Term
|
Definition
| all the bacteria, yeast, etc that reside in our gut |
|
|
Term
|
Definition
| differ biochemically and physiologically |
|
|
Term
|
Definition
|
|
Term
|
Definition
| differ in antigenic properties |
|
|
Term
| Describe G+ structure and stain |
|
Definition
Large peptidoglycan layer
Contain lipotechoic acid and techoic acid in PG layer
Stain Purple/Blue |
|
|
Term
| Describe G- structure and stain. |
|
Definition
Outer membrane contains porins, LPS(activator of immune system), murein proteins
PG layer-small
Periplasmic space
Cytoplasmic space-contains embedded protiens |
|
|
Term
|
Definition
1. Crystal violet - stains
2. Iodine - mordant(makes stain insoluble)
3. Alcohol- decolorizer...dissolves PG layer(cannot do this in G+ bc it is so large)
4. Safranin - counterstain |
|
|
Term
| Mycobacteria and Nocardia characteristic |
|
Definition
|
|
Term
| Describe bacterial growth curve. |
|
Definition
| Lag -> Log -> Stationary -> Death |
|
|
Term
|
Definition
| Planktonic is stages before bacteria become biofilm |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Streptococci, Candida, Anaerobes in crevices, some G- |
|
|
Term
|
Definition
| Staph, Strep (pneumo and Viridans), H. influ, N. meningitidis |
|
|
Term
|
Definition
| no endogenous flora that we know of |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Anaerobes, Enterobacteriaceae(Escherichia, Klebsiella, Serratia, Enterobacter), Candida, |
|
|
Term
|
Definition
| anaerobes, Vibrio, Shigella, Salmonella, Enterococci, Bacteroides(esp fragilis) |
|
|
Term
|
Definition
females: lactobacilli
enterococci, candida, clostridium perfringens |
|
|
Term
| obligate anaerobes lack what? |
|
Definition
| enzymes to protect them from superoxide anions, H2O2, and OH radicals |
|
|
Term
| Strict vs Moderate Obligate Anaerobes? |
|
Definition
Moderate: cannot multiply with O2 > 2-8%
Strict: cannot multiply with O2 > 0.5% |
|
|
Term
| What group establishes therapy by S,I,R? |
|
Definition
| Clinical and Lab Standards Institute (CLSI) |
|
|
Term
|
Definition
| concentration of antimicrobial that classifies microbes as sensitive versus resistant...safety margin called intermediate |
|
|
Term
| Describe disk diffusion MIC |
|
Definition
| Kirby-Bauer; Qualitative and Semi-Quantitative....larger area = more susceptible to that drug |
|
|
Term
| Describe broth dilution MIC |
|
Definition
Quantitative.
MIC: first tube w/o turbidity
MBC: first plate w/o growth |
|
|
Term
|
Definition
strip with conc gradient of antimicrobial
MIC is where growth ellipse intersects with strip |
|
|
Term
|
Definition
| overall antimicrobial susceptibility profle of a bacterial isolate to several different agents...used to monitor resistance patterns |
|
|
Term
| What are the 3 points of a disease triangle? |
|
Definition
Susceptible host
virulent pathogen
favorable environment |
|
|
Term
| What are the 4 different main MOAs of antibiotics? |
|
Definition
1. Inhibit Cell wall Synthesis
2. Inhibit Protein Synthesis(30S or 50S)
3. Inhibit Nucleic Acid Synthesis or Function....humans do not synthesize folic acid
4. Inhibit cell membrane permeability or function...possible toxicity problems |
|
|
Term
| 4 different kinds of antimicrobial resistance? |
|
Definition
acquired or intrinsic
vertical or horizontal(staph to other genus) |
|
|
Term
|
Definition
| level > MIC for at least 40-50% of the dosing interval |
|
|
Term
|
Definition
| AUC >25X MIC or Peak >10X MIC |
|
|
Term
| 6 Mechanisms of Resistance |
|
Definition
1. Penetration- entry into human cell
2. Porins- entry of drug into bacteria
3. Pumps- efflux
4. Penicillin-Binding Proteins (PBPs)- target mod...alters receptor proteins
5. Penicillinases- inactivate penicillin
6. Pathway Modification- use alternative metabolic pathway |
|
|
Term
| When RNA copy of DNA is first made w/o removal and new DNA made and inserted, this is called what? |
|
Definition
| Retrotransposon - copy and paste |
|
|
Term
| When DNA is lost from original location and relocated to new location is known as what? |
|
Definition
|
|
Term
When bacteria sense one another's presence and produce virulence factors or protective biofilm is called what?
