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PLAB Pharmacology > Anti-Microbials > Flashcards

Anti-Microbials Flashcards

1
Q

Penicillin G, V–form and type of antibiotic

A
  • Penicillin G–IV and IM form
  • Penicillin V–oral form
    • prototype beta lactam antibiotics
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2
Q

penicillin G, V–mechanism

A
  • D-Ala-D-Ala structural analog
  • bind penicillin binding proteins (transpeptidases)
  • block transpeptidase cross linking of peptidoglycan in cell wall
  • activate autolytic enzymes
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3
Q

penicillin G, V–use

A
  • mostly used for gram + organisms–S. pneumoniae, S. pyogenes, Actinomyces
  • also used for gram - organisms–mainly N. meningitidis
  • also used for spirochetes–T. pallidum
  • bactericidal for gram + cocci, gram + rods, gram - cocci, and spirochetes
  • penicillinase sensitive
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4
Q

penicillin G, V–toxicity

A
  • hypersensitivity reactions
  • direct Coombs + hemolytic anemia
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5
Q

penicillin G, V–resistance

A
  • penicillinase in bacteria (a type of beta lactamase) cleaves beta lactam ring
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6
Q

name the penicillinase sensitive penicillins

A
  • amoxicillin
  • ampicillin
  • aminopenicillins
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7
Q

penicillinase sensitive penicillin–mechanism

A
  • same as penicillin
  • wider spectrum
    • “AMinoPenicillins are AMPed up penicillin”
    • penicillinase sensitive
  • also combine with clavulanic acid to protect against destruction by beta lactamase
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8
Q

penicillinase sensitive penicillins–oral bioavailability

A
  • “AmOxicillin has greater Oral bioavailability than ampicillin”
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9
Q

penicillinase sensitive penicillins–use

A
  • extended spectrum penicillin
    • H. influenzae
    • H. pylori
    • E. coli
    • Listeria monocytogenes
    • Proteus mirabilis
    • Salmonella
    • Shigella
    • enterococci
  • coverage:
    • ampicillin amoxicillin HHELPSS kill entercocci
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10
Q

penicillinase sensitive penicillins–toxicity

A
  • hypersensitivity reactions
  • rash
  • pseudomembranous colitis
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11
Q

penicillinase sensitive penicillins–mechanism of resistance

A
  • penicillinase in bacteria (a type of beta lactamase) cleaves beta-lactam ring
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12
Q

name the penicillinase-resistant penicillins

A
  • dicloxacillin
  • nafcillin
  • oxacillin
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13
Q

penicillinase-resistant penicillins–mechanism

A
  • same as penicillin
  • narrow spectrum
    • penicillinase resistant b/c bulky R group blocks access of beta-lactamase to beta-lactam ring
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14
Q

penicillinase-resistant penicillins–use

A
  • S. aureus–except MRSA: resistant b/c of altered penicillin binding protein target site
    • “use naf (nafcillin) for staph”
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15
Q

penicillinase-resistant penicillins–toxicity

A
  • hypersensitivity rxns
  • interstitial nephritis
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16
Q

name the antipseudomonal penicillins

A
  • piperacillin
  • ticarcillin
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17
Q

antipseudomonal penicillins–use

A
  • Pseudomonas spp. and gram - rods
  • susceptible to penicillinase
  • use with beta lactamase inhibitors
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18
Q

antipseudomonal penicillins–toxicity

A
  • hypersensitivity rxns
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19
Q

name the beta lactamase inhibitors

A
  • Clavulanic Acid
  • Sulbactam
  • Tazobactam
    • CAST
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20
Q

what are beta lactamase inhibitors often taken with? Why?

A
  • often added to penicillin to antibiotics
    • to protect the antibiotic from destruction by beta-lactamase (penicillinase)
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21
Q

cephalosporins (gen I-IV)–mechanism

A
  • beta lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases
  • bactericidal
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22
Q

what are the organisms not covered by 1st-4th generation cephalosporins? what is the exception?

