3 - ABX inhibiting Protein Synthesis Flashcards
1
Q
Aminoglycosides are (bactericidal/bacteriostatic). MoA?
A
Bactericidal. Inhibit protein synthesis by:
- binding to specific 30S subunit –> interfere with the initiation complex of peptide formation
- bind to 30S subunit –> misreading of mRNA –> incorporation of incorrect amino acid
- break up polysome into nonfunctional monosomes.
2
Q
Usage of aminoglycosides?
A
Treat infections caused by aerobic gram - bacteria
3
Q
Aminoglycosides are used with ____ to treat serious infection of gram -, and with _____ for gram + endocarditis
A
b-lactams, vancomycin or b-lactam
4
Q
What side effect limits aminoglycoside usage?
A
serious toxicity
5
Q
Streptomycin is the first member of aminoglycoside. T/F?
A
T
6
Q
Aminoglycosides is produced from ____. The ones obtained from streptomyces have suffix ____. The ones obtained from micromonospora have suffix ____.
A
Actinomyces, mycin, micin.
7
Q
Structure of aminoglycosides
A
2 or more amino sugar bound to hexose. If hexose is in the form of streptidine –> streptomycin. If in the form of 2-deoxystreptamine –> kanamycin, amikacin
8
Q
Name 2 topical aminoglycosides
A
neomycin, framycetin
9
Q
Name 2 systemic aminoglycosides
A
streptomycin, amikacin
10
Q
9 class of antibiotic that targets protein synthesis
A
Tetracycline Aminoglycoside Spectinomycin Oxazolidinones Macrolides Streptogramins Clindamycin Chloramphenicol Mupirocin
(TAS O MSCC M)
Tetapi Ami Sperti Orang Makan Strepsil, Cepat-Cepat Mampir
11
Q
Some abx in aminoglycoside groups share cross resistance. T/F?
A
T
12
Q
How is aminoglycoside classified?
A
Based on route of Administration
13
Q
Aminoglycosides are highly polar basic drugs. T/F?
A
T
14
Q
Aminoglycosides are excreted unchanged relatively ____ (rapid / slowly) by the normal kidney.
A
Rapid
15
Q
Aminoglycoside should be avoided if renal function is impaired. T/F?
A
T.
16
Q
Route of administration of Aminoglycosides?
A
Injection (parenteral).
Oral administration results in inadequate absorption.
17
Q
Can aminoglycosides be used for patients with renal insufficiency?
A
Yes, but adjustments should be made to prevent accumulation of drug and toxicity.
18
Q
How long does the post antibiotic effect of aminoglycoside last?
A
several hours
19
Q
What are 4 common side effects of aminoglycosides?
A
NANO: 1. Nephrotoxicity Avoid concurrent use with loop diuretics or other nephrotoxic antimicrobial agents. 2. Allergic reactions (hypersensitivity) Frequent 3. Neurotoxicity very high dose produce neuromuscular blockade (respiratory paralysis) 4. Ototoxicity Auditory damage resulting in: -tinnitus -high-frequency hearing loss initially Vestibular damage: -vertigo, ataxia, loss of balance
20
Q
Is it possible to reverse neurotoxicity caused by very high doses of aminoglycoside? How?
A
Yes, by promptly giving calcium gluconate or neostigmine
21
Q
Which aminoglycosides are the most nephrotoxic?
A
NTG (neomycin, tobramycin, gentamicin)
22
Q
Which aminoglycosides are the the most ototoxic?
A
KAN (kanamycin, Amikacin, Neomycin)
23
Q
Which aminoglycosides are the most vestibulotoxic?
A
SG (Streptomycin and Gentamicin)
24
Q
Name 3 examples of aminoglycoside!
A
Tobramycin Amikacin Neomycin Gentamicin Streptomycin Kanamycin Netilmicin (TANGS KN)
25
Streptomycin (aminoglycoside) indication?
Mycobacterial infections
Non tuberculosis infection
- +tetracyclin tularemia, brucellosis
- + penicillin : enterococcal (resistant to gentamicin) endocarditis
26
Which aminoglycoside cannot be given as a single agent due to fast development of resistance?
Streptomycin
27
Gentamicin (aminoglycoside) indication?
1) Severe infections caused by gram - bacteria resistant to other drugs (p aeruginosa, enterobacter sp, Serratia marcescens, Proteus SP, Acinobacter sp, Klebisella sp)
2) combined with cell wall-active ABX, indicated for endocarditis gram + bacteria --> synergy
28
Gram - bacteria susceptible to gentamicin (aminoglycoside) are usually susceptible to _____ (an aminoglycoside)
amikacin
29
Gentamicin is effective against both gram + and -, but not to anaerobs. T/F?
