4.6 Introduction to Antimicrobial Drugs

MRSA and other bacteria have evolved an enzyme called penicillinase or beta-lactamase that can..

destroy the beta-lactam ring

• this neutralizes the antibotic and makes it ineffective

modern penicillins are chemically modified in a laboratory and are called…

semisynthetic

many of these semisynthetic penicillins…

are not easily destroyed by beta-lactamse

even the, resistance to penicillin…

evolves so rapidly that new semisynthetic penicillins are constantly introduced

for many penicillin-resistant infections medicine has reserved the use of a newer drug called…

vancomycin

vancomycin attacks cell wall synthesis but disrupts a…

different enzyme in the synthesis process

vancomycin is a…

broad-spectrum antibiotic

use of vancomycin has bred…

antibiotic resistance in the normal microbiota

a growing risk in hospital environments is a new kind of…

opportunistic infection called VRE

enterococcus is part of the normal microbiota but during…

dysbiosis caused by vancomycin use, it can use cause an opportunistic infection (mostly in hospital settings)

disruption of…

protein translationp

proteins…

perform most of the work of the cellg

growth requires…

translation of new proteins by the ribosome

drugs in this group…

bind to the ribosome and block its ability to make new proteins

this provides selective toxicity because bacterial ribosomes are…

smaller and have a different molecular structure than eukaryotic ribosomes

drugs called macrolides will block the part of the ribosome where..

peptide bonds are formed

ribosome can no longer assemble…

chains of amino acids

macrolides do not affect human cells because they..

only bind to the bacterial ribosome

• macrolide drugs have names that end in -mycin

a Z-pak is a long-acting, extendned release macrolide called

azithromycin (Z-PAK)

disrupting the…

bacterial cell membrane

these drugs can…

preferentially dissolve or punch holes in bacterial cell membranes

bacterial cells typically die as…

the cytoplasm leaks out through the holes made by the drug

this provides selective toxicity if it targets molecules..

found only in bacterial cell membranes

where does selective toxicity come from

Selective toxicity is when a drug targets parts of a microbe that are different from human cells, so it kills the microbe without harming you.

colistin dissolves gram-negative cell membranes when it…

binds to LPS

because it requires LPS, colistin is narrow spectrum

effective against.. specific types of Gram-negative bacterial only

LPS is also..

endotoxin

colistin is often given with anti-inflammatory steroids to…

reduce the body’s reaction to released endotoxin

disrupting the…

microbial cell membrane

it does this by binding to a molecule in the membrane called…

ergosterol (a sterol)

ergosterol is a closely related molecule to..

cholestol

amphotericin must be used carefully because it can..

bind to cholesterol in kidney cells and cause nephrotoxicity

blocking…

DNA replication

DNA replication is one of the first steps of…

cell division

most microbes reproduce using…

cell divison in one form or another

if cells cannot replicate their DNA, they..

cannot grow/reproduce

this provides selective toxicity because…

the enzymes of DNA replication have a different 3D structure in prokaryotes

Fluoroquinolones are antibacterial drugs that block the enzymes…

DNA gyrase and topoisomerase

topoisomerase unwinds

DNA supercoiling in bacterial cells

DNA gyrase separates the DNA strands..

during DNA replication

blocking both of these enzymes…

effectively shut off the process of DNA replication (and will kill a bacterial cell)

blocking..

synthesis of folic acid

folic acid is a molecule that bacteria need…

as part of the 3D structure of their enzymes that build nucleotides

drugs in this group..

block the enzymes that make folic acid for bacteria

this provides selective toxicity because..

humans do not have the enzymes to make folic acid; we must get it from our diet

sulfa drugs are a combination of..

two medications that block folic acid synthesis

the combination of the two drugs is..

more effective than either one is alone