A
  • LAME
    • Listeria
    • Atypicals–Chlamydia, Mycoplasma
    • MRSA
    • Enterococci
  • exception: ceftaroline–5th generation cephalosporin which covers MRSA
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23
Q

1st gen cephalosporins:

name 2

what organisms do they cover?

A
  • cefazolin
  • cephalexin
  • gram + cocci
  • Proteus mirabilis
  • E. coli
  • Klebsiella pneumoniae
    • ​“PEcK”
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24
Q

why would cefazolin be used prior to surgery?

A
  • to prevent S. aureus wound infections
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25
Q

2nd gen cephalosporins:

name 3

what organisms do they cover?

A
  • cefaclor
  • cefoxitin
  • cefuroxime
    • “Fake fox fur”
  • gram + cocci
  • H. influenzae
  • Enterobacter aerogenes
  • Neisseria spp.
  • Serratia marcesvens
  • Proteus mirabilis
  • E. coli
  • Klebsiella pneumoniae
    • ​”HENS PEcK”
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26
Q

3rd gen cephalosporins:

name 3

what organisms do they cover?

A
  • ceftriaxone
    • meningitis
    • gonorrhea
    • disseminated Lyme dz
  • cefotaxime
  • ceftazidime
    • Pseudomonas
  • serious gram - infections resistant to other beta lactams
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27
Q

4th gen cephalosporins:

name 1

what organisms do they cover?

A
  • cefepime
  • gram - organisms
  • with increased activity against Pseudomonas and gram + organisms
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28
Q

5th gen cephalosporins:

name 1

what organisms do they cover?

A
  • ceftaroline
  • broad gram + and gram - organism coverage, including MRSA
  • does NOT cover Pseudomonas
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29
Q

cephalosporins–toxicity

A
  • hypersensitivity rxns
  • autoimmune hemolytic anemia
  • disulfiram like rxn
  • vitamin K deficiency
  • exhibit cross reactivity with penicillins
  • inc nephrotoxicity of aminoglycosides
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30
Q

cephalosporins–mechanism of resistance

A
  • structural change in penicillin binding proteins–transpeptidases
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31
Q

name the carbapenems

A
  • imipenem
  • meropenem
  • ertapenem
  • doripenem
    • newer carbapenems include ertapenem (limited Pseudomonas coverage) and doripenem)
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32
Q

imipenem–mechanism

A
  • (carbapenems)
  • imipenem is broad spectrum, beta lactamase resistant carbapenem
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33
Q

what is imipenem always administered with? why?

A
  • cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules
    • with imipenem, “the kill is lastin’ with cilastin”
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34
Q

carbapenems–use

A
  • gram + cocci
  • gram - rods
  • anaerobes
    • wide spectrum but significant side effects limit use to life threatening infections or after other drugs have failed
    • meropenem–dec risk of seizures and is stable to dehydropeptidase I
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35
Q

carbapenems–toxicity

A
  • GI distres
  • skin rash
  • CNS toxicity at high plasma levels
    • seizures
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36
Q

name the monobactam

A
  • aztreonam
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37
Q

monobactam (aztreonam)–mechanism

A
  • less susceptible to beta lactamases
  • prevents peptidoglycan cross linking by binding to penicillin-binding protein 3
  • synergistic with aminoglycoside
  • no cross allergenicity with penicillins
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38
Q

monobactam (aztreonam)–use

A
  • gram - rods only
    • no activity against gram + rods or anaerobes
  • for penicillin allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides
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39
Q

monobactams–toxicity

A
  • usually nontoxic
  • occasional GI upset
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40
Q

vancomycin–mechanism

A
  • inhibits cell wall peptidoglycan formation by binding D-ala-D-ala portion of cell wall precursors
  • bactericidal against most bacteria
    • bacteriostatic against C. difficile
  • not susceptible to beta lactamases
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41
Q

