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Pharm Unit 6 > Antimicrobials > Flashcards

Antimicrobials Flashcards

0
Q

What are the 5 classes of drugs that inhibit cell-wall synthesis and are all bactericidal?

A 
[all beta lactams]
Penicillin
Cephalosporin
Carbapenem
Monobactam

Glycopeptides [only non-lactam]

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1
Q

What is one positive and one negative effect of an antibiotic target unique to microbials (not normally found in humans)?

A
  • Positive: wide therapeutic index (can give high doses)

- Negative: more likely to cause allergic reaction

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2
Q

What are 3 modes of resistance to penicillins/cephalosporins?

A
  1. Penicillinases (beta-lactamases)-cleave lactam ring structure
  2. Structural changes in PBP (i.e MRSA)
  3. Change in porin structure (Abx can’t cross cell wall in gram(-) i.e pseudomonas)
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3
Q

Which 2 microbes would penicillin G and V be ineffective against?

A

Staph aureus & B. Fragilis

Both have 100% penicillinase activity and Penicillin G & V are narrow spectrum, beta-lactamase sensitive

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4
Q

What are 2 narrow spectrum, beta-lactamase sensitive anti-microbials and what are they used to treat?

A 
Penicillin G (IV) & Penicillin V (oral)
--> useful for streptococci, pneumococci, meningococci and Treponema pallidum
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5
Q

What are 3 very narrow spectrum, beta-lactamase resistant anti-microbials? What are they used to treat?

A

Oxacillin (IV), Dicloxacillin (oral), Methacillin

Only have activity against S. aureus (but NOT MRSA)

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6
Q

What is the mechanism of action of ampicillin and those in its class?

A

(Penicillin)
Interacts with cytoplasmic PBP to inhibit transpeptidation and cross-linking of cell wall (final steps of synthesis) –> lack of cell wall rigidity causes organism to lyse

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7
Q

What is an extended spectrum, beta-lactamase sensitive agent that is primarily used IV in the hospital? Used to treat?

A

Piperacillin
–> increased activity against gram- rods (pseudomonas)

(Usually given with suicide inhibitor)

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8
Q

What are 2 broad spectrum, aminopenicillin, beta-lactamase sensitive anti-microbials? Used to treat?

A

Ampicillin (IV) & Amoxicillin (oral)

Gram+ cocci (not staph)
E.coli
H. Influenzae
Listeria monocytogenes (ampicillin)
Borrelia burgdorferi (amoxicillin)
H. Pylori (amoxicillin)
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9
Q

PBP 2b is the binding site for…?

PBP 2x is the binding site for…?

A

2b: all penicillins and 1st generation cephalosporins
2x: all other cephalosporins, carbapenems & monobactams

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10
Q

What is the purpose of suicide inhibitors? Name 2.

A

Beta-lactamase inhibitor –> enhance activity of penicillins

  • Augmentin: combination of amoxicillin (broad spectrum, lactamase sensitive) and clavulanic acid (suicide inhibitor)
  • Zosyn: pipercillin (extended spectrum, lactamase sensitive) with tazobactam
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12
Q

Which 2 microbes confer resistance by altering PBP?

A

Pneumococcus- 30% PBP 2b mutation (resistance to all penicillins and 1st generation cephalosporins)

MRSA- PBP 2b and 2x (resistance to all lactam drugs)

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13
Q

What is the cross-reactivity of penicillins? What is the difference between an IgE and IgM mediated response?

A
  • penicillins will cross-react with other penicillins and 1st generation cephalosporins
  • no cross reaction with monobactam or aztreonam (due to lack of ring adjacent to lactam structure)
  • IgE: anaphylaxis (hives, angioedema, stridor, hypotension)
  • IgM: maculopapular rash (no cross-reactivity with other penicillins)
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14
Q

What is the mechanism of action of cefpodoxime and those in its class?

A

(cephalosporins)
identical to penicillins- Interacts with cytoplasmic PBP to inhibit transpeptidation and cross-linking of cell wall (final steps of synthesis) –> lack of cell wall rigidity causes organism to lyse

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15
Q

Name 2 1st generation cephalosporins. spectrum? common use?

A

Cefazolin (IV) & Cephalexin (oral)
–> gram+ cocci (not MRSA), E. coli, Klebsiella pneumoniae

-commonly used in surgical prophylaxis

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16
Q

Name a 2nd generation cephalosporin. spectrum?

