Antibacterial Agents III: Protein Synthesis Inhibitors Flashcards
(139 cards)
1
Q
Clindamycin penetrates most tissues well, especially ____, but not well into ____.
A
bone; CSF
1
Q
Pts with myasthenia gravis or that take other neuromuscular blocking agents can have respiratory arrest after taking ______.
A
aminoglycosides
2
Q
What is the mechanism of action for Linezolid?
A
binds to the 23s portion of the 50s ribosome to inhibit early phase protein synthesis
3
Q
What is the mechanism of resistance in the aminoglycosides?
A
chemical mods to the abx that prevents uptake and ribosomal binding (plasmid mediated)
3
Q
Where do the aminoglycosides accumulate?
A
the renal cortex and inner ear
4
Q
_____ are VERY TOXIC!
A
Aminoglycosides
5
Q
Why do ventricular arrhythmias occur with macrolides?
A
they prolong the QT interval
5
Q
What are the mechanisms of chloramphenicol resistance?
A
emergence of mutant strains impermeable to drug; inactivation of bacterial enzymes
5
Q
Why does chloramphenicol cause gray baby syndrome?
A
immature hepatic and renal fxn leads to toxic accumulation of the drug
6
Q
What impairs the absorption of tetracyclines?
A
milk products, Al, Ca, Mg, and Fe salts
6
Q
Tx for Borrelia burgdorferi Lyme disease (early)?
A
doxycycline
6
Q
Quinupristin/Dalfopristin inhibits cytochrome 3A4, which may cause increased plasma levels of _____ (6).
A
- benzodiazepines cisapride 2.. calcium channel blockers 3. carbamazepine 4. cyclosporine 5. HMG CoA reductase inhibitors 6. HIV protease inhibitors
7
Q
Name 3 tetracyclines.
A
- tetracycline 2. doxycycline 3. minocycline
8
Q
Azithromycin is not metabolized; its high tissue penetration and slow release allows _____ dosing.
A
once-daily
9
Q
_____ in aminoglycoside use is usually reversible when the drug is discontinued.
A
Renal toxicity
10
Q
How should clindamycin be taken?
A
food doesn’t affect it
11
Q
Tx for Chlamydia trachoma, C.A. pneumonia, urethritis?
A
azithromycin
11
Q
Which tetracyclines have the best bioavailability?
A
minocycline, doxycycline
11
Q
How do antacids and iron supps interact with tetracyclines?
A
decrease bioavail of the tetracyclines by forming insoluble salts
11
Q
_____ has limited use in the US and is only used for severe infections.
A
Chloramphenicol
11
Q
Tx of Strep pneumonia (C.A. and nosocomial)?
A
Linezolid, Quinupristin/Dalfopristin
12
Q
Tx for C. diptheriae diptheria?
A
erythromycin
13
Q
Avoid _____ if leukopenias, anemia, or thrombocytopenia present bc of bone marrow tox.
A
chloramphenicol
14
Q
Why does admin of aminoglycosides have to be so carefully monitored?
A
they are subject to wide variation of pharmacokinetics, even in pts with healthy kidney function, and have a narrow therapeutic index
15
What is Telithromycin/Ketek?
a ketolide Abx derived from erythromycin
16
Describe the hepatotoxicity via macrolides.
reversible acute cholestatic hepatitis
17
Name 6 drugs that can be toxic in combination with a macrolide.
theophylline, warfarin, methylprednisolone, cyclosporine, SSRIs, benzodiazepines
17
Why is there some selective toxicity with tetracyclines?
mammalian cells have an active efflux mechanism preventing accumulation of drugs, and lack active transport of drugs into the cell
17
Tx of Enterococci (including VRE) bacteremia, endocarditis?
Linezolid, Quinupristin/Dalfopristin
18
Tx for Enterococci bacteremia, endocarditis, intra-abd infections?
gentamycin + penicillin or vancomycin
19
What drug can cause gray baby syndrome?
chloramphenicol
20
\_\_\_\_\_\_ is metabolized in the liver and excreted in the bile.
