Protein Synthesis Inhibitors Flashcards
(76 cards)
1
Q
30s drugs
A
- tetracyclines: doxycycline
- aminoglycosides: gentamicin
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2
Q
50s drugs
A
- macrolides: eryhromycin, clarithromycin, azithromycin
- clindamycin
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3
Q
Protein synthesis overview
A
- Imitation: the charged imitation tRNA carries fMet to the ribosome which binds to the AUG start codon
- Elongation: a charger tRNA enters the ribosome at the At site, the enzyme peptidyl transferase cleaves the peptide chain form the P site and transfers it to the A site tRNA, the P site tRAN exits the ribosome, the ribosome movies exactly 3 nucleotides (one codon) which moves the tRNA at the A site to the P site (translocation)
4
Q
Imitation of protein synthesis
A
The charged initator tRNA carriers fMet to the ribosome which binds tot he AUG start codon
5
Q
Protein elongation
A
A charged tRNA enters the ribosome at the A site, the enzyme peptidyl transferase cleaves the peptide chain from the P site transfers it to the A site tRNA, the P site tRNA exits the ribosome, the ribosome moves exactly 3 nucleotides (codon) which moves the tRNA at the A site and to the P site (translocation)
6
Q
what is the tetracycline drug
A
Doxycycline.
7
Q
How many rings are in a tetracycline
A
4 fused ring
8
Q
MOA of tetracycline (doxycycline)
A
- bacteriostatic
- blocks protein synthesis by binding to the 30s ribosomal subunit and blocks the access of tRNA to the A site.
No tRNA can get to A site, no docking occurs
9
Q
What drugs block translocation
A
Macs
Clundamycin
50s
10
Q
What do tetracycline do to bacteria
A
Block docking of tRNA
11
Q
How do AGs inhibit bacteria
A
- Formation of initiation complex
- Cause misreading of the code
- Inhibit translocation
12
Q
Translocation
A
Moving from A to P
13
Q
Clinical uses of tetracycline (doxy)
A
- broad spectrum Abx
- limited by resistance
- rickettsia (Rocky Mountain spotted fever) and borrelia (Lyme disease)
14
Q
What drug is good for treating bacterial infections associated with ticks
A
Tetracycline (doxy)
15
Q
Resistance of tetracycline (doxy)
A
Widespread
- accomplished by a Mg++ depends active effluent of the drug by the protein TetA
- pumps drug right back out
16
Q
Absorption of tetracycline (doxy)
A
- should not be taken with dairy food because they chelate with calcium ions
- cannot take with antacids due to chelation with magnesium and aluminum
Binds metals
17
Q
Elimination of tetracycline (doxy)
A
By the kidneys (adjust in renal failure)
Doxy is the exception as it is preferentially excreted via the bile (good for renal failure)
18
Q
What is th exception to renal elimination of tetracycline
A
Doxy can be eliminated by the liver
19
Q
Adverse effects of tetracyclines (doxy)
A
- GI discomfort
- deposition of calcium in bone and teeth
- causes discoloration of teeth
- stunts growth in children -
- phototoxicitiy to exposed skin
20
Q
Why are tetraclyines not good for children
A
Cause stunted growth
21
Q
What is the only alone protein synthesis inhibitory that is bactericidal
A
Aminoglycosides (gentamicin)
22
Q
Is gentamicin 30s or 50s
A
30s
23
Q
MOA of aminoglycosides (gnetamcicin)
A
- bactericidal because of all of the different mechanisms
- entry of drugs into bacterial cells
- block protein synthesis
24
Q
How do aminoglycosides gain entry into bacterial cells
A
- passive diffusion across cell wall
- active O2 dependent transport (low pH or anaerobic conditions prohibit entry)
- transport into cells is enchanted by cell wall active drugs like penicillins or vancomycin and is the likely basis for synergism between these compounds
25
How is transport of a aminoglycosides drug such as gentamicin enhanced
With the addition of a penicillin
26
How do aminoglycosides (gentamicin) block protein synthesis
- bind to 30S ribosomal subunit
- interfere with a invitation copmplex of peptide formation
- induce misreading
- inhibit translocation
- activities occur simultaneously and overall effect is lethal for the cell
27
Clinical use of aminoglycosides (gentamicin)
- Active against aerobic gram negative organisms
| - synergistic use with penicillins-especially important for organisms like pseudomonas
28
How do you kill pseudomonas
With an aminoglycosides (Gentamicin) + penicillin (pipericillin)
29
Resistance of aminoglyvosides (gentamicin)
Can have some, not super important
30
Elimination of aminoglycosides (gentamicin)
Kidney
| Adjust in renal failure
31
Adverse effects of aminoglycosides (gentamicin)
Nephrotoxicity
Ototoxicity
Neuromuscular paralysis
32
Nephrotoxicity in aminoglycosides (gentamicin)
Happens when used for more than 5 days
33
