Antibiotics MOA and Resistance Mechs. Flashcards
T or F: drugs that mess with the structure of bacteria are typically bacteriostatic
False
What are the most common drugs to form allergies?
-Penicillin
What is the preferred oral treatment for non-penicillinase producing streptococci?
-Penicillin V
Differentiate between
- Penicillin
- Monobactam
- Carbapenem
- Cephalosporins
- Vancomycin
Penicillin – Thiazole Ring
Monobactam –sulfonic acid
- gets it inside the cell wall
Carbapenem
- Replaces thiazole sulfur with carbon giving it MORE RESITANCE to ß-lactamases, better penetration and affinity for more PBP
Cephalosporins
- 6 membered ring to make it more stable
Vanco – inhibits d-ala d-ala binding by transpeptidases
What drugs bind the 30S RSU? Which bind 50S?
Buy AT 30, CELL at 50
A = Aminoglycosides
T = Tetracyclines
30S
C = Chloramphenicol E = Erthromycin (macrolides) L = Linezolid L = cLindomycin 50S
Why use muti-drug therapy?
- Treat polymicrobial infections
- Decrease emergence of resistance
- Descrease Dose-related toxicity
- Enhanced cell-kill
Why might tetracyclines and chloramphenicol antagonize bactericidal cell wall agents?
Cell wall agents require that the cell be dividing to be effective
Why might giving a ß-lactam antagonize an infection?
Some gram (-) bacilli possess inducible lactamases that will be induced by the presence of ß-lactams
Bactericidal Antibiotics
- Aminoglycosides*
- Fluroquinolones
- Nitrofurantion
- Sulfonamides with DHFR inhibitors
- Metronidazole
Bacteriostatic antibiotics
Protein synthesis inhibitors
Sulfonamides
What bacteria are often treated by combining Penicillins with aminoglycosides?
- Staphylococci
- Enterococci
- Streptococci
- P aeruginosa
4 methods by which antibiotic work
- Inhibition of Cell Wall Synthesis
- Inhibition of Protein Synthesis
- Inhibition of Folic acid biosynthetic paths
- Inhibition of DNA/RNA synth
MOA of ß-lactams
Bind Penicillin binding proteins (transpeptidase) which causes destruction of the bacterial cell wall gram (+) bacteria are really the only type of microbe affected by this
What are the protype penicillins?
Penicillin G and Penicillin V
What are the narrow spectrum penicillins?
Oxacillin and Nafcillin
What are the aminopenicillins?
Ampicllin and Amoxicillin
What are the broad spectrum penicillins?
Pipercillin
What are 2 examples of ß-lactamase inhibtors being combined with penicillins?
- Clavulanic acid with Amoxicillin
- Tazobactam with Piperacillin
What is a common structural characteristic of Broad Spectrum Penicillin?
- why are they called broad spectrum ?
- What are they usually administered with?
Broad spectrum because AMINO group added increases ability to cross lipid layer in gram (-) bacteria
Usually administered with ß-lactamase inhibitors (clavulanic acid, or Tazobactam)
What are narrow spectrum penicillins?
Have larger molecules on their side chain that confers steric hinderance and ß-lactamase can’t twist molecule into different stereoisomers
- these are narrow spectrum because bulky side groups limit the amount of different bacterias that can be targeted
What are the 3 major categories of ß-lactams?
- Penicillins
- Carbaenems
- Cephalosporins
General problem with aminoglycoside administration:
- affected organs?
Poorly absorbed in GI Tract so oral administration is not possible. In general intracellular concentrations are low except in proximal tubule of the kidney where they can accumulate and cause NEPHROTOXICITY
Drugs ending in –mycin or –micin typically have what general function?
- mycin = macrolides
- micin = aminoglycosides
- both inhibit protein synthesis
T or F: most protein synthesis inhibitors are bactericidal
False, they are bacteriostatic with the exception of aminoglycosides, and Synpristin/dalfopristin (streptogramins) that are bactericidal
What is the general trend of cephalosporins across generations?
