Principles of Antimicrobial Use Flashcards
define empiric therapy
therapy based on knowledge of the antimicrobial spectrum
define broad spectrum
targeting a wide range of bacterial organisms
define narrow spectrum
targeted to more specific classes of bacteria
- less impact on normal flora
define bactericidal
killing of organisms
define bacteriostatic
preventing further growth
define bacterial resistance
untreatable infections that require the use of toxic drugs
what activity or structure is always a potential target?
anything that is different from the host organism
list 2 beta-lactam drug classes
- penicillin
- cephalosporins
describe alexander fleming’s contribution
in 1928 discovered the inhibition of Staph. Aureus on agar plates of penicillium
what are the 2 wall synthesis inhibitors?
- beta-lactams
- Glycopeptides
beta-lactams are a broad spectrum drug that are primarily effective against
gram + bacteria
what is a characteristic of beta-lactams?
they are bactericidal
beta-lactams have poor entry into the CNS therefore they are
actively transported out
what is the most common adverse reaction to beta-lactams?
hypersensitivity
how do bacteria become resistant to beta-lactams?
they synthesize beta-lactamases or penicillinases
what is the MOA of beta-lactams?
to inhibit the crosslinking of peptidoglycan strands
- peptidoglycan is a chief component for cell wall synthesis
penicillin’s are not active against what type of organisms?
those that lack a peptidoglycan cell wall
list examples of organisms that are resistant to penicillin
- mycobacteria
- protozoa
- fungi
- viruses
explain the concept of using beta-lactamase inhibitors in combination with other beta-lactam antibiotics
amoxicillin is not resistant to beta-lactamases so its combined with beta-lactamase inhibitors to increase their therapeutic value
list an example of a beta-lactam antibiotic that is used in combination with a beta-lactamase inhibitor
augmentin
amoxicillin + clavulanic acid
calvulanic acid is a
beta-lactamase inhibitor
explain why penicillin has such a poor oral absorption
due to ion trapping and stomach acidity
as much as 60% of penicillin that is absorbed is bound to
plasma proteins
beta-lactam drugs differ by what 3 characteristics?
- organisms inhibited
- pharmacokinetics
- bacterial resistance of certain organisms to different drugs
list 2 examples of inhibitors of DNA synthesis
- folate antagonists
- DNA topoisomerase inhibitors
which if the following 2 is bacteriostatic?
folate antagonists
DNA topoisomerase
folate antagonists
which of the following is bactericidal?
folate antagonists
DNA topoisomerase
DNA topoisomerase
tetrahydrofolate is the active form of
folic acid
tetrahydrofolate is a coenzyme that is required for the synthesis of what in bacteria and humans?
- nucleotides
- A.A
what is the difference between folate synthesis in humans and in bacteria?
humans: dietary dependence
bacteria: synthesized intracellularly
what is an additional way of inhibiting bacterial growth that involves folate?
inhibiting the synthesis of folate stops synthesis of a.a and nucleotides
drugs that affect the ____________ but not the _____________ of folic acid affects the bacteria but not the eukaryotic host
- synthesis
- utilization
folate antagonists can be described as being
bacteriostatic
what are 2 examples of folate antagonists?
- sulfonamides
- trimethoprim
sulfonamides are
structural analogs of para-aminobenzoic acid (PABA)
PABA is a substrate necessary for
folic acid synthesis
what are 2 examples of sulfonamides?
- sulfanilamide
- sulfadiazine
sulfonamides competitively inhibit the enzyme
dihydropteroate synthase
what is the effect of inhibiting dihydropteroate synthase?
- depletes folate production
- slows bacterial division
sulfonamides are
broad spectrum
DNA topoisomerase inhibitors can be described as being
bactericidal
what is an example of a DNA topoisomerase inhibitor?
fluoroquinolones
what is the MOA of DNA topoisomerase inhibitors?
inhibits the unwinding of DNA therefore the DNA is not available for transcription or translation
what are the 3 types of protein synthesis inhibitors?
- aminoglycosides
- macrolides
- tetracyclines
bacterial RNA polymerase is smaller and less complex than in human therefore…
transcription and translation can occur within the same compartments of bacterial cells
what are the 5 sites of action for drugs that inhibit bacterial protein synthesis?
- freeze initiation (no ribosome progression along mRNA)
- prevent tRNA from binding to mRNA
- block peptide formation
- block translocation step
- misread mRNA so wrong amino acid is inserted
what are 2 examples of aminoglycosides?