Erythromycin
21
What is the mechanism of action of clindamycin?
inhibits protein synthesis by binding to the 50s ribosome- prevents translocation of peptidyl tRNA and peptide bond formation
22
How do the tetracyclines work?
reversibly bind to 30s ribosome to prevent access of aminoacyl-tRNA to site
22
Aminoglycosides have ____ killing and a _____ which allows their admin in a single, large daily dose.
concentration-dependent; postantibiotic
22
What are the adverse affects of Linezolid?
minor GI, thrombocytopenia, drug interaction with MAO and SSRI
23
Choose: The macrolides ARE/ARE NOT excreted in breast milk and ARE/ARE NOT ok to use in breastfeeding women.
ARE; ARE
25
When should Telithromycin/Ketek be prescribed?
ONLY in community acquired pneumonia due to Strep. pneumoniae
26
Choose: Chloramphenicol is BACTERIOCIDAL/BACTERIOSTATIC.
normally static, but cidal against bacteriodes, H. influenzae, N. meningitidis
27
How is Linezolid metabolized/distributed/excreted?
nonenzymatic oxidation; well-perfused tissues; renally
28
Tx for Chlamydia trachoma, C.A. pneumonia, urethitis?
doxycycline
28
Name 6 general adverse rxns for the tetracyclines.
1. teeth and bone 2. GI upset 3. photosensitivity 4. yeast/candida overgrowth 5. liver/kidney toxicity 6. drug interactions
29
Aplastic anemia, although rare, can be fatal and appears weeks to months post-\_\_\_\_\_ treatment.
chloramphenicol
30
What drugs does Linezolid interact with?
MAOs, SSRIs
31
Choose: Linezolid is BACTERIOSTATIC/BACTERIOCIDAL.
static
32
Tx for Richettsia rocky mtn spotted fever, Q fever?
doxycycline, chloramphenicol
33
Which tetracycline is choice for pts with renal disease or for breastfeeding mothers?
doxycycline
34
\_\_\_\_\_ should be used to treat severe anaerobic infections.
Clindamycin
36
Tx for Strep and Pneumococci pneumonia and pharyngitis?
any macrolide
37
Tx for Myco. avium pneumonia?
clarithromycin, azithromycin
38
Name 3 adverse rxns for clindamycin.
1. pseudomembranous colitis 2. GI upset or skin rashes 3. impaired liver function, neutropenia (rare)
38
Aminoglycosides have concentration-dependent killing and a postantibiotic effect which allows their admin in a \_\_\_\_\_\_.
single, large daily dose
39
Azithromycin and clarithromycin accumulate in higher concentrations in _____ and \_\_\_\_.
certain tissues (skin, lungs, tonsils, cervix, sputum); macs
40
Tx for Bacillus anthracis anthrax?
doxycycline
41
Tetracyclines can lead to disturbance of normal gut flora, leading to ____ and \_\_\_\_\_.
thrush, vaginitis
41
Tx for MRSA localized cutaneous infection?
clindamycin
42
Tx for Strep. pneumonia, pharyngitis?
clindamycin
43
What are the s/s of gray baby syndrome?
vomiting, abnormal respirations, cyanosis, vasomotor collapse and ashen-gray color
44
Tx for Myco. tuberculosis Tb?
streptomycin + anti-Tb drugs
45
Is clindamycin bacteriocidal or bacteriostatic?
static, but can be cidal against certain orgs and high concentrations
47
Which of the macrolides causes the most GI upset? How?
erythromycin; directly stimulates gut motility
48
How do the aminoglycosides work?
inhibits initiation of protein synthesis by interacting with mRNA on the 30s ribosome- breaks up the polysomes, misreads the code
48
Why does chloramphenicol have a diminished selective toxicity?
it inhibits mammalian mitochondrial protein synthesis in the bone marrow
49
Tx for Bacteriodes fragilis intra-abd. and brain abscesses?
clindamycin, chloramphenicol
50
Choose: Macrolides are BACTERIOSTATIC/BACTERIOCIDAL.
bacteriostatic at normal concentrations
51
Tx for Salmonella typhi typhoid fever?
chloramphenicol
52
\_\_\_\_\_\_\_ inhibits metabolism of phenytoin, oral anticoagulants, and 1st gen oral hyperglycemic agents.
