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Inhibitors of Protein Synthesis Flashcards

1
Q

Macrolide Drugs

A

Erythromycin, Clarithromycin, Azithromycin

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2
Q

Macrolide Key Notes

A

G+ (similar to Pen G)
Binds 50S
Bacteriostatic typically, but concentration/organism dependent
Oral absorption, biliary excretion, fecal elimination

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3
Q

Treating H. Pylori

A

Clarithromycin + Omeprazole + Ampicillin

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4
Q

Macrolide Resistance

A 
Efflux Pumps (main resistance)
Methylation of drug binding site (50S)
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5
Q

Macrolide Toxicity

A

GI disturbances- nausea, vomiting, diarrhea, etc. (E>A>C)
QT prolongation (A>E=C)
Drug interactions - CYP3A4 inhibitor (E=C>A)
IV erythro - Ototoxicity
Hepatic changes

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6
Q

Ketolide Drugs

A

Telithromycin (Ketek)

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7
Q

Telithromycin key notes

A

Broad Spectrum
Binds 50S at TWO sites
Bacteriostatic
Oral

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8
Q

Telithromycin Use

A

CAP (Good against respiratory pathogens, ie. erythromycin- and penicillin-resistant pneumococci)

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9
Q

Telithromycin Toxicity

A

Diarrhea, N/V, Dizziness
Contraindicated in patients with Myasthenia Gravis
Drug interactions - Metabolized by CYP3A4

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10
Q

Clindamycin Key Notes

A

Spectrum: aerobic G+ cocci and some anaerobic G- and G+ organisms. G- aerobes and enterococci are resistant.
Binds 50S
Bacteriostatic OR Bactericidal (concentration/organism dependent)
Metabolized by liver, minimally excreted by kidneys
Oral, Parenteral, and Topical

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11
Q

Clindamycin Use

A

OSTEOMYELITIS
Streptococci and staphylococci are extremely susceptible (MRSA).
Toxoplasma Encephalitis (NOT good for Meningitis)
Gram+ anaerobes
NOT for enterococci

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12
Q

Clindamycin Toxicity

A

CDAD (C. Diff Associated Diarrhea) - Well-known cause of pseudomembranous colitis (overgrowth of c. diff)
Rashes, GI disturbances

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13
Q

CDAD Treatment

A

STOP Clindamycin and START Metronidazole (DOC for c diff)

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14
Q

Clindamycin Contraindications

A

Pregnant and Nursing - Crosses placenta and distributed into breast milk

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15
Q

Streptogramin Drugs

A

Dalfopristin; Quinupristin (Synercid)

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16
Q

Streptogramin MOA

A

Dalfopristin - Binds 50S and inhibits EARLY phase

Quinupristin - Binds 50S and inhibits LATE phase

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17
Q

Two drugs that act synergestically

A

Dalfopristin & Quinipristin (Synercid) - Bactericidal

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18
Q

Synercid Use

A

Aerobic G+ including: PCNR S. pneumonia, MDR-streptococci
MSSA and MRSA
Vancomycin resistant enterococcus faecium

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19
Q

Synercid Administration

A

IV

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20
Q

Synercid Adverse Reactions

A

Hepatotoxicity, N/V, pain, pruritus, rash

Drug reactions - Inhibits CYP3A4

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21
Q

Synercid Contraindications

A 
Breast-feeding
Children
Hepatic Disease
Pregnancy
Streptogramin hypersensitivity
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22
Q

Ozazolidinone Drugs

A

Linezolid

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23
Q

Linezolid Spectrum

A

Aerobic G+ organisms

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24
Q

Linezolid MOA

A

Binds 23S RNA of the 50S subunit - unique to this drug
Prevents formation of a functional 70S
Bacteriostatic; except for streptococci (bactericidal)