A

Cefuroxime (IV, oral)

–> gram+ cocci (except MRSA), increased gram_ coverage- H. flu, anaerobes

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17
Q

Name three 3rd generation cephalosporins. spectrum? use?

A

Ceftriaxone (IV), Ceftazidime (IV) & Cefpodoxime (oral)

  • -> broad spectrum: gram+ cocci, gram- cocci, gram- rods
  • used in empiric management of meningitis and sepsis
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18
Q

Name a 4th generation cephalosporin. spectrum?

A

Cefepime (IV)

–> very broad spectrum (gram+ cocci and rods, gram- rods)

19
Q

Name a carbapenem. Mechanism? Spectrum and use?

A

Imipenem (IV)

  • -> binds to PBP to prevent cell wall cross-linking but is also resistant to beta-lactamases
  • -> very broad spectrum (gram+ cocci, gram- rods, anaerobes)
  • -> in-hospital agent for severe, life-threatening infections (sepsis)
20
Q

What drug is given with Imipenem? why?

A

Cilastatin (renal dehydropeptidase inhibitor)

–> inhibits kidney from metabolizing impinenem to its nephrotoxic metabolite too quickly

21
Q

What is aztreonam? Mechanism, use, cross-allergenicity?

A
  • monobactam, given IV
  • -> binds PBP to prevent cell wall cross-linking and is beta-lactamase resistant
  • -> only active against gram- rods
  • -> NO cross-allergenicity with penicillins/cephalosporins
22
Q

Describe the class, mechanism, and use of vancomycin

A

glycopeptide used IV or oral

  • ->binds D-ala-D-ala muramyl pentapeptide and sterically hinders transglycosylation/peptide elongation of cell wall [slower onset (hrs) than lactams]
  • -> used for MRSA, enterococci and metronidazole-resistant C. difficile (oral)
23
Q

What is the acronym/orgranisms not covered by cephalosporins?

A 
LAME
Listeria monocytogenes (amoxicillin)
Atypicals- Chlamydia, Mycoplasma 
MRSA (vancomycin)
Enterococci (ampicillin + aminoglycosides)
24
Q

What is the mode of resistance to vancomycin?

A
  • enterococci: change in muramyl pentapeptide such that the terminal D-ala is readily replaced by D-lactate and vancomycin can’t bind
  • increased cell wall thickness
25
Q

Other than typical allergic side effects, what are 3 other adverse effects of vancomycin?

A
  1. “red man syndrome” (flushing, tachycardia, hypotension from histamine/vasodilatory effect)
  2. ototoxicity
  3. nephrotoxicity (mild)
26
Q

Which lactam agents can enter the CNS?

A
  • Cefuroxime (only 2nd generation)
  • most 3rd generation cephalosporins
  • 4th generation cephalosporins
  • imipenem
27
Q

What drug may be given for vancomycin resistant enterococci (VRE) and vancomycin resistant S. aureus (VRSA)? Class, mechnism, use, adverse effects?

A

Daptomycin (cell membrane toxin)

  • Mechanism: inserts into cell membrane forming a channel that allows leakage of intracellular ions
  • Use: Gram+ ONLY, serious infections that are otherwise resistant
  • SE: allergy, rhabdomyolysis (use >7days)
28
Q

What is Colistin? Mechanism, use and adverse effects?

A

(polymixin- cell membrane toxin)

  • -> binds LPS disrupting outer cell membrane of gram- and leakage of intracellular ions
  • Use: gram- ONLY that are otherwise resistant (mainly Pseudomonas)
  • SE: highly nephrotoxic
29
Q

What are 3 classes that inhibit bacterial nucleic acid synthesis? General descriptor of each?

A
  1. Floroquinolones- inhibit DNA gyrase (top. II) and topoisomerase IV
  2. Rifampin- inhibits DNA-dependent RNA polymerase
  3. Metronidazole- unknown (free radicals?)
30
Q

What is the action of DNA gyrase? What are the 1st and 2nd generation floroquinolones that inhibit its action? Contraindications?

A
  • DNA gyrase- negative supercoiling that orients DNA for replication [not present in humans]
  • Ciprofloxacin (1st generation)
  • Levofloxacin (2nd generation)
  • ->contraindicated in pregnancy/children
31
Q

What agent may be used for lactam-resistant pneumococci? What is a potential adverse effect?

A

levofloxacin (floroquinolone)

–>may cause QT prolongation and v. tach (torsades de points)

32
Q

What is the mechanism of action, spectrum and adverse effects of Metronidazole?

