Pharmacology 30 (Protein Synthesis Inhibitors)

Front 1

what are the components of the bacterial ribosomes?

Back 1

30S + 50S => 70S

Front 2

what is the size of the mammalian ribosomes?

Back 2

80S ribosomes

Front 3

how do antibiotics selectively target bacterial ribosomes?

Back 3

human: 80S
bacterial: 70S

proteins on the surface differ enough to allow selective binding

Front 4

what is the first amino acid in all bacterial proteins?

Back 4

N-formylmethionine (fMet)

Front 5

what are the steps in bacterial protein synthesis?

Back 5

1) initiation (30S subunit binds start codon and adds fMet)
2) subunit association (50S subunit associates with 30S subunit)
3) codon recognition (tRNA, assisted by rRNA, but not ribosomal proteins)
4) peptidyl transferase (linking of amino acid in P site with amino acid in A site)
5) translocation (rRNA moves to next position on mRNA sequence)
6) continued elongation
7) termination process (reach a stop codon and release)

Front 6

what are the two sites in the 50S subunit of rRNA?

Back 6

A site = acceptor site
P site = peptide site

Front 7

if antibiotics inhibit action of mitochondrial rRNA, how can they be used without causing too much toxicity?

Back 7

mitochondria have a double membrane, which is difficult for the antibiotic to penetrate, so the antibiotic is selective for microorganisms

Front 8

what is the usual effect of protein synthesis blockade?

Back 8

bacteriostatic
(not usually bacteriocidal)

Front 9

what is the davis model for bactericidal activity of aminoglycosides?

Back 9

low concentrations of aminoglycosides to enter the cell and halt protein synthesis
a) initially AGs are present at low conc. inside bacterial cell, despite therapeutic extracellular conc. of drug (poor uptake across bacterial membranes)
b) low intracellular concentrations of AGs bind to bacterial ribosomes and causes misreading
c) abnormal proteins insert into the bacterial membranes, forming pores and causing membrane damage
d) damaged membranes allow addtl AG molecules to flood into cells, causing complete inhibition or ribosome activity
e) drug is trapped inside cell (caging) so effect is irreversible
f) new proteins cannot be synthesized, so membrane damage cannot be repaired, and cell death ensues

Front 10

what are the old aminoglycosides?

Back 10

streptomycin
neomycin
kanamycin

Front 11

what are the newer aminoglycosides?

Back 11

gentamicin
tobramycin
amikacin

Front 12

why is there no oral absorption of aminoglycosides?

Back 12

they have many amino groups, which are charged at plasma pH (polycationic) and are very hydrophilic

Front 13

why do aminoglycosides have trouble treating infections in such places as the CNS?

Back 13

large number of charged amino groups make it difficult for them to cross the blood-brain barrier

Front 14

what is the predominant route of excretion of aminoglycosides?

Back 14

glomerular filtration

Front 15

what is the main site of aminoglycoside uptake?

Back 15

kidney

proximal tubule mistakes amino groups of these drugs for amino groups of amino acids

Front 16

what is the drug of choice for Rickettsia infections?

Back 16

doxycycline

Front 17

what is the drug of choice for Lyme disease?

Back 17

doxycycline

Front 18

what antibiotic causes the highest incidence of antibiotic-associated diarrhea?

Back 18

clindamycin

ampicillin is another important cause

Front 19

why is loperamide not recommended as a Tx for antibiotic associated diarrhea?

Back 19

loperamide decreases gastric motility

antibiotic-associated diarrhea is caused by a toxin produced by C. difficile and loperamide does nothing to stop the production of the toxin, but does increase the exposure time of the intestine to the toxin

use VANCOMYCIN to treat C. diff

Front 20

what are lipopeptide antibacterial agents?

Back 20

new class of antibiotics with a spectrum of activity similar to vancomycin