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25
Inhibitor of MAO (monoamine oxidase)
Linezolid
26
Linezolid Use
``` G+ Infections: Pneumonia Skin infections Vanco-resistant enterococcal (VRE) infections MRSA ```
27
Linezolid Administration
IV or Oral
28
Oral admin is 100%
Linezolid
29
Linezolid Adverse Reactions
Diarrhea, HA, n/v
30
Linezolid Contraindications
Hypersensitivity Pheochromocytoma Drug interactions (ie. MAO inhibitors) Tyramine rich food interactions (aged cheese, pork, smoked or pickled food)
31
Aminoglycoside Drugs
Streptomycin, Gentamicin, Tobramycin, Amikacin, Neomycin
32
Which aminoglycoside is NOT topical?
Amikacin
33
Which aminoglycoside is NOT IV/IM?
Neomycin
34
Which aminoglycoside can be given orally?
Neomycin
35
TB treatment
Isoniazid; Streptomycin is 2nd line; Ofloxacin 3rd
36
Gentamicin, Tobramycin, Amikacin Spectrum
G-
37
Aminoglycoside MOA
Binds 30S | BACTERICIDAL
38
Which drugs require oxygen to be transported into the cell?
Aminoglycosides - Therefore they are only effective against aerobic organisms. Anaerobic are not susceptible.
39
Aminoglycoside spectrum
Almost exclusively for Aerobic G- enteric bacteria (rods), or when there is suspicion of sepsis or endocarditis
40
Streptomycin Uses
Tularemia (rabbit fever) Bubonic plague TB Endocarditis when it is given along with other agents
41
Gentamicin/Tobramycin/Amikacin Use
P. aeruginosa (DOC w/ antipseudomonal PCN)
42
Neomycin and gentamicin use
Topical application of wounds and burns caused by G- organisms
43
DOC for Enterococci infections
Streptomycin or Gentamicin + Pen G or Vancomycin
44
Aminoglycoside toxicity
Ototoxicity and Nephrotoxicity dependent on duration of time the conc of drug is above threshold
45
Which drugs have concentration dependent killing?
Aminoglycosides - Increasing concentrations kill an increasing population of bacteria, and at a more rapid rate
46
Benefit of aminoglycosides
PAE (post antibiotic effect). Single, large dose has better efficacy than multiple smaller doses by reducing the toxic side effects. This also helps with concentration dependent killing
47
Downside of aminoglycosides
None is absorbed orally (only IM/IV and topical) None penetrate CSF readily Normal kidney rapidly excretes all.
48
Aminoglycoside use should be...
In combination with other antibiotics
49
Broad Spectrum IPS Abx
Chloramphenicol, Tetracyclines, Glycylcyclines
50
Chloramphenicol Spectrum
BROAD SPECTRUM | One of the BEST synthetic abx we have, but very toxic. Used for life threatening infections.
51
Chloramphenicol Toxicity
Fatal aplastic anemia (dose-INDEPENDENT) Bone marrow suppression (dose-DEPENDENT) "Gray baby" syndrome - inadequate glucuronyl transferase: can't METABOLIZE
52
Chloramphenicol Uses
RESTRICTED TO LIFE THREATENING CONDITIONS: Typhoid Fever Meningitis (Crosses CNS 100%) - Penicillin is DOC unless allergic Rikettsia, Brucellosis, Rocky Mountain Spotted Fever, Melioidosis Bacterial Conjunctivitis (topical)
53
Chloramphenicol MOA
Binds 50S | Bacteriostatic (can be cidal against certain organisms)
54
Reason for Chloramphenicol Toxicity
Inhibits mitochondrial protein synthesis in host cells!
55
Distribution of Chloramphenicol
Distrubted WIDELY to all tissues, including EYES and CNS - Best CNS penetration of any medication.
56
Metabolism of Chloramphenicol
Metabolized in liver (90%) Conjugated with GLUCURONIC ACID Metabolite excreted in the kidney Potent inhibitor of CYP3A4 and CYP2C19
57
Chloramphenicol Resistance
Acetyl Transferase - Acetylates and inactivates drug Binding site modified Efflux pumps
58
Tetracycline Drugs
Tetracycline (oral/topical) Doxycycline (oral) Minocycline (oral)
59
Tetracycline MOA
Binds 30S | Bacteriostatic
60
Tetracycline Spectrum
BROAD SPECTRUM
61
Tetracycline Resistant Organisms
B. fragilis Proteus Pseudomonas
62
Tetracycline Uses
``` H. Pylori (w/ Metronidazol and Bismuth) Cholera (DOC) Mycoplasma pneumonia (DOC, erythro) Chlamydia (DOC, azithro/erythro) Rickettsia (DOC for rocky mountain spotted fever) Lyme Disease (early DOC, amoxicillin) Vibrio species (DOC) Amebiasis, acne, and gonorrhea (acute) Brucellosis Plague (in combo with aminoglycoside) ```
63
Tetracycline Resistance
Tetracycline is susceptible to Efflux Pumps, but... | Tetracycline resistant strains can be treated with doxy, mino, and tigecycline which are resistant to efflux pumps
64
Which tetracyclines have better oral absorption?
Doxy and Minocycline
65
Chelating drugs
Tetracyclines chelate with Ca, Fe, and Al: DON'T TAKE WITH VITAMINS Can cause dental discoloration and inhibit bone growth
66
Tetracycline Metabolism
Most are metabolized by liver and excreted in urine. Doxycycline is EXCEPTION - Not hepatically metabolized and is excreted in feces. Doxy --> Deuce
67
Long acting tetracyclines
Doxycycline and Minocycline - Require less frequent administration
68
Tetracycline Adverse Reactions
``` GI disturbances Bone growth inhibition/Dental discoloration Liver damage Fanconi syndrome (kidney damage) Photosensitivity Hypersensitivity is UNCOMMON ```
69
Tetracycline Contraindications
Children <8 yrs old Pregnant women Nursing women
70
Glycylcycline Drug
Tigecycline (Tigacil) - Synthetic derivative of minocycline
71
Synthetic derivative of minocycline
Tigecycline
72
Tigecycline administration
IV only!
73
Tigecycline MOA
Binds 30S | Bacteriostatic
74
Tigecycline Spectrum
BROAD Spectrum | Similar to tetracyclines, but shows activity against tetracycline-resistant organisms
75
Tigecycline Uses
MRSA S. epidermidis (MRSE) PCN-resistant S. pneumoniae (PRSP) Vancomycin-resistant enterococci (VRE)
76
Tigecycline Adverse Reactions
Similar to tetracyclines. | Main adverse effect is n/v

Pharmacology Exam 2 (4 decks)

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