Protein Synthesis Inhibitors Flashcards
1
Q
inhibits subunits of peptidoglycan
A
Cycloserine
2
Q
hinders the elongation of peptidoglycan
A
Vancomycin
3
Q
interferes with transport of precursors across plasma membrane
A
Bacitracin
4
Q
Inhibition of transcription and DNA replication
A
Nucleic acid synthesis
5
Q
sulfa drugs block PABA to folic acid used to make nucleotides by competitive inhibition of enzyme trimethoprim and sulfamethoxazole SXT
A
Sulfonamides
6
Q
bind to 30s subunit blocks translation and misreading of mRNA
A
Aminoglycosides - (streptomycin, gentamicin)
7
Q
bind to 30s subunit and block attachment of tRNA
A
Tetracycline
8
Q
binds to 50S subunits and prevents peptide bonds from being formed
A
Chloramphenicol
9
Q
- bind to 50s subunits and prevents the continuation of protein synthesis - used in many G(+) and walking atypical pneumonia instead of penicillin
A
Macrolides
10
Q
binds with phospholipids in membrane - not as selectively toxic - topical
A
Polymyxin
11
Q
•Inhibition of enzymatic activities
A
Like sulfa and PABA blocked to folic acid
12
Q
Cell membrane
A
Polyxmyxins
13
Q
Cell wall inhibitors
A
Bacitracin Cephalosporin Cycloserine Fosfomycin Penicillin Isoniazid Vancomycin
14
Q
Inhibit replication and transcription
Inhibit gyrase
A
Ciprofloxacin ( quinolones )
15
Q
Inhibit RNA polymerase
A
Rifampin
16
Q
Protein synthesis inhibitor
Site of action is 50S subunit
A
CECO
Cholorampenicol
Erythromycin
Clindamycin
Oxazolidinones
17
Q
Protein synthesis inhibitor
30s sub unit is the location
A
ATSA
Aminoglycosides
Tetracycline
Streptomycin
Amikacin
18
Q
Blocked pathways and inhibit metabolism
A
Sulfonamides
Trimethoprim
19
Q
Protein synthesis inhibitor
Usually act at the _________ level, taking advantage of the major differences between prokaryotic and eukaryotic ribosome structures
A
ribosome
20
Q
the point of entry for the aminoacyl tRNA
A
A site
21
Q
where the peptidyl tRNA is formed in the ribosome.
A
P site
22
Q
the exit site of the now uncharged tRNA after it gives its amino acid to the growing peptide chain.
A
E site
23
Q
Initiation
involves formation of an initiation complex that contains
A
mRNA,
both subunits of ribosomes and
the first aminoacyl-tRNA (formyl-methionyl tRNA)
24
Q
synthesis of the first peptide bond to addition of the last amino acid.
A
Elongation
25
polypeptide is transferred from peptidyl-tRNA in the P site to aminoacyl-tRNA in the A site
Peptide bond formation
26
moves ribosome one codon; places peptidyl-tRNA in the P site; deacylated tRNA leaves via the E site; A site is empty for next aa-tRNA
Translocation
27
•encompasses the release of the completed polypeptide chain and dissociation of the ribosome from the mRNA.
Termination
28
the charged tRNA unit carrying amino acid 6 binds to the acceptor site on the 70S ribosome.
Step 1
29
The peptidyl tRNA at the donor site, with amino acids 1 through 5, then binds the growing amino acid chain to amino acid 6 (peptide bond formation)
Step 2
30
The uncharged tRNA left at the donor site is released
Step 3
31
the new 6-amino acid chain with its tRNA shifts to the peptidyl site (translocation)
Step 4
32
bind to the 50S subunit and block peptide bond formation (step 2).
Chloramphenicol (C) and macrolides (M)
33
bind to the 30S subunit and prevent binding of the incoming charged tRNA unit (step 1).