What is an example of this? |
|
Definition
Quorum Sensing
Pseudomonas and alginates in lungs -> biofilms |
|
|
Term
|
Definition
| Thiazolidine 5-member S-containing ring fused to B-Lactam ring with variable side chains |
|
|
Term
| Where do penicillinase and amidase act? |
|
Definition
Penicillinase acts on the B-Lactam ring
Amidase acts on the N-C bond between the B-Lactam and R group |
|
|
Term
| Antistaphylococcal structure changes |
|
Definition
Penicillinase/B-Lactamase Resistant
*Bulky R group |
|
|
Term
| Aminopenicillins structure changes |
|
Definition
*amino R group
*increase h-philic properties
*allows better entry into G- via porins |
|
|
Term
| Aminopenicillin/B-Lactamase Inhibitor Combos...what is the BLI for? |
|
Definition
| BLI used to protect the drug...aka BOOSTER! |
|
|
Term
| Antipseudomonal (Extended Spectrum) Penicillins structure change |
|
Definition
larger R group
*increase entry via porins into G- |
|
|
Term
| Antipseudomonal/BLI Combos include what drugs? |
|
Definition
Piperacillin/Tazobactam
Ticarcillin/Clavulanate |
|
|
Term
|
Definition
Inhibits Glycopeptide transpeptidase(PBP), which mediates cross-linking reaction (transpeptidation) that strengthens the cell wall
*Irreversible suicide inhibitor!!
**BacteriCIDAL |
|
|
Term
|
Definition
PenG-oral absorption low; IV/IM
PenV-better oral stability/absorption;PO
Nafcillin,Oxacillin-IV
Ampicillin,Dicloxacillin,Amoxacillin-PO |
|
|
Term
|
Definition
*mostly to extracellular fluids of the body
*60% bound to plasma protein
*poor CNS |
|
|
Term
|
Definition
*rapid; short t1/2=30-60 mins
*50-90% renal elimination....dose adjust
*Antistaph Penicillins do not require dose adjustment (only 50% renal elim) |
|
|
Term
|
Definition
1. Hypersensitivity most common
2. Diarrhea
3. Cation Toxicity |
|
|
Term
| TRUE/FALSE. Cephs have same MOA as Penicillins. |
|
Definition
|
|
Term
| What are the structure differences in Cephalosporins that make them different from Penicillins? |
|
Definition
6-membered S-containing ring
2 R side chains (R1:lactam ring R2:dihydrothiazine ring)
R1 modification = changes in spectrum
R2 modification = changes in ADME/PK |
|
|
Term
| What are 1st gen cephs most commonly used for what kind of infections? |
|
Definition
| SSTIs, prophylaxis, recurring endocarditis |
|
|
Term
| 2nd Gen cephs are most commonly used for what type of infections? |
|
Definition
|
|
Term
| What makes 2nd gen cephamycins different from normal 2nd gen cephs? |
|
Definition
| methoxy group of B-lactam ring |
|
|
Term
| 3rd gen ceph has what structural difference and what are the advantages of this change? |
|
Definition
R1=aminothiazolyl
Enhances 3 properties:
1. increase movement through outer cell membrane
2. increase PBP affinity
3. increase G- B-lactamase stability(but not for Pseudomonas) |
|
|
Term
| 3rd gen ceph used for Pseudomonas(Ceftazidime) has what differences from the other 3rd gen cephs? |
|
Definition
*aminothiazolyl R1 modified by addition of carboxypropyl group
*increase passage through porins
