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Antibacterials Flashcards

1
Q

Lactulose

A

MOA: degraded by intestinal flora to lactic acid and other acids
Effect: acids trap the ammonia in the GIT so it cannot enter circulation and exacerbate the encephalopathy
Uses: hepatic encephalopathy, use as osmotic laxative, prebiotic
SE: osmotic diarrhea, flatulence, abd pn

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2
Q

Quinolones Drug Interactions

A

Theophylline, NSAIDS, corticosteroids = enhanced toxicity of quinolones
3rd and 4th gen = raide serum levels of Warfarin, Caffeine and Cyclosporine

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3
Q

Clindamycin PK and SE

A

PK: PO or IV, good penetration (gets to abscesses/bones)
SE: C. difficile, GI sx’s, skin rash, neutropenia and impaired liver fxn

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4
Q

2nd Gen Quinolones

A

Ciprofloxacin
Spectrum: extended G-ve activity, some G+ve, and some atypicals
DOC: anthrax
Use: ETEC, Pseudomonas (CF pt’s), meningitis prophylaxis (alt to Ceftriaxone and Rifampin)

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5
Q

Cefaclor / Cefoxitin / Cefotetan / Cefamandole

A

2nd generation Cephalosporins
Active against: H.influenzae, Enterobacter, some Neisseria
Use: sinusitis, otitis infections and LTIs
Cefotetan/Cefoxitin use: prophylaxis and therapy of abd/pelvic cavity infections

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6
Q

Sulfonamides PK, SE, CI

A

PK: PO or topical, acetylated in liver, eliminated via urine
SE: photosensitivity, crystalluria, HS rxn, hematopoietic disturgances (G6PD), kernicterus
CI: newborns/infants < 2 yo
Drug interaction: displace Warfarin, Phenytoin and Methotrexate from albumin

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7
Q

Tetracyclines (names)

A

Doxycycline / Minocycline / Tetracycline

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8
Q

Concentration-dependent Killing

A

Bigger the dose the better effect (covalent bonding so it doesnt matter if you keep giving it, the blockade is already in place)
*e.g. - aminoglycosides

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9
Q

Oxacillin

A

Excretion: renal and biliary
SE: hepatitis
Use: meningitis s/p trauma or surgery (S. aureus)

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10
Q

Aminoglycosides PK and SEs

A

PK: once daily admin, IV only, well distributed, high levels in renal cortex and inner ear
Excretion: kidney
SE: ototoxicity, nephrotoxicity, NM blockade
CI: MG (bc of NM blockade), pregnancy (unless benefits outweigh risks)

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11
Q

Tetracyclines DOC

A

Chlamydia, M. pneumoniae, Lyme dz, cholera, anthrax prophylaxis, RMSF, Typhus
Combo therapy for: H. pylori eradication, Malaria prophylaxis/tx, tx plague, Tularemia, Brucellosis

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12
Q

Polymyxin B

A 
Spectrum: G-ve (bactericidal)
MOA: acts as detergent, attach to and distrupt the cell membrane, binds and inactivates endotoxin
Effect: cell lysis
Use: topically for skin infections
SE: nephrotoxic if given systemically
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13
Q

Ampicillin / Amoxicillin

A

‘Extended spectrum penicillins’
MOA: sensitive to β-lactamases, so activity is enhanced w/ β-lactamase inhibitor
PK: Amoxicillin has higher oral bioavailability than other penicillins
Use: children and pregnancy for acute otitis media, GAS pharyngitis, pneumonia, skin infection, UTIs, URIs (H. flu and S. pneumo)
SE: maculopapular rash, C. difficile

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14
Q

Neomycin

A

Use: bowel surgery, adjunct in hepatic encephalopathy, topical infections
SE: dermatitis

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15
Q

Cephalosporins SE

A

Pain @ infections ite, thrombophlebitis, superinfections (C. difficile), kernicterus (pregnancy)