T
30
Which aminoglycoside is the most commonly used (usually in combination)?
Gentamicin. Usually combined with cell wall-active ABX
31
Streptococci and enterococci are relatively resistant to gentamicin (aminoglycoside) because?
drug cannot penetrate
32
Activity of gentamicin (aminoglycoside) increases when there is presence of pus. T/F?
F. activity of gentamicin decreases with the presence of pus.
33
Why should gentamicin (aminoglycoside) serum level be monitored?
to prevent irreversible ototoxicity
34
Which aminoglycoside is second most widely used after gentamicin?
Amikacin
35
________ is a semisynthetic derivative of kanamycin. It is ____ (more/less) toxic, and _____ (share/does not share) resistance with kanamycin.
Amikacin, less, shared
36
Amikacin (aminoglycoside) is resistant to many enzymes that inactivate gentamicin and tobramycin. T/F?
T
37
Is amikacin (aminoglycoside) effective against strains of multidrug resistant tuberculosis?
Yes
38
Amikacin (aminoglycoside) indication?
Multi drug resistant tuberculosis
39
Neomycin and Kanamycin (aminoglycoside) route of administration?
Topical and oral.
Neomycin is too toxic for parenteral. Oral neomycin damages intestinal vili (lead to superinfection, malabsorption syndrome, and damages colonic flora).
40
Neomycin and kanamycin (aminoglycoside) is active against gram +, gram -, and some mycobacteria. T/F?
T
41
Which bacteria are generally resistant to neomycin and kanamycin (aminoglycoside)?
P aeruginosa and streptococci
42
Does kanamycin and neomycin (aminoglycoside) exhibit cross-resistance?
Yes, complete cross resistance.
43
Which aminoglycoside has similar antibacterial spectrum to gentamicin?
Tobramycin
44
Are there cross-resistance between gentamicin and tobramycin?
Yes, some cross-resistance
45
Which aminoglycoside share many characteristics with gentamicin and tobramycin?
Netilmicin
46
Sore tobramycin and gentamicin resistant bacteria may be susceptible to _____ (an aminoglycoside)
Netilmicin
47
Spectinomycin is structurally related to aminoglycosides. Which 2 structure does it lack?
Amino sugar and glycosidic bonds
48
Spectinomycin is active against many gram + and gram - organisms in vitro, but it is used almost solely as an alternative treatment for?
drug-resistant gonorrhea or gonorrhea in penicillin-allergic patients.
49
Side effect of spectinomycin?
- pain at injection site
- sometimes fever and nausea
- nephrotoxicity and anemia (rare)
50
Spectinomycin MOA?
inhibit protein synthesis via 30S.
51
Free tetracyclines are crystalline amphoteric substance with (high/low) solubility. Therefore, it is usually available as _____ salts.
low, hydrochloride
52
Tetracycline is a broad spectrum (bacteriostatic/bactericidal) antibiotic.
bacteriostatic
53
Tetracycline should not be consumed together with antacids (contain divalent metal ions). Why?
Tetracycline chelates divalent metal ions.
54
What is the structure of tetracycline like?
four 6-carbon rings attached to each other.
55
What is the MOA of tetracycline?
Inhibition of protein synthesis via 30S --> block binding of aminoacyl-tRNA to acceptor site on mRNA ribosome complex --> prevent addition of amino acids.
56
Is the binding of tetracycline to 30S subunit reversible?
Yes
57
How does tetracycline enter microorganisms?
Passive diffusion and active transport
58
Tetracycline are active against many gram + and - bacteria, including certain anaerobes ad chlamydiae. T/F?
T
59
Tetracycline resistant strains may be susceptible to ____, ____, and ____.
Doxycycline, minocycline, tigecycline
60
Different efficacy of drugs in the class tetracycline is largely due to?
absorption, distribution, and excretion features of individual drugs.
61
Which 2 factors impair absorption of tetracycline?
cation and alkaline pH.
but doxycycline and minocyline absorption is not impaired.
62
Arrange these drug groups (tetracyclines) according to their bioavailability (increasing in order, from lowest to highest bioavailability) after oral absorption:
A) tetracycline, oxytetracycline, demeclocycline, methacycline
B) Chrlortetracycline
C) doxycycline and Minocycline
lowest to highest BA:
| B < A < C
63
How should tigecycline (tetracycline) be administered (ROA)?
IV, since it is poorly absorbed orally.
64
Where are tetracyclines distributed in the body?