*decrease binding to staph PBPs...so less effective for G+
*95% renal elim -> need dose adjustment |
|
|
Term
| what structure change made the 4th gen cephs evolve? |
|
Definition
Changing R2 group instead of R1
*high affinity PBP binding |
|
|
Term
| Cephalosporin general Absorption |
|
Definition
most IV
PO(cefadroxil,cephalexin; cefaclor, cefprozil,loracarbef; cefdinir,cefixime) |
|
|
Term
| General Ceph Distribution |
|
Definition
| distributes widely; CNS penetration! |
|
|
Term
|
Definition
50-95% kidney excretion
dose adjust in renal excretion for ceftizoxime,ceftazidime,ceftaroline ...not cefotaxime or ceftriaxone bc these are both only 50% renal elimination
MOST t1/2 = 0.5-2 hours EXCEPT Ceftriaxone(IV) t1/2 = 6-9 hours... dosed QD |
|
|
Term
|
Definition
| ceftriaxone(IV) bc t1/2=6-9 hours |
|
|
Term
|
Definition
Common: Hypersensitivity (cross rxn between penicillin and ceph)
Less Commmon: nephrotox, GI problems, Biliary "Sludging", Chelation(w/ceftriaxone), coag issues(w/ cefotetan), and ROH intolerance(w/ cefoperazone)....coag issues and ROH intolerance due to 1-methyl-5-thiotetrazole(MMT) group as R2 side chain...also "Disulfuram-like" effect |
|
|
Term
|
Definition
MOA:binds to PBPs and disrupts cell wall synthesis
*bacteriCIDAL
*resistant to many B-lactamases
*t1/2 = 1.7 hours |
|
|
Term
| Why is imipenem formulated with cilastin? |
|
Definition
| cilastin blocks degradation by a renal tubular dehydropeptidase....which in turn preserves imipenem |
|
|
Term
| List the main clinical uses for carbapenems. |
|
Definition
lower resp tract infections (pneumonia)
intra-abdominal infections
UTIs
SSTIs
CSF/CNS infections |
|
|
Term
|
Definition
| *renally elim - dose adjust |
|
|
Term
|
Definition
*CNS/headaches at high doses
*NVD
*seizures
*some cross-reactivity |
|
|
Term
| How does clavulanic acid work? |
|
Definition
| Suicide inhibitor of B-lactamases...protects the antibiotic with B-lactam |
|
|
Term
| Generally ADME/PK of BLIs. |
|
Definition
*only Clavulanate given PO
*all renally eliminated
*t1/2 = 1 hour and increases in renal failure and newborns |
|
|
Term
|
Definition
| Inhibit cell wall synthesis by blocking Polymerization, the addition of the new NAG-NAM peptide subunit by binding directly to 2 terminal D-Ala/D-Ala residues of the peptide chain on NAM.... the enzyme inhibited is transglycosylase |
|
|
Term
| What makes Televancin different from Vanc? |
|
Definition
*Televancin has additional MOAs that make it act more rapidly.
*also disrupts structure of bacterial cell membrane (inner membrane) |
|
|
Term
|
Definition
*Poor Oral Absorption...except for C.diff
*enter CSF if meninges is inflamed
*t1/2 = 6 hours
*80-95% renal elimination->dose adjust! |
|
|
Term
|
Definition
1. Infusion tox-Redman's syndrome
2. Ototoxicity
3. Nephrotoxicity
4. Risk in Prego - Category C
5. CV- QT prolongation...leads to ventricular repolarization
6. Misc (phlebitis, fever, chills, rash, decrease WBCs and platelets) |
|
|
Term
|
Definition
Urine specimen containing minimal bacteria contamination.
