Antibiotics Flashcards
1
Q
What is the mechanism of action for penicillins?
A
- mimic PBP ligand and irreversibly inhibit transpeptidase
- activate murein hydrolases
2
Q
Penicillins are limited to what bacteria cell populations?
A
those that are growing or proliferating
3
Q
Penicillins are best for which classes of bacteria?
A
gram+, but anti-Staph, anti-pseudomonas, and extended spectrum penicillins are available
4
Q
Penicillins are typically available in what preparations?
A
- although it is acid liable, it is usually given orally
- also available in IV and depot preparations
5
Q
Describe the distribution of penicillins.
A
it doesn’t reach the CNS, eyes, or prostate well
6
Q
How are penicillins cleared and what is its half-life?
A
- cleared via tubular secretion
- half-life of 30-60 minutes unless you add probenecid
7
Q
What drug is often given alongside penicillins to extend their half life? How does this drug work?
A
probenecid inhibits tubular secretion of penicillins, extending their half life
8
Q
Penicillin is a _____-dependent cell killer.
A
time dependent
9
Q
What is ampicillin?
A
an extended spectrum penicillin
10
Q
What is amoxicillin?
A
an extended spectrum penicillin
11
Q
How do extended spectrum penicillins differ from penicillin G or V?
A
- they have more gram- activity
- they are more susceptible to beta-lactamase
12
Q
Name the two important extended spectrum penicillins.
A
- ampicillin
- amoxicillin
13
Q
List the four important anti-Staph penicillins.
A
- methicillin
- nafcillin
- oxacillin
- cloxacillin
14
Q
How do anti-Staph penicillins differ from penicillin G or V?
A
they are beta-lactamase resistant
15
Q
What is methicillin?
A
an anti-Staph penicillin (beta-lactamase resistant)
16
Q
List the four important anti-pseudomonas penicillins.
A
- ticarcillin
- mezlocillin
- piperacillin
- carbenicillin indanyl
17
Q
What is the problem with anti-pseudomonas penicillins? How is this overcome?
A
resistance is emerging so they must be used in combination with ahminoglycosides or fluroquinolones
18
Q
How does MRSA achieve beta-lactam resistance?
A
it altered PBP structure, so penicillin could no longer bind
19
Q
Describe the onset, cross-reactivity, and dose-dependence of the penicillin hypersensitivity reaction.
A
- rapid onset
- dose-independent response
- complete cross-reactivity
20
Q
List three ways bacteria achieve resistance to penicillins.
A
- lack a cell wall or are dormant
- produce a modified PBP that isn’t accessible to penicillin
- produce beta-lactamases
21
Q
What is the mechanism of action of cephalosporins?
A
they are beta-lactams
22
Q
In what ways are cephalosporins better than penicillins?
A
- greater gram- activity
- greater beta-lactamase resistance
23
Q
What are the major side effects of cephalosporins?
A
- renal toxicity (enhanced by ahminoglycosides)
- inject site reaction
- moderate cross-reactivity with PCN-sensitive patients
- disulfiram effect with bleeding disorders (mostly cefotetan and cefoperazone)
24
Q
Which cephalosporin has a disulfiram effect and causes bleeding disorders? How is this compensated for?
A
- cefotetan
- co-administer Vit K
25
List the important first generation cephalosporins.
- cephalothin
- cephalexin
- cefazolin
26
List the important second generation cephalosporins.
- cefuroxime
- cefotetan
- cefactor
27
List the important third generation cephalosporins.
- cefotaxime
- ceftriaxone
- ceftazidimine
28
What is cefepime?
the only fourth generation cephalosporin
29
What is the mechanism of action of aztreonam?
it is a beta-lactam and ICWS
30
List three advantages of aztreonam over penicillin.
- beta-lactamase resistance
- crosses the BBB
- no cross-reactivity for PCN-sensitive patients
31
What is special about the distribution of aztreonam?
it crosses the BBB
32
Aztreonam is effective against which classes of bacteria?
only gram-, it has no gram+ or anaerobe activity
33
What is the mechanism of action of imipenem?
it is a beta-lactam
34
List three advantages of imipenem over penicillin.
- it is broad spectrum
- it crosses the BBB
- it is beta-lactamase resistant
35
Why is imipenem co-adminsitered with cilastatin?
because cilastatin inhibits inactivation of impenem by renal dipeptidase
36
How is imipenem metabolized?
it is inactivated by renal dipeptidase
37
What is meropenem?
a carbapenem (beta-lactam) with renal dipeptidase resistance
38
What is the mechanism of action of clavulanic acid?
it is a beta-lactam
39
What is the mechanism of action of sulbactam?
it is a beta-lactam
40
What is the mechanism of action of tazobactam?
it is a beta-lactam
41
What is the mechanism of action of bacitracin?
it is a ICWS
42
What is the mechanism of action of vancomycin?
it is a ICWS that acts by inhibiting transglycosylation
43
Vancomycin is primarily used for which class of bacteria?
gram+
44
Vancomycin is a preferred treatment for which two difficult to treat infections?
