Ch 14: Antimicrobial Drugs Flashcards
Antibiotic
a substance produced by living organisms which kill or inhibit the growth of bacteria
antimicrobial agent
a chemical whch is synthesized to kill or inhibit the growth of bacteria or microorganims
there are also anti-viral, anti-fungal, anti-protozoan compounds
bacteriostatic
compound inhibits the growth of bacteria without killing it as long as it is present
(when the compound is removed the bacteria can grow again)
prolonged exposure can lead to death by the immune system killing them
bactericidal
if enough of the compound is absorbed by the bacteria they are killed
Wide spectrum
active against many types and groups of bacteria
ex/ gram positives and Gram negatives => BOTH
narrow spectrum
active agaisnt few types of only one group of bacteria
ex/ only Gram-positives or only Staphylococcus
most narrow spectrums work against Gram +
antibiotics against gram negatives are very rare. Most antibiotics that target them are wide spectrum, killingh off both gram + and - bacteria
MIC
minimal inhibitory concentration
lowest concentration of an antibiotic whihc stops the growth of that species of bacteria under the conditions tested
important because the higher the dose of an antibiotic the worst the side effects
common
MLC
minimal lethal concentration
lowest concentration of an antibiotic which kills all the bacteria (of that species)
not as common as MIC
AUC
area under the curve
integrated time where in vivo concentration of the antibiotic is greater than the MIC
if drug is dosed by time interval there will be spikes in concentration of the drug in the blood and troughs as teh drugs is eliminated
want to maintain the concentration of the drug in the blood above the MIC
Therapeutic index
the ratio of the dose of the antibiotic whihc is toxic to a human to the dose whihc is effective at inhibiting of killing the bacterium
a measurement of selective toxicity
toxic to bacteria but not to humans
the higher the therapeutic index, the more useful the antibiotic
good and bad MIC range
good
=> 1mg/ml
really good 0.1/0.05 or less
=> fluroquinolines and some penicillines agaisnt gram + and streptococci
with pseudomonas aerginosa, can be upwards of 16
Oral administration of antimicobials
rug must be acid stable, absorb through the stomach or intestines
parenteral administration of antimicrobials
intraventous or intramuscular
drug acid labile or unable to absorb through GI tract
drug may be sparingly soluable - need continuous infusion
maintains higher concentration in blood/ tissue
Targets of antibiotics
antimetabolites (metabolism)
inhibition of cell wall (peptidoglycan) synthesis
inhibition of DNA/RNA biosynthesis
Inhibition of protein biosynthesis
Inhibition of energy production
Antimetabolites
compounds which interfere with cellular metabolism
=> mostly the small molecule metabolism
the only commercially available antimetabolite are the sulfoanamides (sulfa drugs)
really not antibiotics - synthetic chemicals
=> discovered by extension of Ehrlich’s search for a magic bullet screening of organic chemicals
Sulphanilamide
what does it do
competitive inhibitor of p-aminobenzoic acid and prevents the incorporation of p-ABA into folic acid
folic acid is a co-factor in many essential enzymes including C1 metabolism needed for the biosynthesis of purines, pyrimidines, methionine
Bacterial targets of Sulphanilamide
broad spectrum antimicrobial agents
GAS Strep pneumonia Staphylococci Neisseria spp Haemophilus influenzae Bordetella pertussis Yersinia pestis Chlamydia spp
The use of Sulphanilamide today
the use of sulphonamides is now limited by widespread resistance in bacteria and toxicity
most common sulfa drugs now used are sulfisoxazole and sulphamethoxale
use is restricted to treating UTIs
Dapsone- the main drug used in leprosy treatment
Inhibition of cell wall biosynthesis
most important target is peptidoglycan biosynthesis
most important inhibitors of peptidoglycan synthesis are the beta-lactams
penicillin was discovered in 1928 by Fleming
=> observed lysis of Staphylococcus colonies on a plate contaminated with mold (penicilliium notatum) (today penicillum crysogenmum is used commercially)
