Inhibitors of Protein Synthesis (IPS) Flashcards
1
Q
Prokaryotic ribosome subunits
A
50s and 30s (combined = 70s)
2
Q
7 Inhibitors of PS
A
- Macrolides
- ketolides
- Clindamycin
- Streptogramins
- Oxazolidinones
- Aminoglycosides
- Broad spectrum abx
3
Q
Inhibits 30s
A
Aminoglycosides & tetracyclines
4
Q
Macrolide drugs
A
Erythromycin (oral, IV)
Clarithromycin (oral)
Azithromycin (oral, IV)
5
Q
Macrolide properties
A
G+
reversibly bind to 50s
bacteriostatic; concentration/organism dependent
Oral absorption, biliary excretion, fecal elimination
6
Q
Macrolide elimination
A
Fecal
7
Q
H. pylori alternative tx with macrolide
A
clarithromycin + omeprazole (+ ampicillin)
8
Q
DOC for macrolides
A
Chlamydia- azithromycin (or tetracylcine)
Mycoplasma pneumonia (erythromycin or tetracycline)
Legionella spp (azithromycin + rifampin or quinolone)
Syphilis in those allergic to Pen G
9
Q
Resistance to macrolide
A
efflux pump
methylation of drug binding site (ribosome)
10
Q
Toxicity of macrolide
A
GI sx (clarithro-least, Erythro- most) QT prolongation- torsades Ototoxicity (IV erythro) hepatic changes (jaundice, hyperbillirubinemia, abnormal LFT)
11
Q
QT wave
A
time for heart to contract and refill; represents depolarization and repolarization of ventricles
12
Q
macrolide with least drug interaction
A
Azithromycin
13
Q
Drug with worst drug interactions
A
Erythromycin
14
Q
Erythromycin
A
potent inhibitor of CYP3A4; inhibits hepatic metabolism of other drugs that require CYP3A4, increasing their serum concentrations and potential toxicity
15
Q
Erythromycin drug interactions
A
Carbamazepine Clozapine Cyclosporine Methadone Quinidine Protease inhibitors
16
Q
Macrolide with worst QT prolongation
A
Azithromycin
17
Q
Increased QT when erythromycin is administered with
A
cisapride or pimozide
sparfloxacin or grepafloxacin
18
Q
GI macrolides
A
clarithro < azithro < erythro
19
Q
Drug interactions macrolide order
A
azithro < clarithro = erythro
20
Q
Ketolide drug
A
Telithromycin (ketek)
21
Q
MOA of telithromycin
A
bind to TWO sites on 50s to inhibit protein synthesis
22
Q
Telithromycin properties
A
BROAD-SPECTRUM
static
50s
Good against repiratory pathogens including erythromycin and PCN-resistant pneumococci
activity against intracellular and atypical bacteria
VERY HEPATOTOXIC
23
Q
Kinetics of telithromycin
A
oral
metabolized by CYP3A4
side effects: diarrhea, GI
24
Q
Contraindication of telithromycin
A
myasthenia gravis
25
Telithromycin use
only CAP (not DOC: use macrolide)
26
Clindamycin properties
```
oral, parenteral and topical
50s
G+ cocci, anaerobic G-/G+
Resistant: G- aerobes and enterococci
static or cidal
metabolized by liver, minimally excreted by kidneys
```
27
Clindamycin use
Strep (not enterococci), staph (MRSA); gram + anaerobes (clostridia);
TSS (w/ vanco, nafcillin, or first gen cephalosporin)
OSTEOMYELITIS- obtains high concentration in bone
Toxoplasma encephalitis
28
Toxoplasma encephalitis tx
clindamycin
29
Osteomyelitis tx
clindamycin
30
Clindamycin toxicity
```
well-known cause of pseudomembranous colitis
crosses placenta (avoid in prego and nursing)
```
31
Streptogramin drug
Dalforpristin; quinupristin (synercid) (IV)
32
Synercid mechanism
