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Sulfonamides are broad specturm for both gram+ and gram- organism
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YES
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What are the topical sulfonamides
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Silver sulfadizine
Mafenide |
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Only 5% of the populatino has a TRUE allergy, and 15% belive they have an allergy
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YES
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IgE mediates Sulfa allegy is from
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N1 SO2NH2 group
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What group on sulfa is assoicated with analyphaixs (1-3 days)
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N1 SO2NH2
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What are typicall alelrgic to N1 SO2NH2
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maculopapualr eruptions and urticarial
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What group is assoiced with the toxic metabolite allegy (7-14 days)
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N4 hydroxlmaine metabolic
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What are sign of the toxic metabolic N4 Haptenation
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fever, rash, mutli-organ toxicity
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What are the 3 sulfonamide drug groups
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1. Sulfonylarylamine
2. NON-sulfonarlyamine 3. Sulfonamide |
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What is the structure of the sulfonarylamine group
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Sulfonamide moiety is connected to benzene ring, and UN-substiation NH2 at position 4
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Individuals with a SULFA allergy have 100% cross reactivity with the presence of what structure
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FREE NH2 at poistion 4
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What is the structure of the NON-sulfonlarylamine
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Sulfonamide moetiy connect to a beneze ring, WITHOUT an unstitutated amine at poistion
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What is the cross reactivity of NON-sulfonarlyamine with SULFA allergy
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<5%
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What is group 3
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Sulfomaide, NOT connect to a benzene ring
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What is cross reactivity of a sulfa allergy with Sulfonamide
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<0.1% is the least likely to cross react
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Is ethancrinic acid completely safe with Sulfa allergy
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YES--no sulfa moeity
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Sulfonamides are sturcutral analogs to PABA, and trimethoprim is sturcutal analog to
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dihydrofolic acid
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What is the MOA of Trimethoprim
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binds to DHFR (dihydrofolate reducatase and inhibts formation of tetrahydrfolic acid
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Trimethoprim is orall absrobed, and widely distributed, and the majority is exreted UNCHANGED in
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urine
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What is the half life of trimehtoprim
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10-12
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What are adverse effects of Trimehtoprim
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N/V, pancytopenia, renal disorder, and hyperkalmemia
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Trimehtoprim resistance is also chormosomal and plasmid mediated HOW
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Decred affinty to DHFR
Hyperproduction of DHFR Decrease porin permeability |
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The addition of BOTH Sulfa nad + Trimethoprim results in
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synergistic combination
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TMP/SMX combination is a fixed dosing combination with
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1 of TMP
to 5 SMX |
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What is spectum of activity of TMP/SMX
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Gram - aerobes
Enterobacteriacae, Pseumoas, Stenorptohmas, Haemophilus and Neisseria |
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Does TMP/SMX have any effect against Pesdomaons aruginosa
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NO
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SMX is a GREAT GRAM- drug, what is affect against ANAerobes
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ok
Bacteriodes Gardenerella |
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What gram + bacterica does TMP/SMX have against
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Listeria
Actinomcetes Nocardia Stap Auereus/ STrep |
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What other activity does TMP/SMX have besides Gram+ and Gram- organism
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Protozoal infections and Mycoses
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What is the main indicuation of SMX/TMP
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UTI
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What is the MAJOR drug intercation with SMX/TRM
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coumadin--affect protien binding
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What are other drug interaction of SMX/TRM besides warfarin
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Pheyntoin
Azthioprine Methotreaxte Sulfonylerea agents |
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What drug class is rifampin
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rifamycin
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Rifampin is BACTERICDIALS and either broad or narrow spectrum
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BROAD spectrum
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Why molecular stucture gives rifampin is activity
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OH grousp
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Modificaiton of what side chain yields other rifamycins
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C3
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What is MOA of Rifampin
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Binds to the Beta subunit bacterial RNA polmerase, and inhibits iniation of transcriptino
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Why type of bacterial killing is Rifampin (time or concentration dept)
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concentration dept
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Rifampin has GOOD oral bioavailability, is it availabe IV
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YES
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What is volume of distribtion of Rifampin
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GOOD--penetration most tissue
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What is protein of Rifampin
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high 85%
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What is elimination of Rifampin
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hepatic and bile
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Rifampin is AUTOINDCUCER of what
