Pharm - Antibiotics Flashcards
1
Q
What is the mechanism of action for penicillins and the derivatives of penicillins?
A
Competitive inhibitors of transpeptidase, inhibits cell wall synthesis
2
Q
What are the different sub-classes of penicillins?
A
Natural, Penicillinase-Resistant, Aminopenicillins, Carboxypenicillins, Ureidopenicillins, and beta lactamase inhibitor combinations
3
Q
What are the major adverse events associated with penicillin?
A
Allergic hypersensitivity leading to anaphylaxis, hives, and rash. The use of penicillin can also lead to superinfections like C. Diff
4
Q
Are penicillins bacteriostatic or bacteriocidal?
A
Bacteriocidal
5
Q
What is the spectrum of activity for Penicillin G?
A
Bacteriocidal against: Gram positive (S. pneumo, S. pyogenes, actinomyces), gram negative cocci (N. meningitidis), anaerobes (Clostridium), spirochetes (T. pallidum)
6
Q
What are the mechanisms of resistance against penicillin?
A
Resistance developed by preventing entrance to penicillin, enzymatically cleaving beta lactam ring, altering the structure of the transpeptidase enzyme
7
Q
What is the primary reason for prescribing oral penicillin VK?
A
Strep throat caused by S. pyogenes
8
Q
What are the main penicillinase resistant penicillins?
A
Nafcillin, Oxacillin and Dicloxacillin
9
Q
What is the spectrum of activity for penicllinase resistant penicillin?
A
Skin infections when penicillinase producing S. aureus is suspected (Target organism: MSSA)
10
Q
Name the two aminopenicillins
A
Ampicillin and amoxicillin
11
Q
What is the spectrum of activity for aminopenicillins?
A
Broad gram negative coverage (P. miribalis, E. Coli, Salmonella, Shigella, H Flu) and enterococcus, listeria
12
Q
What is the main carboxypenicillin?
A
Ticarcillin
13
Q
What is the spectrum of activity for ticarcillin?
A
Enhanced gram negative activity (enterobacter, pseudomonas)
14
Q
What is the main ureidopenicillin?
A
Piperacillin
15
Q
What is the spectrum of activity for piperacillin?
A
Even more enhanced gram negative activity (enterobacter, pseudomonas, serratia, klebsiella) as well as anaerobes
16
Q
What is the mechanism of action for the beta-lactamase inhibitor combination drugs?
A
Competitive inhibitor of transpeptidase, inhibits cell wall synthesis AND beta-lactamase inhibitor
17
Q
List the 3 major beta-lactamase inhibitor combination drugs
A
Ampicillin-Sulbactam (Unasyn)
Amoxicillin-Clavulanate (Augmentin)
Piperacillin-Tazobactam (Zosyn)
18
Q
What is the spectrum of activity for the beta-lactamase inhibitor combination drugs?
A
Enhanced activity against beta lactamase producing organisms including G+ (S. Aureus), G- (H. flu, Moraxella), and anaerobes (bacteroides)
19
Q
How are the beta lactams primarily excreted?
A
Primarily elmated by the kidneys (Except nafcillin and oxacillin eliminated by the liver)
20
Q
What is the general mechanism of action for the aminoglycosides?
A
Bind to 30S ribosomal subunit and inhibits protein synthesis
21
Q
What class of drugs are aminoglycosides often used with?
A
Cell wall inhibitors (synergy)
22
Q
List the major aminoglycosides
A
Gentamycin, tobramycin, amikacin and streptomycin
23
Q
What is the most commonly used aminoglycoside?
A
Gentamycin
24
Q
What are the major adverse events associated with aminoglycosides?
A
Ototoxicity, nephrotoxicity, neuromuscular blockade
25
What is the spectrum of activity of gentamycin?
Gram negative enterics (E. coli, K. pneumoniae, proteus, serratia, pseudomonas) and gram positive (enterococcus, s. aureus, viridans, s. pyogenes)
26
What is the difference in spectrum activity between tobramycin and gentamycin?
Tobramycin is more active against pseudomonas, but less active against other gram negatives compared to gentamycin
27
What is the spectrum of activity of amikacin?
Amikacin is the broadest spectrum AG.
Most active AG against nosocomial gram negatives (except for Tobra with pseudomonas), mycobacteria, nocardia
28
How does the aminoglycoside dosing plan differ for treatment of G+ versus G- bacteria?
