Antimicrobials Flashcards
Pre-antibiotic era
-We were powerless against infections. Wounds=death; TB in urban areas; Sexually transmitted infections
-used vials of mercury injected into blood or urethra
-Antibiotics not used until 1940s
Fleming’s Observation
-found that mould on petri dish was preventing the growth of staphylococcus colonies (lysis)
When was drug discovery at its peak?
From 1940s-1960s… then few drugs developed.
Been a few more developed since 2010
How do antibiotics work?
-They attack physiological processes or structures unique to bacteria
Structures include:
-cell wall
-cell membrane
-nucleic acid synthesis, metabolism, organization
-protein synthesis
How do bacteria resist antibiotics?
- Prevent entry (decreased permeability)
- Pump out (active efflux)
- Destroy (enzymes)
- Disguise (target modification)
- Use alternative pathways
6.Lack target (remove target receptors to allow for resistance)
Minimum inhibitory concentration
-minimum drug concentration that will inhibit an organism’s growth
**reported on log scale
Minimum bactericidal concentration
-minimum drug concentration that will kill an organism
Bacteriostatic vs. bactericidal
Bacteriostatic: When MBC> 4x MIC
Bactericidal: When MBC less than or equal to 4x MIC
Concentration dependent drugs
-activity relies on maximally exceeding organism MIC at site of infection
Time dependent drugs
Activity relies on how long drug concentrations exceeding organisms MIC are maintained at site of infection
Beta-lactams
Antimicrobials that are cell wall synthesis inhibitors by binding to the penicillin binding proteins within the wall.
**prevents final stage of peptidoglycan synthesis
Super family of antimicrobials
Types of beta-lactams
-penicillins
-cephalosporins
-Carbapenems
-beta-lactamase inhibitors
Beta-lactams basica structures
-All have a 4 membered ring (beta lactam ring)
**common structure that bacteria can try and avoid
beta-lactam/inhibitor combinations
Act by irreversibly binding to the serine catalytic site of certain (NOT ALL) bacterial beta-lactamases
>only active against class A enzymes
beta-lactam/inhibitor combinations that are available
- Clavulanic acid (amoxicillin and clavulanic acid)
- Sulbactam (ampicillin + sulbactam)
- Tazobactam (piperacillin +tazobactam)
Increasing generations of cephalosporin
As generations increase, get improved activity against gram negatives and increasing resilience to beta-lactamases
Carbapenems
-reserved for human medicine to prevent any resistance selection in animals
-very broad spectrum, most gram positive, gram negative, and anaerobes
Tetracyclines
-bind to 30S ribosomal subunit reversibly- bacteriostatic
prevents protein synthesis
-Increasing lipophilicity from tetra, to doxy, to minocycline. Means they are better able to cross cell membranes
Fluoroquinolones
Inhibits DNA gyrase and topoisomerase IV, preventing replication and organization (supercoiling)= bactericidal
Fluoroquinolones drug concentration
Too low and too high concentrations of these drugs results in poor drug activity because these drugs will interfere with DNA and prevent transcription
Aminoglycosides
-bind to 30S ribosomal subunit but also effects ETC, DNA metabolism, and cell membranes
**bactericidal
MLSBK
-reversible binding to 50S ribosomal subunit
*bacteriostatic
Phenicols
-reversible binding to the 50S ribosomal subunit
**bacteriostatic
-banned in food animals, rare idiosyncratic aplastic anemia in people (destruction of bone marrow)
Folate synthesis inhibitors
- Sulfa
- competitive inhibition of PABA in folate pathway - trimethoprim AND Sulfamethoxazole
-target gram positive, gram negative, MRSA/MRSP, parasites (some protozoas and toxoplasma)
Nitroimidazoles (Metronidazole)
-low molecular weight molecule (171.16 Da)
-readily enters cells, is reduced and forms unstable free radicles which bind to DNA and prevent synthesis
-very overused antibiotic
-used to fight anaerobes
-bactericidal
-banned in food animals
Antimicrobial resistance
-resistance is natural
-we select for resistance with antimicrobial usage, we dont create it
Pharmacodynamics
The interactions of a drug or substance with its target, mechanisms of action and correlation of actions with effects
“drug-bug interactions”
Pharmacokinetics
The processes of absorption, distribution, metabolism, and excretion of a drug or substance.
“host-drug interactions”