vancomycin–use

A
  • gram + bugs only
    • serious, multidrug-resistant organisms, including MRSA, S. epidermidis, sensitive Enterococcus species, Clostridium difficile
      • oral dose for pseudomembranous colitis
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42
Q

vancomycin–toxicity

A
  • well tolerated in general but NOT trouble free
    • Nephrotoxicity
    • Ototoxicity
    • Thrombophlebitis
    • diffuse flusing–red man syndrome
      • can largely prevent by pretreatment with antihistamines and slow infusion rate
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43
Q

vancomycin–mechanism of resistance

A
  • occurs in bacteria via amino acid modification of D-ala-D-ala to D-ala-D-lac
    • “Pay back 2 D-alas (dollars) for vandalizing (vancomycin)”
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44
Q

protein synthesis inhibitors–mechanism

A
  • specifically, target smaller bacterial ribosome (70S, made of 30S and 50S subunits), leaving human ribosome (80S) unaffected
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45
Q

name the 30S and 50S inhibitors

A
  • 30S inhibitors
    • A = Aminoglycosides [bactericidal]
    • T = Tetracyclines [bacteriostatic]
  • 50S inhibitors
    • C = Chloramphenicol, Clindamycin [bacteriostatic]
    • E = Erythromycin (macrolides) [bacteriostatic]
    • L = Linezolid [variable]
      • “Buy AT 30, CCEL (sell) at 50”
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46
Q

name the aminoglycosides

A
  • Gentamicin
  • Neomycin
  • Amikacin
  • Tobramycin
  • Streptomycin
    • “Mean” (aminoglycoside) GNATS caNNOT kill anaerobes”
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47
Q

aminoglycosides–mechanism

A
  • bactericidal
    • irreversible inhibition of initiation complex thru binding of the 30S subunit
  • can cause misreadin gof mRNA
  • also block translocation
  • require O2 for uptake
    • therefore ineffective against anaerobes
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48
Q

aminoglycosides–use

A
  • severe gram - rod infections
  • synergistic with beta lactam antibiotics
  • neomycin for bowel surgery
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49
Q

aminoglycosides–toxicity

A
  • Nephrotoxicity
  • Neuromuscular blockage
  • Ototoxicity
    • especially when used with loop diuretics
  • Teratogen
    • “Mean” (aminoglycoside) GNATS caNNOT kill anaerobes”
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50
Q

aminoglycosides–mechanism of resistance

A
  • bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation
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51
Q

name the drug classes that block cell wall synthesis by inhibition of peptidoglycan cross linking?

A
  • penicillinase sensitive penicillins
  • penicillinase resistant penicillins
  • antipseudomonals
  • cephalosporins
  • carbapenems
  • monobactams
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52
Q

name the drugs that prevent cell wall synthesis by inhibiting peptidoglycan synthesis

A
  • vancomycin
  • bacitracin
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53
Q

name the drugs that block nucleotide synthesis by inhibiting folic acid synthesis (involved in methylation)

A
  • sulfonamides
  • trimethoprim
54
Q

name the drug that damages DNA via free radicals

A
  • metronidazole
55
Q

name the drug that blocks mRNA synthesis

A
  • rifampin
56
Q

name the drug classes that block DNA gyrase

A
  • fluoroquinolones
  • quinolone
57
Q

name the drugs that block protein synthesis at the 50S subunit

A
  • chloramphenicol
  • clindamycin
  • linezolid
  • macrolides
  • streptogramins
58
Q

name the drugs that block protein synthesis at the 30S subunit

A
  • aminoglycosides
  • tetracyclines
59
Q

name the tetracyclines

A
  • tetracycline
  • doxycycline
  • minocycline
60
Q

tetracyclines–mechanism

A
  • bacteriostatic
    • bind to 30S and prevent attachment of aminoacyl tRNA
    • limited CNS penetration
61
Q

how is doxycycline eliminated, and in which patients can it be used?

A
  • fecally eliminated
  • can be used in patients with renal failure
62
Q

what should you avoid when taking tetracyclines, and why?

