Ch. 39 Protein synthesis inhibitors Flashcards
1
Q
may cause toxic effects as a result of interaction with mitochondrial mammalian ribosomes
A
chloramphenico or the tetracyclines
2
Q
ribosomes composed of 30S and 50S subunits
A
bacterial ribosomes
3
Q
ribosomes composed of 40S and 60S subunits
A
mammalian ribosomes
4
Q
consists of 4 fused rings with a system of conugated double bonds
A
tertracyclines
5
Q
enter susceptible organisms via passive diffusion and also by an energy-dependent transport protein mechanism unique to the bacterial inner cytoplasmic membrane
A
tetracyclines
6
Q
binds reversibly to the 30S subunit of the bacterial ribosome , preventing binding of tRNA to the mRNA-ribosome complex, thereby inhibiting bacterial proetin synsthesis
A
tetracyclines
7
Q
bacteriostatic antibiotics
against : gram(+) and (-)
protozoa, spirochetes , mycobacteria , atypical
A
tetracyclines
8
Q
tetrayclines treatment
A
acne and chlamydia infections (doxycycline)
9
Q
naturally occuring resistance to tetracyclines
A
efflux pump that expels drug out of the cell
-prevents intracellular accumulation
10
Q
Spirochete: Lyme disease : cause , s/s (signs and symptoms), treatment
A
Borrelia burdorferi, bite of infected ticks,
skin lesions, headache and fever, followed by meningoencephalitis and evetually arthritis
bull’s eye pattern rash with a red outer ring (erhema migrans.
doxycycline
11
Q
Cholera
cause , s/s (signs and symptoms), treatment
A
fecally contaminated food or water (vibrio cholerae)
enterotoxin that produces diarrhea
doxycycline
12
Q
Chlamydial infections
cause , s/s (signs and symptoms), treatment
A
Chlamydia trachomatis
-nongonococcal , urethritis, PID, lymphogranuloma venerum
Chlamydia psittaci
-pneumonia, hepatitis, myocarditis , coma
doxycyline or azithromycin
13
Q
mycoplasma pneumoniae
cause , s/s (signs and symptoms), treatment
A
mycoplasma pneumoniae
community-acquired pneumonia
—-military camps
Macrolide or doxycycline
14
Q
Rocky Mountain Spotted fever
cause , s/s (signs and symptoms), treatment
A
rickettsia rickettsii
-fever, chills, aches in bones and joints
tetracyclines-started early in the disease process
15
Q
dairy products will create nonabsorbable chelates thus decrease oral absorption for ?
-divalent and trivalent cations: mg and aluminum anta acids or iron supplements
A
tetracyclines
16
Q
tetracyclines that are oral and IV
A
minocycline and doxycycline
17
Q
where do tetracyclines concentrate?
A
bile, liver, kidney, gingival fluid, and skin
18
Q
minocycline and doxycycline achieve therapeutic levels in the
A
CSF
19
Q
achieves high levels in saliva and tears, eradicating the meningococcal carrier state
A
minocycline
20
Q
tetracycline is primarily eliminated unchanged in
A
urine
21
Q
not hepatically metabolized
A
tetracycline and doxycycline
22
Q
undergoes hepatic metabolism
A
minocycline
- lesser extent in kidney
23
Q
in renally compromised patients we prefer?
because?
A
doxycycline
because eleminated via bile into feces
24
Q
adverse effects of tetracyclines
A
gastric discomfort, calcified tissues, hepatotoxicity , phototxicity (severe sunburn), vestibular dysfunction, pseudotumor cerebri,
25
Contraindication of tetracyclines:
less than 8yrs of age
pregnant
lactation
26
tetracycline should be taken on an empty or full stomach?
empty stomach
27
why is tetracycline CI in the kids less than 8yrs of age
deposition in the bone and primary dentition occurs during the calcification process in growing children
-discoloration and hypoplasia of teeth and temporary stunting of growth
28
why do people taking tetracycline and demeclocycline need to wear adequate sun protection?
phototoxicity
| --severe sunburn
29
minocycline and doxycycline have a common adverse effect, what is it?
vestibular dysfunction,
| dizziness, vertigo, and tinnitus
30
benign intracranial hypertension : headache and blurred vision
tetracyclines
31
Protein inhibitor Group: tetracyclines
demeclocycline
doxycycline
minocycline
tetracycline
32
Protein inhibitor Group: Aminoglycosides
drivin a "Stang"!
Streptomycin, tobramycin, amikacin, neomycin, amikacin, gentamicin
33
Protein inhibitor Group: Macrocyclic
think "Mother Fucker"
thus, Macrocyclic:
-Fidaxomicin
34
Protein inhibitor Group: Macrolides/Ketolides
azithromycin,
clarithromycin
erythromycin
telithromycin
35
Protein inhibitor Group: Lincosamides
clindamycin
36
Protein inhibitor Group: oxazolidinones
linezolid
37
Protein inhibitor Group: others
cloramphenicol
| quinupristin/dalfopristin
38
what are the Protein inhibitor Group?