Chloramphenicol
53
What is the absorption, distribution, metabolism, and excretion of chloramphenicol?
rapid and complete from GI tract; widely distributed in all tissues and fluids, inc CNS and CSF; metabolized by glucuronidation or reduction except in fetus and neonate; excreted in breast milk
55
Tx for H. pylori peptic ulcers?
tetracycline
56
\_\_\_\_\_\_ have concentration-dependent killing and a postantibiotic effect which allows their admin in a single, large daily dose.
Aminoglycosides
58
How should each of the macrolides be taken?
1. erythromycin = depends on salt form 2. clarithromycin = doesn't matter- food may help absorb 3. azithromycin = take on empty stomach
59
Tx for H. influenzae URI/bronchitis?
azithromycin, clarithromycin
61
Tetracyclines should be used with caution in pts with \_\_\_\_.
impaired liver function
62
Tx for Vibrio cholera cholera?
doxycycline
63
How does resistance to the macrolides occur?
methylation of the 50S ribosome, preventing binding of drug
65
Tx for Myco. pneumoniae C.A. pneumonia?
any macrolide
66
How does resistance to tetracyclines work?
1. changes in protein receptors or transporters 2. produce proteins to block and protect the ribosome
66
\_\_\_\_\_ penetrates most tissues well, especially bone, but not well into CSF.
Clindamycin
66
What are the important drug interactions with Quinupristin/Dalfopristin?
inhibits cytochrome 3A4
68
\_\_\_\_ is short-acting (t1/2 of 6-8 hours); ____ and _____ are long-acting (t1/2 of 16-18 hours).
tetracycline; doxycycline, minocycline
70
What are the macrolides?
1. erythromycin 2. clarithromycin 3. azithromycin
71
What is the mechanism of action for Quinupristin/Dalfopristin?
inhibits bacterial protein synthesis by binding to the 50S ribosome to inhibit elongation
72
Tx for Clost. perfringens gas gangrene, food poisoning?
clindamycin
73
Tx for Pseudo. aeruginosa (any)?
gentamycin, tobramycin, amikacin
74
Does tetracycline cross into the placental/fetal circulation?
yes
75
Tetracycline is short-acting (t1/2 of \_\_\_\_); doxycycline and minocycline are long-acting (t1/2 of \_\_\_\_\_).
6-8 hours; 16-18 hours
77
Aminoglycosides are _____ at low concentrations and _____ at high concentrations (clinically).
bacteriostatic, bactericidal
79
Tx for Prop. acnes acne?
minocycline, doxycycline, clindamycin
81
Which drug requires oxygen and is therefore ineffective in anaerobic organisms?
aminoglycosides
82
Name the 6 aminoglycosides.
1. streptomycin 2. tobramycin 3. gentamycin 4. amikacin 5. kanamycin 6. neomycin
83
How are the aminoglycosides absorbed, distributed, metabolized, and excreted?
highly polar, so not sig. absorbed after oral admin- use IM- distributed into extracellular fluid- excluded from CNS but accumulates in the renal cortex and inner ear; not metabolized; excreted thru kidneys
84
Tx for H. influenzae otitis media, C.A. pneumonia?
doxycycline
85
Tx of Staph (including MRSA) complicated skin infections?
Linezolid, Quinupristin/Dalfopristin
86
\_\_\_\_\_\_ should be avoided in pregnancy and breastfeeding because it cannot be conjugated by the fetal and neonate liver, causing toxicity.
Chloramphenicol
88
Tx for MSSA osteomyelitis?
clindamycin
89
Pts with myasthenia gravis or that take other neuromuscular blocking agents can have _____ after taking aminoglycosides.
respiratory arrest
90
What happens when an aminoglycoside and penicillin are given together?
the aminoglycoside is inactivated
92
Clarithromycin is ____ eliminated.
renally
93
What is the distribution of the macrolides?
widely except brain and CSF; crosses placenta
94
Tx for H. influenza meningitis?
chloramphenicol
95
How do the macrolides work?
inhibit protein synthesis by binding to the 50s subunit and block translocation of peptidyl tRNA and peptide bond formation
97
Tx for E. coli, Klebsiella, Serratia, Proteus, Enterobacter UTIs, lower RIs, bacteremias, post-surg bowel sterilization, wound infections?
neomycin
99
Chloramphenicol inhibits metabolism of \_\_\_\_, \_\_\_\_, and \_\_\_\_\_.
phenytoin, oral anticoagulants, and 1st gen oral hyperglycemic agents
100
What is the main adverse rxn for clindamycin?
pseudomembranous colitis
101
\_\_\_\_\_\_ is not metabolized; its high tissue penetration and slow release allows once-daily dosing.