A
  • milk (Ca2+), antacids (Ca2+ or Mg2+), or iron containing preparations
  • b/c divalent cations inhibit drugs’ absorption in the gut
63
Q

tetracyclines–use

A
  • Borrelia burgforferi
  • M. pneumoniae
  • drugs ability to accumulate intracellularly makes them very effective against Rickettsia and Chlamydia
  • used to treat acne
64
Q

tetracyclines–toxicity

A
  • GI distress
  • discoloration of teeth and inhibition of bone growth in children
  • photosensitivity
65
Q

what is a contraindication for taking tetracyclines?

A
  • pregnancy
66
Q

tetracyclines–mechanism of resistance

A
  • dec uptake or inc efflux out of bacterial cells by plasmid encoded transport groups
67
Q

chloramphenicol–mechanism

A
  • blocks peptidyltransferase at 50S ribosomal subunit
  • bacteriostatic
68
Q

chloramphenicol–use

A
  • meningitis (Haemophilus influenzae, Neisseria meningitidis, Stretococcus pneuomoniae) and Rocky Mountain Spotted Fever (RIckettsia rickettsii)
  • limited use owing to toxicities but often still used in developing countries b/c of low cost
69
Q

chloramphenicol–toxicity

A
  • anemia–dose dependent
  • aplastic anemia–dose independent
  • gray baby syndrome–in premature infants b/c they lack liver UDP glucuronyl transferase
70
Q

chloramphenicol–mechanism of resistance

A
  • plasmid encoded acetyltransferase inactivates the drug
71
Q

clindamycin–mechanism

A
  • blocks peptide transfer (translocation) at 50S ribosomal subunit
  • bacteriostatic
72
Q

clindamycin–use

A
  • anaerobic infections (ie. Bacteroides spp., Clostridium perfringens) in aspiration pneumonia, lung abscesses, and oral infections
  • also effective against invasive group A streptococcal infection
73
Q

clindamycin vs. metronidazole

A
  • clindamycin–treats anaerobic infections above the diaphragm
  • metronidazole–treats anaerobic infections below the diaphragm
74
Q

name the oxalidinones

A
  • linezolid
75
Q

oxalidinones–mechanism

A
  • inhibit protein synthesis by binding to 50S subunt and preventing formation of the initiation complex
76
Q

oxalidinones–use

A
  • gram + species including MRSA and VRE
77
Q

oxalidinones–toxicity

A
  • bone marrow suppression–especially thrombocytopenia
  • peripheral neuropathy
  • serotonin syndrome
78
Q

oxalidinones–mechanism of resistance

A
  • point mutation of ribosomal RNA
79
Q

name the macrolides

A
  • azithromycin
  • clarithromycin
  • erythromycin
80
Q

macrolides–mechanism

A
  • inhibit protein synthesis by blocking translocation (“macroslides”)
  • bind to the 23S rRNA of the 50S ribosomal subunit
  • bacteriostatic
81
Q

macrolides–use

A
  • atypical pneumonias–Mycoplasma, Chlamydia, Legionella
  • STIs–Chlamydia
  • gram + cocci–streptococcal infections in patients allergic to penicllin
  • B pertussis
82
Q

macrolides–toxicity

A
  • MACRO
    • gastrointestinal Motility issues
    • Arrhythmia caused by prolonged QT interval
    • acure Cholestatic hepatitis
    • Rash
    • eOsinophilia
  • increases serum concentration of theophylline, oral anticoagulants
  • clarithromycin and erythromycin inhibit cytochrome P-450
83
Q

macrolides–mechanism of resistance

A
  • methylation of 23S rRNA -binding site prevents binding of drug
84
Q

name the sulfonamides

A
  • sulfamethoxazole (SMX)
  • sulfisoxazole
  • sulfadiazine
85
Q

sulfonamides–mechanism

A
  • inhibit dihydropteroate synthase, thus inhibiting folate synthesis
  • bacteriostatic
    • bacteriocidal when combined with trimethoprim
86
Q