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16
Q

Tetracyclines PK and SE

A

PK: variable PO absorption (decreased by divalent and trivalent cations)
Excretion: kidney
SE: teratogenic (category D), N/V/D, discoloration and hypoplasia of teeth, stunting growth, fetal hepatotoxicity, photosensitization, dizziness

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17
Q

Calvulanic acid / Sulbactam / Tazobactam

A

MOA: β-lactamas inhibitors
Effect: bind to and inactivate β-lactamases
Use: used in fixed combinations w/ specific penicillins but never used as abx themselves

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18
Q

Quinolones PK, SE, CI

A

PK: good oral bioavailability, high Vd, divalent cations interfere w/ absorption, adjust dose w/ renal dysfunction pt
SE: connective tissue damage (tendon rupture), peripheral neuropathy, QT prolongation, superinfections
CI: pregnancy/nursing mother, children < 18

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19
Q

Fosfomycin

A

MOA: inhibition of enolpyruvate transferase
Effect: inhibits CW synthesis
Admin: PO
Use: uncomplicated lower UTI

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20
Q

Aminoglycosides MOA

A

Amikacin / Gentamicin / Tobramycin / Streptomycin / Neomycin
Bactericidal, assoc. w/ serious toxicities so used mostly in combo w/ other Rx
MOA: passively diffuse across membrane of G-ve, then actively transported (O2 dependent) across cytoplasmic membrane then bind irreversibly (covalently) to 30S subunit of ribosome
Effect: prevent complex formation = prevent transcription = death of organism

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21
Q

Penicillin V

A

Administration: PO
Use: URIs, skin infections d/t strep
DOC: GAS pharyngitis
SE: +ve Coomb’s Test

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22
Q

β-lactamase inhibitors

A

Protect penicillins (β-lactams) from inactivation

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23
Q

Vancomycin

A

MOA: binds D-Ala-D-Ala pentapeptide terminus of PG, inhibits transglycosylation
Effect: inhibits CW synthesis and prevents elongation/polymerization of PG
Spectrum: G+ve only (MRSA, enterococci, PRSP)
Resistance G-ve (intrinsic), plasmid-mediated changes in drug permeability, modification of attachment site (adding D-lactate to terminus)

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24
Q

Minimal Bactericidal Concentration (MBC)

A

Lowest concentration of abx that results in a 99.9% decline in colony count after overnight incubation
*MBC of truly bactericidal agent is = to or slightly above the MIC

