Antimicrobial Treatment (Chapter 10) Flashcards
What is the goal of antimicrobial chemotherapy?
To administer a drug to an infected person that destroys the infective agent without harming the hosts cells.
What is an antibiotic?
Microbial products or their derivatives that kill susceptible microbes or inhibit their growth.
Go through the timeline of when the first chemotherapies and antibiotics were developed.
PAUL Ehrlich (1904) - identified trypan dyes that effectively treated African sleeping sickness
Sahachiro HATO (1910) - working with Ehrlich, identified arsenic compounds that effectively treated syphillis
Domagk, Jaques & Therese Trefouel (1935) - discovered sulfonamides and sulfa drugs
Give a timeline of Penicillin
FIRST discovered by ERNEST Duchesne (1896)
NEXT Accidentally discovered by Alexander FLEMING
THEN effectiveness demonstrated by FLOREY, CHAIN, HEATLY (1939) - they got the Nobel prize in 1945 for discovery and production of penicillin
What are the characteristics of antimicrobial drugs and the meanings?
- Selective toxicity
ability of a drug to kill or inhibit pathogen while damaging host as little as possible - Therapeutic dose
drug level required fro clinical treatment - Toxic dose
drug level at which drug becomes too toxic for patient (produces side effects)
What is the Therapeutic Index?
The ratio of a drug that is toxic to humans compared to its minimum effective dose:
the smaller the ratio, the more toxic is it
TI = 1.1 is risky
TI-10 is safer
significane: the drug with the highest TI has the widest margin of safety.
What is a narrow- spectrum drug, a broad-spectrum drug and what’s the difference?
a narrow spectrum drug only attacks a few different pathogens
a broad spectrum drug attacks many different pathogens
What causes the effects of an antimicrobial drug to vary?
concentration, microbe, host
What are the two ways effectiveness is expressed? define them.
- minimal inhibitory concentration (MIC)
lowest concentration of drug that INHIBITS GROWTH of pathogen - minimal lethal concentration (MLC)
lowest concentration of drug that KILLS pathogens
How do disk diffusion tests work?
A disk impregnated with a specific drug are placed on agar plates inoculated with test microbe
the drug DIFFUSES from the disk into the agar, establishing a concentration gradient
clear zones (zones that show inhibition) form around the disks, preventing the growth of that microbe in that region
What are the 3 mechanisms of action for Cell wall synthesis inhibition?
Penicillin
Cephalosporins
Carbapenems
Miscellaneous drugs that target the cell wall
What are the mechanisms of action for cell membrane structure or function?
Polymyxins
What are the 4 mechanisms of action for protein synthesis inhibition?
Amino-gly-co-sides
tetracyclines
Gyl-cyl-cy-clines
Macrolides
Miscellaneous drugs that target the cell wall
What are the mechanisms of action for nucleic acid structure or function inhibition?
fluoro-qui-nolones
What are the mechanisms of action for Folic acid metabolism?
Sulfonamides
What do the folic acid metabolic antagonists do?
block pathways and inhibit metabolism
What do the cell wall inhibitors do?
Block synthesis and repair
What is the significance pf Beta-lactam rings in penicillin and the problems of enzymes that attack it?
bacteria can create penicillinase which is a class of enzymes that cuts the b-lactam ring in penicillin
Why is it difficult to treat organisms growing in biofilm?
They act different than when they are free living.
Antibiotics often cannot penetrate the sticky extracellular material surrounding biofilms
Bacteria in biofilms express a different phenotype and have different antibiotic susceptibility profiles than free living bacteria.
What do you use to treat fungal infections?
Ampho-tercin B
flu-cytosine
What do you use to treat Protozoan disease?
Metro-nidazole
What do you use to treat helminth disease?
Pyrantel
How do you treat viral infections?
Cant use antimicrobiotics but can be prevented with vaccines.
Tamiflu can shorten the course of the flu.
What are the challenges in developing drugs for non-bacterial agents?
disrupting viral metabolism requires disruption of cellular metabolism of host
What are the 4 factors that influence the efficacy of antimicrobial drugs?
- ability of drug to reach site of infection
- ability of drug to reach concentrations in body that exceed the MIC of pathogen
- depend in mode of administration (oral, topical)
- drugs can be excluded by blood clots or necrotic tissue
- speed of uptake vs rate of clearance (elimination)
What are the 5 mechanisms of drug resistance ?
Preventing Inactivate Modification Pump. Alternative
- Preventing entry - bacteria can change its permeability and transporters so the drug can’t go through the cellular membrane
- Drug Inactivation - Chemical modification of drug by pathogen
- Modification of target enzyme of cell structure
- Can add a functional group of change the metabolism - Pump drug out using efflux pumps
- Use of an alternative pathway or increased production of target metabolite.
How is drug resistance spread through bacterial populations?
Chromosomal genes
R plasmids
Composite transposons
What are the new treatment being developed as antimicrobials?
- Teixobactin
- using bacteriophages as treatment
- Pre & ProBIOTICS
- Microbial transplants
Most drugs that inhibit protein synthesis or translation block the action of the _____
ribosome
Sulfonamides interfere with folate metabolism by blocking enzymes required for the synthesis of ______.
tetrahydrofolate
Antibiotics that affect nucleic acid synthesis specifically affect the processes of replication and ______
transcription
What are some known was of treating biofilms?
DNase, disrupting quarum sensing, daptomycin
_____ are particularly challenging to inactivate with antimicrobial chemotherapy because a single metabolic system is responsible for both the microbe and the host cell.
Viruses
Antibiotics that affect __ and ___ synthesis specifically affect the processes of replication and transcription, respectively.
DNA, RNA
Identify the three major modes of action of antiviral drugs.
Barring virus penetration into host cell
Preventing virus maturation
Blocking virus transcription and translation
