Inhibitors of Protein Synthesis I/II Flashcards
1
Q
7 inhibitors of protein synthesis
A
SMACKBO
streptogramins
macrolides
aminoglycosides
clindamycin
ketolids
broad spectrum antibiotics
oxazolidinones
2
Q
3 Macrolide drugs
A
ACE
erythromycin - oral, IV
clarithromycin - oral
azithromycin - oral, IV
3
Q
Macrolides: G+/G-
A
G+
4
Q
Which subunit of ribosomes do macrolides bind to?
A
50S
5
Q
What is the spectrum of macrolides similar to?
A
Pen G
6
Q
Erythromycin, Clarithromycin, azithromycin: bacteriostatic or cidal
A
Static
7
Q
A majority of G- organisms are resistant to what macrolides?
A
erythromycin
8
Q
Clarithromycin + Omeprazole + amp is one option for trearing
A
H pylori
9
Q
Erythromycin is DOC for which urogenital infection occurring when?
A
Chlamydia occurring during pregnancy
10
Q
Azithromycin is an alternative to tetracycline in treating uncomplicated _____ infections.
A
Chlamydia
11
Q
Erythromycin or tetracycline is effective at treating what “atypical” disease?
A
Mycoplasmal pneumonia
12
Q
Erythromycin is effective in treating what STD when people are allergic to Pen G
A
Syphilis
13
Q
Azithromycin is effective at treating (DOFC) what disease?
A
Legionnaire’s Disease
14
Q
How does resistance work in macrolides?
A
Efflux pumps (drug leaves cell quickly and in increased concentrations)
Methylation of drug binding site on ribosome so drug no longer recognizes binding site
15
Q
Adverse side effects of macrolides?
A
diarrhea
QT prolongation
16
Q
What is the problem with QT prolongation?
A
time it takes heart to contract and then refill with blood before beginning next contraction – if QT is too long, there is the potential for torsades
17
Q
Drug interactions of erythromycin/clarithromycin? (Azithromycin has less of this drug interaction)
A
potent inhibitor of CYP3A4 - increases serum concentrations of other drugs that require CYP3A4 potentially causing toxicity
18
Q
Drug interactions of erythromycin/clarithromycin: prolonged ______. Azithromycin is more favorable.
A
QT segment
19
Q
Macrolides; diarrhea side effect?
A
Erythromycin - most
Azithromycin - next highest
Clarithromycin - least
20
Q
Macrolides: drug interactions due to CYP3A4 inhibition
A
Most: Clarithromycin and Erythromycin
Least: Azithromycin
21
Q
Macrolides: QT prolongation
A
Most: Azithromycin
Least: Clarithro, Erythro
22
Q
Ketolides: bind tightly to how many sites on ribosomal RNA?
What does this mean when comparing to macrolides?
A
2 binding sites
Stronger
23
Q
Name of ketolides
A
Telithromycin
24
Q
Telithromycin is what kind of spectrum antibiotic
A
Broad
25
Telithromycin: static or cidal?
static
26
Telithromycin binds to what ribosomal subunit
50S
27
During what specific type of infections do we use telithromycin?
good against respiratory pathogens including erythromycin and penicillin resistant pneumococci
28
How do you take telithromycin?
orally - very effective as a once a day dose
29
Telithromycin is metabolized by what hepatic cytochrome
CYP3A4
30
Telithromycin can cause what adverse side effects (2)
diarrhea
hepatotoxicity - severe - only on market for community acquired pneumonia
31
Despite serious hepatotoxicity, why is telithromycin still on the market?
community acquired pneumonia
32
Clindamycin reversibly binds to
50S ribosomal subunit
33
Clindamycin is active against what three types of bacteria (general - not names)
aerobic G+ cocci
anaerobic G-
anaerobic G+
34
Clindamycin: static or cidal?
both - depends on concentration and specific susceptibility of organism
35
Clindamycin - used with vanco, nafcillin, or first gen cephalosporin to treat what?
Why used together?
Toxic Shock Syndrome
Because the toxin is produced by the bacteria. If you just used a cidal drug, the bacteria would rupture and toxins would seep out. If you use a protein inhibitor first, the toxins die - then lyse the cells with a cidal drug
36
Clindamycin is used to treat _____. Why?
osteomyelitis -obtains high concentration in bones
37
Clindamycin is a well-known cause of:
pseudomembranous colitis - overgrowth of c-diff. switch to metronidazole
38
Clindamycin can/cannot be used while pregnant/breast-feeding?
cannot
39
Streptogramins: used together
Dalfopristin and Quinupristin -- to make Synercid
40
How do streptogramins work?
inhibit protein syn by blocking ribosomal function
Dalfopristi - binds to 50S early
Quinupristin 0- binds to 50S late
41
How is synercid administered?