A
  • Mech: prodrug activated in an ANAEROBIC environment that is toxic to nucleic acids
  • Spectrum: DOC pseudomembranous colitis (C. difficile), works for most anaerobic gram- species; DOC as antiprotozoal for Giardia, Trichomonas, Entamoeba
  • SE: inhibits aldehyde dehydrogenase (dont use EtOH)
33
Q

What are the 5 classes of bacteria protein synthesis inhibitors? Which act on 30S and which on 50S?

A

30S inhibitors:
Aminoglycosides & Tetracyclines

50S inhibitors:
Macrolides, Linezolid & Clindamycin

34
Q

Of the protein synthesis inhibitors, which inhibit formation of initiation complex by blocking association of 30S with 50S? Which one also causes code misreading and is the only bactericidal agent?

A

Aminoglycosides (30S) & Linezolid (50S)

–>aminoglycosides also cause misreading due to steric hinderance

35
Q

Name 2 Aminoglycosides. Mechanism? Spectrum? Adverse effects?

A

Gentamicin & Tobramycin
Mech: Oxygen-mediated active uptake- blocks initiation and induces code misreading
Spectrum: aerobic or facultative aerobic Gram- rods (due to O2 uptake)
(Amp + Gent for enterococci)
SE: nephrotoxicity but ONLY w/prolonged use [best to use as initial dose in gram- sepsis due to rapid lethality then switch to safer drug]

36
Q

What is the mechanism, spectrum and adverse effects of Linezolid?

A

(protein synthesis inhibitor)
Mech: inhibits peptidyl transferase and the formation of initiation complex
Spectrum: VRSA, MRSA
SE: allergies, agranulocytosis with prolonged use (>2wks)

37
Q

Which synthesis inhibitor blocks attachment of tRNA to acceptor site? Spectrum? Adverse effects?

A

Doxycycline (tetracycline)
Spectrum: intracellular pathogens (mycoplasma, chlamydia, legionella, rickettsia); resistant gram+
SE: phototoxicity; contraindicated in pregnancy/children; chelator (Ca2+, Mg2+, etc) so don’t take with food

38
Q

Which protein synthesis inhibitors act to inhibit translocation of peptidyl-tRNA from acceptor to donor site?

A

Macrolides and Clindamycin

39
Q

Name the DOC for Legionella. What is its spectrum and adverse effects?

A

Azithromycin (protein synthesis inhibitor of translocation)
Spectrum: wide; intracellular pathogens, gram+ cocci, H. influenzae
SE: GI distress (increase peristalsis), potential for v. tach (TdP)

40
Q

Which antibacterial agent is the most closely associated with C. difficile colitis (pseudomembranous colitis)? What is its spectrum?

A

Clindamycin (protein synthesis inhibitor of translocation)

–> all anaerobes except for C. difficile; used for resistant pneumococci and MRSA (Especially osteomyelitis)

41
Q

What is Bactrim? Mechanism? Spectrum? Adverse effects?

A

Anti-metabolite- Inhibits Folic Acid synthesis:
Sulfamethoxazole- inhibits Dihydropterate synthase
Trimethoprim- inhibits DHFR
–>Uncomplicated UTIs; Pneumocystis pneumonia & Toxoplasmosis infections in AIDS
-SE: Hyperkalemia in patients with severe renal insufficiency (TMP analog to triamterene)

42
Q

What are the 4 agents used in combination for active TB? Which one of these is given for 9 months if +PPD but no active disease?

A

Isoniazid - given as chemoprophylaxis
Rifampin
Ethambutol
Pyrazinamide

43
Q

What is the mechanism of Isoniazid? What are its side effects and what should be co-administered to prevent these?

A

Isoniazid is a congener of vitamin B6
–>prodrug, inhibits mycolic acid synthesis unique to mycobacterium cell walls
(Therapeutic index: M.tb utilizes B6 to a greater extent than human cells)
-SE: peripheral neuropathy, sideroblastic anemia, status epilepticus if OD
–>NEED TO CO-ADMINISTER PYRIDOXINE

44
Q

What is a common adverse effect of the anti-tubercular anti-metabolites? What is specific for rifampin? for pyrazinamide? for ethambutol?

A
  • All associated with centrolobular hepatitis except ethambutol
  • Rifampin: serious flu-like hypersensitivity if used in intermittent dosing regimens
  • Pyrazinamide: increase uric acid -> gout
  • Ethambutol: optic neuritis (loss red-green discrimination), gout

Pharm Unit 6 (5 decks)

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