```
tetracyclines
glycylcyclines
aminoglycosides
macrolides/ketolides
macrocyclic
oxazolidinones
```
39
Protein inhibitor Group: Glycylcyclines
tigecyclines
40
- minocycline derivative
- treatment of complicated skin and soft tissue infections
- intra-abdominal infections
Tigecycline
41
tigecycline MOA:
bacteriostatic
- reversibily binding 30S ribosomal subunit
- inhibits protein synthesis
42
resistant to MRSA (methicillin resistant-staphylococci), multi-drug resistant streptococci, Vancomycin-Resistant Enterococci (VRE), Extended Spectrum B-lactamase- producing gram(-) bacteria, ACINETOBACTER BAUMANNI, and many anaerobic organisms
-
Tigercycline
43
tigecycline is not active against
morganella
proteus
providencia
pseudomonas species
44
resistance of tigecycline is due to
overexpression of efflux pumps
45
dose reduction is recommended in sever hepatic dysfunction
tigecycline
| -route of elimination is biliary/fecal
46
poor option for bloodstream infections
tigecycline
47
acute pancreatitis , fatality, nausea, vomiting , photosensitivity, pseudotumor cerebri, discoloration of permanent teeth when used during tooth development, teratogenic
adverse effects for tigecycline
48
elevation in liver enzymes and creatinine
tygecycline
49
decrease the clearance of warfarin and increase prothrombin time
tygecycline
| -monitor closely when tigecycline is coadministered with warfarin.
50
aminoglycosides treatment
serious infections due to aerobic gram(-) bacilli
| -clinical utility is limited by serious toxicities
51
diffuse through porin channels in the outer mebrane of susceptible organisms
aminoglycosides
52
bind the 30S ribosomal subunit
- interfere with assembly of the functiional ribosomal appartus
- cause the 30S subunit of the completed ribosome to misread the genetic code
- distrupt protein synthesis
- bacteriostatic
aminoglycosides
53
Cmax (concentration max) is 8-10 times the MIC (minimum inhibitory concentration)
- exhibit postantiobiotic effect (PAE)
- --larger the dose . longer the PAE
aminoglycosides
54
dosages for aminoglycosides
a single dose daily
| -reduces risk of nephrotoxicity
55
effective:
aerobic gram(-) bacilli (AeG(-)b)
multi drug resistance (MDR): P. aueruginosa, Klebsiella pneumoniae, Enterobacter sp,
aminoglycosides
56
cobined with B-lactam antibiotic provides synergistic effect, treatment of Enterococcus faecalis, and enterococcus faecium infective endocarditis
aminglycosides
57
4 commonly used aminoglucosides
I have my "GATS" locked and loaded
streptomycin, tobramycin, amikacin, gentamicin
58
efflux pumps, decreased uptake or modificiation and inactivation by plasmid associated synthesis of enzymes
resistance to aminoglycoside
59
all aminoglycosides must be given parenterally except
neomycin
60
neomycin administration
| why?
-topically for skin infections or
-orally for bowel preparation prior to colorectal surgery
parental will cause severe nephrotoxicity
61
concentrations in the CSF are inadequate
| -CNS infection which route?
```
aminoglycosides
intrathecal route (IT)
```
62
dose adjustments due to renal dysfunction
aminoglycosides
63
while on aminoglycosides the elderly are
susceptible to nephrotoxicity and ototoxicity
64
adverse effects of aminoglycosides are
ototoxicity
nephrotoxicity
neuromuscular toxicity
allergic reactions
65
accumulates in the endolmph and perilymph of the inner ear
ototoxicity
adverse effects of aminoglycosides
-cisplatin or loop diruretics
66
distrupts calcium-mediated transport process of the PCT cells
adverse effects of aminoglycosides
| -nephrotoxicity
67
calcium gluconate or neostigmine can reverse the block that causes
- neuromusclar paralysis caused by aminoglycosides
| - myasthenia gravis patients are at risk
68
contact dermititis is common reaction
adverse effects of aminoglycosides
neomycin
allergic reaction
69
alternative for individuals with an allergy to B lactam antibiotics
macrolides
| -erythromycin
70
macrocyclic lactone structure
| - one or more deoxy sugars
macrolides
71
methylated for of erythromycin
clarithromycin
72
have larger lactione ring
azitrhromycin
73
first ketolide antimicrobial agent
telithromycin
74
active against many macrolide-resistant gram(+) strains
Ketolides
| -telithromycin
75
bind irreversibly to 50S subunit of bacterial ribosome, inhibiting translocation steps of protein synthesis
microlides/ketolides
76
Cornybacterium Diphtheriae
Erythromycin or penicillin
77
Legionnaires disese
| -Legionnellosis
fluroquinoloones or azithromycin
78
Mycoplasma pneumonia
atypical pneumonia
| azithromycin or doxycycline
79
mycobacterium avium complex
| MAC
azithromycin in combination with:
rifampin and ethambutol
-once weekly azithromycin is used as MAC prophylaxis in patients with AIDS
80
Chlamydial infections
Azithromycin or doxycycline
81
- used in patients with penicillin allergy
| - effective towards many of the same organisms as penicilin G
Erythromycin
| -penicillin G alternative
82
effective against Haemophilus influenzae
erythromycin similairity
