Lecture 18 antimicrobial agents Flashcards
Paul ehrlich
german physician and bacteriologist
observed dyes stain in bacterial cells
searched for magic bullet that would kill pathogens without harming human
Salvarsan
Gerhard domagk
Red dye prontosil
used to treat step infections in animal
Chemotherapeutic agents
Salvrsan, red dye prontosil
chemicals used to treat disease
Who discovered penicillin
Fleming
First antibiotic
Penicillin G
Selman waksman purified
Streptomycin
Selective toxicity
Causes greater harm to microbes than human host
Toxicity is relative and expressed as
therapeutic index
Therepeutic index
lowest dose toxic to patient divided by dose used for therapy
Penicillin G has a ______ therapeutic index
high
TI equation
LD50/ED50
Bacteriostatic
chemicals inhibit bacterial growth
Patient’s defense must eliminate pathogen
Bactericidal
chemical kills bacteria
broad-spectrum antimicrobials are important for treating ______ dsiease
acute, life-threatening
Negative side effect of broad-spectrum antibmicrobials
can disrupt microbiome that helps keep out pathogens, dysbiosis
Narrow spectrum antibiotics
affectlimiated range
Narrow spectrum antibiotics requires
identification, susceptibility of pathogen
Half life of medication
time it takes for serum concentration to decrease by 50%
Half life medication dictates
frequency of doses required
adverse effects of antibiotics
allergic reactions, toxic effects, dysbiosis
intrinsic resistance
structural resistance of bacteria, outer membrane of gram negatives block any meds
Bacterial may develop ______ resistance
Acquired
Bacterial processes affected by antibiotics
cell wall synthesis
protein synthesis
nucleic acid synthesis
metabolic pathways
cell membranes
Beta lactam antibiotics have a ______ and ______ therapeutic infex
Beta lactam ring, high
Beta lactam antibiotics competitively inhibit ______
Penicillin binding proteins (PBPs)
PBPs
catalyze formation of peptide bridges between adjacent glycan strands, disrupt cell wall sythesis
PBPs are only effective against
actively growing cells
what does Beta lactam antibiotics do to gram cells
peptidoglycan of gram positives exposed
outer membrane of gram negatives blocked
Penicillinase
inactivates members of penicillin family
______ inactive a wide variety of beta lactam meds
extended spectrum beta lactamase (ESBLs)
gram ______ produce more Beta lactamase than gram ______
Negatives, positives
Extended spectrum penicillins have greater activity against ______ species
enterobacteriaceae, Pseudomonas
ESBLs have reduced activity against gram______
positives
Augmentin
Penicillin + beta lactamase inhibtor added to protect penicillin from being degraded by B-lactamase
Cephalosporins
resistant to B-lactamase
has low affinity for PBPs of gram positives
Glycopeptide antibiotics
bind to amino acid side chain of NAM molecules
Blocks peptidoglycan synthesis
Glycopeptide antibiotics are only effective against gram ______
positives
Side effects of glycopeptide antibiotics give ______ TI
Low
most widely used glycopeptide
Vancomysin
Bacitracin
Toxicity limits to topic applications
Ribosomes of prokaryotes
70S
Ribosomes of eukaryotes
80S
Ribosomes of mitochondria
70S
Aminoglycosides ______ bind to 30S, causing malfunction
Bacteriocidal
Irreversibly
Aminoglycosides block initiation of ______,
causes misreading of ______
translation
mRNA
Aminoglycosides is ineffective against
Anaerobes, enterococci, streptococci
inhaled form of ______ treats pseudomonas lung infections in cystic fibrosis
Tobramycin
Tetracyclines ______ bind to 30S
Reversibly
Tetracyclines block ______ attachment, prevent translation
tRNA
Tetracyclines are effective against
Gram positives, gram negatives
Glycylcyclines are effective against bacteria resistant to ______
Tetracyclines
Macrolides ______ bind to ______ unit
reversibly, 50S
When is macrolides used
When patient is alelrgic to penicillin
Macrolides is a bacteriostatic against gram ______
positives
Macrolides are not effective against
Enterebacteriacaea
Resistance of macrolides occurs from modification of ______
Ribosomal RNA target
Chloramphenical binds to ______ subunit
50S
Chloramphenicol is used to ______ side effect
lethal
Fluoroquinolones inhibits ______
Topoisomerases
What is topoisomerases
Enzymes that maintain supercoiling of DNA
Fluoroquinolines is when ______ breaks, rejoins strands to relieve strain from localized unwinding of DNA
DNA Gyrase
Rifamycins block ______, prevents initiation of ______
RNA polymerase, transcription
Rifampin is a bactericidal against gram ______
positives
Folate inhibitors are most useful for
interfering with metabolic
Animals lack enzymes to synthesize folate, requires in ______
diet
Sulfonamides are ______ drugs
Sulfa
Sulfa drugs are similar to ______, so enzymes binds chemical
PABA
______ inhibits enzyme in later step
Trimethoprim
Sulfa drugs is an example of ______
competitive inhibition
Combination of trimathoprim and sulfonamide forms
Co-trimoxazole
Daptomycin inserts into ______
cytoplasmic membrane
Daptomycin is ineffective against ______
gram negatives
Polymyxins bind to membranes of ______
gram negatives
______ drugs are effective to mycobacterium
First line
______ inhibits mycolic acid synthesis
Isoniazid
______ inhibits enzymes required for other cell component synthesis
Ehtambutol
______ interferes with protein synthesis
Pyrazinamide
kirby bauer disc diffusion test
sample of strain uniformly spread on agar with different antibiotics placed
drugs diffuse outwards
zone of inhibition used to determine whether strain is susceptible
minimum inhibitory concetrion
lowest concentration that prevents growth in vitro
Minimum bacterial concentration
lowest concentration that kills all cells in vitro
Resistance to antimicrobial meds is increasing because
increasing use, misuse for resistant microorganisms
Antibiotic inactivation enzymes
bacteria produce enzymes that interfere with drug
example of antibiotic inactivation enzymes
Penicillinase, extended spectrum B-lactamase
Alteration in target molecule
Minor structural changes to target can prevent binding
Decreased uptake of medication
caused by changes in porin proteins which selectively permit molecules to pass membrane
stops entry of antibiotic
Decreased uptake of medications occurs in gram ______
negatives
Increased elimination of medication
Cell makes more efflux pumps, compound is ejected faster
Spontaneous mutations can be caused by a single ______ change in gene
base-pair, encodes a ribosomal protein
Combination therapy
combining multiple medications to a cell with a spontaneous mutation so that at least one of them will kill it
gene transfer is commonly ______
conjugative transfer of R plasmids which carry several different resistance genes
Resistance genes on R plasmids originate from
spontaneous mutations
microbes that naturally produce the antibiotic