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25
Respiratory Quinolones
Levofloxacin / Moxifloxacin / Gemifloxcin (3rd and 4th gen) Target: S. pneumoniae, H. influenzae, M. catarrhalis Use: when 1st line agents have failed, in presence of comorbidities, inpt management
26
Tetracyclines
MOA: entry via passive diffusion and energy-dependent transport, then bind the 30S subunit of ribosome to prevent attachment of animoacyl tRNA Effect: protein synthesis halted = bacteriostatic Spectrum: aerobic and anaerobic G+ve and G-ve Resistance: impaired influx or increased efflux (plasmid-encoded), enzymatic inactivation, proteins that interfere w/ binding Use: severe acne, rosacea, syphilis (pt’s w/ penicillin allergy)
27
Nafcillin
Excretion: primarily in bile PK: not good for PO administration
28
Penicillins SEs
HS rxn, diarrhea, interstitial nephritis, hepatitis
29
Linezolid PK and SE
PK: PO, weak inhibitor of MAO, high Vd SE: BM suppression, neuropathy, lactic acidosis CI: caution when coadministration of drugs to increase adrenergic and serotonergic neurotransmitter levels
30
Penicillins resistance
Inactivation by β-lactamase, modification of target PBP, impaired penetration, increased efflux by pumps *MRSA: altered target PBPs (low affinity for β-lactam abs)
31
Bacitracin
``` MOA: interferes w/ CW synthesis Active against: G+ve organisms Admin: topical use mainly Use: skin infections etc SE: nephrotoxic ```
32
Macrolides
Erythromycin / Clarithromycin / Azithromycin / Telithromycin *Bacteriostatic (bactericidal @ high concentration)* MOA: reversibly bind 23S rRNA of 50S subunit (same binding site as Clindamycin and Chloramphenicol) Effect: blocks translocation halting transcription
33
Amoxicillin DOC
For endocarditis prophylaxis during dental or respiratory tract procedures (S. viridans) *Amoxicillin + clavulanic acid is prophylactic for bites
34
Aminoglycosides DOC
Used in combo - septicemia, nosocomial RTIs, complicated UTIs, endocarditis *once organism is identified these abx are usually d/c'd
35
Ampicillin Use/SE
Used in combo w/ Aminoglycosides to tx Enterococcus and Listeria (meningitis) SE: pseudomembranous colitis
36
Chloramphenicol Uses
Serious infections resistant to less toxic drugs, or if it can reach the site of infection better it can be used, infections w/ VRE, topical tx of eye infections
37
Penicillins G Procaine
Developed to prolong duration of Penicilling G Administration: given IM, seldom used (increases resistance) PK: t1/2 = 12-24h
38
Co-trimoxazole (TMP-SMX)
Trimethoprim + Sulfamethoxazole = bactericidal MOA: synergistic inhibition of sequential steps in folic acid synthesis PK: PO, high Vd DOC: uncomplicated UTIs, PCP, Nocardiosis Use: toxoplasmosis (alt drug), URI d/t H. inflluenzae, M. catarrhalis SE: dermatologic, GI, hematolytic anemia, high incidence of SE in AIDS pt CI: pregnancy
39
Penicillin G Benzathine
Prolongs duration of Penicillin G Administration: IM PK: t1/2 = 3-4 wks DOC: Syphilis, and RF prophylaxis
40
1st Gen Quinolones
Nalidixic acid Spectrum: moderate G-ve activity Use: uncomplicated UTIs
41
CW Synthesis Inhibitors
Require actively proliferating bacteria
42
3rd Gen Quinolones
Levofloxacin Spectrum: G-ve, G+ve, atypicals but especially *S. pneumoniae* Use: DOC for prostatitis (E. coli), non-syphilis STDs, CAP, TB, sinusitis, bronchitis
43
Minimal Inhibitory Concentration (MIC)
lowest concentration of abx that prevents visible growth of a bacteria (so you have to target above the MIC)
44
Quinolones MOA and Resistance
MOA: enter via porins, inhibit topoisomerase II aka DNA gyrase (G-ve) and IV (G+ve) Effect: inhibit DNA replication Resistance: efflux pumps, diff subunits of the enzyme target, cross-resistance
45
Sulfonamides
MOA: structural PABA analogues so they competitively inhibit dihydropteroate synthase Effect: inhibition of folic acid synthesis Resistance: altered enzyme, decreased permeability Use: topical for infections, PO for simple UTIs