Widely to tissues and body fluids, except for CSF.
65
Tetracycline are excreted mainly in ______ and ______.
Bile and urine
66
Tetracycline can cross the placenta and is also excreted in milk. T/F?
T
67
Does tetracycline undergo enterohepatic circulation?
Yes
68
Which 2 tetracyclines are not eliminated through the kidneys?
doxycycline and tigecycline
69
How are tetracycline classified?
```
Duration of action:
Short acting (half life 6-8h)
Intermediate acting (half life 12h)
Long-acting (half life 16-18h), except tigecycline (T1/2 = 36h)
```
70
Give 3 examples of short acting tetracycline
Chlortetracycline
Oxytetracycline
Tetracycline
71
Give 2 examples of intermediate-acting tetracycline
Demeclocycline
| Methacycline
72
Give 3 examples of long-acting tetracycline
Doxycycline
Minocycline
Tigecycline
73
Tetracycline indication?
Infection caused by rickettsiae, mycoplasma pneumonia, some spirochetes, most chlamydial indections
74
Tetracyclines are no longer recommended for gonococcal disease, epidemic cholera, and UTI infections due to?
Resistance
75
Tetracycline + other antibiotic indicated for ___, ____, and ____.
plague, tularemia, brucellosis
76
Tetracycline is considered category __ for pregnancy.
D. (Positive evidence of human fetal risk, but potential benefits may warrant use of the drug in pregnant women despite potential risks).
77
State 4 adverse reaction of tetracyclines
1. Gastrointestinal:
- direct irritation on GIT (nausea, vomiting, diarrhea)
- alter normal GIT flora
2. Hyppersensitivity (uncommon)
3. Deposition in bony structures and teeth
(avoid in pregnant, nursing woman & children under 8 yo)
4. Other toxicities
- impair hepatic function
- injection : venous thrombosis (iv), pain (IM)
- systematically administered : induce sunlight or UV sensitivity
78
The structure of macrolides have _____ _____ ring where _____ _____ are attached.
macrocyclic lactone, deoxy sugars
79
Erythromycin and other macrolides share complete cross resistance. T/F?
T
80
There are 2 types of macrolides: natural and semisynthetic. Name one example for each.
Natural: erythromycin obtained from Streptomyces erythreus
Semisynthetic: Clarithromycin
azithromycin
ketolides
81
a semisynthetic macrolide have activity against some macrolide-resistant strains. What is the drug?
Ketolides
82
What limits the use of ketolides?
hepatoxicity
83
MOA of macrolides?
inhibit protein synthesis by binding to 50S ribosomal RNA --> inhibit translocation step where newly synthesized peptidyl tRNA move from acceptor to peptidyl donor site.
84
Macrolides are similar to penicillin in regards to their spectrum of activity. However, they are effective against penicillin resistant strains. T/F?
T
85
Which synthetic macrolide is absorbed rapidly from the GI tract but its bioavailability is reduced to 50% due to first pass metabolism?
Clarithromycin
86
Which macrolide is formulated in the form of enteric coating to prevent degradation by stomach acid?
Erythromycin
87
Which synthetic macrolide is absorbed rapidly and well tolerated orally?
Azithromycin
88
Can macrolides penetrate BBB and CSF?
No
89
Which macrolide has the longest T1/2?
Azithromycin (almost 3 days)
90
Where are macrolides metabolized?
liver
91
What are the adverse effects of macrolides?
1. Hepatotoxicity
- estolate related
2. GI toxicity
- common for erythromycin
3. Cardiac Toxicity
- erythromycin, clarithromycin, telithromycin could cause cardiac arrhythmia
4. Other toxic and irritative effects
- allergic reaction
- high dose of estolate --> temporary audio impairment
- telithromycin may cause loss of consciousness and visual disturbances
92
Macrolides (except for azithromycin) could increase serum level of other drugs due to?
Altered metabolism of other drugs in the liver (macrolide inhibit p450 enzyme).
93
Macrolide indication?
- UTI by streptococcus pneumoniae, haemophilus influenzae, and atypical pathogens
- uncomplicated skin and soft-tissue infection
- STD
- lower respiratory tract infection
- ulcer
94
Route of Administration of macrolides?
oral and IV
95
Is macrolide bacteriostatic or bactericidal?
bacteriostatic
96
MoA of Clindamycin?
inhibit protein synthesis by binding to 50S ribosomal RNA (same as macrolide)
97
clindamycin share cross resistance with macrolides. T/F?
T
98
Clindamycin are not effective against gram-negative aerobic species. Why?
Poor permeability
99
Can clindamycin penetrate into BBB and CSF?
