Quiz 1 - Smith - AMDs Flashcards
What is an antibiotic?
Low molecular substance produced by a microorganism that inhibits or kills other microorganisms while causing little or no damage to itself
What is an antimicrobial?
A natural, semisynthetic, or synthetic origin that kills or inhibits the growth of microorganisms while causing little or no damage to the host
All antibiotics are ____________, but not all antimicrobials are ___________.
Antimicrobials
Antibiotics
Antifungals are also called what?
Antimycotics
Bacterocidal does what?
Kills
Bacteriostatic does what?
Stops growth
Broad spec is what?
Drugs that are active against a wide range of microorganisms
*Tetracyclines
Narrow spec does what?
Limited activity and are used against particular species of microorganisms
No _______ is effective against all microbes.
Antimicrobial
With AIDS patients, only use what type of anticmicrobial?
BACTERIOCIDAL
What is the MIC and what does it mean?
Minimal inhibitory concentration - based on the diameter of the zone of inhibition
*The minimum lowest conc of an antimicrobial drug that inhibits the growth of the bacterial strain plated
What does MBC mean?
Minimum bactericidal concentration
What phase of bacterial growth is most sensitivity to antimicrobial intervention?
Log phase - Period of most rapid growth
Empiric vs definitive AMT
Empiric - After symptoms, but before pathogen has been identified.
Definitive - When we know what bug it is
Pharmacokinetics vs pharmacodynamics?
PK - What the body does to the drug (ADME)
PD - What the drug does to the body
What does ADME stand for?
Absorption - Route of administration and determines the compound’s bioavailability
Distribution - Lipid or H2O soluble, bbb crossing?
Metabolism - Usual routes of clearance are thru liver and kidneys. Cytochrome P450 enzymes
Excretion - Low potency drugs are often used for UTI’s since they concentrate in urine b/c their resorption is so low
Although MIC is often compared to plasma concentrations, these concentrations may NOT reflect ______ concentrations at the infection site.
Drug
Ideally, antimicrobial therapy will be dosed to provide overkill w/o causing what in the host?
Toxicity
What distinguishes antimicrobials from disinfectants?
Selective toxicity
*When selectivity is high, the risk of adverse effects are reduced
The ideal AMT is defined by what?
It’s specificity of action in host vs bacteria
Not all, but many, adverse effects are dependent upon what?
Dosage
Therapeutic index is calculated how?
TD50/ED50
Toxic dose / effective dose
*Higher or wider the therapeutic index, the better/safer the antibiotic
Adverse effects of AMTs can be __________ to antimicrobial action.
Analogous
Adverse effect of AMTs may be ____________ of antimicrobial action.
Independent
*There may be an irritation or an allergy that the patient has
AMDs target all essential microbial processes which include what 4 things?
Cell wall synthesis and cell membrane function/permeability
Protein synthesis - inhibits the 50s and/or 30s ribosomal subunits
Inhibition of metabolic pathways
Nucleic Acid synthesis of DNA and/or RNA
What are 4 reasons to use combination therapy?
Treat inherently mixed infections - Antimicrobial combos broaden spectrum of coverage
Improve efficacy - However, NOT ALL COMBOS INCREASE EFFICACY
Initial empiric therapy of uncharacterized serious infection
Prevent emergence of resistance - lowers probability of selection of naturally occurring drug-resistant mutants
What is a superinfection?
An overgrowth of pathogenic bacteria
How are superinfections caused?
Use of broad-spec antimicrobial agents
Use of higher than normal concentrations of even narrow-spec antimicrobial agents
What is antimicrobial resistance (AMR)?
Natural process by which microbes evolve to resist the effects of the medications used to treat them
Bacteria can mutate in 3 main ways. Name them.
By chance
By horizontal gene transfer
By strong selective evolutionary pressures (like the increased use of antibiotics in both clinical and agricultural settings)
What is horizontal gene transfer (HGT)?
Process whereby genetic material in small packets of bacterial DNA are t-ferred b/t individual bacteria of either the same or different species.
This material often conveys antimicrobial resistance b/t bacteria.
HGT has three mechanisms. Name them.
Conjugation - MAIN MECHANISM FOR HGT - Plasmid transfer (bacterial sex)
Transformation - Resistant gene can be taken up from a dead bacteria
Transduction - Viral route via bacteriophage
What are the major mechanisms of resistance?
Restrict AMD access - Prevent entry, or to pump in back out of the bacterial cell before the desired effect (efflux pumps)
Modify AMD’s target - Alter target protein or overexpress target protein requiring more drug
Modification of the AMD - Inactivate the AMD before affecting its target
or Prevent AMD activation - changing expression of bacterial factors/enzymes needed to activate the precursor
Antibiotics fit in to their target proteins like a key in a lock, so how do bacteria modify the target?
Change protein sequence
Add chemical groups (Methylation, etc.)
*Change the key and/or change the lock
How are beta-lactams inactivated?
Beta-lactams target PBP (penicillin-binding proteins) by binding them and inactivating them.
Bacteria alter the PBP site to prevent binding and normal bacterial function is restored
What do beta-lactamase enzymes do?
Destroy the antibiotic by breaking open the beta-lactam ring
*The more beta-lactamase produced, the higher the level of resistance
Resistance by modifying expression of bacterial factors needed to activate the antibiotic - prodrug
This renders the pro-drug inactive
Antimicrobial effects may be classified based on three types. Name and describe them.
Type I - Conc-dependent - Goal maximize concentrations
Type II - Time-dependent - Maximize duration of exposure
Type III - Time-dependent with persistent effects - Maximize amount of drug