Ototoxicity in aminoglycosides (gentamicin)
- auditory damage=tinnitus, high frequency hearing loss
- vestibular damage-vertigo, ataxia, loss of balance
- Tx greater than 5 days
- do not give with loop diuretics
34
Neuromuscular paralysis in aminoglycosides (gentamicin)
Can cause respiratory paralysis at very high doses
- blocks Ach releases
- Botox like effect
- not good in MG patients
35
What are the macro lines
Erythromycin
Azithromycin
Clarithromycin
“Thromycin”
36
Are the macrolides (thromycin) 30s or 50s
50s
37
MO of macrolides (thromycin)
- baceriostatic
| - block protein synthesis
38
How do macrolides (thromycin) block protein synthesis
Bind to the 50s subunit
| -inhibit the translocation reaction
39
Clinical use for macrolides (thromycin)
- community acquired pneumonia due to strep pneumo and atypical such as legionella, chlamydophila, and mycoplasma
- mycobacterium Avium (MAComplex)
- chalmydia trachomatis (STD)
- alternative to B lactams in allergic individuals
40
Resistance of macrolides (thromycin_
10-15% of strep pneumonia in the US is completely resistant to macrolides (if the strain is penicillin resistant, then 50% will also be resistance to macrolides)
Resistance happens when the binding site has been methylated
41
Adverse effects of macrolides (thromycin)
-epigastric distress, commonly used to increased GI motility and gastric emptying (gastroparesis)
42
What abx is used for people with gastroparesis (such as diabetics)
Macrolides (thromycin)
43
Which macrolides are P450 inhibitors
Erythromycin and clarithromycin
44
Which macrolides are not P450 inhibitors
Azithromycin
| Most popular one for this reason
45
Other protein synthesis inhibitors that do not fall into the other groups
Clindamycin
46
MOA of clindamycin
- binds to the 50S subunit, inhibits translocation
| - macrolides wannabe
47
Clinical use of clindamycin
Anaerobes, especially severe infection due to bacteroides
48
What’s the difference between macrolides and clindamycin
Used for anaerobes like bacteroides
49
Adverse effects of clindamycin
Superinfection of C diff, which causes pseudomembranous colitis
-fever, cramping, abdominal pain
50
What drug can cause a superinfection of C diff
Clindamycin
51
How do you treat a superinfection of C diff caused by clindamycin?
Metronidazole
52
MOA of metronidazole (flagyl)
Don’t really know, think it ends up being a free radial
Targets DNA
53
Is metronidazole bateriostatic or bacteriocoidial
Bactericidal
54
Clinical used of metronidazole
Anaearobes and some parasites
- bactericides, clostridium (difficult, non-difficile) DOC
- trichamonas vaginalis, entamaeba histalytica, giardia lamblia, gardenerella
GET BaC on the METRO, G
55
Elimination of metronidazole
Liver
56
Adverse effects of metronidazole
Metallic taste
| Disulfiram-like effect with alcohol (hangover because of acid aldehyde accumulation)
57
What drugs do we not need to adjust for in renal failure
Ceftriaxone
Doxycylcine
Metronidazole
Antisthaph
58
Intro to fluoroquinolones
Fluorinated quinolone
| Limited to gram negative organisms
59
DOC for bactericides and clostridium
Metronidazole
60
MOA of fluoroquinolones
Inhibition of DNA gyrase (topoisomerase II)
| -makes sure the super coils stay in there and tension will break the DNA
61
Is fluoroquinolones bactericidal or bacterostatic
Bactericidal
62
Clinical uses for fluoroquinolones
Gram negative
63
Why are fluoroquinolones back up drugs
Too many people Rxed I pro for UTIs even though TMX-SFX was DOC
-now there is resistance
64
Generations of fluoroquinolones
1. Not important
2. Ciprofloxacin
3. Levofloxacin
4. Gemifloxacin
65
Of the different generations of fluoroquinolones, which ones are more frame negative and which ones are more gram positive
Gram negative for 1st generation
| More gram positive as you go towards 4th generation
66
Spectrum of fluoroquinolones
- UTIs
- gram negative infections
- CAP (community acquired pneumonia), alt to macs
67
Which fluoroquinolones are used doe community acquired pneumonia
3rd and 4th generations
- levofloxacin
- gemifloxacin
68
Resistance of fluoroquinolones
Mutation of the bacterial DNA gyrase
69
Adverse effects of fluoroquinolones
- black box warning: tendinitis and tendon rupture
- not for kids or pregos because effects on collagen metabolism and cartilage development
- phototoxicity
70
Drug interactions of fluoroquinolones
Avoid antacid
| -chelates metals
71
What drug is a urinary tract antiseptic
Nitrofurantoin
72
MOA of nitrofurantoin
IDK
73
Spectrum of nitrofurantoin
Used for uncomplicated UTIs
| -alt to TMP-SMX
74
DOC for neisseria gonrrhea
Ceftriaxone
75
Drug of choice for treponema (syphillus)
Beneath one Pen G
76
Chlamydia trachomatis
Azithromycin (or doxy)