Method: cleanse genitals and collect specimen from midstream prevents contamination of speciment with resident bacteria |
|
|
Term
| what enzyme binds to DNA and uses it to preparte complementary strand of mRNA? |
|
Definition
|
|
Term
| RNA polymerase copies template DNA strand in ___ to ___ direction making mRNA in ___ to ___ direction. |
|
Definition
|
|
Term
| RNA polymerase is a part of transcription or translation? |
|
Definition
|
|
Term
| What is the bacterial large ribosomal subunit called and what is it most responsible for? |
|
Definition
|
|
Term
| What is the bacterial small ribosomal subunit called and what is it most responsible for? |
|
Definition
| 30S- affinity and recognition |
|
|
Term
| What are the subunits for eukaryotic ribosomes? |
|
Definition
| 80S composed of 60S and 40S |
|
|
Term
| Bacterial Ribosome Structure |
|
Definition
Asite: aminoacyl; binds incoming aa-tRNA
Psite: peptidyl; holds peptidyl-tRNA that just reacted to join the new protein
Esite: exit; holds empty tRNA that has just donated its aa and is ready to be ejected from ribosome |
|
|
Term
| What is peptidyl transferase? |
|
Definition
| a ribozyme (catalytic RNA), which catalyzed formation of new peptide bond to elongate the peptide...the growing peptide squeezes through the exit tunnel. Transfers peptide from tRNA at Psite to the new aa-tRNA in Asite, formining a new peptide bond to that AA |
|
|
Term
| When can secondary, tertiary, etc occur? |
|
Definition
| After the peptide has exited the exit tunnel! |
|
|
Term
| What are the 3 drugs that inhibit 30S? |
|
Definition
Aminoglycosides
Tetracyclines
Glycylcyclines |
|
|
Term
|
Definition
| polar amino sugars with multiple amino groups and 1+ glycosidic linkages; polycationic! |
|
|
Term
| Aminoglycosides are narrow/broad? |
|
Definition
|
|
Term
| Aminoglycosides are bacteri-(CIDAL/STATIC)? |
|
Definition
|
|
Term
| Aminoglycoside MOA and 3 effects of this class. |
|
Definition
*inhibit 30S
3 effects:
1. interfere with initiation
2. premature termination
3. incorrect amino acids added
Secondary MOA: disrupt cell structure since these are cationic and phospholipids are anionic! |
|
|
Term
| How are Aminoglycosides take up by bacteria? |
|
Definition
| Taken up across bacterial inner membrane by active/energy-dependent transport process which can be blocked by low O2, low pH, elevated Ca/Mg, or increased osmolarity |
|
|
Term
| Which microbes have natural resistance to Aminoglycosides? |
|
Definition
| anaerobes...AG entrance into bacteria requires O2 |
|
|
Term
| Which Aminoglycoside has the least resistance and why? |
|
Definition
| Amikacin...has multiple rings, OH, and N2Hs that encirlce the molecule |
|
|
Term
|
Definition
*poor oral absorption, so IV or IM
*Neomycin orally only for GIT cleansing
*poor uptake into host cells
*RENAL elim-dose adjust!
*monitor blood levels due to narrow therapeutic window |
|
|
Term
|
Definition
1.Ototoxicity- retrograde degeneration of auditory nerve (CNVIII)
2.Nephrotoxicity- AGs normally penetrate poorly, but proximal renal tubular cells are an exception(here they cause decreased renal function: decreased GFR and thus increased SCr)
Rare:
3.Neuromuscular Paralysis
4.Hypersensitivity |
|
|
Term
| What are the main nephrotoxic agents to be worried about with Aminoglycosides? |
|
Definition
| AmphoB, cyclosporine, cisplatin, vanc, loop diuretics |
|
|
Term
|
Definition
| 4 fused rings with conjugated bonds |
|
|
Term
| Tetracyclines are bacteri(CIDAL/STATIC)? |
|
Definition
|
|
Term
|
Definition
| Bind 30S and block access of tRNA to the A site of mRNA-ribosome complex |
|
|
Term
