Antibacterial Basics Flashcards
Antibiotics (ABs) are substances produced to kill microorganisms or to protect from toxins produced by microorganisms, what are the 3 ways ABs are produced?
by microorganism
precursor by microorganism - semi synthetic
synthetic
in 1936 what noted to kill streptococci?
sulfanilamide
what was discovered in 1928 and began mass production of it in 1941
penicillin
most of the over 100 AB drugs in clinical use are what?
semi synthetic
What are the properties of a ideal AB
stability, Solubility, diffusibility (crosses the BBB), slow excretion (protein binding, drug combos), and large therapeutic index= SELECTIVE
PEN G (Benzyl penicillin) vs PEN V (phenoxy-benzyl penicillin), which one is stable in acids thus can be take orally
PEN V is stable in ACIDS
PEN G is NOT stable in acids
Therapeutic index = TD50 / ED50
what is TD 50?
what is ED50?
do you want a large or small Therapeutic index?
TD50= toxic dose
ED50= effective dose
want a HIGH therapeutic index bc that means drug is safer and more SELECTIVE
the microbe response to a AB can be resistance or secondary products of bacterial destruction, what 3 things are taken into consideration when resistance by a microbe is occurring?
resistance tells you to consider:
- choice of drug
- the dosage of the drug
- drug combos
what 5 ABs are considered Bacteriostatic?
sulfonamides trimethoprim tetracyclines erythromycin Vancomycin*
what 5 ABs are considered Bactericidal?
Vancomycin * quinolones penicillins cephalosporins aminoglycosides
what is the 1 AB that was considered bactericidal but due to INC resistance has led to it becoming more of a bacteriostatic drug
Vancomycin
what do bacteriostatic drugs do
bacteriostatic drugs stop the growth of that microbe. so on a graph static drugs will just halt the growth thus not allowing microbe to inc in number
what do bactericidal drugs do
bacteriocidal kills the microbe! so on a graph cidal drugs will bring the amount of microbe to 0
what is prophylaxis?
how much AB drug use is for prophylaxis?
prophylaxis temporarily decs the most likely pathogens below a critical level required to cause infection.
Prophylaxis accounts for .25-.5 of AB drug use
what is empiric therapy?
initiation of treatment (tx) before etiology of infection is known with agents known to be effective against the most likely pathogen acquired (suspected from source of infection)
what are the differences between gram + and gram - bacteria
gram + : many lactamases, thick cell wall of peptidoglycans, membrane has PBPs, 1 cell membrane
gram - : few lactamases, thin cell wall of 1-2 layers of peptidoglycan, 2 cell membranes, 1 on outside then cell wall layer then 2 cell membrane
What is MIC
MIC - minimum inhibitory concentration - the lowest concentration of drug which completely inhibits growth at 24 hrs
what is MBC
MBC- minimum bactericidal concentration
what does Vancomycin work against?
GRAM + bacteria!
Too big to work against gram -
what is the note about choosing a AB
once sensitivity profile is known, choose the effective drug with the narrowest spectrum to avoid emergence of resistance microbes
what variables are used to determine AB sensitivity? aka susceptibility guided therapy.
MIC
MBC
disk diffusion assays and etest
what is the Gold Standard for determining MIC
Broth dilution assay
the location of infection is important for choosing AB and agents in the CNS are hard to treat, what kind of AB will treat a CNS infection
ABs that are lipophilic that can cross the BBB will treat a CNS infection
what are the variables of pharmacokinetics that need to be taken into consideration about ABs?
ADME+T
absorption, distribution/ excretion, metabolism + toxicity (nephro, ototoxicity, hypersensitivity)
Metabolism is important in Prodrugs why?
Prodrugs require activation and are based on cytochrome p450 activation or inactivation
What host factors must be considered when prescribing a AB?
what is the importance of age?
age (young people metabolize, clear drugs faster than older)
allergies, food/ hydration (Ca can limit absorption of ciprofloxacin)
hepatic function (will pro drug be activated?)
pharmacogenetics (fast vs slow metabolism)
pregancy
immune status
Describe the 3 AB cocktail situations
a) empiric therapy
b) mixed infections
c) synergism
a) empiric therapy- for serious infections of unknown etiology
b) mixed infections: intra abdominal- potentially several microbes, use 2 narrow spectrum ABs
c) synergism: more than additive effects of using 2+ ABs, different MoA leading to one drug making the other more effective
An example of synergism is use of B lactam and aminoglyoside combo, what are the functions of each and how is this synergism?
