Pharmacology: Antibiotics Flashcards
Why are synthetic antibiotics not “true” antibiotics?
By definition, ABX are naturally occurring substances produced by a microorganism to target another microorganism
What is the ideal trait of antibiotics to effectively treat a patient? What microbes present an issue for this?
Selective toxicity
Viruses, cause they use our cell’s machinery
Fungi and Parasites: they’re euks and have similar functions
What is the minimum inhibitory concentration?
The concentration of an antibiotic where the colony cannot grow its numbers
What is the minimum bacteriocidal concentration?
The concentration that kills 99.9% of microorganisms in a colony
Why is MIC or MBC unreliable for clinical dosing?
Pharmacokinetic functions, such as first pass metabolism, protein binding, and metabolism, may decrease the effective dose of ABX in a patient
What areas are difficult to reach and may require a larger dose of antibiotics?
CNS, bone, adipose tissue
What is the reason some people have allergic responses to ABX?
ABX are antigenic, so they can react with the host immune system
What are bacteriostatic and bactericidal ABX?
Static: halt growth of bacterium
Cidal: kill and decrease concentration of ABX
Knowing the action of bacteriostatic ABX, how does a infection clear? What is a contraindication for this type?
Via host immune system
Compromised immunity
What are the chemotherapeutic spectrum types?
Broad, narrow, and extended
What are the three general areas that ABX target in a bacterial cell?
Nucleic acid synthesis, ribosomal protein synth, and the cell wall
Describe a few ways bacterium can defend and adapt against ABX?
Reduced entry or drug, efflux pumps (MDR protein), alteration of target proteins, alteration of metabolism
What kind of antibiotic destabilizes the cell wall of a bacterium?
Bactericidal
What enzyme links the layers of sugars in the peptidoglycan walls? What residues are used in this linkage?
Transpepditases
D-alanine
What do beta-lactam drugs target in a cell?
Transpeptidase in the cell wall
What is another name for transpeptidase?
Penicillin binding protein
What does penicillin target? What types of bacterium does this work against? What are its extended-spectrum agents? What do they work against?
1&2)Transpeptidases; & Gram positive bacterii and syphilis
3&4) amoxicillin, ampicillin, amniopenicillin; gram + and -
How effective is Penicillin against today’s bacterium?
Not good due to resistance; only acts well with syphilis
What class are cephalosporins? How can they be recognized via nomenclature?
Beta-lactams; largest B-lac class; have ceph- or cef- in name
What class is carbapenem ABX? What is its spectrum? Potency? What are common clinical uses?
B-lactam; broad spectrum and potent; usually used as a combination therapy drug; NEEDS INHIBITORS WITH ITS MOST UNSTABLE FORM
Are monobactams considered true B-lactams? What does it target? What is its spectrum?
No; Gram -; narrow-spectrum
What are common allergic responses to B-lactams?
Anaphylaxis/cytolytic anemia
How are B-lactams allergenic? What if a patient is allergic to penicillin, what B-lactams can be prescribed?
Bind to human proteins;
NO B-lactams can be prescribed, it is a classwide (monobactams are safe since it does not have extra ring structure)
What enzyme gives bacteria resistance to B-lactams?
B-lactamase
What are some ways around B-lactamases? How does this work?
Combination therapy: strong B-lact with weak B-lact- weak B-Lac binds to enzyme, strong kills the bacteria
Chemical modifications to drugs (ie Methicillin from penicillin)
How do glycopeptides work to be an ABX?
Bind to D-alanine and prevent crosslinking from transpeptidase
What antibiotic is historically effective against MRSA? What class is this ABX? What is this drug not effective against? How has MRSA adapted to this drug?
- Vancomycin
- Glycopeptide
- gram - bacteria
- changed transpeptidases to not use D-alanine links in cell wall
What type of antibacterial inserts into the plasmalemma and disrupts the cell wall? What are these effective against?
Lipopeptides (like Daptomycin)
-vancomycin resistant strains
How do lipopeptides kill bacteria?
Create pores in the cell mem to disrupt osmolarity
What does bacitracin do?
Prevents peptidoglycan subunits from reaching cell surface
Are bacitracin and lipopeptides bacteriostatic or bactericidal? What are their draw backs? How are they typically administered?
- cidal
- very toxic to humans (nephrotoxic due to lipid mems in the kidney)
- topical administration
What are polymixins? What are they effective against? What are its drawbacks?
Positively charged peptides that disrupt cell membrane structure
- gram -
- cannot be taken orally due to charge
Are direct nucleotide synthesis inhibitors cidal or static? Broad or narrow spectrum?
Cidal and broad
How can bacteria become resistant to nucleotide synthesis disrupting ABX?
Changing the antibiotic, altered protein targets, expression of protective proteins
What do quinolones do?
Inhibit topoisomerases on bacterial DNA during replication
What does rifampin target?
RNA polymerase to prevent mRNA synth
What does metronidazole do?
Cleaves daughter strand of DNA to prevent replication
Are indirect DNA/RNA synth inhibs bacteriostatc or cidal? Broad or narrow?
Static; broad spectrum (even protozoa)
How do sulfonamides function on bacteria?
Targets dihydropteroate synthase (in folic acid synthesis)
How does trimethoprim target bacteria?
Inhibits dihydofolate reductase (in folic acid synthesis)
How are indirect RNA/DNA synth inhibs resisted?
Increased substrates for their target proteins to overpower them
Are protein synth inhibs bacteriocidal or static? Where do they function? Broad or narrow? Gram + or -?
Mostly static, but can be cidal
Mostly on the ribosome
Can be broad or narrow
Can be Gram - or +
Why shouldnt protein synth inhibs be used as first line against infections?
Toxicity is abundant in this class
Where does tetracycline bind? What does it do?
Binds to 30s subunit/ disrupts tRNA interaction
Where does erythromycin bind? What does it do?
Binds to ribosome/ prevents translocation of peptide chain
Where does chloramphenicol bind? What does it do?
Mimics/binds to amino group attached to tRNA; prevents formation of peptide chain
What are some reasons to do combination therapy?
Multiple microbes, very ill patients, prevent spread of drug resistant pathogens, reduce chances of toxicity
Cons: drug-drug interactions
What are addative and synergistic combinations?
Addative is the addition of each drug’s potency
Synergy is 1+1=4 (more than sum of parts)
What is a good example of antagonistic combinations?
Tetracyclines and penicillins- tet reduce efficacy of penicillin
(Penicillin better on growing bacterial colonies)