| Do Tetracyclines have cross resistance? |
|
Definition
|
|
Term
|
Definition
*good when avoid cations (chelation)
*nonlinear PK
*Tetracycline - 60-80% absorbed
*Doxycycline/Minocycline 90% absorbed
*Minocycline crosses BBB
*best on EMPTY stomach |
|
|
Term
| Tetracycline Distribution |
|
Definition
*Distribute widely
*accumulate in reticuloendothelial cells of liver, spleen, bone marrow, and in tissues undergoing calcification |
|
|
Term
|
Definition
Mostly renal
Minocycline- liver
Doxycycline- excreted in feces
Tetracycline t1/2 = 6-12 hours
Doxy/Minocycline t1/2 = 16-20 hours |
|
|
Term
|
Definition
1.GI discomfort (possible Cdiff overgrowth)
2.Photosensitivity
3.Hepatotoxicity
4.Renal Toxicity
5.Teeth Discoloration due to Chelation(CI'd in <8yo and Prego)
Rare:
6.Vestibular Tox with Minocycline
7.Benign Intracranial HTN
8.Fanconi Syndrome when using aged TCs |
|
|
Term
|
Definition
| glycylamido moeity attached to 9 position of TC phenyl ring |
|
|
Term
|
Definition
| Bind 30S and block access of tRNA to the A site of mRNA-ribosome complex |
|
|
Term
| What is special about glycylcyclines that makes them different from tetracyclines? |
|
Definition
*glycylamido moiety causes them not to be affected by major TC resistance mechanisms
*no Cross resistance
*no known antagonism |
|
|
Term
| Are Glycylcyclines broad or narrow? |
|
Definition
|
|
Term
|
Definition
*good penetration
*long t1/2 = 27-42 hours
*renal and hepatic metab |
|
|
Term
|
Definition
*GI:NVD
*CV
*CNS
*Hypersensitivity
*Increase Liver Enzymes(causes discoloration of teeth)
*decrease elim of warfarin |
|
|
Term
| What is the main structure of Macrolides? |
|
Definition
|
|
Term
| Clarithromycin structure different from Erythromycin |
|
Definition
|
|
Term
| Azithromycin structure different from Erythromycin |
|
Definition
*removal of upper ketone
*addition of methyl substituted nitrogen into lactone ring |
|
|
Term
| Modifications in Clarithromycin and Azithromycin improve what? |
|
Definition
1.oral stability
2.penetration into host cells
3.increase passage via porins which broadens spectrum |
|
|
Term
|
Definition
| Inhibit 50S by blocking the exit tunnel; this creates backlog near Psite and disrupts synthesis |
|
|
Term
| TRUE/FALSE. Macrolides show cross resistance. |
|
Definition
|
|
Term
|
Definition
*completely absorbed, but destroyed by gastric acid
*food decreases absorption
*estolate or ethylsuccinate salts improve absorption |
|
|
Term
| Clarithromycin absorption |
|
Definition
*better/more rapid absorption
*PO only
*stable to gastric acid, so can be taken with food which improves absorption
*QD dosing |
|
|
Term
|
Definition
*oral/IV for QD dosing
*food decreases absorption |
|
|
Term
| Severity of P450 and QT prolongation problems in Macrolides |
|
Definition
|
|
Term
|
Definition
| distribute to intracellular fluids and all sites except Brain and CSF |
|
|
Term
|
Definition
Liver elim - dose adjust
t1/2 = 1.6 hours |
|
|
Term
| Clarithromycin Metab/Elim |
|
Definition
Renal and liver elim...maybe dose adjust
t1/2 = 3-8 hours |
|
|
Term
|
Definition
Liver elim
t1/2 = 40-68 hours |
|
|
Term
|
Definition
*Thrombophlebitis - E
*CI'd in liver dysfunction
*Epigastric distress (E>>A/C)
*Allergic Rxns
*Cholestatic Jaundice- E
*Ototoxicity- E
*Metallic Taste- C |
|
|
Term
| What is the rate of QT that is dangerous? |
|
Definition
| >450 ms...can progress to Torsades de Pointes(ventricular tachycardia)... normal is ~400 ms |
|
|
Term
| What are other QT prolongation meds besides Macrolides? |
|
Definition
| antiarrhythmics, CNS agents, FQs, antifungals, some H1AHs |
|
|
Term