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Incudes its own metabolism increased metabolism of other CYP enzymes (CYP3A4, CYP 2C8/2C9
REDUCES DRUG LEVELS |
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Does Rifampin undergo extensive enterohaptic reciculation
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YES
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What are adverse effects of Rifampin besides NV, HA, dizziness
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Organe red discoloration of body fluid
Hepatoxocity (jaundice) |
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Rifampin is BROAD spectrum antibiotic, what is spectrum of activity
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Gram+ aerobes (Staph/Strep/Corenbacterium and Listeria)
Gram - Enterbaceriaceae ANAERBOES NONE AYPTICAL--EFFECTIVE |
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Does Rifampin have effects against atypical bacteria
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YES
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What are the MAIN clinical uses of Rifampin
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Tuberculosis, endocarditis, menigtits
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What is resistance to Rifampin
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SINGLE mutationin the RNA polmerase beta subunit
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Rifampin is rarely used as monoterapy, due to acquired resistance, what can prevent this
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using antmycobacterial drug, or another antibiotic
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What is the structure on NItrofurantion that gives it its antmicrobial activity
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Nitro moeity
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The MOA of nitrofuantion is NOT really known, generally what
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reduced to a reactive metabolite that interacts with CAC, DNA, RNA and protein synthesis
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Nitrofunatoin is bacterostatic at LOW concentration, where is it bactericidal
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high concetration in URINE
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Nitrofunatoin is 90% bioavailable, its Volume of distrubtuion is MAINLY in
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URINE
ONLY Place Nitrofuntoin concentration is IN THE URINE |
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How is Nitrofunatoin eliminated
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renally
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Nitrofuntoin should be avoided in CrCl <60 why
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can increase plasma concetnration
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What is spectum of activity of Nitrofurantoin
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Gram+ aerobes (Stap, Strep Enterococcus)
Gram - Enterobacteraceae NO ANAERBOIC |
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Resistance to Nitrofunatoin is not common, but may be due to
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reduced nitrfuan redutase activity or changes in cell wall permeability
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What are the MAIN clinical uses of Nitrofunatoin
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Uncomplication UTI--(concentrates in the urine or phyplactic tx of UTI
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Should Nitrofurantoin be used for systemic infections
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NO
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What are some adverese effect of Nitrofurantoin besides N/V, HA, dizzines
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Brown urine
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What are some adverese effects of Nitrofurantoin is systemic concentrations are HIGH
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Pulmonary reactions
Pancertisis Hepatotoicty Hemolysis or Megalobalistc anemia |
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What is a drug reaction with Nitrofurantoin
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Probeneicd, b/c it inhibts tubular secretion
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What is MOA of Chloramphenicol
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binds to the 50S ribosomal subunit and inhibits protein sysntehis
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Is Chloramphenicol bacteriostatic or CIDAL
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STATIC on most
CIDAL on S. Pneumonia, H. influenzae and menigidits |
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What is resistance of Chlorampenicol
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Alteration in 50S ribosomal subunits
Efflux/Reduced permability Inactivation by acetylransferase |
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Chlorampenicol is ONLY available IV in the US, well absrobed, and what is penetration in tiisu
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GOOD
GREAT CSF penetration into brain |
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What is the only area chlorampenicol does NOT have good penetration
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bile
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What is metabolism of Chlorampenicl
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heatpic
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What is spectrum of activity of Chlorampenicol
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Gram+ aerobes
Stapy/Step/Enteroccocoss, and Listeria Gram- Enterobacteraia Anerboses (Gram+/-_ AYTYPCIAL bacterial (like Rifampin) |
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Does Chloramphenicol have acitivty against Psedumonas aerguinosa
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NO--sulfa does not either
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What are the MAJOR adverse effects of Chlorphenicol
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GRAY BABY syndrome
Hematologic toxicty Neurtoxocity |
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What causes Gray baby syndrome with Chlorophenicol
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infants due to decrease hepatic conjufation
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Why does Chloropenicol cuase hematoligc toxicity
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inhibits mitrochorndrial enzymes necessary for heme synthesis
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Are peak or trough concentrations related to chlorophenicol toxcity
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PEAK concetrations
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Peak concetration should be measured 1 hours after infusion, and geal is
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10-25
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Concetnration of chlorophenicol >25 are associated with
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bone marrow suppresion
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Concentrations of chlorphenicol >40 are assoicted with
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gray baby syndrome
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B/c Chlorophenicol is metabolized by liver, what enzymes does it inhibt
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CYP3A4, and CYP2C8/2C(
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What other drugs may result in competive inhbition of chlorophenicol
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Macrolides and clindamycin
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What is really the only time to use chlorophenicol
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allergies to other medications
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