Antimicrobial Chemotherapies Flashcards
what are chemotherapeutic agents?
chemical agents used to treat disease that destroy pathogenic microbes or inhibit their growth within the host
what are most chemotherapeutic agents classified as?
antibiotics
what are antibiotics?
microbial products or their derivative that kill susceptible microbes or inhibit their growth
how was penicillin discovered?
accidentally by Alexander Fleming
observed penicillin activity on a contaminated plate but did not think it could be developed further
what is selective toxicity?
ability of a drug to kill or inhibit a pathogen while damaging the host as little as possible
what is a therapeutic dose?
drug level required for clinical treatment
what is a toxic dose?
drug level at which drug becomes too toxic for the patient
what is the therapeutic index?
ratio of toxic dose to therapeutic dose
what are side effects?
undesirable effects of drugs on host cells
what are narrow spectrum drugs?
attack only a few different pathogens
what are broad spectrum drugs?
attack many different kinds of drugs
what do cidal agents do?
kills the target pathogen
what do static agents do?
reversibly inhibits growth of microbes
how does the effect of an agent vary?
with concentration, microbe, and host
how is effectiveness expressed? (2 ways)
minimal inhibitory concentration and minimal lethal concentration
what is minimal inhibitory concentration?
lowest concentration of drug that prevents growth of the pathogen
what is the minimal lethal concentration?
lowest concentration of drug that kills the pathogen
what are the main modes of action of antimicrobial drugs?
inhibitors of cell wall synthesis
protein synthesis inhibitors
metabolic antagonists
nucleic acid synthesis inhibition
how does chromosome replication and partitioning occur?
most bacteria have a single circular chromosome
what is the single origin of replication?
site at which replication begins
what is the terminus?
site at which replication is terminated, located opposite of the origin
what is the replisome?
group of proteins needed for DNA synthesis?
what is septation?
formation of cross wall between two daughter cells
what are the steps of sepatation (cytokinesis)?
selection of site for septum formation
assembly of Z ring (composed of protein FtsZ)
assembly of cell wall-synthesizing machinery
constriction of cell and septum formation
what is the main protein of interest in septation?
FtsZ
what are the steps of cell wall synthesis?
fliptadase moves the bactoprenol across the membrane and attaches to and moves the NAG-NAM complexes
glycosyltransferase joins all of the sugar layers together
transpeptidase (penicillin binding protein) attaches the amino acid chains and brings the layers together
would cell wall synthesis inhibitors work better against gram positive or gram negative bacteria?
gram positive because there is not the protection of the outer membrane that is present in gram negative cells
what is the most crucial feature of penicillin?
B-lactam ring
why is the B-lactam ring so important?
essential for bioactivity
what makes penicillin resistant organisms resistant?
many penicillin resistant organisms produce B-lactamase which hydrolyzes a bond in the ring
what is the mode of action for penicillin?
blocks the enzyme that catalyzes transpeptidation (formation of cross-links in peptidoglycan)
prevents the synthesis of complete cell walls leading to lysis of cell
acts only on growing bacteria that are synthesizing new peptidoglycan
what kind of penicillin is narrow spectrum?
penicillin V and G are narrow spectrum
why do semisynthetic penicillins have a broader spectrum than naturally occurring ones?
bulkier side chains make them more difficult for B-lactamase enzymes to degrade
what can include in an antibiotic to increase efficiency?
B-lactamase inhibitors
what are the characteristics of cephalosporins?
structurally and functionally similar to penicillin
broad spectrum antibiotics that can be used by most patients that are allergic to penicillin
there are four categories based on their spectrum of activity
what are the characteristics of vancomycin?
glycopeptide antibiotic
inhibits cell wall synthesis
vancomycin- important for treatment of antibiotic-resistant staphylococcal and enterococcal infections
previously considered “drug of last resort” so rise in resistance to vancomycin is of great concern
what do protein synthesis inhibitors do?
bind to the bacterial ribosome
what are the four steps that can be targeted by PSIs?