| What causes drug interactions in Macrolides? |
|
Definition
CYP3A4!! E>C>A
when CYP3A4 is inhibited, the other drug has increased conc of other drugs which causes decreased clearance, increase t1/2, and increased oral bioavailability |
|
|
Term
| Major DIs with Erythromycin |
|
Definition
1.ergotamine-> vasospasm
2.statins-> rhabdomyelysis
3.midazolam-> excessive sedation
4.felodipine-> hypotension
5.warfarin-> excessive bleeding |
|
|
Term
|
Definition
*Derived from Erythromycin
*keto group instead of carbohydrate group at position 3 of large ring
*C11-C12 carbamate sub'd by imidazolyl and pyridyl ring through butyl chain |
|
|
Term
| What are the ketolide structure advantages? |
|
Definition
1.acid stability
2.minimal cross resistance
3.increased affinity for 50S |
|
|
Term
|
Definition
2 point binding: near exit tunneland other site nearby which is contacted by extended heterocyclic side chain
*this increases binding affinity which slows resistance |
|
|
Term
|
Definition
*good for PO
*QD dosing, t1/2 = 10 hours
*Liver metab
*CYP3A4 and CYP2D6 |
|
|
Term
|
Definition
NVD
visual disturbances
syncope(fainting)
worsens Myasthenia Gravis(neuromusc dis)
Liver tox
CV- QT prolongation
CYP problems |
|
|
Term
|
Definition
| 5-membered heterocyclic N-containing ring joined via amide link to a cyclic octose sugar residue with 7-chloro and thiol in the sugar moeity |
|
|
Term
|
Definition
| Inhibit 50S by blocking the exit tunnel; this creates backlog near Psite and disrupts synthesis |
|
|
Term
| Do Lincosamides show cross resistance? |
|
Definition
|
|
Term
|
Definition
*almost complete absorption
*peak reached around 1 hour
*dist widely and accumulates in abscesses, leukocytes, and macrophages
*t1/2 = 3 hours
*inactivated by liver metab - dose adjust |
|
|
Term
|
Definition
*Diarrhea
*Pseudomembranous Colitis(care with opiates, bc they decrease GI motility and make the condition worse)
*skin rashes
*local thrombophlebitis
*increase liver enzymes
*decrease neurotransmission |
|
|
Term
| What is the combo of Quinupristin and Dalfopristin? |
|
Definition
|
|
Term
|
Definition
Dalfopristin(A)- binds and changes conformation at 50S subunit, which increase binding affinity for B (allosterism)
Quinupristin(B)- binds near exit tunnel; inhibits peptide elongation and causes chain termination |
|
|
Term
|
Definition
|
|
Term
|
Definition
*pain
*phlebitis - avoid peripheral; use CENTRAL
*arthralgia
*myalgia
*inhibits CYP3A4 and produces DIs |
|
|
Term
| Chloramphenicol structure |
|
Definition
| *contains nitrobenzene(toxic moiety) *derivative of dichloroacetic acid(topical astringent and eschariotic) |
|
|
Term
| Chloramphenical are broad or narrow? |
|
Definition
|
|
Term
|
Definition
binds to 50S near exit tunnel and blocks binding of AA end of tRNA to the ribosome, so the peptidyl transferase reaction cannot occur
*This can also affect protein synthesis of mitochondrial ribosomes(tox) |
|
|
Term
|
Definition
*rapid, complete GI absorption (PO not in US)
*widely distributed including CNS due to lipophilic nature
*LIVER metab-dose adjust |
|
|
Term
|
Definition
1.Hematological tox- Bone Marrow Suppression or Aplastic Anemia
2.NVD
3."Gray Baby" Syndrome (death in 40%)
4.Hypersensitivity
5.Encephalopathy and cardiomyopathy in tissues with high O2 demand
6.CYP3A4 and 2C19 cause DIs |
|
|
Term
|
Definition
| bind 50S near peptidyl transferase site and interferes with formation of 70S fMet-tRNA initiation complex |
|
|
Term
| Do Oxazolidinones show cross resistance? |
|
Definition
|
|
Term
|
Definition
*oral or IV (both have 100% bioavailability)
*distribute widely
*no P450 problems
*t1/2 = 4-6 hours |