For G- bacteria you want to maximize the peak concentration, but for G+ bacteria low doses are sufficient
29
Aminoglycoside cell entry requires ________
Oxygen
| Cell entry of AGs is oxygen dependent
30
What are the mechanisms of resistance to aminoglycosides?
AG modifying enzymes
Altered uptake (porins or efflux pumps)
Target modification
31
Is the oral absorption of aminoglycosides low or high?
AGs have poor oral absorption
32
How are aminoglycosides eliminated?
99% eliminated by the kidney
33
Aminoglycosides display ______-dependent killing
Aminoglycosides display concentration-dependent killing
| Want to maximize peak concentration
34
What is postantibiotic effect?
Persistent suppression of bacterial growth after drug concentration falls below the MIC
35
What are the two dosing strategies associated with aminoglycosides?
Traditional dosing: same dose every 8-12 hrs
| Extended interval dosing: one large dose given every 24+ hours
36
What is the general mechanism of cephalosporins?
Competitive inhibitor of transpeptidase enzyme, binds to PBPs to inhibit cell wall synthesis
37
What is the general trend of spectrum of activity across the generations of cephalosporins?
With successive generations, G+ activity decreases and G- activity increases
38
What are the mechanisms of resistance against first generation cephalosporins?
Beta lactamase
| Altered penicillin binding proteins
39
What adverse effects are associated with first generation cephalosporins?
Allergy causing anaphylactic shock, hives, rash. Delayed rash (cross reactivity with penicillins). Superinfections.
40
Describe the spectrum of activity of first generation cephalosporins
1st gen have best activity against G+ (MSSA, PSSP, strep, viridans) with some G- activity (P. miribalis, E. coli, K. pneumoniae). Excellent for skin infections, surgical prophylaxis
41
Describe the spectrum of activity of second generation cephalosporins
Covers more G-, including anaerobes, than 1st gen, but less active against G+. Coverage: HENPEK
42
What is the only cephalosporin with activity against anaerobes like B. fragilis?
Cephamycins
43
Describe the excretion of cephalosporins
All are excreted renally, except ceftriaxone, which is excreted through the biliary system
44
Describe the spectrum of activity of 3rd generation cephalosporins
Greater activity against gram negative aerobes, including some beta lactamase producing strains. Excellent CSF penetration, used for meningitis (HENPECKSSS)
45
What are the 4th generation cephalosporins used for?
Extended spectrum of activity with combined activity of ceftriaxone and ceftazimidime. Used for pseudomonas
46
What are the 5th generation cephalosporins used for?
MRSA, skin and soft tissue infection, pneumonia
47
Are cephalosporins bacteriostatic or bacteriocidal?
Bacteriocidal
48
What is cross-allergenicity?
Similarities in drug structure or function lead to allergic hypersensitivity in multiple distinct drugs
Example: Pts with penicillin allergy may exhibit reactions to cephalosporins
49
What is the significance of the MTT side chain found on some cephalosporins?
Can cause hypoprothrombinemia by inhibiting Vitamin K metabolism, reducing vitamin K producing bacteria
Also causes ethanol intolerance
50
What is the general mechanism of action of carbapenems?
Inhibit bacterial cell wall synthesis by binding to PBP2
51
What is the spectrum of activity for carbapenems?
G+, G- aerobes and anaerobes, including beta lactamase producing strains, Pseudomonas (except for ertapenem)
52
What adverse events are associated with carbapenems?
Hypersensitivity, GI (nausea, vomitting), CNS (seizures, confusion, dizziness)
53
What drug must be administered with imipenem? Why?
Imipenem is hydrolized by DHP brush border enzyme which must be blocked with cilastatin
"Cilistatin makes it last"
54
Which bacteria are carbapenems not active against?
"MVP SACC"
| MRSA, VRE, PRSP, Coagulase-negative staph, C diff, atypical bacteria, senotrophomonas maltophilia
55
How are carbapenems excreted?
Renal excretion
56
Are carbapenems bacteriostatic or bacteriocidal?
Bacteriocidal
57
What are the 4 main carbapenems?
Imipenem, meropenem, ertapenem, doripenem
58
What are the mechanisms of resistance against carbapenems?
beta lactamase production
decreased permeability
alteration of PBPs
59
What class of drug is considered the broadest spectrum agent available?
Carbapenems
60
What are the target organisms of carbapenems?
MSSA, Pseudomonas, and Bacteroides
61
Are carbapenems functional in the presence of beta lactamase?
Yes. They are resistant to beta lactamase degradation
62
What is the major monobactam drug?
Aztreonam
63
What is the mechanism of action of monobactams?