Tetracycline
34
50 S INHIBITORS
```
●Chloramphenicol
●Macrolides (Erythromycin)
●Clindamycin
●Oxazoladinones (linozelid)
●Streptogramins
```
35
30 s inhibitors
Aminoglycosides
| Tetracycline
36
Older Aminoglycosides
* Streptomycin
| * Kanamycin
37
Newer Aminoglycosides:
```
●Gentamicin
● Netilmicin
●Tobramycin
●Sisomicin
●Neomycin
●Paromomycin
●Amikacin
```
38
Aminoglycosides
Antimicrobial spectrum
```
•Gram (-) Aerobic Bacilli
•Beta-lactamase producers:
Staph. aureus
N. gonorrhea
•Mycobacteria
```
39
Aminoglycosides MOA
* Irreversible inhibitors of protein synthesis
| * Exact mechanism for bactericidal activity unknown
40
used to achieve bactericidal activity in treatment of enterococcal endocarditis
Penicillin plus aminoglycosides
41
Penicillin plus aminoglycosides
to shorten duration of therapy for
viridans streptococcal & staphylococcal endocarditis
42
AMINOGLYCOSIDES ADVERSE EFFECTS
All are ototoxic & nephrotoxic
43
Aminoglycosides that can cause ototoxicity
Neomycin, Kanamycin & Amikacin
44
Aminoglycosides that cause nephrotoxicity
vancomycin & amphotericin
45
Aminoglycosides
Most nephrotoxic
Neomycin, Tobramycin, Gentamicin
46
Aminoglycosides that can causes most ototoxic
Neomycin, Kanamycin, Amikacin
47
Aminoglycosides
•Respiratory Paralysis
–In very high doses, can produce a curarelike effect with neuromuscular blockade
Reversed by
Ca gluconate or neostigmine
48
•Mainly used as 2nd line agent for the treatment of TB at 0.5-1 g/d , IM or IV.
Streptomycin
49
In plague, tularemia and sometimes brucellosis:
Streptomycin
50
Streptomycin + penicillin
for enterococcal endocarditis and 2 week therapy of viridans streptococcal endocarditis
51
Streptomycin + penicillin can cause
pain at the injection site, fever, skin rashes and other allergic reactions
52
Streptomycin + penicillin most serious toxic effect
Vestibular dysfunction
53
Streptomycin + penicillin if given during pregnancy, can cause
deafness in the newborn
54
•effective against both gram –positive and gram-negative organisms
Gentamycin
55
very similar to the C1a component of gentamicin
Sisomicin
56
Gentamycin –inhibits in vitro many strains of
staphylococci and coliforms and other gram-negative bacteria
57
active alone, but also as a synergistic companion with β-lactam antibiotics
Gentamycin
```
Escherichia coli ,
Proteus ,
Klebsiella pneumoniae,
Enterobacter,
Serratia ,
Stenotrophomonas ,
and other gram-negative rods that may be resistant to multiple other antibiotics.
```
58
Gentamycin Like all aminoglycosides, it has no activity against
anaerobes
59
relatively resistant to gentamicin
Streptococci and entero cocci
60
Gentamycin in combination with Nafcillin in
selected cases of staphylococcal endocarditis
61
Neither gentamicin nor any other aminoglycosides should be used for single agent therapy of
pneumonia
62
–treatment of infected burns, wounds, or skin lesions
| –prevention of intravenous catheter infections.
Gentamicin sulfate 0.1% - 0.3% cream, ointment
63
Gentamicin
partly inactivated by purulent exudates
Topical gentamicin
64
Gentamicin Intrathecal:
obsolete
65
Gentamicin adverse effect
* Nephrotoxicity is reversible and usually mild
* Ototoxicity is Irreversible manifested as vestibular dysfunction
* hypersensitivity reactions are uncommon
66
Antimicrobrial spectrum and pharmacokinetic properties identical to gentamicin
Tobramycin
67
Tobramycin Slightly more active against pseudomonas but not to
E. faecium
68
Tobramycin AE
Ototoxicity
| Nephrotoxicity
69
* semisynthetic derivative of kanamycin
| * resistant to many inactivating enzymes
Amikacin
70
Strains of multiple drug resistant tuberculosis, including Streptomycin resistant are usually susceptible
Amikacin
71
Amikacin AE
Nephrotoxic and ototoxic (auditory portion of CN VIII)
72
shares many characteristics with gentamicin and tobramycin
Netilmicin
73
* Also Paromomycin
| * Used for bowel preparation for elective surgery
Kanamycin and neomycin
74
Too toxic for parenteral use, now limited to topical and oral use
Kanamycin and neomycin
75
applied on infected surfaces or injected into joints, pleural cavity, tissue spaces or abscess cavities where infection is present.