Dalfopristin: inhibits early protein synthesis
Quinupristi: inhibits late protein synthesis
BACTERICIDAL TOGETHER
33
Synercid use
Aerobic G + including:
PCN-resistant pneumonia, MDR-strep
compicated skin infections due to MSSA or MRSA
VRE
34
VRE tx
synercid
35
Adverse reaction of synercid
hepatotoxicity
| inhibit P450 system (CYP3A4), many metabolic interactions (warfarin, diazepam)
36
Drug interactions of synercid
warfarin, diazepam
37
Contraindication of synercid
```
breast-feeding
children
hepatic disease
pregnancy
streptogramin hypersensitivity
```
38
Linezolid (oxazolidinones) activity
aerobic G+ organisms
39
MOA of linezolid
bind to 50s, preventing formation of 70s ribosome;
bacteriostatic (except for in strep)
Reversible, non-selevtive inhibitor of MAO
40
Inhibitor of MAO
linezolid
41
Linezolid use
```
G+ infections:
bacterial pneumonia
skin infections
VRE
MRSA
```
42
Kinetics of linezolid
IV/oral
| metabolized via oxidation but oxidation is non-enzymatic and does not involve hepatic microsomal oxidative system
43
Doesn't require enzymes fro oxidation
Linezolid
44
Adverse reactions of linezolid
GI
insomnia, constipation, rash, dizziness, fever
MAO inhibitor Sx
superinfection
45
Contraindications of linezolid
hypersensitivity
| PHEOCHROMOCYTOMA
46
pheochormocytoma is a contraindication for
Linezolid
47
Drug interaction of Linezolid
beta-blockers, anesthetics, MAO inhibitors;
antidepressants (amoxapine, maprotiline, mirtazapine, trazodone, tricyclics, SSRIs)
tyramine rich foods (aged cheese, pork, smoked/pickeld foods)
48
Aminoglycoside drugs
```
streptomycin (IV/IM)
gentamicin (IV/IM/Topical)
Tobramycin (IV/IM/topical)
Amikacin (IV/IM)
Neomycin (IV/IM)
```
49
Topical aminoglycosides
gentamicin, neomycin, tobramycin
50
Oral aminoglycoside
Neomycin
51
Streptomycin
TB, second line (isoniazid is first line)
52
Aminoglycoside spectrums
G-, most combo
53
Aminoglycoside properties
polycations, high polarity
54
MOA of aminoglycosides
Irreversibly inhibit protein synthesis by bind to 30s; bactericidal
55
Bactericidal PSI
Synercid, aminoglycosides
56
Functions of aminoglycosides
1. block initiation of protein synthesis
2. blocks translation and elicits premature termination
3. incorporation of incorrect AA
57
Uptake of aminoglycosides
must be ACTIVELY TRANSPORTED (oxygen requiring) to enter and bind 30s
58
Spectrum of aminoglycosides
AEROBIC G- enteric bacteria (rods) (usually combined w/ beta-lactam) or when there is suspicion of sepsis or endocarditis
59
Streptomycin use
tularemia
bubonic plague
TB (2nd line)
endocarditis (combo)
60
Gentamicin/tobramycin/amikacin
effective against P. aeruginosa
61
Neomycin and gentamycin
topical application of wounds and burns cause by gram-negative organism
62
Enterococcus species DOC
aminoglycoside + PCN
63
Synergism of aminoglycoside
PCN
64
Toxicity of aminoglycosides
ototoxicity
nephrotoxicity
neuromuscular weakness
65
Aminoglycoside kinetics
concentration-dependent killing; PAE (single large dose)
IM/IV/topical
none is absorbed enough for oral administration
none penetrates CSF readily
normal kidney rapidly excretes all
66
Resistance to aminoglycosides
deficiency of ribosomal receptors
lack of permeability of drug into bacteria