|
|
Term
|
Definition
*NVD
*Headache/Dizziness
*Increase liver/pancreas enzymes
*myelosuppression(severe)
*pseudomembranous colitis(severe)
*peripheral or optic neuropathy(severe)
*DI:since linezolid is weak inhibitor of MAOs it enhances adrenergic agents(pseudoephedrine, dopamine, epinephrine)
**may lead to Serotonin Syndrom
*Cheese reaction: avoid food and drink high in Tyramine, which is an indirect sympathomimetic amine which relies on MAO |
|
|
Term
| Fluoroquinolones structure |
|
Definition
*nalidixic acid, by product of chloroquine synthesis for malaria
*addition of F to aromatic ring: increases activity and decreases resistance |
|
|
Term
| Are Fluoroquinolones Bacteri(CIDAL/STATIC)? |
|
Definition
|
|
Term
|
Definition
| inhibit enzyme that regulates supercoiling of DNA(DNA Gyrase - topoisomerase II) and the enzyme that separates interlinked DNA after replication(topoisomerase IV).....these two enzymes are normally responsible for resealing nicks of both types of "planned" DNA breaks, but they cannot repair the nicks if they are inhibited |
|
|
Term
| Which enzyme inhibited in Fluoroquinolones MOA is associated with G+ vs G-? |
|
Definition
*DNA gyrase (topo II) more effective against G-
*Topo IV more effective against G+ |
|
|
Term
| Which Fluoroquinolone has a structural modification enhancing G- activity? |
|
Definition
| Cipro has piperazine side chain at R7 that enhances G- activity, however, it does weaken G+ activity |
|
|
Term
|
Definition
*well orally absorbed (PO or IV)
*dist widely except CSF
*bioavailability reduced by chelation
*Gemi has no IV
*t1/2 = 3-20 hours
*renal elim - dose adjust...with 1 EXCEPTION: moxifloxacin which has liver elim |
|
|
Term
|
Definition
*NVD...also C.diff
*CNS...esp with theophylline or NSAIDs
*rash,phototoxicity
*achilles and rotator cuff tendonities and rupture(black box warning)...esp with 60+, kidney/heart/lung transplants, steroid use
*QT prolongation
*P450 inhibition |
|
|
Term
|
Definition
| reduce NO2 group to active agent that inhibits bacterial enzymes and damages their DNA |
|
|
Term
|
Definition
*orally absorbed but inconvenient 4xday dosing
*short t1/2 = 0.3-1.1 hours
*1/2 renal elim |
|
|
Term
|
Definition
*NVD
*hypersensitivity
*hemolytic anemia in G6PDH defic
*CNS
*acute pneumonitis or interstitial pulmonary fibrosis |
|
|
Term
|
Definition
| NO2 group reduced by available electrons to form reactive species; reactive metabolite attacks DNA; its structure is disrupted and strands break |
|
|
Term
| Nitroimidazoles are bacteri(CIDAL/STATIC)? |
|
Definition
|
|
Term
|
Definition
*PO,IV,topical,intravaginal
*penetrates well including CSF
*t1/2 = 8 hours
*LIVER metab to metabolites eliminated in urine - dose adjust for both! |
|
|
Term
|
Definition
Common: headache, dry mouth, furry tongue, unpleasant metallic taste w/ PO
Rare: Stevens-Johnson syndrome, carcinogenic/teratogenic, neurotoxicity, disulfuram-like effect |
|
|
Term
| WHat is another term for the group of Rifamycins? |
|
Definition
| "accessory" abx; aka BLING - extra accentuation of killing effect |
|
|
Term
|
Definition
| 2 central aromatic rings with heterocyclic side chain (piperazine good for G-) and a large 15C handle that loops around in a giant cyclic link |
|
|
Term
|
Definition
| decrease synthesis of mRNA |
|
|
Term
| Are Rifamycins bacteri(CIDAL/STATIC)? |
|
Definition
|
|
Term
|
Definition
| inhibits RNA polymerase (copies and makes mRNA)...suppresses initiation of RNA chain |
|
|
Term
| What are the different Rifamycins and what are their key differences? |
|
Definition
Rifampin- IV/PO
Rifabutin- PO;avoids P450 problems!
