3 - ABX inhibiting Protein Synthesis Flashcards
Aminoglycosides are (bactericidal/bacteriostatic). MoA?
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.
Usage of aminoglycosides?
Treat infections caused by aerobic gram - bacteria
Aminoglycosides are used with ____ to treat serious infection of gram -, and with _____ for gram + endocarditis
b-lactams, vancomycin or b-lactam
What side effect limits aminoglycoside usage?
serious toxicity
Streptomycin is the first member of aminoglycoside. T/F?
T
Aminoglycosides is produced from ____. The ones obtained from streptomyces have suffix ____. The ones obtained from micromonospora have suffix ____.
Actinomyces, mycin, micin.
Structure of aminoglycosides
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
Name 2 topical aminoglycosides
neomycin, framycetin
Name 2 systemic aminoglycosides
streptomycin, amikacin
9 class of antibiotic that targets protein synthesis
Tetracycline Aminoglycoside Spectinomycin Oxazolidinones Macrolides Streptogramins Clindamycin Chloramphenicol Mupirocin
(TAS O MSCC M)
Tetapi Ami Sperti Orang Makan Strepsil, Cepat-Cepat Mampir
Some abx in aminoglycoside groups share cross resistance. T/F?
T
How is aminoglycoside classified?
Based on route of Administration
Aminoglycosides are highly polar basic drugs. T/F?
T
Aminoglycosides are excreted unchanged relatively ____ (rapid / slowly) by the normal kidney.
Rapid
Aminoglycoside should be avoided if renal function is impaired. T/F?
T.
Route of administration of Aminoglycosides?
Injection (parenteral).
Oral administration results in inadequate absorption.
Can aminoglycosides be used for patients with renal insufficiency?
Yes, but adjustments should be made to prevent accumulation of drug and toxicity.
How long does the post antibiotic effect of aminoglycoside last?
several hours
What are 4 common side effects of aminoglycosides?
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
Is it possible to reverse neurotoxicity caused by very high doses of aminoglycoside? How?
Yes, by promptly giving calcium gluconate or neostigmine
Which aminoglycosides are the most nephrotoxic?
NTG (neomycin, tobramycin, gentamicin)
Which aminoglycosides are the the most ototoxic?
KAN (kanamycin, Amikacin, Neomycin)
Which aminoglycosides are the most vestibulotoxic?
SG (Streptomycin and Gentamicin)
Name 3 examples of aminoglycoside!
Tobramycin Amikacin Neomycin Gentamicin Streptomycin Kanamycin Netilmicin (TANGS KN)
Streptomycin (aminoglycoside) indication?
Mycobacterial infections
Non tuberculosis infection
- +tetracyclin tularemia, brucellosis
- + penicillin : enterococcal (resistant to gentamicin) endocarditis
Which aminoglycoside cannot be given as a single agent due to fast development of resistance?
Streptomycin
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
Gram - bacteria susceptible to gentamicin (aminoglycoside) are usually susceptible to _____ (an aminoglycoside)
amikacin
Gentamicin is effective against both gram + and -, but not to anaerobs. T/F?
T
Which aminoglycoside is the most commonly used (usually in combination)?
Gentamicin. Usually combined with cell wall-active ABX
Streptococci and enterococci are relatively resistant to gentamicin (aminoglycoside) because?
drug cannot penetrate
Activity of gentamicin (aminoglycoside) increases when there is presence of pus. T/F?
F. activity of gentamicin decreases with the presence of pus.
Why should gentamicin (aminoglycoside) serum level be monitored?
to prevent irreversible ototoxicity
Which aminoglycoside is second most widely used after gentamicin?
Amikacin
________ is a semisynthetic derivative of kanamycin. It is ____ (more/less) toxic, and _____ (share/does not share) resistance with kanamycin.
Amikacin, less, shared
Amikacin (aminoglycoside) is resistant to many enzymes that inactivate gentamicin and tobramycin. T/F?
T
Is amikacin (aminoglycoside) effective against strains of multidrug resistant tuberculosis?
Yes
Amikacin (aminoglycoside) indication?
Multi drug resistant tuberculosis
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).
Neomycin and kanamycin (aminoglycoside) is active against gram +, gram -, and some mycobacteria. T/F?
T
Which bacteria are generally resistant to neomycin and kanamycin (aminoglycoside)?
P aeruginosa and streptococci
Does kanamycin and neomycin (aminoglycoside) exhibit cross-resistance?
Yes, complete cross resistance.
Which aminoglycoside has similar antibacterial spectrum to gentamicin?
Tobramycin
Are there cross-resistance between gentamicin and tobramycin?
Yes, some cross-resistance
Which aminoglycoside share many characteristics with gentamicin and tobramycin?
Netilmicin
Sore tobramycin and gentamicin resistant bacteria may be susceptible to _____ (an aminoglycoside)
Netilmicin
Spectinomycin is structurally related to aminoglycosides. Which 2 structure does it lack?
Amino sugar and glycosidic bonds
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.
Side effect of spectinomycin?
- pain at injection site
- sometimes fever and nausea
- nephrotoxicity and anemia (rare)
Spectinomycin MOA?
inhibit protein synthesis via 30S.
Free tetracyclines are crystalline amphoteric substance with (high/low) solubility. Therefore, it is usually available as _____ salts.
low, hydrochloride
Tetracycline is a broad spectrum (bacteriostatic/bactericidal) antibiotic.
bacteriostatic
Tetracycline should not be consumed together with antacids (contain divalent metal ions). Why?
Tetracycline chelates divalent metal ions.