Antibiotics: Protein Synthesis Inhibitors

Question 1

Selective toxicity:

Answer 1

Describes the phenomenon where a compound causes toxicity to one group of organisms (i.e., bacteria) without creating toxicity to another group (i.e., humans), due to various structural and functional differences.

Question 2

Aminoglycoside (gentamicin, streptomycin, tobramycin, and amikacin) mechanism of action:

Answer 2

Bind to both the 30S subunit (18S) and 50S subunit (23S) of the bacterial ribosome. It leads to: misreading of the mRNA, blocking initiation (STREPTOMYCIN), blocking translocation (30S binding), and inhibiting recycling (50S binding). They are the only BACTERIOCIDAL protein synthesis inhibitors, due to the production of mutated proteins.

Question 3

Aminoglycoside resistance:

Answer 3

Multiple enzymes are capable of inactivating these compounds (often by adenylation, phosphorylation, or acetylation). There are other, rarer mechanisms of inactivation.

Question 4

Aminoglycoside spectrum:

Answer 4

Aerobic GNRs, GPs (synergy with penicillins). ANAEROBES ARE RESISTANT.

Question 5

Aminoglycoside pharmacokinetics:

Answer 5

Parenteral administration.
Renal excretion.
Significant post-antibiotic effect (GNs only).

Question 6

Aminoglycoside side effects:

Answer 6

NEPHROTOXICITY (acute tubular necrosis), OTOTOXICITY, rashes, bone marrow suppression, muscle weakness.

Question 7

Aminoglycoside dosing:

Answer 7

Concentration-dependent killing (CDK) rather than time-dependent killing (TDK). Thus, one should administer a SINGLE, ENORMOUS dose rather than multiple smaller doses (except in patients with renal problems).

Question 8

Tetracyclines (doxycycline, teracycline, minocycline) mechanism of action:

Answer 8

Binds to 30S subunit, and blocks aminoacyl-tRNA binding, resulting in elongation block.

Question 9

Tetracycline resistance:

Answer 9

Reduced cell permeability and increased efflux pump expression. Other rarer causes also exist.

Question 10

Tetracycline spectrum:

Answer 10

Mycoplasma, chlamydia, legionella, rickettsia, borellia, and Strep pneumo. Also used for malaria prevention.

Question 11

Tetracycline pharmacokinetics:

Answer 11

Reduced gut absorption with food and chelators. Good tissue penetration. Mainly hepatic metabolism.

Question 12

Tetracycline toxicity:

Answer 12

GI problems, hepatotoxicity, SKIN PHOTOSENSITIVITY. Deposits in teeth and bones of neonates and children, so don’t give to them or pregnant women.

Question 13

Macrolide (azithromycin, clarithromycin) mechanism of action:

Answer 13

Binds to and blocks the polypeptide release channel on the 50S subunit.

Question 14

Macrolide resistance:

Answer 14

Efflux, reduced permeability, modification of the 23S rRNA (nucleotide 2058), production of esterase by Enterobacter.

Question 15

Macrolide spectrum:

Answer 15

GPC, mycoplasma, legionella, chlamydia, H. flu, mycobacteria. Used clinically for RESPIRATORY TRACT INFECTIONS.

Question 16

Macrolide pharmacokinetics/toxicity:

Answer 16

Azithromycin half-life = 68 hours. Hepatic metabolism. May cause allergic reaction (rash), hepatitis, GI upset, and OTOTOXICITY (especially in the elderly).

Question 17

Clindamycin (a lincosamide) mechanism of action:

Answer 17

Binds to the 50S subunit (23S rRNA) and interferes with peptide bond formation. Binding site partially overlaps with macrolide binding site.

Question 18

Clindamycin resistance:

Answer 18

Mutual interference if co-prescribed with the macrolides. Same resistance mechanisms as macrolides (efflux, reduced permeability, modification of 23S rRNA).

Question 19

Clindamycin pharmacokinetics/spectrum:

Answer 19

GPCs, ORAL AND BOWEL ANAEROBES. Often used for deep seated infections (intra-abdominal infections), skin and soft-tissue infections, dental infections.
Good tissue penetration, concentrated intracellularly.

Question 20

Clindamycin toxicity:

Answer 20

Hypersensitivity (skin rashes), GI upset, PSEUDOMEMBRANOUS COLITIS, hepatitis, bone marrow suppression.

Question 21

Linezolid mechanism of action:

Answer 21

Binds 23S rRNA (50S subunit) at the A-site and blocks formation of the initiation complex.

Question 22

Linezolid resistance:

Answer 22

Mutation of 23S rRNA. No cross resistance with other drug classes.

Question 23

Linezolid spectrum:

Answer 23

GPC (staph, enterococci, strep), VRE, VRSA, MRSA.

Question 24

Linezolid toxicity:

Answer 24

Leukopenia, thrombocytopenia, aplastic anemia. GI upset, hepatitis.