Inhibits bacterial cell wall synthesis by binding to PBP3
64
Do monobactams exhibit cross reactivity with penicillin?
No. Patients allergic to penicillin do not have hypersensitive reactions to aztreonam
65
What is the spectrum of activity of aztreonam?
G- aerobes (including Pseudomonas), little to no activity against G+ or anaerobes
66
Are monobactams bacteriocidal or bacteriostatic?
Bacteriocidal
67
What are the mechanisms of resistance of monobactams?
Beta lactamase hydrolysis
| Decreased permeability
68
What adverse events are associated with monbactams?
Nausea and diarrhea
69
What is the mechanism of action of vancomycin?
Inhibits synthesis of G+ peptidoglycan by inhibiting transpeptidation of D-alaninne
70
How does the elimination of vancomycin differ between oral and IV administration?
IV --> renal excretion, Oral --> not absorbed well, high stool concentration
71
What are the adverse events associated with vancomycin?
Ototoxicity
Nephrotoxicity
Red man syndrome: due to rate of IV infusion
72
What is the spectrum of activity of vancomycin?
All gram positive organisms, C. Diff (oral)
73
What is the main mechanism of resistance to vancomycin?
Increasing resistance to vancomycin recently due to modification of D-ala D-ala bindng site
VISA: thickened cell wall
74
What is the spectrum of activity of dalbavancin?
Used for resistant G+ organisms, MRSA, VISA, VRE (vanB, vanC)
75
What is the mechanism of action of Linezolid?
Binds to 50S preventing formation of 70S initiation complex, inhibiting protein synthesis
76
What adverse events are associated with linezolid?
Lactic acidosis, peripheral neuropathy, thrombocytopenia, anemia
Possible serotonin storm with SSRIs/MAOIs
77
What is the spectrum of activity of linezolid?
Used for serious/complicated G+ infections.
| Activity against resistant G+ including VRE, MRSA and VISA
78
If a patient is on SSRIs, what drug can be perscribed instead of linezolid?
Tedizolid is also an oxazolidinone like linezolid, but does not react with SSRIs
79
What is the mechanism of action for daptomycin?
Binds bacterial membranes causing rapid depolarization that inhibits DNA, RNA and protein synthesis, leadiing to cell death
80
What is the spectrum of activity for daptomycin?
Serious/complicated infections caused by resistant bacterias (MSSA, MRSA, S. pyogenes, S. aureus bacteremia).
No G- activity
81
What are the adverse effects associated with daptomycin?
myopathy
CPK elevation
pneumonia
82
Is linezolid bacteriostatic or bacteriocidal?
Bacteriostatic (except against S. pneumo)
83
True or false: daptomycin can be used to treat pneumonia
FALSE
| Daptomycin should NOT be used in the treatment of pneumonia
84
What is the general mechanism of action of tetracyclines?
Reversibly binds to 30S ribosomal subunit and inhibits protein synthesis
85
What is the spectrum of activity for tetracyclines?
G+ (primarily MSSA), G- (burkholderia) , Rickettsia, chlamydia, legionella, mycoplasma
86
Describe the absorption of tetracyclines
Oral absorption from the stomach, which can be impaired by food, milk, divalent cations
87
What adverse events are associated with tetracyclines?
GI (nausea, vomiting, diarrhea), hypersensitivity, photosensitivity, renal failure (Fanconi syndrome)
Category D drug for pregnant women: discolored teeth and bone growth abnormalities
88
What are the mechanisms of resistance to tetracyclines?
Resistance can develop due to efflux pumps, ribosomal protection proteins, or enzymatic inactivation
89
What is the difference between tigecycline and the tetracyclines?
Tigecycline has broader coverage than teracyclines, but not covering Proteus or psedomonas
90
What is the mechanism of action of sulfonamides?
Inhibits DNA synthesis by Inhibiting dihydropteroate synthesis, preventing PABA from incorporating into tetrahydropteroic acid
Bacterostatic
91
What is the spectrum of activity of Trimethoprim-Sulfamethoxazole?
Acute, chronic, recurrent UTIs, prostatitis, skin infections from CA-MRSA, Nocardia
92
What adverse events are associated with TMP-SMX?
GI (nausea, vomiting, diarrhea), leukopenia, thrombocytopenia, hypersensitivity, renal toxicity
93
What is the mechanism of action of Chloramphenicol?
Inhibits protein synthesis by binding to the 50S ribosome
94
What adverse events are associated with chloramphenicol?