IV infusion - two antibiotics act synergistically
42
Independently, dalfopristin and quinupristin are ______. Together, they are ______.
static
cidal
43
Spectrum of synercid
aerobic G+
MDR
MSSA
MRSA
44
Oxazolidinones
Linezolid
45
Linezolid spectrum
aeorbic G+
46
Linezolid: mechanism of action
inhibits protein syn
binds to 50S ribosome
prevents formation of 70S ribosome complex
47
Linezolid is static/cidal?
static
48
Linezolid is a:
| relates to MAO
reversible, non-selective inhibitor of monoamine oxidase?
49
Linezolid indicated for:
Save it for:
G+ infections
MDR strains (like MRSA)
50
Unique bioavailability property of linezolid
Can also be given
oral bioavailability 100%
IV
51
How is linezolid metabolized?
oxidative - does not involve hepatic microsomal oxidative system
52
Important drug interactions
beta-blockers, anesthetics, SSRIs (IMPORTANT ONE), MAO inhibitors
53
Important contraindications for linezolid (2)
hypersensitivity
pheochromocytoma (IMPORTANT - on test)
54
5 aminoglycosides
streptomycin
gentamycin
tobramycin
amikacin
neomycin
55
Aminoglycosides: special physical characteristic
really large
really polar
polarity responsible for pharmacokinetic properties
56
Aminoglycosides: mechanism of action
irreversibly inhibit protein syn of susceptible microorganisms by inhibiting the 30S subunit
57
Aminoglycosides - which subunit of ribosomes
30S
58
Aminoglycosides: cidal/static under aerobic conditions
cidal
59
Aminoglycosides: active transport and O2
to be effective, aminoglycosides first must be _____ ____ (requiring ____) into susceptible bacteria and bind to what subunit?
actively transported
oxygen
30S
60
Are aminoglycosides effective against aerobes or anaerobes? Think mechanism of action.
AEROBES
61
Aminoglycosides spectrum
aerobic G- enteric bacteria
sepsis
endocarditis
62
When do you use gentamycin, tobramycin, amikacin
P. aeruginosa
63
When are neomycin and gentamycin used?
topical application to wounds and burns
64
DOC: aminoglycosides + antipseudomonal penicillin for:
p. aeurginosa (immunocompromised)
Tularemia
65
Why do you use two cidal drugs to attack p. aeruginosa?
Bacteria is an opportunistic infection --> there is synergy that occurs that makes sure the immune system of host does not have to fight (because it cannot)
66
DOC: aminoglycoside + penicillin
enterococci
67
How do aminoglycosides and penicillins work together?
Penicillins create hole in membrane so aminoglycosides (which are very polar and can't get in by themselves) can get through and reach protein for protein inhibition
68
What two types of toxicity are aminoglycosides known for?
ototoxicity
nephrotoxicity
69
What do the levels of ototoxicity and nephrotoxicity depend on?
duration of time the concentration of drug is above threshold
70
Aminoglycosides: concentration-dependent killing
increasing concentrations kill an increasing population of bacteria and an increased rate
71
Do aminoglycosides have a post-antiobiotic effect? If they do, what does this mean?
Yes -- this means that a single large dose has better efficacy than multiple smaller doses - this reduces toxic side effects
72
By giving aminoglycosides only once/day, time spent over the threshold concentration is more/less?
What does this mean?
Less
Less toxic effects.
73
Pharmacokinetics of aminoglycosides
administration?
CNS penetration?
excretion?
IM, IV, topical
NOT GIVEN ORALLY
DO NOT penetrate CNS
Normal kidney excretion
74
Cross resistance of aminoglycosides?
bacteria that acquire resistance to one amino-glycoside may exhibit cross-resistance to all aminoglycosides
75
How does resistance to aminoglycosides occur?
deficiency of ribosomal receptors
lack of permeability of drug into bacteria
enzymatic modification by bacteria
76
Aminoglycosides are usually given alone/in combination with other antibiotics?
in combo
77
What is important when treating pseudomonas?
never give only one antibiotic!