No
100
Where is clindamycin metabolized and excreted?
metabolized: Liver
| excreted : bile and urine
101
Clindamycin indication
1. Skin and soft tissue infections caused by streptococci and staphylococci
2. respiratory tract infections
3. Prophylaxis of endocarditis in patients with valvular heart disease
102
Adverse Effect of Clindamycin?
Common : diarrhea, nausea, skin rash
Rare: impaired liver function and neutropenia
103
Streptogramin MoA
similar to macrolide and clindamycin (bind to 50S)
104
Streptogramin are rapidly metabolized. T/F?
T
105
Streptogramin indication?
Indection caused by staphylococci or vancomycin-resistant srains of E. faecium
106
Streptogramins are eliminated through feces. T/F?
T
107
Adverse effect of clindamycin?
Pain at infusion site, arthralgia-myalgia syndrome
108
Chloramphenicols are bactericidal broad spectrum antibiotics. T/F?
F. chloramphenicols are bacteriostatic broad spectrum antibiotics.
But in some strains (H influenzae, Neisseria meningitidis, and some strains of bacteriosides), it may be bactericidal.
109
What side effect limits chloramphenicol usage?
irreversible bone marrow activity
110
Chloramphenicol MoA?
Bind reversibly to 50S subunit, inhibit peptide bond formation
111
which organisms does chloramphenicol have activity against?
- aerobic, non aerobic gram +
- gram -
- rickettsiae
112
Chloramphenicol is distributed widely into all tissues and body fluids, including CSF. T/F?
T
113
Where is chloramphenicol metabolized and eliminated?
Metabolized: Liver
Eliminated: urine, bile, and feces
114
What limits the use of chloramphenicol?
Potential toxicity and resistance
115
Chloramphenicol is used topically to treat eye infections. T/F?
T
116
Chloramphenicol can be used to treat bacterial meningitis as an alternative to b-lactam antibiotics. T/F?
T
117
What are the adverse reactions of chloramphenicol?
1. Gastrointestinal disturbance
2. Oral or vaginal candidiasis
3. Aplastic anemia (irreversible)
4. Gray baby syndrome
5. inhibition of CYP450
118
Oxazolidinones are primarily (bactericidal / bacteriostatic), but is (bactericidal / bacteriostatic) against streptococci.
Bacteriostatic, bactericidal
119
Oxazolidinones are active against gram + , gram - rods, and mycobacterium tuberculosis. T/F?
T
120
Oxazolidinone MoA?
Prevent formation of ribosome complex that initiate protein synthesis by binding to 50S.
binding site: 23S ribosomal RNA of 50S subunit
121
What makes oxazolidinone not have cross resistance with other drug classes?
Oxazolidinones have a unique binding site (23S ribosomal RNA of 50S subunit)
122
Which antibiotic class has 100% bioavailability? (Route of administration both oral and parenteral)
Oxazolidinones
123
Oxazolidinone indication?
1. Vancomycin-resistane E faecium infection
- Nosocomial (gained in hospital) and community-acquired pneumonia
- complicated and uncomplicated skin and soft tissue infections caused by gram + bacteria
124
Should Oxazolidizone be used for non-resistant strains?
No, it should be reserved as an alternative for infections caused by multiple-drug-resistant strains.
125
3 Adverse effect of Oxazolidone?
1) Hematologic (mild, reversible):
- thrombocytopenia (low blood platelet count)
- anemia
- neutropenia
2) optic and peripheral neuropathy
3) inhibitor of monoamine oxidase
- avoid use in patients that use selective serotonin reuptake inhibitor (cause serotonin syndrome)
126
Mupirocin is derived from a fermentation product of Pseudomonas Fluorescens. T/F?
T
127
Route of administration of mupirocin?
Topical
128
MoA of mupirocin?
Reversibly bind and inhibit isoleucyl tRNA synthetase --> supress bacterial protein synthesis
129
Mupirocin spectrum of activity?
many gram + and selected gram -
130
Indication of mupirocin?
- Dermatologic preparation: traumatic skin lesions and impetigo
- nasal ointment : eradication of S. aureus nasal carriage
131
Adverse effects of mupirocin?
- irritation and sensitization at site of application
| - if is in contact with the eyes: tearing, burning, irritation
132
One example of oxazolidinones?
Linezoid
133
Which antibiotics bind to 50S subunit?
```
Oxazolidinone
Macrolide
Streptogramin
Clindamycin
Chloramphenicol
```
134
Which antibiotics bind to 30S subunit?
Tetracycline
Aminoglycoside
Spectinomycin