They get increasingly better at attacking gram (-) bacteria and worse at gram (+) bacteria
Fluroquinolones to know
CIPROFLOXACIN
Levofloxacin
Rifamycins to know
RIFAMPIN
Rifaximin
DHFR drugs to know
COTRIMOXAZOLE
Trimethroprim
Sulfonamides to know
COTRIMOXAZOLE
Sulfamethoxazole
MOA for Aminoglycosides
Initial site of Action:
Outer bacterial membrane creating holes
Low conc.
Irreversibly bind the 30S ribosomal subunit at low concentrations causing misreading of mRNA.
High conc.
Halt protein synthesis by trapping AUG codon
Are aminoglycosides more effective against gram (+) or gram (-) bacteria?
- aerobic bacteria or anaerobic bacteria?
- Bacteriostatic or Bactricidal
- Why?
Gram (-) because they deteriorate the outer membrane which is more protected in gram positive
Aerobic because energy is needed for aminoglycoside uptake
Typically bactericidal against aerobic gram (-) bacteria
MOA for Lincosamides
(protein synth targeting)
Bind 50S ribosomal subunit (23S rRNA part) and inhibit Peptidyl Transferase, are phagocytosed by macrophages carrying them to the site of infection (ideally)
**also slows toxin production by inhibiting bacterial growth
Lincosamides to know
CLINDAMYCIN
MOA of Tetracyclines
Bind 30S RSU (16S part) and inhibit protein synthesis by weaking ribosome-tRNA interaction
Tetracyclines to know:
DOXYCYCLINE
TIGECYCLINE
Minocycline
Tetracycline
MOA for Macrolides
(protein synth targeting)
Bind 50S ribosomal subunit (23S rRNA part) and inhibit Peptidyl Transferase, are phagocytosed by macrophages carrying them to the site of infection (ideally)
Macrolides: Bacteriostatic or Bactericidal
Bacteriostatic at most concentrations but become bactericidal at high enough concentrations
Why would you give penicillin with an aminoglycoside?
Penicillin can break the cell wall and the aminoglycoside can then be absorbed
Aminoglycosides to know
GENTIMICIN Amikacin Neomycin Stretomycin Tobramycin
Macrolides to know
AZITHROMYCIN
CLARITHROMYCIN
ETYHTROMYCIN
MOA for Streptogramins
Binds 50S ribosomal subunit (at the same site as macrolides)
Bacterial response to Aminoglycosides
- Gram (+)
- Gram (-)
- Anaerobes
- MRSA
- VRE
- Pseudomonas
- Gram (+) – Poor
- Gram (-) – Great
- Anaerobes – Resistant
- MRSA – Resitant
- VRE – Resistant
- Pseudomonas - Good
Bacterial response to macrolides
- Gram (+)
- Gram (-)
- Anaerobes
- MRSA
- VRE
- Pseudomonas
- Gram (+) – Good
- Gram (-) – Good
- Anaerobes – Resistant
- MRSA – Resistant
- VRE – Resistant
- Pseudomonas - Resistant
Bacterial response to Lincosamides
- Gram (+)
- Gram (-)
- Anaerobes
- MRSA
- VRE
- Pseudomonas
- Gram (+) – Good
- Gram (-) – Resitant
- Anaerobes – Very Good
- MRSA – Pretty good
- VRE – Resistant
- Pseudomonas – Resistant
Bacterial response to Tetracyclines
- Gram (+)
- Gram (-)
- Anaerobes
- MRSA
- VRE
- Pseudomonas
- Gram (+)- Good
- Gram (-) – Good
- Anaerobes – Pretty good
- MRSA – Resistant
- VRE – Resistant
- Pseudomonas – Resistant
What is Cilastin?
- how does it work?
- Cilastin is a reversible, competitive inhibitor of Renal Dehydropeptidase (DHP-1), an enzyme that breaks down Imipenem to inactive BUT NEPHROTOXIC metabolites
What group of bacteria is thought to be intrinsically resistant to aminoglycosides because of permability barriers?
Enterococci
Why are gram (-) bacteria less prone to lysis via ß-lactams?
They have a thinner peptidoglycan layer and LPS layer
When is a bacteria determined to be resistant to a drug?
When the MIC exceeds the breakpoint