B lactam: cell wall synthesis inhibitors
Aminoglycosides: inhibitors of protein synthesis
use of B lactam compromises cell walls allowing Aminoglycosides to accumulate inside the cell thus killing it
An example of synergism is the use of trimethoprim and sulfamethoxazole, what is the combo used for?
tx of gram - urinary tract infections
what is antagonism? what example was provided?
antagonism- less than additive effects.
use of bacteriostatic drug with B lactam, bacteriostatic drug inhibits cell growth thus requiring no new cell wall synthesis making B lactam useless
what 4 ABs of inhibitors of Nucleic acid synthesis?
2 classes describe the two classes and the drugs in each class
Inhibits folic acid synthesis= sulfonamides, trimethoprim and antifolates
RNA synthesis inhibitor= Rifampin
Rifampin does what
inhibits RNA synthesis
sulfonamides, trimethoprim and antifolates do what
inhibits folic acid synthesis
What 4 Abs are DNA damaging agents?
quinolones
Nitrofurantoin
Metronidazole
Methenamine
what do quinolones do?
DNA gyrase A, Topoisomerase 4 inhibitors
what do Nitrofurantoins do?
free radical generator
What do Metronidazoles do?
anaerobic enzymatic reduction then metabolite DNA binding
What do Methenamines do?
breaks down to form formaldehyde which alkylates DNA and protein
what 3 ABs are inhibitors of cell wall synthesis
B Lactams
Vancomycin
Bacitracin
What do B lactams do? What drugs are under the class of B lactams?
B lactams inhibit the transpeptidation cross linking of peptidoglycan B lactams include: penicillin cephalosporins, monobactams (aztreonam) carbadpenems (imipenem)
what does Vancomycin do?
what bacteria does Vancomycin work against?
Vancomycin binds to D-ala-D-Ala preventing polymerization of cell wall components
Vancomycin= Gram +!!
what does Bacitracin do?
binds to and prevents functioning of lipid carrier of peptidoglycan
Penicillin is what type of drug and MoA?
penicillin is a beta lactam that inhibits cell wall synthesis by inhibition of transpeptidation cross linking of peptidoglycan
What 2 Abs are responsible for damage of cell membrane?
polymyxins
daptomycin
polymyxins do what to damage cell membrane
polymyxins are cationic detergents that disrupts the cell membrane
daptomycin does what?
daptomycin is a lipopeptide that disrupts membrane function
cephalosporins are what type of drug and what is its MoA
Cephalosporins are a beta lactam that inhibits cell wall synthesis by inhibition of transpeptidation cross linking of peptidoglycan
What are the 7 (1 combo) Abs that are inhibitors of protein synthesis by ribosomal protein binding to 30s or 50s
aminoglycosides- bactericidal tetracyclines= bacteriostatic tigecycline macrolides clindamycin linezolid Quinupristin/ dalfopristin= bactericidal
monobactams are what type of drug and what is its MoA
monobactams are a beta lactam that inhibits cell wall synthesis by inhibition of transpeptidation cross linking of peptidoglycan
what are the 3 Abs under the class called macrocodes? and what are their MoA
Macrolides= erythromycin, clarithromycin, azithromycin
Macrocodes are inhibitors of protein synthesis
carbapenems are what type of drug and what are their MoA
carbapenems are a beta lactam that inhibits cell wall synthesis by inhibition of transpeptidation cross linking of peptidoglycan
what is a inhibitor of dihydrofolate reductase (DHFR) that is a structural analog of pteridine?
is it bacteriostatic or tidal?
trimethoprim
Trimethoprim is bacteriostatic!!
can be tidal if with a sulfonamide
what is trimethoprims selectivity
very selective needs much higher concentration to inhibit human DHFR
