Protein Synthesis Inhibitors

Question 1

AMINOGLYCOSIDES

Answer 1

produced by a variety of soil actinomycetes
MOA: Binds to 30s ribosomal subunit and interferes with initiation of protein synthesis =
1. Blocking of initiation of protein synthesis
2. Premature termination of translation
3. Incorporation of incorrect amino acid
Cidal and broad spectrum
Poorly absorbed orally
Reserved for systemic infections

Question 2

Streptomycin

Answer 2

MOST OTOTOXIC
Administered deep IM or IV
Poorly absorbed orally
Uses: Bacterial endocarditis, Tularemia, Plague, Tuberculosis

Question 3

Tobramycin

Answer 3

Most active among Nebramycins
Opthalmic use

Question 4

Neomycin

Answer 4

Tx of GI infections, skin infections and peritonitis
Decreased absorption, no systemic effect
Available topical and oral
NEPHROTOXIC

Question 5

Spectinomycin

Answer 5

Bactereostatic
Most inferior aminoglycoside
Use: uncomplicated gonorrhoea

Question 6

Netilmicin

Answer 6

Latest aminoglycoside to be marketed
Resistant to aminoglycoside modifying enzymes

Question 7

Kanamycin

Answer 7

Obsolete
Kantrex

Question 8

Gentamicin

Answer 8

Less nephrotoxic

Question 9

ADRs of aminoglycoside

Answer 9

AMINO
Allergy
Muscular blockade
Incompatibility with PCN
Nephrotoxicity
Ototoxicity

Question 10

Amikacin

Answer 10

Derivative of Kanamycin produced in Japan with broadest spectrum of activity
Amikin

Other Uses: Pneumonia, Meningitis, UTI, Peritoneal Dialysis associated Peritonitis, Bacterial endocarditis,
Sepsis

Question 11

Tetracyclines

Answer 11

Broad-spectrum, bacteriostatic agents
Has activity against G(+) and G(-) MRCS
Contains four fused rings with a system if conjugated double bonds
Forms stable complexes with trivalent and divalent cations
Used in animal feeds

MOA: Inhibit bacterial protein synthesis by binding to the 30s subunit and blocking tRNA binding to the A site

Untoward Effects: GI irritation, Photosensitivity, Hepatic and Renal toxicity, Ca chelation

Bacterial Resistance
1. Decreased antibiotic influx or acquisition of an energy-dependent efflux pathway
2. Production of a ribosomal protection protein that displaces tetracycline from its target
3. Enzymatic inactivation of tetracyclines

Question 12

Macrolides

Answer 12

Bacteriostatic and broad spectrum
Basic in nature due to the presence of a glycosidically linked amino sugar
Resembles that of Penicillin
Used as an alternative to PCN
Generally active against G(+), Neisseria and Treponema

MOA: Inhibits protein synthesis by binding reversibly to 50s ribosomal subunits of sensitive microorganisms

Bacterial Resistance
1. Reduced permeability of the cell membrane or active efflux
2. Production of esterases that hydrolize macrolides
3. Modification of the ribosomal binding site

Question 13

Erythromycin

Answer 13

From: Streptomyces erythraeus
Free base is bitter and has irregular oral absorption

Spectrum of Activity:
1. Alternative to PCN
2. Prophylaxis for Bacterial Endocarditis
3. Chlamydia
4. Eaton agent pneumonia
5. Bacterial enteritis

Adverse Effects: Acute cholestatic hepatitis (estolate salt)

Question 14

Clarithromycin

Answer 14

6-methyl ether of erythromycin
Increased stability and oral bioavailability than Erythromycin
Reduced GI distress and less frequent dosing

Spectrum of Activity
1. Effective against Borrelia burgdorferi
2. More active than Erythromycin against Strep. Pneumonia
3. Presence of food does not significantly affect absorption
4. AE: CYP3A4 inhibitor

Question 15

Azithromycin

Answer 15

MOST POTENT
Does not inactivate CYP450 enzymes
Not to be administered with food
Unique dosing: OD for 3d

Question 16

Ketolides

Answer 16

Telithromycin (Ketek)
Effective against macrolide-resistant G(+)
Disadv: Reversible inhibitor of CYP3A4 enzyme

Question 17

CHLORAMPHENICOL

Answer 17

Bacteriostatic and broad spectrum
From Streptomyces venezuelae
May cause blood dyscrasias

Spectrum of Activity
1. Bacteriostatic
2. Bactericidal: H. influenzae, N. meningitides, B. fragilis
3. Ineffective for chlamydial infections

MOA:
1. Inhibits protein synthesis in bacteria and to a lesser extent in humans
2. Binds to the 50S ribosomal subunit at the peptidyltransferase site and inhibits the transpeptidation reaction
3. Inhibit mitochondrial protein synthesis in mammalian cells

Adverse Effects: Hypersensitivity Reactions, Gray Baby Syndrome, Aplastic anemia

Question 18

LINCOMYCINS

Answer 18

Bacteriostatic and broad spectrum
Sulfur containing antibiotics from Streptomyces lincolnensis
Resemble macrolides in spectrum of activity
Bactericidal activity at high doses
Used in osteomyelitis and infections of the peritoneal and pleural cavities
Useful against G(+) -soft tissue infections and infections caused by nonspore forming anaerobes

Question 19

Clindamycin

Answer 19

Congener of Lincomycin 7-chloro-7-deoxy Lincomycin Improved absorption and distribution than Lincomycin
Most potent agent against anaerobes
For Staph infections, cellulitis and osteomyelitis
Cannot penetrate CSF
Binds exclusively to the 50S subunit of bacterial cell
Clindamycin, Erythromycin, Chloramphenicol: Binding by one of these antibiotics to the ribosome may inhibit the interaction of the others
Adverse Effects: Pseudomembranous colitis DOC vancomycin and metronidazole