Antibiotics

Front 1

what are characteristics of an ideal antimicrobial drug?

Back 1

-selective toxicity
-microbicidal
-soluble in water
-potent
-stable
-unlikely for microbial resistance to develop
-complements host's defenses
-not inactivated by other metabolites
-does not cause allergies
-does not increase host susceptibility to future infection

Front 2

what are the general mode of action of antibiotics?

Back 2

an antibiotic is a poison that kills a microorganism but does not harm the host

most poisons are in one way or another enzyme inhibitors

antibiotics kill undesirable bacteria by inhibiting enzymes that are important for the life cycle of the bacteria but are not found in the cells of the host organism

Front 3

what are the general classes of antibiotics based on specific modes of actions?

Back 3

inhibitors of peptidoglycan biosynthesis - prevent growth of bacterial cell wall

inhibitors of translation of 70S ribosomes - stop bacterial protein synthesis

inhibitor of folic acid biosynthesis

inhibitor of bacterial RNA polymerase or DNA polymerase

disruption of cell membranes

Front 4

explain antibiotics that inhibit peptidoglycan biosynthesis

Back 4

ex: penicillins and cephalosporins

penicillin binding protein is a bacterial enzyme that forms peptide bonds between the amino acids in the side chains of peptidoglycan to form cross link between peptide chains

the B-lactam drugs are competitive inhibitors of this enzyme

if the synthesis of peptidoglycan is inhibited, the bacterial cell wall becomes weak and the bacteria may break open due to osmotic pressure

Front 5

antibiotics that inhibit protein synthesis by bacterial ribosomes

Back 5

aminoglycosides: streptomycin; bind to the 30S subunit of the 70S ribosome and cause the mRNA to be misread. cause the ribosome to slip, sometimes moving 4 bases when changing from one codon to the next when it needs to move exactly 3 bases. causes the incorporation of incorrect amino acids into the growing protein chain

tetracyclines: block binding to tRNAs to ribosome-mRNA complex

chloramphenicol: antibiotic blocks the formation of peptide bonds between the amino acids of the growing protein chain

macrolides: erythromycin; stop movement of the ribosome down the mRNA

quinolones: inhibit bacterial gyrase which is involved in controlling the amount of supertwisting in DNA. blocking action of DNA gyrase blocks replication

polymyxin: detergent-like drug that disrupts bacterial cell membranes

nucleotide analogs: block DNA replication and cause mutations

Front 6

what are the mechanisms of resistance to antibiotics?

Back 6

1. bacteria may produce an enzyme that degrades or modifies the antibiotic. genes for these drug resistance factors are often found on plasmids. drug resistance plasmids can often be transferred from species to species

2. altered pore proteins may slow diffusion of the drug into the bacterial wall

3.gene for the drug receptor may be mutated so the receptor no longer binds to the antibiotic

4. resistant cells may alter their metabolism so they can by-pass the inhibited step

5.resistant cells may acquire a gene for an active transporter protein that pumps the antibiotic out of the cell using energy from ATP. this type of resistance gene is often found on a plasmid or transposon.

Front 7

what is minimum inhibitory concentration (mic)?

Back 7

mic is the lowest concentration of an antimicrobial drug that will inhibit a pathogen

low mic indicates a potent drug for inhibiting a certain microorganism

for a given drug the mic varies with the species and strain of the microorganism and the environmental conditions

Front 8

what is the kirby-bauer test?

Back 8

standard laboratory test that can be used to predict the effectiveness of antibiotics in the treatment of a patient

Front 9

in the kirby-bauer test what indicates the more effective antibiotic?

Back 9

a larger clear zone around a disk impregnated with the antibiotic indicates a more effective drug

no clear zone around the disk and the bacterium is resistant to the antibiotic

Front 10

what is the therapeutic index (ti)?

Back 10

the therapeudic index of a drug is the ration of the toxic dose divided by the effective dose

ti = (toxic dose)/(effective dose)

higher ti indicates a safer drug

low ti indicates there is a smaller margin for error as a physician tries to give the patient enough of the drug to kill the infectious microorganism but not so much that it hurts the patient

Front 11

what are antifungal, antihelminthic, antiprotozoan drugs?

Back 11

work on organisms that have 80S ribosomes, no cell walls made of peptidoglycan

often have a low ti and toxic side effects

e.g. allyamines and azoles such as miconazol, inhibit ergosterol synthesis in fungi

quinine inhibits metabolism in malaria parasites (protozoan)

Front 12

what are antiviral drugs?

Back 12

usually very specific inhibitors of certain enzymes that are found in virally infected cells that are not found in uninfected cells

compounds that have an affect on the reproduction or maturation of one type of virus may have no effect on other types of viruses

e.g. HIV protease inhibitor is useful in the treatment of AIDs but it is very specific for a protein found in HIV infected cells - the HIV protease. this compound is not useful against the majority of other viruses because they do not make a protease enzyme like the one found in HIV infected cells

acyclovir inhibits an enzyme that is involved in the cytoplasmic replication of the DNA genomes of some viruses such as herpes and chickenpox. it is not effective against RNA viruses or DNA viruses that do not use a similar virally encoded kinase enzyme

zanamivir inhibits an enzyme found on the surface of influenza virus called neuraminidase which is involved in the entry and exit of the virus in host cells.