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Protein Synthesis Inhibitors Flashcards

1
Q

Inhibitors of 70S (initiation complex)

A

Oxazolidinones (linezolid)

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2
Q

Inhibitors of 30S (elongation)

A

Aminoglycosides

Tetracyclines

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3
Q

Inhibitors of 50S (elongation) (MSCC)

A

Macrolides
Clindamycin
Streptogramins
Chloramphenicol

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4
Q

Natural aminoglycosides (fungi) GeNTS

A

Gentamycin (G+ cocci)
Tobramycin (pseudomonas)
Neomycin
Streptomycin (TB)

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5
Q

Semisynthetic aminoglycoside

A

Amikacin (kanamycin +)

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6
Q

Aminoglycoside spectrum (SEA)

A

Aerobic gram -
Enterobacteriaceae
Staph

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7
Q

Aminoglycosides NOT effective against (SEA)

A

Strep (unless used with B-L)
Enterococci
ANAEROBES (no oxygen-transport mech)

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8
Q

Aminoglycoside for mycobacteria? (2) (might go back to the S.A.)

A

Streptomycin

Amikacin

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9
Q

AG for gram positive cocci? (grandpas are gentle)

A

Gentamycin

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10
Q

AG dynamics

A

concentration-dependent
persistent effects
high levels MIC –> better efficacy
LARGE ONCE DAILY doses preferred

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11
Q

B-lactam contrast to AG’s

A

Time-dependent vs. AG concentration
So killing observed at different concentrations
Regrowth started almost immediately, unlike persistent AG effects

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12
Q

AG resistance (3)

A

Mutation at ribosome binding site
Enhanced efflux (pseudomonas and G- bugs)
Inactivating enzymes (MOST IMPORTANT) –> plasmid-mediated
e.g. kanamycin inactivated by 8 enzymes
Amikacin (semi-synthetic) only inactivated by 1 bc addition of side group

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13
Q

AG pharmacology

A

Water soluble!
Poor oral absorption, ECF/CNS distribution
Renal elimination
The above are common to all water solubles
IC permeability with long duration of therapy

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14
Q

AG side effects (NO)

A

Nephrotoxicity (accum in cortex, entry via tubular side via PINOCYTOSIS); Must first bind to megalin (on brush border); Megalin sites are saturable –> don’t give in small, frequent doses; Reversible b/c cells can regenerate

Ototoxicity (permeates endolymph) irreversible; once daily high dose may prevent

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15
Q

Main clinical uses of AG’s (B-LETUPS)

A

Plague and Tularemia
Gram negative UTI’s
Combo w/BL’s for PSEUDOMONAS, G-, staph/strep/enterococcal (e.g. ENDOCARDITIS)
Oral neomycin for surgical prophylaxis
2nd line mycobacterial agents (combo w/others)
Rarely effective by themselves
EXCEPT FOR UTI’s (high levels in urine)

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16
Q

In what case are AG’s effective mono therapy?

A

UTI’s

Achieve high conc in urine

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17
Q 
Semisynthetic Tetracyclines (2)
Glycylcycline
A

Doxycycline
Minocycline

Tigecycline

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18
Q

Spectrum of Tetracyclines (my ma climbs spirals w rick)

A

BROAD

G+, G-, Mycoplasma, chlamydia, rickettsia, spirochetes, malaria

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19
Q

Tetracyclines are NOT GOOD FOR

A

Enterococci

Pseudomonas

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20
Q

Which tetracycline for staph and MRSA?

A

Minocycline&raquo_space; doxy

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21
Q

TC dynamics

A

Static
Cidal for pneumococci
TIME-DEPENDENT
Persistent effects

This pattern is shared with macros, chloramph, clinda, streptogrammins

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22
Q

TC resistance

A

EFFLUX
Ribosomal protection (inadequate concentration)
Glycylcyclines active agains all resistance mechs

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23
Q

TC pharmacology

A

Good oral abs
Good tissue dist and IC concentration
Doxy/mino eliminated in urine

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24
Q

TC side effects (tetracy-clean your teeth while you’re still eating, watch out for the candy)

A

Teeth discoloration –> avoid in pregnancy and kids <8y
GI: NVD (DO NOT TAKE ON EMPTY STOMACH)
Oral/vaginal candidiasis