clarithromycin
83
chlamydia, legionella, moraxella, ueraplasma species, helicobacter pylori, erythromycin
Clarithromycin
84
less active against streptococci and staphylococci than erythromycin , far more active against respiratory infections due to H. inflenzae and moraxella catarrhalis
AZITHROMYCIN
85
extensive use of azithromycin results in
growing streptococcus pneumoniae resistance
86
resistance to macrolides is associated with
the inability of the organisms to take up the antibiotic
presens of efflux pumps decreaseed affinity of the 50Sribosomal subunit for the antibiotic, methylation of an adenine in the 23Sbacterial ribosomal RNAin gram(+) organisms presence of gram(-) organisms such as enterbacteriaceae
87
clarithromycin and azithromycin share some cross-resistance with
erythromycin
88
telithromycin may be effective against
macrolide organisms
89
erythromycin and azithromycin are available in
IV
| enteric coated tablets
90
interaction with the cytochrome P450 system
| -interference with theophyllline statins , antiepileptics reported for clarithromycin
erythromycin and telithromycin
91
adverse effects of macrolides/ketolides
-GI distress and motility
-cholestatic jaundices
----erythromycin
-ototoxity
---erythromycin (high dosages)
------Azithromycin
-
92
contraindications of macrolides/ketolides
- hepatic dysfunction( erythromycin, telithromycin, azithromycin)
- proarrhythmic agents
93
Drug interactions of macrolides/ketolides
interaction with digoxin
| -inhibit hepatic metbolism
94
macrocyclic antibiotic
Fidaxomicin
95
distrupting bacterial transcription
fidaxomicin
96
very narrow spectrum of activity limited to gram(+) aerobes and anaerobes
fidaxomicin
97
used primarily for colstridium difficile
| -remains with the GI tract
fidaxomicin
98
angioedema, dyspnea and pruritis hypersensitivity
fidaxomicin
99
restricted to life-threateninng infections for which no alternatives exist
chloramphenicol
100
binds revisebly to bacterial 50S ribosomal subunit and inhibits protein syntheses at the peptidyl transferase reactions
chloramphenicol
101
high chloramphenicol level circulating
bone marrow toxicity
102
chlamydiae, rickettsiae, spirochetes, and anaerobes
| -bacteriostatic
chloramphenicol
103
decreased ability to penetrate the organism and ribosomal binding site alterations
resistance of chloramphenicol
104
adverse effects of chloramphenicol
anemias, gray baby syndrome, drug interactions with warfarin and phenytoin(elevates concentration)
105
gray baby syndrome
cyanosis
deperessed breathing, cardiovascular collapse and death,
adults can exhibit this if taken in high doses
---
106
anemia from AE of chloramphenicol
- glucose-6-dehydrogenase deficiency and dose-realted anemia
| - hemolytic anemia
107
clidamycin treat
infections cause by gram(+) organisms, includin MRSA and streptococcus and anaerobic bacteria
108
C. difficile is always resistant to
clindamycin
109
common adverse effect of clindamycin
diarrhea caused by overgrowth of c. difficle
110
treatment of c. difficle?
metronidazole and vancomycin
111
quinupristin/dalfopristin is reserved for the treatment of ?
| -in the absence of other therapeutic options
vancmycin-resistent enterococcus faecium VRE
112
distrupts enlongation interfering with addition of new amino acid to the peptide chain
dalfpristin and quinupristin
113
active primarily against gram positive cocci . primary treats E. faecium , VRE strains
-not effective against E. faecalis
quinupristin/dalfopristin
114
plasma mediated actyltransferase inactivates
| active efflux pump can decrease levels of the antibiotics
dalfopristin
| -resistance mechanism
115
injected intravenously
| -excretion in feces=hepatic metabolism
quinupristin/dalfopristin
116
excretion in feces
hepatic metabolism
| biliary route
117
adverse effects of quinuprist/dalfopristin
hyperbilirubinemia
| 25%
118
comats ressitant gram(+) organisms such as methicillin resistant staphylococcus aureus , VRE, penicillin resistant streptococci
linezolid
119
binds to the bacterial 23S ribosomal RNA of the 50S subunit, inhibiting formation of the 70S intiation complex
linezolid
120
against corybacterium and listeria monocytogenes
moderately active against M tuberculosis
-bacteriostatic
linezolid
121
alternative to daptomycin for infections caused by VRE
linezolid
122
linezolid is not recommended to treat
MRSA bacteremia
123
resistance to S. aureus and enterococcus sp
cross-resistance with other protein inhibitors does not occur
Linezolid
| -resistance
124
oral administration, iv, metabolized via oxidation, no dose adjustments for renal or hepatic dysfunction
linezolid
125
Adverse Effects of linezolid
GI upset, nausea, diarrhea, headach, rash
- thrombocytopenia-->10 days
- irreversible peripheral neuropathies and optic neuritis (BLINDNESS)----> 28 days
126
possesses nonselective monoamine oxidases activity and leads to serotonin syndrome if given with tyramine-containing foods, selctive serotonin reuptake inhibitors, or MAO inhibitors
linezolid