sulfonamides–use

A
  • gram +
  • gram -
  • Nocardia
  • Chlamydia
  • SMX for simple UTI
87
Q

sulfonamides–toxicity

A
  • hypersensitivity rxns
  • hemolysis if G6PD deficient
  • nephrotoxicity–tubulointerstitial nephritis
  • photosensitivity
  • kernicterus in infants
  • displace other drugs from albumin (ie. warfarin)
88
Q

sulfonamides–mechanism of resistance

A
  • altered enzyme (bacterial dihydropteroate)
  • decrease uptake
  • increase PABA synthesis
89
Q

dapsone–mechanism

A
  • similar to sulfonamides
    • but structurally distinct agent
90
Q

dapsone–use

A
  • leprosy (lepromatous and tuberculoid)
  • Pneumocystis jirovecii prophylaxis
91
Q

dapsone–toxicity

A
  • hemolysis if G6PD deficient
92
Q

trimethoprim–mechanism

A
  • inhibits bacterial dihydrofolate reductase
  • bacteriostatic
93
Q

trimethoprim–use

A
  • used in combination with sulfonamides (trimethoprim-sulfamethoxazole [TMP-SMX])
    • causes sequential block of folate synthesis
  • combination used for UTIs, shigella, Salmonella, Pneuomocystis jirovecii pneuomonia treatment and prophylaxis, toxoplasmosis prophylaxis
94
Q

trimethoprim–toxicity

A
  • megaloblastic anemia
  • leukopenia
  • granulocytopenia
    • may alleviate with supplemental folinic acid
      • “TMP Treats Marrow Poorly”
95
Q

name the fluoroquinolones

A
  • ciprofloxacin
  • norfloxacin
  • levofloxacin
  • ofloxacin
  • moxifloxacin
  • gemifloxacin
  • enoxacin
96
Q

fluoroquinolones–mechanism

A
  • inhibit prokaryotic enzymes topoisomerase II (DNA gyrase) and topoisomerase IV
  • bactericidal
  • must not be taken with antacids
97
Q

fluoroquinolones–use

A
  • gram - rods of urinary and GI tracts (including Pseudomonas)
  • Neisseria
  • some gram + organisms
98
Q

fluoroquinolones–toxicity

A
  • GI upset
  • superinfections
  • skin rashes
  • headache
  • dizziness
  • less commonly, can cause leg cramps and myalgias
  • may prolong QT interval
  • may cause tendonitis or tendon rupture in people > 60 years old and in patients taking prednisone
    • “fluoroquinolones hurt attachments to your bones”
99
Q

what are contraindications for fluoroquinolones?

A
  • pregnant women
  • nursing mothers
  • children < 18 yo due to possible damage to cartilage
100
Q

fluoroquinolones–mechanism of resistance

A
  • chromosome encoded mutation in DNA gyrase
  • plasmid mediated resistance
  • efflux pumps
101
Q

daptomycin–mechanism

A
  • lipopeptide that disrupts cell membrane of gram + cocci
102
Q

daptomycin–use

A
  • S. aureus skin infections (especially MRSA)
  • bacteremia
  • endocarditis
  • VRE
103
Q

why is daptomycin not used for pneumonia?

A
  • daptomycin avidly binds to and is inactivated by surfactant
104
Q

metronidazole–mechanism

A
  • forms toxic free radical metabolites in the bacterial cell that damage DNA
    bactericidal
  • antiprotozoal
105
Q

metronidazole–use

A
  • treats:
    • Giardia
    • Entamoeba
    • Trichomonas
    • Gardnerella vaginalis
    • Anaerobes–Bacteroides, C. difficile
    • used with a proton pump inhibitor and clarithromycin for “triple therapy” against H. pylori
      • ​“GET GAP on the Metro with metronidazole”
106
Q