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25
TC clinical use (Rick and Ma lost My CAP at Lyme's St)
``` STI's Borrelia (Lyme's) Ehrlichia CAP (typical + atypical) MYCOPLASMA Rickettsial (Rocky Mt Spotted Fever) Malaria Anthrax prophylaxis Doxy/mino for SSTI's (ESPECIALLY MRSA) ```
26
Chloramphenicol
Nitrobenzene --> acetylation = inactivation | Bacteriostatic b/c reversible binding
27
Chloramph spectrum | What does it not work against? (Lee col Sue)
BROAD | Pseudomonas, Legionella
28
Chloramphen resistance
Plasmid-mediated production of CAT --> acetylates nitro group
29
Chloramphen pharmacology
Highly lipid soluble Good IC conc Elim via glucoronidation in liver and then URINE
30
Water soluble drug elimination? | Lipid soluble drug elimination?
Urine | Liver --> urine
31
Chloramphen SE's (A grey bones)
Bone marrow suppression (reversible) if doses are high and long enough (hits stem cells b/c these are growing and synthesizing proteins) Aplastic anemia - not dose related; via nitroso derivative formed in GI tract Gray syndrome in newborns - vascular collapse bc newbs can't metabolize the chloramph --> widespread inhibition of protein synthesis (hits vessels first)
32
When to use Chloramphenicol? (men are ana's typ)
Salmonella (typhoid fever) Meningitis in B-L allergic pts Anaerobic CNS infections (abscess)
33
Natural macrolide
Erythromycin | Produced by streptomyces
34
Semisynthetic macrolide
Azithromycin | Clarithromycin
35
Macrolide spectrum (no staph GASH)
G+ (strep, pneumococci, not staph) Atypicals H. pylori
36
Why is macrolide action weak in H. flu?
It has an efflux pump
37
Macrolide resistance
Methylation of 23S (Erm genes in Europe) Enhanced efflux pumps (Mef gene, pneumococci in US) Mutation of 50S G- esterases --> inactivation
38
Good option for GAS? | Hit pyogenies with the Tide
Macrolide (low resistance) | S. pneumoniae (20-30% resistant)
39
Macrolide pharmacology
Erythromycin --> acid labile (absorbed less than...) | Azithro/Clarithro --> acid stable (better oral absorption)
40
Macrolide achieve high concentrations where? | Allow for good tx of what?
Lung epithelium | Pneumonia
41
Macrolide elimination (lides slide w the bile)
Liver --> biliary excretion
42
Macrolide SE's (HOver guy)
``` GI INTOLERANCE (NVD) Hepatitis in pregnant women Ototoxicity in high IV doses but DOES NOT DAMAGE THE HAIR CELL --> reversible ```
43
Macrolide clinical use (RASH from your CAP) | DOC for?
``` DOC: OUTPATIENT CAP Respiratory infections Strep in pen-allergic pts Atypical mycobacteria H. pylori ```
44
Macrolide used for prophylaxis of what?
Mycobacterium avian complex
45
Drug for pseudomonas pulmonary exacerbations in CF pts? (thro a zit at the pseudo-films)
Azithromycin Reduces biofilms ("talking") NO direct impact on bug
46
Clindamycin activity (PASS)
Staph/strep; Anaerobes --> B. fragilis >> Toxoplasma; Pneumo. jiroveci
47
B. fragilis drug
Clindamycin
48
Clindamycin not good for? (only normal guys date linda)
Atypicals
49
Clinda resistance
Similar to macrolides except not effluxed
50
Resistance to macrolide and clindamycin suggests presence of which gene?
Erm
51
Resistance to macros but susceptible to clinda suggests presence of which gene?
Mef (efflux)
52
Clinda pharmacology
liver/biliary excretion
53
Clinda SE's (police dept)
Diarrhea | Pseudomembranous colitis
54
C. diff produces which two toxins that lead to pseudomembranous colitis?
Enterotoxin | Cytotoxin (causes damage to bowel)
55
Clindamycin uses (PASST)
``` Anaerobic infections ABOVE THE DIAPHRAGM e.g. lung abscess Strep (with PEN for GAS cellulitis TSS) STAPH (much better than macrolides) including MRSA Toxoplasmosis, pneumocystis ```
56
Oxazolinones
Linezolid Synthetic Binds to 50S and inhibits 70S formation
57
Oxazo spectrum (grandpas are resistant to change)
Gram positive mostly: Staph (MRSA), strep, pneumococci, enterococci (both, including VRE) ``` VRE MRSA (especially in VAP) MRSE Coag-neg staph CNS infections Very expensive ```
58
Oxazo dynamics
Static, but does kill slowly | meaning won't kill if higher concentrations
59
Oxazo resistance (must face binding change)
primarily faecium some in staph MUT in binding site on ribosome
60
Oxazo pharmacology
Excellent CSF levels | Great levels in respiratory tract
61
Oxazo SE's (psycho TAN)
Thrombocytopenia Anemia/neutropenia Long-term use --> peripheral neuropathy Also enhancement of psych drugs
62
Streptogramins (power in #'s)
A: dalfopristin B: quinupristin When used alone STATIC, together CIDAL
63
Streptogramins used for (sven's face)
Staph (MRSA) Strep Enterococcus faecium (VRE) NOT ORALLY ABSORBED
64
Streptogramin SE's (grammas have flabby muscle)
Phlebitis | Myalgias/arthralgias
65
Nitrofurantoin
Urinary agent | NF Reductase --> derivatives bind and reduce protein synthesis
66
NitroF spectrum (UGEE guy)
E. coli Enterococci GBS UTI's (good in urine, destroyed in blood)
67
NitroF resistance
reduced NF reductase activity
68
Nitro pharmacology
Rapid enzymatic degradation | Only adequate conc achieved in URINE
69
Nitro SE's
GI, pulmonary hypersensitivity

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