- MRSA
| - C. diff
45
What are the major side effects of vancomycin?
- it enhances the ototoxicity and renal toxicity of aminoglycosides
- it triggers histamine release to cause "red man" syndrome
46
What is "red man" syndrome?
a major side effect of vancomycin caused by histamine release
47
What drug is preferred in the treatment of C. diff?
vancomycin
48
In what preparations is vancomycin available?
- IV for systemic infection
| - oral for C. diff infection
49
What is the mechanism of action of fosfomycin?
it inhibits the cytoplasmic step of cell wall precursor synthesis
50
What receptors mediate fosfomycin uptake?
- glycerophosphate transporter
| - G6P transporter
51
How is fosfomycin cleared from the system?
in the active form via the kidneys
52
What is one dose fosfomycin therapy administered for?
it's active excretion from the kidneys makes it a good therapy for UTI
53
What is the mechanism of action of the polymixin drugs?
they are basic peptides that serve as detergents to disrupt cell membranes
54
What is colistin?
another name for polymixin E, a basic peptide that serves as a detergent to disrupt cell membranes
55
Which class of bacteria are polymixins effective against?
gram- bacteria except neisseria and proteus
56
What are the limitations of polymixins?
they have systemic toxicity and are therefore restricted to topical applications or as salvage therapy for highly resistant bacteria
57
Which three classes of antibiotics are inhibitors of protein synthesis?
- tetracyclines
- macrolides
- aminoglycosides
58
What is the mechanism of action for tetracyclines?
they reversibly bind and inhibit 30S ribosomal subunits as IPS
59
What is the basis for the selectivity of tetracyclines?
bacterial uptake, not ribosomal affinity
60
What are the five major side effects of tetracyclines?
- GI irritation
- photosensitization
- liver impairment
- superinfection
- bone and teeth growth retardation or deformation
61
Against which bacteria are tetracyclines effective.
- broad spectrum
| - particularly used against mycoplasma, chlamydia, rickettsia, and lyme disease
62
Why does tetracycline cause bone deformities?
because it is a chelator of metal ions
63
Describe the distribution of tetracyclines.
- does not reach the CNS or synovial fluid
| - does cross the placenta and enter breast milk
64
List four important tetracyclines.
- tetracycline
- doxycycline
- minocycline
- tigecycline
65
How do most bacteria achieve resistance to tetracyclines?
efflux pumps
66
What is tigecycline?
a newer tetracycline that is resistant to most bacterial efflux pumps but has a black box warning for increased risk of death
67
What is the mechanism of action of macrolides?
they are inhibitors of protein synthesis
68
What is unique about macrolides compared to most other protein synthesis inhibitors?
they can be bacteriocidal at high dose
69
How are macrolides administered?
orally with an enteric coating or as esters because they are acid liable
70
What is special about azithromycin compared to other macrolides?
it has a 2-4 day half life
71
What is the clinical utility of macrolides?
they are used for gram+ infections in PCN-sensitive patients
72
What are side effects of macrolides?
- GI distress
- hepatotoxicity
- DDIs with microsomal enzyme inhibition
73
How do most bacteria achieve resistance to macrolides?
by methylation of rRNA
74
Name the three important macrolides.
- azithromycin
- clarithromycin
- erythromycin
75
What is the mechanism of action of telithromycin?
it is a macrolide-like protein synthesis inhibitor
76
What is telithromycin used to treat?
respiratory tract infections
77
What are the two major side effects of telithromycin?
- inhibits CYP3A4
| - causes QT prolongation
78
Which protein synthesis inhibitors can be bactericidal?
- macrolides at high dose
| - aminoglycosides
79
What is the mechanism of action of aminoglycosides?
- it targets 30s ribosomal subunits
| - causes mRNA misreading, disrupts initiation, and breaks up polysomes
80
What are strep monosomes?
a term used to describe the way streptomycin disrupts bacterial polysomes
81
Which antibiotic was an example of concentration dependent cell killing?
aminoglycosides
82
Describe the side effects of aminoglycosides.
- time and dose dependent
- nephrotoxicity likely reversible
- ototoxicity may be reversible
- causes a neuromuscular blockade at high dose
83
What is gentamicin?
an aminoglycoside effective against pseudomonas
84
List the three most important aminoglycosides.
- gentamicine
- streptomycin
- neomycin
85
What is the mechanism of action of chloramphenicol?
it is an inhibitor of protein synthesis
86
How is chloramphenicol metabolized?
via glucuronidation
87
What are the advantages of chloramphenicol?
- excellent pharmacokinetics
| - resistance is slow to development is minimal
88
Under what circumstances do we use chloramphenicol?
only for typhoid and rocky mountain fever because of SEs
89
Why is our use of chloramphenicol so limited?