aminoacyl-tRNA binding
peptide bond formation
mRNA reading
translocation
aminoglycoside characteristics
large group, all with a cyclohexane ring, amino sugars
bind to the 30S ribosomal subunit, interfere with protein synthesis by directly inhibiting the process and by causing misreading of the messenger RNA
tetracycline characeristics
all have a four-ring structure to which a variety of side chains are attached
broad spectrum, bacteriostatic
target the 30S subunit of the ribosome that inhibits protein synthesis
macrolide characteristics
contain 12- to 22- carbon lactone rings linked to one or more sugars
ex: erythromycin
broad spectrum bacteriostatic
binds to 50S ribosomal subunit to inhibit bacterial protein elongation
used for patients allergic to penicillin
metabolic antagonists characteristics
act as antimetabolites and are structural analogs
what are antimetabolites?
antagonize or block functioning of metabolic pathways by competitively inhibiting the use of metabolites by key enzymes
what are structural analogs?
molecules that are structurally similar to, and compete with, naturally occurring metabolic intermediates to block normal cellular metabolism
sulfonamide drug characteristics
structurally related to sulfanilamide, a para aminobenzoic analog, which are used for the synthesis of folic aid and is made by many pathogens
makes them selectively toxic due to the competitive inhibition of folic acid synthesis
trimethoprim characterisitics
synthetic antibiotic that also interferes with folic acid production
broad spectrum
can be combined with sulfa drugs to increase efficacy of treatment
-combo blocks two steps of the pathway
what are the two most commonly used antibacterials drugs that inhibit nucleic acid synthesis?
fluroquinolones
rifamycins
why ae nucleic acid synthesis targeting drugs not as selectively toxic?
because bacteria and eukaryotes fo not differ greatly in the way they synthesize nucleic acids
fluoroquinolone characteristics
synthetic drugs that contain a 4-quinolone ring
act by inhibiting bacterial DNA gyros and topoisomerase II
broad spectrum, bactericidal, treat a wide variety infections
what does bacitracin do?
inhibits dephosphorylation
what does furazolidone do?
block DNA transcription
what does optochin do?
interferes with ATPase and ATP production
why has antiviral drug development been slow?
because it is difficult to specifically target viral replication bc many target cells are similar to our celss
tamiflu
anti-influenza agent
neuraminidase inhibitor
shortens course of illness
what are nucleoside reverse transcriptase inhibitors?
anti-HIV drugs that target and interfere with critical steps in viral replicative processes
what are non nucleoside reverse transcriptase inhibitors?
prevent HIV DNA synthesis by selectively binding to and inhibiting the viral reverse transcriptase enzyme
protease inhibitors
block the activity of the HIV protease needed for the production of all viral proteins
integrase inhibitors
present the incorporation of the HIV genome into the host’s chromosomes
fusion inhibitors
prevent HIV entry into cells
what is the most successful way to avoid resistance with HIV drugs?
drug cocktails
antifungals
fewer effective agents because of similarity if eukaryotic fungal cells and human cells
many have low therapeutic indexes and are toxic
superficial mycoses
Candida
topical and oral
disrupt membrane permeability and inhibit sterol synthesis
disrupts the mitotic spindle; may inhibit protein and DNA synthesis
systemic mycoses
difficult to control and can be fatal
what are the three common drugs to treat systemic mycoses?
amphotericin B-binds sterols in membrane
5-flucytosine-disrupts RNA function
fluconazole- low side effects, used prophylactically
examples of antiprotozoan drugs
quinine (chloroquine and mefloquine)-malaria
metronidazole- entamoeba
what are the three types of drug resistance?
intrinsic
acquired
drug-tolerant
intrinsic resistance
mycoplasma resistance to B-lactam antibiotics and other cell wall inhibitors because they lack a cell wall
acquired resistance
occurs when there is a change in the genome of a bacterium that converts it from one that is sensitive to an antibiotic to one that is resistant
i.e, plasmids
drug tolerant resistance
bacteria lacks the mechanisms for antibiotic resistance and ignore the presence of antibiotics
ex: bacteria embedded in biofilms
what are the 4 mechanisms of drug resistance?
modify the target of the antibiotic
drug inactivation using the enzyme from a plasmid
minimize the concentration of antibiotic in the cell by pumping them out
bypass the biochemical reaction inhibited by the agent or increase the production of the target metabolite
how can we overcome drug resistance?
give the drug in appropriate concentrations to destroy susceptible microbes and most spontaneous mutants
give two or more drugs at a time
use drugs only when necessary
continue development of new drugs
possibly use bacteriophages to treat disease