metronidazole–toxicity

A
  • disulfiram-like rxn (severe flushing, tachycardia, hypotension) with alcohol
  • headache
  • metallic taste
107
Q
  • M. tuberculosis*
    1. prophylaxis
    2. treatment
A
  1. Isoniazid
  2. Rifampin, Isoniazid, Pyrazinamide, Ethambutol
    1. RIPE for treatment
108
Q
  • M. avium-intracellulare*​
    1. prophylaxis
    2. treatment
A
  1. azithromycin, rifabutin
  2. more drug resistant than M. tuberculosis
    1. azithromycin or clarithromycin + ethambutol
    2. can add rifabutin or ciprofloxacin
109
Q
  • M. leprae*
    1. prophylaxis
    2. treatment
A
  1. N/A
  2. long term treatment with dapsone and rifampin for tuberculoid form
    1. add clofazimine for lepramatous form
110
Q

name the rifamycins

A
  • rifampin
  • rifabutin
111
Q

rifamycins–mechanism

A
  • inhibit DNA dependent RNA polymerase
112
Q

rifamycins–use

A
  • Mycobacterium tuberculosis
    • delay resistance to dapsone when used for leprosy
  • used for meningococcal prphylaxis and chemoprophylaxis in contacts of children with Haemophilus influenzae type B
113
Q

rifamycins–toxicity

A
  • minor hepatotoxicity
  • drug reactions–inc cytochrome P-450
  • orange body fluids–non hazardous side effect
114
Q

when is rifabutin favored over rifampin and why?

A
  • RIfabutin favored over rifampin in patients with HIV infection due to less cytochrome P-450 stimulation
    • “Rifampin ramps up cytochrome P-450, but rifabutin does not”
115
Q

rifamycins–mechanism of resistance

A
  • mutations reduce drug binding to RNA polymerase
  • monotherapy rapidly leads to resistance
116
Q

Rifampin: 4 things to remember

A
  • 4 R’s
    • ​RNA polymerase inhibitor
    • Ramps up microsomal cytochrome P-450
    • Red/orange body fluids
    • Rapid resistance if used alone
117
Q

name the 4 antimycobacterial drugs

A
  • Rifamycins–rifampin, rifabutin
  • Isoniazid
  • Pyrazinamide
  • Ethambutol
  • Streptomycin
118
Q

Isoniazid–mechanism

A
  • dec synthesis of mycolic acids
  • bacterial catalase-peroxidase (encoded by KatG) needed to convert INH to active metabolite
119
Q

Isoniazid–use

A
  • Mycobacterium tuberculosis
    • this is the only agent used as solo prophylaxis against TB
    • also used as monotherapy for latent TB
120
Q

isoniazid–toxicity

A
  • hepatotoxicity
  • P-450 inhibition
  • drug induced SLE
  • vitamin B6 deficiency–peripheral neuropathy, sideroblastic anemia
    • INH Injures Neurons and Hepatocytes
121
Q

what should be administered with isoniazid?

A
  • puridoxine (vitamin B6)
122
Q

isoniazid–mechanism of resistance

A
  • mutations leading to underexpression of KatG
123
Q

pyrazinamide–mechanism

A
  • mechanism uncertain
  • prodrug that is converted to the active compound pyrazinoic acid
  • works best at acidic pH (ie. in host phagolysosomes)
124
Q

pyrazinamide–use

A
  • Mycobacterium tuberculosis
125
Q

pyrazinamide–toxicity

A
  • hyperuricemia
  • hepatotoxicity
126
Q

ethambutol–mechanism

A
  • dec carbohydrate polymerization of mycobacterium cell wall by blocking arabinocyltransferase
127
Q

ethambutol–use

A
  • Mycobacterium tuberculosis
128
Q

ethambutol–toxicity

A
  • optic neuropathy (red-green color blindness)
    • pronouce “eyethambutol”
129
Q

streptomycin–mechanism

A
  • interferes with 30S component of ribosome
130
Q

streptomycin–use

A
  • Mycobacterium tuberculosis (2nd line)
131
Q

streptomycin–toxicity

A
  • tinnitus
  • vertigo
  • nephrotoxicity

PLAB Pharmacology (17 decks)

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