46
4th Gen Quinolones
Gemifloxacin / Moxifloxacin Spectrum: G+ve and anaerobes Use: CAP
47
Trimethoprim
MOA: similar structure to folic acid, inhibits bacterial dihydrofolate reductase Effect: inhibits purine, pyrimidine and AA synthesis Spectrum: G+ve and G-ve (bacteriostatic) Use: UTIs, bacterial prostatitis and vaginitis PK: excreted via kidney, reaches high concentrations in sex fluids CI: pregnancy (bc anti-folate effects)
48
Tx of Hepatic Encephalopathy
PO Neomycin, Lactulose, PO Vancomycin, PO Metronidazole, Rifaximin (the abx are aiming to reduce the # of intestinal bacteria that are responsible for responsible for the production of ammonia)
49
Ceftriaxone / Cefoperazone / Cefotaxime / Cefatazimide / Cefixime
3rd generation cephalosporins Active against: G-ve cocci, Enterobacteriacae, Neisseria, H. influenzae, Pseudomonas Cefotaxime/Ceftriaxone: active against pneumococci Use: prophylaxis fo meningitis, tx Lyme dz DOC: gonorrhea, meningitis d/t ampicillin-resistant H. influenzae PK: only generations that reaches adequate levels in CSF
50
Daptomycin
MOA: binds to cell membrane via Ca2+ dependent insertion of lipid tail Effect: depolarization of cell membrane w/ K+ efflux = cell death Spectrum: resistant G+ve (MRSA, enterococci, VRE, VRSA) Inactive against: G-ve (ineffective in tx of pneumonia too)
51
Cefepime
4th generation Cephalosporins Admin: IV only Active against: wide spectrum (H. influenza, Neisseria, E. coli, S.pneumo, Proteus, Pseudomonas) Use: mixed infections w/ susceptible organisms
52
Abx Combinations (antagonistic or nah)
NOT to give: tetracyclines (static) + β-lactam (cidal) = nothing happens if you're targeting one bacteria DO give: macrolide (static) + β-lactam (cidal) = good bc macrolide is for atypicals and β-lactam is targeting S. pneumoniae (diff bacteria are targets)
53
Ceftaroline
5th generation Cephalosporin Admin: IV only Active against: MRSA, similar spectrum to 3rd generations Use: skin and soft tissue infections d/t MRSA, particularly w/ G-ve confection, CAP (when first-line agents are unsuccessful)
54
Time-dependent Killing
Exposure to the drug for longer will cause more of an effect (four small doses better than one big dose) *e.g. - penicillins, cephalosporins
55
Clindamycin Uses
Anaerobic infections, skin and soft tissue infections (Strep, Staph, and some MRSA), combo w/ Primaquine as alt in PCP, combo w/ Pyrimethamine as alt tx for brain Toxoplasmosis, prophylaxis of IE in valvular pt's w/ penicillin allergy
56
Macrolides Resistance
Decreased influx or increased efflux, production of esterase that hydrolyzes the drug, modification of binding site (plasmid encoded) *complete cross resistance of all macrolides except Telithromycin), partial cross-resistance w/ clindamycin and streptogramins
57
Telithromycin
Resistance: no cross-resistance like other macrolides SE: fatal hepatotoxicity, exacerbations of MG, visual disturbances *(so dont use this abx for minor illnesses)
58
Carbapenems
Resistant: β-lactamases PK: admin IV only, Active against: penicillinase-producing G+ve, aerobes and anaerobes, Pseudomonas Inactive against: carbapenemase producers, MRSA DOC: Enterobacter infections, extended spectrum β-lactamase producing G-ve organisms SE: N/V/D, sz, allergic rxns
59
CW Synthesis Inhibitors (names)
β-lactam abx (penicillins, cephalosporins, carbapenems, monobactams), Vancomycin, Daptomycin, Bacitracin, Fosfomycin
60
Mupirocin
Spectrum: G+ve cocci including MRSA and streptococci (but not enterococci) PK: topical/intranasal MOA: binds isoleucyl transfer-RNA syhtnetase Effect: inhibit protein synthesis Use: intranasal to eradicate nasal colonization w /MRSA, topically to t impetigo or skin infections
61
Vancomycin PK and SE