- despite good pharmacokinetics and limited resistance, it is high toxic
- can cause aplastic anemia, grey baby syndrome, or fungal superinfection
90
What are the side effects of chloramphenicol?
- GI disturbance followed by fungal superinfection
- aplastic anemia, which is often fatal
- gray baby syndrome
91
What is gray baby syndrome?
a side effect of chloramphenicol due to the poor glucuronidation abilities of babies
92
What is the mechanism of action of clindamycin?
it is an IPS
93
What is clindamycin used for?
- mostly anaerobes
- B. fragilis
- MRSA
- endocarditis prophylaxis
94
What is the primary side effect of clindamycin?
it can cause of C. diff superinfection
95
What are quinupristin and dalfopristin?
they are streptogrim protein synthesis inhibitors
96
Why are streptogrims (quinupristin and dalfopristin) so clinically important?
- they have no cross resistance with any other IPS
| - they are approved for vancomycin and MD resistant E. faecium and MRSA
97
What is the mechanism of action of oxazolidinones?
they inhibit 70s ribosomal formation
98
What is the primary indication of oxazolidinones?
vancomycine resistant E. faecium
99
What is the mechanism of action of sulfonamides?
they are PABA analogs that block folate synthesis via competitive inhibition of dihydrofolate synthesis
100
What is silver sulfadiazine?
a sulfonamide used topically for burns
101
What is sulfasalazine?
a sulfonamide used for ulcerative coilitis
102
Sulfonamides are usually combined with what other therapy?
trimethoprim
103
What are the adverse effects of sulfonamides?
- Steven-Johnson syndrome reaction
- hematuria
- hematopoietic effects
104
How do bacterial cells achieve resistance to sulfonamides?
- overproduction of PABA
- loss of permeability
- modification of dihydropteroate synthesis
105
What is co-trimoxazole?
trimethoprim-sulfamethoxazole combination therapy
106
What two enzymes are used in the folate synthesis pathway?
- dihydropteroate synthase
| - dihydrofolate reductase
107
What is the mechanism of action of trimethoprim?
it is a dihydrofolate reductase inhibitor
108
How do we use trimethoprim clinically?
- monotherapy for UTI
| - with a sulfonamide (co-trimoxazole) otherwise
109
What mediates the selectivity of trimethoprim?
high selectivity for bacteria dihydrofolate reductase
110
What are the side effects of trimethoprim? How do we compensate for this?
- anemia, leukopenia, etc.
| - administer with folinic acid
111
What is nalidixic acid?
the prototype quinolone
112
What is the mechanism of action of quinolones?
they are DNA gyrase inhibitors and target topoisomerase II and IV
113
Name the fluroquinolones.
- ciproflaxacin
- levofloxacin
- ofloxacin
114
What is the primary clinical use of fluroquinolones?
gram- bacteria, and particularly GI and GU infections
115
How are fluroquinolones superior to nalidixic acid?
they are more slowly metabolized and excreted
116
How do bacteria develop resistance against fluoroquinolones?
they modify their DNA gyrases
117
What is the primary urinary tract antiseptic currently in use?
nitrofurantoin
118
How can we increase the utility of nitrofurantoin against UTI?
keep urine pH below 5.5
119
In what cases does nitrofurantoin cause side effects?
cleared so quickly, it has none unless the individual has a renal insufficiency
120
List five first line anti-mycobacterial drugs.
- isoniazid
- ethambutol
- rifampin
- streptomycin (aminoglycoside)
- pyrazinamide
121
The primary drug used against leprosy is what?
dapsone
122
What is the mechanism of action of isoniazid?
it blocks mycologic acid synthesis
123
How is isoniazid used clinically?
- alone for TB prophylaxis
| - in combination for TB treatment
124
Describe the adverse effects of isoniazid.
dose and time dependent nephropathy and hepatotoxicity
125
How does resistance form against isoniazid?
bacteria delete KatG gene, which is needed for activation of isoniazid
126
How is isoniazid metabolized?
via acetylation, and some polymorphisms make individuals fast acetylators requiring a higher dose
127
What is the mechanism of action of ethambutol?
inhibit mycobacterial cell wall glycan synthesis
128
What is the major side effect of ethambutol?
it has a dose-dependent optic neuritis that affects red-green differentiation and visual acuity
129
What is the mechanism of action of rifampin?
it inhibits RNA synthesis
130
How is rifampin used clinically?
- in combination for active TB
| - alone for TB prophylaxis if isoniazid isn't an option
131
What are the side effects of rifampin?
- distinct orange color to body fluids
- flu-like illness
- inducer of microsomal enzymes (alters anticoagulants and oral contraceptive half life)
132
What is pyrazinamide?
an anti-mycobacterial of unknown mechanism
133
What are the disadvantages of using pyrazinamide?
- requires bacterial activation
- contraindicated by pregnancy
- causes gout
134
What is dapsone used to treat?
- leprosy
| - P. jiroveci pneumonia
135
What two drugs are used form TB prophylaxis?
isoniazid and rifampin