78
3 classes of broad spectrum antibiotics
chloramphenicol
tetracyclines
glycylcyclines
79
Chloramphenicol: what special "broad spectrum" characteristics does it have?
one of the best broad spectrum but also really toxic -- saved for really serious infections when you don't have other choices
80
What fatal adverse effect of chloramphenicol is it known for?
fatal aplastic anemia
81
Chloramphenicol: mechanism of action
reversibly binds to 50S subunit --> protein synthesis is inhibited
82
Chloramphenicol: static or cidal
static
83
Chloramphenicol:
can also inhibit:
mitochondrial protein synthesis in mammalian cells -- this is thought to be the basis of their adverse effects
84
Chloramphenicol: what kind of spectrum?
broad - G+, G-, anaerobes, aerobes, atypicals
85
Can be used for what infections? Is it the DOFC?
Typhoid fever, Meningitis, Rocky Mountain Spotted Fever,
NOT drug of first choice
86
How is Chloramphenicol adminstered?
IV, parenterally
87
What drug has the best CNS penetration without inflammation?
Chloramphenicol
88
What must occur for chloramphenicol to be eliminated/excreted?
metabolized in the liver and conjugated with glucuronic acid to form inactive metabolite which is excreted in the kidney
89
Chloramphenicol: toxicity
hematopoietic problems: dose-dependent
bone marrow suppression - leads to anemia, leukopenia
90
Chloramphenicol toxicity
hematopoietic problems: dose-independent
fatal aplastic anemia -- can develop months after drug has been discontinued OR from a single dose
CAN BE LETHAL
91
Chloramphenicol: what syndrome is associated with this drug and infants?
gray baby syndrome
92
Chloramphenicol: Gray Baby Syndrome occurs how?
inadequate activity of glucuronyl transferase in premature or newborn liver --> cannot be excreted so increased concentrations
93
Chloramphenicol: Resistance works how?
acetyl transferase produced by resistant organisms acetylates and inactivates chloramphenicol - this leads to binding sites being modified.
Efflux pumps
94
Can you give Chloramphenicol to pregnant mothers?
Yes - will not cross placenta
95
Tetracyclines: 3 drugs in this class
tetra, doxy, mono
96
Tetras: which subunit?
30S
97
Tetras: cidal or static?
static
98
Tetras MOA
inhibition of bacterial protein synthesis; binds to 30S and prevents addition of amino acids to the growing peptide chain
99
Spectrum of the tetras?
G+, G-, anaerobes, aerobes, atypicals
100
What are the three organisms resistant to tetras?
B gragilis
proteus
pseudomonas
101
Because tetras are widely used....
resistance is high
102
Tetras:
H. pylori treated how
with metronidazol and bismuth
103
Tetras: DOC for what diarrheal disease?
cholera
104
Tetras: used but not DOC for what atypical pneumonia?
mycoplasma pneumonia
105
Tetras: used but not DOC for what STD?
chlamydia
106
Tetras: used but not DOC for what type of "outdoorsy" infection?
rickettsial infection
107
Doxy is the DOC for what?
rocky mountain spotted fever
108
Tetras: treats what stage of lyme disease?
early
109
Tetras: DOC for what species?
vibrio
110
Tetras: resistance occurs how?
efflux pumps
111
Are all tetras (tetra, doxy, mono) susceptible to same resistance?
No - if efflux pumps are mode of resistance, you can still potentially use mono or doxy. Therefore, tetra resistant strains may be susceptible to doxy, mono, tigecycline.
112
Which of the following is worst for chelation with Ca2+, Fe2+, and Al3+
Tetracycline
113
Which of the tetras has the worst oral absorption?
tetracycline
114
Tetras deposit themselves where?
bone and teeth
115
Which of the tetras are the longest lasting?
Doxy, Mino
longer half life and less frequent administered
116
Adverse effects of tetras?
normal flora changes
bone and teeth issues
photosensitivity
117
To whom should you not give tetras? Why?
prengnat women or children below age of 8
can cross placenta and excreted in breast milk
bone issues in young children
118
Glycylcyclines: name
Tigecycline
119
Glycylcyclines: tigecycline
binds to what subunit
static or cidal
30S
static
120
Glycylcyclines: tigecycline
spectrum similar to what?
tetras; however, tigecycline shows activity against tetra-resistant organisms
121
How is glycylcyclines: tigecycline administerd?
IV
122
Glycylcyclines: tigecycline has activity against wide variety of resistant pathogens
MRSA
MRSE
PRSP
VRE
123
Why is ampicillin given with clavilanate but not vanco?
Vanco does not have beta-lactam ring