enzymatic modification by the bacteria
67
Broad spectrum abx
Chloramphenicol
Tetracylcines
Glycylcyclines
68
Chloramphenicol
broad spectrum (synthetic)
69
MOA of chloramphenicol
reversibly bind to 50s inhibiting protein synthesis;
bacteriostatic
inhibits mitochondrial protein synthesis in mammalian cells (adverse effects)
70
Inhibit mammalian mitochondria
chloramphenicol
71
Spectrum of chloramphenicol
broad spectrum: G+/-, aerobes, anaerobes, atypicals
72
Chloramphenicol use
LIFE-THREATENING CONDITIONS ONLY:
typhoid fever
meningitis (Hib, n. meningitidis, s. pneumoniae)
Rickettsia, Brucellosis, Rockey mountain, meliodosis
Bacterial conjunctivitis
73
Chloramphenicol kinets
```
parenteral
widely distributed (eyes and CNS)
metabolized in liver; CONJUGATED W/ GLUCURONIC ACID
excreted in kidney
potent inhibitor of CYP3A4 and CYP2C19
```
74
Conjugated with glucuronic acid
Chloramphenicol
75
100% CNS penetration
Chloramphenicol
76
Inhibitors of CYP3A4
synercid, erythromycin, chloramphenicol
77
Toxicity of chloramphenicol
hetpatopoietic problems:
dose dependent: bone marrow supression
dose-independent: fatal aplastic anemia
Gray baby syndrome
78
Gray baby syndrome
Chloramphenicol- inadequate activity of glucuronyl transferase in premature or newborn liver (w/i 48 hours; discontinue tx to recover)
79
Resistance to chloramphenicol
acetyl transferase: acetylates and inactivates chloramphenicol
binding site modified (acetylated)
efflux pumps
80
Tetracycline drugs
Tetracycline (oral, topical)
Doxycycline (oral)
Minocycline (oral)
81
MOA of tetracycline
inhibition of protein synthesis (30s); bacteriostatic
82
Spectrum of tetracyclines
broad
83
Organisms resistant to tetracyclines
B. fragilis, proteus, pseudomonas
84
Tetracycline use
```
H. pylori: (w/ metronidazol + Bismuth)
cholera (DOC)
mycoplasma pneumonia (DOC, erythro)
Chlamydia (DOC, Azithro/erythro)
Rickettsia (DOC)
Lyme disease (early)
Vibrio (DOC)
```
85
Lyme disease DOC
Early- doxycycline, amoxicillin
| Late- ceftriazone
86
Resistance to tetraycline
efflux pump
87
Tetraycycline resistant strains may be susceptible to
doxycycline, minocycline, tigeycline (poor substrates for efflux pumps)
88
Tetracycline kinetics
oral is adequate but incomplete (D and M are better)
Chelation with Ca, Fe, Al
Deposit in bone and teeth (Ca)
metabolized by liver, excreted through urine and some bile (except doxycycline)
D and M are slowly excreted (less frequent
89
Long acting tetracyclines
Doxycycline and Minocycline
90
Deposit in bone and teeth
Tetracyclines
91
Chelation with Ca, Fe, Al
Tetracyclines
92
Adverse reactions of tetraycyclines
```
normal flora changes
bone and teeth
photosensitivity
liver damage
Fanconi syndrome
```
93
Contraindications of tetracyclines
pregnant women
| CHILDREN <8 YO
94
<8 YO don't give
Tetracyclines
95
Gylcylcycline drug
Tigecycline
96
Synthetic derivative of minocycline; developed to circumvent resistance mechanism
Tigecycline
97
Tigecycline
IV
| binds to 30s; static
98
Tigecycline spectrum
```
broad spectrum (like tetracyclines) but also active against tetracycline-resistant organisms
MRSA, MRSE, PRSP, VRE
```
99
Side effects of tigecycline
similar to tetracyclines; main effect: N/V