PK: poor oral absorption, given via slow IV infusion, penetrates CSF, Excretion: kidneys SE: “Red man” syndrome (mediated by histamine release if infused too quickly), ototoxicity, nephrotoxicity
62
Ertapenem
Not active against Pseudomonas
63
Metranidazole
Bactericidal Spectrum: anaerobes (bacteriodes and Clostridium) MOA: requires anaerobic conditions to work, undergoes reduction by ferredoxin Effect: forms cytotoxic products that interfere w/ nucleic acid synthesis DOC: C. difficile infections, Bacteriodes, Giardia, Trichomonas Use: anaerobic/mixed abd infections, vaginitis, brain abscesses, H. pylori eradication (below diaphragm anaerobe infections)
64
Cefamandole / Cefoperazone / Cefotetan SEs
Contain methyl-thiotetrazole group and thus can cause hypoprothrombinemia (vitamin K can prevent this), and Disulfiram-like reactions (pt should avoid EtOH)
65
Tigecycline
MOA: similar to tetracyclines Spectrum: work against MDR G+ve, some G-ve and anaerobic organisms Resistance: Proteus and Pseudomonas (efflux pumps) Use: complicated skin and intra-abd infections PK: IV only Elimination: bile SE: N/V/D, discoloration of teeth, dizziness, photosensitivity (all same as tetracyclines) CI: pregnancy and children < 8yo
66
Streptogramins
Quinupristin / Dalfopristin (alone they're bacteriostatic) *given together as combo so they are bactericidal MOA: they bind to separate sites on 50S ribosome Spectrum: G+ve cocci, MDR bacteria (Streptococci, PRSP, MRSA, E. faecium) PK: IV only, penetrates Mϕ and PMNs, inhibit CYP-3A4 Use: restricted to tx of infections d/t drug resistant Staph or VRE SE: GI sx's, HA, infusion related sx's
67
Penicillin + Aminoglycoside
MOA: synergistic bc penicillins facilitate movement of aminoglycosides through the CW Administration: placed in different infusion fluid (diff IVs etc) Use: empiric tx for infective endocarditis
68
Methicillin / Nafcillin / Oxacillin / Dicloxacillin
Resistance: β-lactamase resistant Use: β-lactamase producing staphylococci, first line for staph endocarditis Excretion: via bile bc they’re lipid soluble
69
Penicillins
Structure: β-lactam ring MOA: bactericidal; inhibit last step in PG synth through binding PBPs in cytoplasmic membrane and autolysin production Effect: CW synthesis disrupted, bacterial lysis induced Spectrum: ability to reach target PBPs based on size/charge/hydrophobicity, Gram staining (+ve is more sensitive in penicillins)
70
Metranidazole PK and SE
PK: PO, IV, rectal or topical; high Vd Elimination: hepatic SE: GI sx's, neuropathy, dark urine, metallic taste, Disulfiram-like effect (avoid EtOH) CI: 1st trimester
71
Imipenem PK and SE
PK: nephrotoxic bc of its metabolism by dehydropeptidase I so must be given w/ enzyme inhibitor (Cilastatin) to prevent the metabolism and nephrotoxicity SE: seizures at high levels
72
Doxycycline
Lipid soluble so preferred for parenteral administration and good choice for STDs and prostatitis Excretion: bile SE: dizziness
73
Ceftriaxone and Cefoperazone Elimination
Excreted by bile not kidneys
74
Macrolides DOC
M. pneumonie
75
Linezolid
*Bacteriostatic for most organisms, -cidal for Strep and C. perfringens Spectrum: G+ve including MRSA and VRE, some activity against M. tuberculosis MOA: binds unique site on 23S ribosomal RNA of 50S subunit (no cross-resistance) Effect: inhibits formation of 70S initiation complex = halting transcription Resistance: decreased binding, point mutation of RNA Use: tx MRD infections
76
Best drugs for targeting anaerobes?
Clindamycin (infections above diaphragm) and Metranidazole (infections below diaphragm)
77
Macrolides Spectrum
G+ve (some activity against G-ve), similar to penicillins (Erythromycin has smaller spectrum than the other 3)
78
Streptomycin DOC
Plague (Y. pestis)
79
Macrolides PK and SE
PK: CYP inhibition (EXCEPT for Azithromycin) SE: GI irritation, hepatic probs (erythromycin and azithromycin, QT prolongation, anyphylaxis is rare
80
