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Bugs & Drugs > Protein Synthesis Inhibitors > Flashcards

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
Q

TC clinical use (Rick and Ma lost My CAP at Lyme’s St)

A 
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)
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26
Q

Chloramphenicol

A

Nitrobenzene –> acetylation = inactivation

Bacteriostatic b/c reversible binding

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27
Q

Chloramph spectrum

What does it not work against? (Lee col Sue)

A

BROAD

Pseudomonas, Legionella

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28
Q

Chloramphen resistance

A

Plasmid-mediated production of CAT –> acetylates nitro group

29
Q

Chloramphen pharmacology

A

Highly lipid soluble
Good IC conc
Elim via glucoronidation in liver and then URINE

30
Q

Water soluble drug elimination?

Lipid soluble drug elimination?

A

Urine

Liver –> urine

31
Q

Chloramphen SE’s (A grey bones)

A

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
Q

When to use Chloramphenicol? (men are ana’s typ)

A

Salmonella (typhoid fever)
Meningitis in B-L allergic pts
Anaerobic CNS infections (abscess)

33
Q

Natural macrolide

A

Erythromycin

Produced by streptomyces

34
Q

Semisynthetic macrolide

A

Azithromycin

Clarithromycin

35
Q

Macrolide spectrum (no staph GASH)

A

G+ (strep, pneumococci, not staph)
Atypicals
H. pylori

36
Q

Why is macrolide action weak in H. flu?

A

It has an efflux pump

37
Q

Macrolide resistance

A

Methylation of 23S (Erm genes in Europe)
Enhanced efflux pumps (Mef gene, pneumococci in US)
Mutation of 50S
G- esterases –> inactivation

38
Q

Good option for GAS?

Hit pyogenies with the Tide

A

Macrolide (low resistance)

S. pneumoniae (20-30% resistant)

39
Q

Macrolide pharmacology

A

Erythromycin –> acid labile (absorbed less than…)

Azithro/Clarithro –> acid stable (better oral absorption)

40
Q

Macrolide achieve high concentrations where?

Allow for good tx of what?

A

Lung epithelium

Pneumonia

41
Q

Macrolide elimination (lides slide w the bile)

A

Liver –> biliary excretion

42
Q

Macrolide SE’s (HOver guy)

A 
GI INTOLERANCE (NVD)
Hepatitis in pregnant women
Ototoxicity in high IV doses but DOES NOT DAMAGE THE HAIR CELL --> reversible
43
Q

Macrolide clinical use (RASH from your CAP)

DOC for?

A 
DOC: OUTPATIENT CAP
Respiratory infections
Strep in pen-allergic pts
Atypical mycobacteria
H. pylori
44
Q

Macrolide used for prophylaxis of what?

A

Mycobacterium avian complex

45
Q

Drug for pseudomonas pulmonary exacerbations in CF pts? (thro a zit at the pseudo-films)

A

Azithromycin
Reduces biofilms (“talking”)
NO direct impact on bug

46
Q

Clindamycin activity (PASS)

A

Staph/strep; Anaerobes –> B. fragilis&raquo_space; Toxoplasma; Pneumo. jiroveci

47
Q

B. fragilis drug

A

Clindamycin

48
Q

Clindamycin not good for? (only normal guys date linda)

A

Atypicals

49
Q

Clinda resistance

A

Similar to macrolides except not effluxed

50
Q

Resistance to macrolide and clindamycin suggests presence of which gene?

A

Erm

51
Q

Resistance to macros but susceptible to clinda suggests presence of which gene?

A

Mef (efflux)

52
Q

Clinda pharmacology

A

liver/biliary excretion

53
Q

Clinda SE’s (police dept)

A

Diarrhea

Pseudomembranous colitis

54
Q

C. diff produces which two toxins that lead to pseudomembranous colitis?

A

Enterotoxin

Cytotoxin (causes damage to bowel)

55
Q

Clindamycin uses (PASST)

A 
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
Q

Oxazolinones

A

Linezolid
Synthetic
Binds to 50S and inhibits 70S formation

57
Q

Oxazo spectrum (grandpas are resistant to change)

A

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
Q

Oxazo dynamics

A

Static, but does kill slowly

meaning won’t kill if higher concentrations

59
Q

Oxazo resistance (must face binding change)

A

primarily faecium
some in staph
MUT in binding site on ribosome

60
Q

Oxazo pharmacology

A

Excellent CSF levels

Great levels in respiratory tract

61
Q

Oxazo SE’s (psycho TAN)

A

Thrombocytopenia
Anemia/neutropenia
Long-term use –> peripheral neuropathy
Also enhancement of psych drugs

62
Q

Streptogramins (power in #’s)

A

A: dalfopristin
B: quinupristin

When used alone STATIC, together CIDAL

63
Q

Streptogramins used for (sven’s face)

A

Staph (MRSA)
Strep
Enterococcus faecium (VRE)
NOT ORALLY ABSORBED

64
Q

Streptogramin SE’s (grammas have flabby muscle)

A

Phlebitis

Myalgias/arthralgias

65
Q

Nitrofurantoin

A

Urinary agent

NF Reductase –> derivatives bind and reduce protein synthesis

66
Q

NitroF spectrum (UGEE guy)

A

E. coli
Enterococci
GBS
UTI’s (good in urine, destroyed in blood)

67
Q

NitroF resistance

A

reduced NF reductase activity

68
Q

Nitro pharmacology

A

Rapid enzymatic degradation

Only adequate conc achieved in URINE

69
Q

Nitro SE’s

A

GI, pulmonary hypersensitivity

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