K and N
76
–applied to infected skin lesions or in the nares for suppression of staphylococci
Ointments (Neomycin-Polymyxin-Bacitracin combination)
77
K and N AE
Nephrotoxic and ototoxic ( Auditory dysfunction)
78
Sudden absorption of postoperatively instilled kanamycin from the peritoneal cavity (3-5 g) has resulted in
curare-like neuromuscular blockade and respiratory arrest
–Calcium gluconate and neostigmine can act as antidotes
79
* chemically related to the aminoglycosides
* binds at the 30 S subunit (bacteriostatic)
* dispensed as the dihydrochloride pentahydrate for IM injection
Spectinomycin
80
•used solely as an alternative treatment for gonorrhea in patients who are allergic to penicillin or whose gonococci are resistant to other drugs
Spectinomycin
81
Short acting tetracycline
Tetracyline, Oxytetracycline, Chlortetracycline
82
Intermediate acting tetracycline
Demeclocycline, Methacycline
83
Long acting tetracycline
Doxycycline, Minocycline
84
– – carrier state of Meningococcal infections, N. asteroides, N. gonnorhea
Minocycline
85
Tetracycline MOA
* binds to 30 S and prevents attachment of aminoacyl tRNA, prevents the addition of amino acids to the growing peptide
* Bacteriostatic
86
–Must not be taken with dairy products or antacids
| –Cross placenta, excreted in milk
Tetracycline
87
Tetracycline DOC
M. pneumoniae, Chlamydia, ricketssiae, spirochetes
88
Tetracycline No longer use in
gonococcal dse. (resistance)
89
Tetracycline In combination regimens for
gastric & duodenal ulcer due to H. pylori
90
Other clinical use of tetracycline
•Borrelia burgdorfi (Lyme disease), Ureaplasma, Acne, Tularemia, Cholera, Leptospirosis, Protozoal infections
91
200 mg orally daily for 5 days – can eradicate the meningococcal carrier state
Minocycline
92
* – inhibits the action of ADH in the renal tubule
| * treatment of inappropriate secretion of ADH or similar peptides by certain tumors
Demeclocycline
93
Tetracycline toxicity
* Renal toxicity
* local tissue toxicity, photosensitization, GI distress, discolors teeth,
* inhibits bone growth in children, potentially teratogenic, hepatotoxicity,
* vestibular toxicity
94
50s inhibitors
* CHLORAMPHENICOL
* MACROLIDES
* CLINDAMYCIN/LINCOMYCIN
* STREPTOGRAMINS
* OXAZOLADINONES
95
Chloramphenicol •Bactericidal
| –
H. influenzae, N. meningitides, B. fragilis
96
Chloramphenicol MOA
* attaches at P sites of 50 S subunit of microbial ribosomes
* inhibits functional attachment of amino-acyl end of AA-t-RNA to 50 S subunit
* inhibits peptidyl transferase step
97
Choramphenicol more effective than Tetracyclines against
Typhoid Fever and other Salmonella infections
98
Chloramphenicol AE
•GIT, oral or vaginal candidiasis, irreversible aplastic anemia, reversible bone marrow depression, Gray Baby Syndrome
99
Old gen macrolides
Erythromycin
100
New generation macrolides
, , Clarithromycin, Azithromycin, , Ketolides
101
has a narrow Gram (+) spectrum similar to Pen. G.
Erythromycin
102
Erythromycin •Also active against
Chlamydia and Legionella organisms
103
Macrolides MOA
binds to the P site of the 50 S bacterial ribosomal subunit.
104
poor CSF penetration
| Macrolides
Erythromycin
105
Erithromycin AE
GIT dysfunction, intrahepatic cholestatic jaundice
106
Erthromycin erythromycin metabolites can inhibit
cytochrome p450 enzymes
107
* hydroxylated derivative of erythromycin
* more active against Gram (+) pathogens, Legionella and Chlamydia than Erythromycin
* lower frequency of GIT effects, less frequent dosing
Clarithromycin
108
* more active than erythromycin against several Gram (-) pathogens
* maintains high concentrations for prolonged periods into a number of tissues (lungs, tonsils, cervix)
Azithromycin
109
Community acquired pneumonia –
Azithromycin
110
Azithromycin
does not inactivate cytochrome p450 enzymes and free of the drug interactions that occur with erythromycin and clarithromycin
111
•: A is the 1st letter, thus aminoglycosides inhibit Initiation (the first step of translation) by preventing formation of the initiation complex.
Aminoglycosides
112
: the only one with a "P", thus the only one inhibiting Peptide bond formation (by peptidyltransferase)
ChloramPhenicol
113
: prevent the Movement of ribosomes (translocation)
Macrolides
114
: makes ribosomes Cling to mRNA (prevents translocation)
Clindamycin
115
(TTC): tRNA Tries but Can't (prevents the aminoacyl-tRNA from attaching to the A site of the ribosome)
Tetracyclines
116
: Like erythromycin (prevents translocation)
Lincomycin
117
: Like an aminoglycoside (prevents initiation)
Linezolid
118
react with enzymes in formation of cross links
lactams like Penicillins and cephalosporin
119
Clindamycin and lincomycin MOA
* attach to 50 S ribosomal subunit
| * inhibits protein synthesis by interfering with the formation of initiation complexes and translocation reaction
119
Clindamycin spectrum
•Narrow Gram (+) spectrum, excellent activity against anaerobic bacteria; strep, pneumococci, staphylococci
120
•prophylaxis of endocarditis in patients with valvular heart disease for dental procedures
Clindamycin
121
Clindamycin most important indication
severe anaerobic infection
122
Clindamycin plus what?
| used to treat penetrating wounds of the abdomen & gut
aminoglycoside or cephalosporin-
123
Clindamycin plus what?
effective alternative to trimethoprim sulfamethoxazole for moderate to moderately severe Pneumocystis carinii pneumonia in AIDS patients
Primaquine
124
Clindamycin plus what?
for AIDS – related toxoplasmosis of the brain.