Azithromycin
102
\_\_\_\_\_, although rare, can be fatal and appears weeks to months post-chloramphenicol treatment.
Aplastic anemia
103
How is Quinupristin/Dalfopristin administered?
IV only
105
Which drugs interact negatively with tetracyclines?
1. antacids and iron supps 2. phenytoin/barbs/carbamazipines 3. oral anticoagulants
106
How do the aminoglycosides get into the bacterium?
active transport
107
Tx for Staph. aureus cutaneous infections, pneumonia, food poisoning?
doxy, tigecycline
108
How do the tetracyclines affect bones and teeth?
temporarily depresses bone growth and permanently discolors teeth
109
How is clindamycin metabolized and excreted?
metabolized by the liver, then into biliary excretion- also excreted into breast milk
110
Erythromycin is metabolized in the ____ and excreted in the \_\_\_\_.
liver; bile
111
Name 5 adverse rxns to chloramphenicol.
1. bone marrow tox 2. gray baby syndrome 3. GI upset 4. oral or vaginal candidiasis 5. drug interactions
113
Tx for Legionella community-acquired pneumonia?
azithromycin
114
How is Quinupristin/Dalfopristin metabolized and excreted?
hepatic conjugation rxns; biliary excretion into the feces
116
Tx for Moraxella catarrhalis otitis media, c.a. pneumonia?
doxycycline
117
\_\_\_\_\_\_ is renally eliminated.
Clarithromycin
118
What drug do the aminoglycosides interact with?
the β-lactams and penicillin
119
Why are the macrolides only selectively toxic?
they don't bind to the 60S ribosome
120
Where is tetracycline metabolized and excreted?
concentrated in the liver, secreted into bile, excreted into the urine (except doxycycline and minocycline)
121
How does chloramphenicol work?
reversible binding of the 50S ribosome, blocking peptidyl transferase action and incorporation of aas in to the newly formed peptide
122
Tx for N. meningitides meningitis?
chloamphenicol
123
Which macrolides can potentially cause toxicity via drug-drug interactions and why?
erythromycin, clarithromycin- inhibit CYP450- increase plasma drug levels
124
Tx for H. pylori peptic ulcer disease?
clarithromycin plus PPI or H2 antagonist
125
\_\_\_\_ and ____ accumulate in higher concentrations in certain tissues and macs.
Azithromycin; clarithromycin
126
How is Linezolid administered?
orally, food doesn't matter
127
What are the common side effects of Quinupristin/Dalfopristin?
infusion site irritation, arthralgia/myalgia, GI upset, skin rashes
128
\_\_\_\_\_ in aminoglycoside use is irreversible and happens at high frequency in elderly pts and those with impaired renal function.
8th nerve damage
129
What must be monitored in aminoglycoside-receiving pts?
1. plasma drug conc 2. 8th cranial nerve function 3. kidney function
130
Tx for Myco. pneumoniae C.A. pneumonia?
doxycycline
131
\_\_\_\_\_\_ and _____ should only be used for life-threatening infections.
Linezolid and Quinupristin/Dalfopristin
133
What are the 4 main adverse rxns of macrolides?
1. GI upset 2. hepatotoxicity 3. ventricular arrhythmias 4. inhibition of CYP450 causing drug/drug interactions
134
Choose: Tetracyclines are BACTERIOCIDAL/BACTERIOSTATIC.
bacteriostatic
135
Linezolid and Quinupristin/Dalfopristin should only be used for \_\_\_\_\_.
life-threatening infections
136
How should tetracycline be administered?
on an empty stomach
137
What sensitivity rxns can occur with aminoglycoside use?
contact dermatitis, skin rashes, bone marrow depression
138
Tx for B. pertussis whooping cough?
any macrolide
139
Macrolides enter the cell via \_\_\_\_.
passive diffusion