Rifapentine- PO; long t1/2; QD dosing
Rifaximin- PO; local action on GIT |
|
|
Term
|
Definition
*adequate oral absorption
*wide dist including CSF
*Liver elim
*t1/2 = 1.5-5 hours |
|
|
Term
|
Definition
*red-orange secretions
*rash,fever,NVD
*hepatitis
*TONS of CYP DIs...less with Rifabutin |
|
|
Term
| What are the unique Rifabutin ADR/Tox |
|
Definition
1.polymyalgia
2.pseudojaundice
3.anterior uveitis |
|
|
Term
|
Definition
derivatives of PABA
S linked to benzene and para-amino grouop
amide NH2 substitutions |
|
|
Term
|
Definition
| inhibit bacterial growth by decreasing synthesis of folic acid...inhibit dihydropteroate synthase(pteridine reductase) which normally would incorporate PABA into dihydropteroic acid, a precursor to folic acid |
|
|
Term
| Sulfonamides are bacteri(CIDAL/STATIC)? |
|
Definition
|
|
Term
| Do sulfonamides show corss-resistance? |
|
Definition
|
|
Term
|
Definition
*Rapid GI absorption after PO
*dist widely includin CSF(rarely used in meningitis due to resistance)
*Liver metab
*t1/2 = 5-10 hours |
|
|
Term
|
Definition
1.Hypersensitivity
2.Anorexia, NVD
3.Hemolytic Anemia- G6PDH defic
4.Agranulocytosis/Aplastic Anemia
5.Crystalluria
6.Stevens-Johnson Syndrome
7.DIs: PO hypoglycemic agents, PO anticoag, hydrantoin antiepileptics |
|
|
Term
| What is the enzyme that converts DHF to THF? |
|
Definition
|
|
Term
| What is the enzyme that converts dUMP to TMP? |
|
Definition
|
|
Term
|
Definition
| 2,4 diaminopyrimadine ring sub'd at the 5 position by a C bridge to an aromatic ring with 3 O-methyl groups |
|
|
Term
|
Definition
| inhibits DHFR which converts DHF to THF |
|
|
Term
| TMP is more/less potent than Sulfonamides? |
|
Definition
|
|
Term
| SMZ/TMP is bacteri(CIDAL/STATIC)? |
|
Definition
|
|
Term
|
Definition
5:1 ratio of sulfamethoxazole: trimethoprim
Vd of TMP is 9X that of SMZ
TMP absorbed faster than SMZ
TMP 40% PPB vs SMZ 65% PPB |
|
|
Term
|
Definition
both renal and liver elim...dose adjust in renal disease
t1/2 = 10 hours |
|
|
Term
|
Definition
Skin or GIT: rashes and hypersensitivity
Bone Marrow Effects: anemias
Jaundice |
|
|
Term
|
Definition
*large molecule w/ open cyclic core nucleus
*3 6-membered rings sub'd with hydroxy and chloro moeities that protrude from a large open 18C core ring |
|
|
Term
|
Definition
*inhibits synthesis of mRNA by binding to beta subunit of RNA polymerase
*inhibits sigma factor from binding to promoter region of DNA |
|
|
Term
|
Definition
| *Not much known bc we need more clinical experience to define and verify uses and lack of ADR/Tox |
|
|
Term
|
Definition
*binds to bacterial cell inner membrane and channels are formed that "leak" ions
*Req's Ca |
|
|
Term
| Daptomycin should NOT be used for which kinds of infections? |
|
Definition
| Lung infections or Pneumonia |
|
|
Term
| Do macrocyclics show cross resistance? |
|
Definition
| NO - no kind of resistance known |
|
|
Term
|
Definition
*IV only
*92% protein binding
*t1/2 = 8 hours (QD dosing)
*80% renal- need dose adjustment
*no CYP problems! |
|
|
Term
|
Definition
*NVD
*Rash, headache, insomnia
*pain and phlebitis
*eosinophilic pneumo
*reversible myopathy
*peripheral nerve disorder(arthralgia, neuoropathy)
*Statin/AG with Daptomycin = neuropathy, nephropathy, myopathy |
|
|
Term
|
Definition
| cyclic polypeptide with 6-8 C fatty acid-like chain attached |
|
|
Term
|
Definition
| insert themselves into cell membrane of bacterial cell and once in place they act as cationic detergents to disrupt membrane integrity; membrane permeability changes immediately on contact |
|
|
Term
|
Definition
*poor oral absorption
*topical by ophthalmic and otic routes
*systemic for Pseudomonas
*renal elim - dose adjust |
|
|
Term
|
Definition
1.Neurotoxicity
2.Nephrotoxicity
3.Bronchospasm |
|
|
Term
|
Definition
act on cell membrane structure and function; bind via sterol(ergosterol)
examples: AmphoB, Nystatin |
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