- streptomycin
- gentamicin
aminoglycosides are effective against
aerobic gram-negative organisms
what is the MOA of aminoglycosides?
freeze the initiation of mRNA and misreads the mRNA
aminoglycosides have a low
TI (therapeutic index )
aminoglycosides are only used for serious infections that have been acquired in what settings?
nosocomial
hospital settings
PHARMACOKINETICS
aminoglycosides have poor oral absorption b/c they are
cationic and polar
aminoglycosides are administered
IM or IV
Where are the two primary areas of potential toxicity in the body listed in your notes that may limit their use only to serious infections?
- ototoxicity
- renal toxicity
tetracyclines prevent
tRNA from binding to mRNA codon
what are the 7 characteristics and methods of viral replication?
- absorption and penetration into host
- uncoating of viral nucleic acid
- synthesis of regulatory proteins
- synthesis of RNA or DNA
- syn. of late regulatory proteins
- assembly & maturation of viral particles (virions)
- release from cells
entry inhibitors block the
entry of viral products
uncoating inhibitors inhibit the
release from lipid capsule
reverse transcriptase inhibitors prevent the
RNA to DNA transcription
translation disruptors promote
- antisense DNA or RNA segments
- ribosomes that cut newly translated DNA or RNA
protease inhibitors inhibit the enzyme involved w/ the
final assembly of newly synthesized viral chains
release inhibitors block
the release of viral replicates from the host cell
HIV virus primarily binds to the
HIV: human immunodeficiency virus
GP120 site on CD4 cells
CD4 cells are aka
T-helper cells
- subtype of t-lymphocytes of the immune system
what conditions are necessary for opportunistic infections and cancers to begin invading the body?
- viral titer increases
- [CD4] decreases
what is known as the outward manifestation of HIV?
AIDS
(Acquired Immunodeficiency syndrome)
is it possible to be HIV positive but not have AIDS by definition?
yes
what are 3 treatment approached to HIV and AIDS
- antiretroviral Agents
- protease inhibitors
- fusion inhibitors
what is an example of an antiretroviral agent?
zidovudine (AZT)
what is an example of an protease inhibitor?
saquinavir
what is an example of a fusion inhibitor?
enfuvirtide (fuzeon)
what is the MOA of COVID
virus uses glycoprotein spikes to connect to ACE2 which then binds to ACE2-receptors and enters the host cell
ACE: angiotensin-converting enzyme
the density of ACE2-receptors in a tissue is directly correlated to the
severity of COVID in that tissue
what has shown to be a protective treatment/ approach to COVID?
decreasing/blocking ACE2 activity at its receptor sites
ACE2 receptors are high expressed in which organ?
the heart
the COVIS virus can cause
- acute myocardial injury
- chronic damage to cardiovascular system
ACE2 is abundantly found throughout the
GI tract
what type of GI issues can present from COVID?
pain and digestive issues w/ loss of nutrients in the body
how does COVID affect the vascular system?
sets off chain of vasoconstrictive responses
how does COVID affect the respiratory system?
- constriction of blood vessels w/in the pulmonary circulation causing decreased oxygenation and viral pneumonia
how does COVID affect the urinary system and kidneys?
it can lead to kidney complications that can be fetal
what are the 7 types of treatments for COVID?
- convalescent plasma
- regerneron
- remdesivir
- chloroquine & hydroxycholorquine
- reverse transcriptase inhibitors
- paxlovid
- vaccines
describe convalescent plasma
plasma that contains the antibodies from patients that have recovered from COVID
regeneron are
polyclonal antibodies that bind to spike regions of the virus
remdesivir is a broad-spectrum anti-viral drug that
inhibits viral replication through early termination of viral transcription
chloroquine & hydroxychloroquine are drugs that originally were prescribed to treat
malaria, lupus, and rheumatoid arthritis
chloroquine and hydroxychloroquine are drug that interfere w/ the binding of COVID virus to ACE2 receptors by inhibiting
glycosylation of ACE2 receptors
chloroquine and hydroxycholorquine have to be taken under close supervision b/c
there’s concern for cardiotoxicity
reverse transcriptase inhibitors are drugs that were used to treat
HIV by inhibiting mRNA from producing DNA for viral replicates
paxlovid are protease enzyme inhibitors that block the replication of
new virons
what are the 2 COVID vaccines?
- Pfizer
- Moderna
the 2 covid vaccines are both
mRNA vaccines that contain a synthetic version of COVID genetic code
the covid vaccines MOA can be described as
body synthesizing the covid spike protein -> an immune response is produce making antibodies w/ the ability to defeat the real virus
the covid vaccines require
2 doses w/ 95% efficacy rate