Sulfasalazine Use
PO for UC, enteritis, IBD
81
Macrolides Uses
Tx of CAP, tx of URT or soft tissue infections (Staph, H. influenzae, S. pneumoniae, enterococci), used in pt w/ penicillin allergy
82
Cefazolin / Cephalexin
1st generation Cephalosporins Active against: G+ve cocci, Proteus, E. coli, Klebsiella Resistant: staph penicillinase Use: penicillin G substitutes DOC (Cefazolin): parenterally for surgical prophylaxis
83
Daptomycin Uses, PK, SE
Use: severe infections d/t MRSA or VRE, tx of complicated skin infections d/t S. aureus PK: IV only, eliminated by kidneys SE: constipation, nausea, HA, insomnia, rhabdomyolysis (so monitor CK and d/c coadministratoin of statins)
84
Vancomycin Uses
Tx infections d/t β-lactam resistant G+ve (or pt’s allergic to β-lactams), used in combo w/ aminoglycoside for empirical tx of IE ❤️, enterococcal endocarditis or PRSP, given PO for tx of Staph enterocolitis or abx-assoc C. difficile
85
Fidaxomicin
Spectrum: C. difficile MOA: binds and inhibits RNA polymerase Effect: inhibits protein synthesis Use: tx recurrent C. difficile in adults
86
Carbenicillin / Ticarcillin / Piperacillin
‘Antipseudomonal’ Spectrum: broad but especially Pseudomonas MOA: often combined w/ β-lactamase inhibitor Use: injectible tx for G-ve, tx of moderate-severe infections of susceptible organisms
87
Erythromycin
PK: less PO absorption, shorter t1/2, less bioavailability than other macrolides, CYP inhibitor DOC: Whooping cough (Bordatella pertussis) SE: hepatic probs
88
Chloramphenicol
MOA: enters via active transport and reversibly binds 50S subunit (site adjacent to site of macrolides and clindamycin) Effect: inhibits peptidyltransferase = stops protein synthesis (bacteriostatic) Spectrum: broad (G+ve and G-ve, aerobes and anaerobes), esp N. meningitidis, H. influenzae, Salmonella and baceriodes Resistance: acetyltransferases inactivate drug, changes in membrane permeability
89
Aminoglycosides Resistance
Inactivate drug by acetylation, phosphorylation and adenylation (plasmid-encoded), altered receptor protein on 30S subunit
90
Aztreonam SEs
Skin rashes or elevation of serum aminotransferases and GI upset,
91
Chloramphenicol PK and SE
PK: PO, IV and topical, high Vd (enters CSF), inhibits CYP-3A4 and CYP-2C9 SE: GI sx's, BM suppression (dose-related), Gray baby syndrome d/t drug accumulation in newborns
92
Penicillins G
aka Benzylpenicillin Administration: IV only Active against: G+ve cocci (not staph), Listeria, C. perfringens, Neisseria sp, anaerobes DOC: syphilis, strep (esp RF), pneumococci SE: +ve Coombs’ Test
93
Cephalosporins
β-lactam MOA: same as penicillin (bactericidal) Inactive against: LAME (Legionella/Listeria, actinobacter, Mycoplasma, Enterococcus) PK: mainly admin IV, elimination mainly by kidneys
94
Nitrofurantoin
Bacteriostatic/bactericidal Spectrum: G+ve and G-ve (specifically E. coli) MOA: reduced then the drug intermediate causes DNA damage Effect: cell lysis Use: prophylaxis and tx of lower UTI PK: rapid elimination SE: anorexia, N/V, neuropathies, hemolytic anemia (G6PD), colors urine brown CI: renal insufficiency, pregnancy after 38 wks gestation, infants < 1 mo
95
Clindamycin
MOA: binds 50S subunit (same as macrolides) Effect: inhibits translocation (bacteriostatic) Spectrum: good for G+ve anaerobes, bacteriodes and G+ve aerobes Resistance: modified receptor site, enzymatic inactivation, G-ve aerobes and enterococci intrinsically resistant *cross-resistant w/ macrolides
96
Aztreonam
Monobactam MOA: same as all PK: IV or IM, via inhalation in CF pt’s, penetrates CSF Elimination: urine Spectrum: aerobic G-ve rods only (Pseudomonas esp) Inactive against: G+ve and anaerobes Resistance: β-lactamases Use: UTI, LTI, septicemia, skin/suture infections, intraabd infections, gym infections d/t susceptible G-ve’s

Pharmacology (27 decks)

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