Bone marrow depression, gray baby syndrome
95
What is the spectrum of activity of chloramphenicol?
Broad spectrum, kiills G+ (except s. aureus and enterococcus), G- (except P. aerugnosa), including anaerobes
96
What is the mechanism of action of nitrofurantoin?
Binds ribosomal proteins, inhibits translation, bacterial respsiration, and pyruvate metabolism
97
Describe the absorption and elimination of nitrofurantoin
Some absorbed in small intestine, large urine concentration, eliminated via urine
98
Spectrum of activity of nitrofurantoin
Acute, uncomplicated UTIs
99
What is the mechanism of action of methenamine?
Broken into ammonia and formaldehyde in acidic pH leading to denatured proteins and nucleic acids
100
What is methenamine used for?
Suppression or prophylaxis against recurrent UTIs
101
Are tetracyclines bacteriostatic or bacteriocidal?
Bacteriostatic
102
What are the two gram negative aerobes that tigecycline does not cover?
Proteus and pseudomonas
103
What are the 3 major tetracyclines?
Tetracycline, doxycycline and minocycline
104
Is chloramphenicol bacteriostatic or bacteriocidal?
Bacteriostatic except for H. influenzae, S. pneumoniae, and N. meningitidis
105
What is the mechanism of action of fluoroquinolones?
Inhibit DNA gyrase leading to breakage in bacterial DNA, inhibited DNA synthesis
106
What is the spectrum of activity of fluoroquinolones?
G+ (MSSA, S. pneumo PRSP), and excellent G- coverage (enterobacteriaceae, H flu, neisseria, Pseudomonas), Legionella, Chlamydia, mycoplasma
107
What are the names of the major fluoroquinolones?
Ciprofloxacin, levofloxacin, moxifloxacin, gemifloxacin
108
What is unique about moxifloxacin?
It is the only FQ that treats anaerobes
109
What are the adverse effects associated with fluoroquinolones?
GI (nausea, vomiting, diarrhea, dyspepsia, C. diff), CNS problems in elderly, hepatotoxicity, phototoxicity, cardiotoxicity (prolonged QT), tendon rupture, divalent and trivalent cations decrease absorption
110
What is the mechanism of action of clindamycin?
Binds to 50S ribosomal subunit and inhibits protein synthesis
111
What is the spectrum of activity of clindamycin?
Anaerobes not in the CNS (bacteroides), G+ (MSSA, CA-MRSA, PSSP, group and viridans strep), and for pts with penicillin allergy
112
Is clindamycin bacteriostatic or bacteriocidal?
Bacteriostatic
113
What adverse events are associated with clindamycin?
Nausea, vomiting, diarrhea, dyspepsia
| Can cause pseudomembranous colitis, which can lead to C. Diff
114
What are the three major macrolides?
Erythromycin, clarithromycin, azithromycin
115
What is the mechanism of action of the macrolides?
Binds to 50S ribosomal subunit and inhibits protein synthesis
116
Which macrolides are time-dependent and which are concentration dependent?
Erythro and Clarithro are time dependent
| Azithromycin is concentration dependent
117
How are macrolides metabolized?
CYP450. This can lead to drug interactions if other meds are also metabolized by CYP450
118
What is the difference between the spectrum of activity of macrolides and clindamycin?
Macrolides also cover gram negative aerobes (Neisseria, M. cattarhalis), and atypical bacteria (legionella, chlamydia) in addition to the G+ aerobes (MSSA, PSSP, group and viridans strep, Bacillus, Corynebacterium)
119
Which macrolide has the best activity against G+ bacteria? Which has the best for G-?
Clarithromycin has the best activity against G+
| Azithromycin has the best activity against G-
120
What are the mechanisms of resistance against macrolides?
```
Active efflux (mef gene)
Altered ribosomal target sites (erm gene)
```
121
What is the mechanism of action of Quinupristin-dalfopristin (Synercid®)?
Inhibits 50S ribosomal subunit to inhibit early and late stages of protein synthesis
122
What s the spectrum of activity for Quinupristin-dalfopristin (Synercid®)?
G+ bacteria
Primarily used to treat VRE
Also has activity against MRSA, S. epi, S. sap, PRSP
123
Is Quinupristin-dalfopristin (Synercid®) bacteriostatic or bacteriocidal?
bacteriostatic
124
What adverse events are associated with Quinupristin-dalfopristin (Synercid®) ?
Venous irrtation, GI (nausea vomiting, darrhea), myalgias, arthralgias, rash