Pyrimethamine
125
Clindamycin
septic abortion,
pelvic abscesses,
aspiration pneumonia
126
Clindamycin adverse effect
•Antibiotic associated colitis caused by toxigenic C. difficile.
127
* action is similar to macrolides except bactericidal for staph and most organisms except Enterococcus faecium
* prolonged postantibiotic effect up to 10 h for Staph. aureus
Streptogamins
128
•inhibits CYP 3A4, which metabolizes warfarin, diazepam, astemizole, terfenadine, cisapride, nonnucleoside reverse transcriptase inhibitors and cyclosporine.
Streptogamins
129
•infections caused by Vancomycin resistant strains of E faecium but not E. faecalis, bacteremia or respiratory tract infections caused by methicillin-resistant staphylococci and penicillin susceptible and resistant strains of S. pneumonia
Streptogamins
130
Streptogamins toxicity imes
infusion related events, pain at the injection site, arthralgia, myalgia
131
* (-) protein synthesis by preventing formation of the ribosome complex that initiated protein synthesis.
* Its unique binding site located on 23 S ribosomal RNA of the 50 S subunit, results in no cross resistance with other drug classes
Linezolid
132
* structural analogs of PABA (paraaminobenzoic acid)
* competitively inhibit dihydropteroate synthase (catalyzed the synthesis dihydropteroic acid)
* inhibits growth by reversibly blocking folic acid synthesis
Sulfonamides
133
Sulfonamide spectrum
* Inhibit the growth both Gm (+) and Gm (-) bacteria, Nocardia, Chlamydia trachomatis & some protozoa
* Enteric bacteria such as E.coli,klebsiella, salmonella,shigella, and enterobacter are also inhibited
* Rickettsia – not inhibited but growth stimulated by sulfas
134
Sulfonamides topical
a. Sodium sulfacetamide ophthalmic sol’n or ointment – for bacterial conjunctivitis
b. Mafenide acetate- prevent bacterial colonization and infection of burn wounds
c. Silver sulfadiazine –prevent of infection in burn wounds
135
Sulfonamide plus what?
• Toxoplasmosis
Malaria
With pyrimethamine:
136
Sulfonamides AE
Hemolytic anemia
| Kernicterus in new born
137
Co trimoxazole
| Combination causes
1. INCREASE POTENCY
2. INCREASE SPECTRUM
3. DECREASE INCIDENCE OF RESISTANCE
138
Co trimoxazole
MOA
MOA: blocks the sequential steps in the obligate enzymatic reaction in bacteria preventing formation of nucleotide
139
Co trimoxazole spectrum
broad gm + & gm –
140
for leishmaniasis & toxoplasmosis
Sulfadiazine plus Pyrimethamine
141
2.
| for Falciparum malaria
Sulfadoxime + pyrimethamine
142
Nucleic acid inhibitors
| first generation
Nalidixic Acid
143
Nucleic acid synthesis inhibitor or gyrase inhibitor
2nd gen
•Second Generation: Ciprofloxacin, Norfloxacin, Ofloxacin, Levofloxacin, Enoxaxin, Lomefloxacin
144
Nucleic acid synthesis inhibitor or gyrase inhibitor
3rd gen
* Third Generation: Gatifloxin, Moxifloxacin,
| * Gemfloxaxin
145
* Inhibits DNA Gyrase or Topoisomerase II - Block the relaxation of supercoiled DNA that is catalyzed by DNA gyrase
* Inhibits Topoisomerase IV – interferes with the separation of replicated chromosomal DNA during cell division
Fluoroquinolones
146
Fluoroquinolones spectrum
broad ; aerobic gm (+) & gm (-) but not anaerobes
147
Fluoroquinolones clinical uses
* UTI
* Sexually transmitted diseases : Gonorrhea, Chlamydia, chacroid, Prostatitis
* Respiratory infection due to H. influenza, M. catarrhalis, Strep pneumoniae, M. pneumoniae
148
* Most widely used
* DOC for anthrax
* Most potent for P. aeroginosa
* Synergistic with beta lactams
* M. tuberculosis
Ciprofloxacin
149
Not effective in systemic infection
Norfloxacin
150
* Prostatitis ,E. coli
* Urethritis, cervicitis
* Skin infections
* S. pneumoniae
Levofloxacin
