EXAM 2: Antimicrobials Flashcards
Drug
A medicine or other substance which has a physiological effect when ingested or otherwise introduced into the body
Antimicrobial
A drug that is active against microscope organisms
Antibiotic
A drug produced by a living organism
Discuss the history of antimicrobials and the their use in the treatment of infectious disease
Paul Ehrlich
- The first to think of trying to use a chemical to fight infectious disease
- Used arsenic compounds that killed microbes–called “Magic bullets”
Alexander Fleming (1928)
- Credited for the discovery of Penicillin
- Actually, the 1st to discover Penicillin by Ernest - Duchesne (1896), but he was only 23 and a nobody, so his dissertation was ignored by the system
Gerhard Domagk
- Discovered sulfanilamide → first commercially available antimicrobial (1931)
Selman Waksman
- Coined the term “Antibiotics” → Antimicrobial agents produced naturally by organisms
List the types of organisms that produce antibiotics
Bacteria and Fungi
Differentiate between “true” antibiotics and synthetic antimicrobials
True antibiotics: antimicrobial agents produced naturally by organisms
Semi-synthetics: chemically altered antibiotics that are more effective than naturally occurring ones
Synthetics: Antimicrobials that are completely synthesized in a lab
List common sources of antibiotics
penicillin
ciproflaxin
bacitracin
Describe the various mechanisms of antimicrobials
VERY IMPORTANT!!!
- Inhibition of cell wall synthesis
- Prevent bacteria from increasing the amount of peptidoglycan
- Have no effect on existing peptidoglycan layer (effective only for growing cells)
Simplest beta-lactams
- Effective only against aerobic Gram-negatives
Semi-synthetic derivatives of beta-lactams
- ex. Ex. penicillin–disrupts 1-4 beta linkage between NAG and NAM
Most common agents prevent cross-linkages of NAM subunits
- Beta-lactams bind to enzymes that cross long NAM subunits, preventing cross-linkages - Inhibition of protein synthesis (translation)
- Disrupts ribosomes of eukaryotes or prokaryotes
E: 60&40 P: 50&30
- Drugs can selectively target translation - Inhibition of nucleic acid synthesis
- Quinolones denatures DNA gyrase etc.
- Nucleotide analogs distort NA shapes
- Several drugs block DNA replication or mRNA transcription - Inhibition of metabolic processes
- Drugs block activation of viruses
- Anti-metabolic agents can be effective when pathogen and host metabolic processes differ
- Antiviral agents can target unique aspects of viral metabolism - Prevention of virus attachment
- Attachment antagonists block viral attachment or receptor proteins
ex. antimicrobials are antagonists - Disruption of cytoplasmic membranes
- Azoles and allyamines inhibit ergosterol synthesis
- Polymyxin disrupts cytoplasmic membranes of Gram negatives
- Some drugs form channels through the cytoplasmic membrane and damage its integrity
- Bacteria lack sterols; not susceptible
Discuss common clinical considerations when prescribing antimicrobial drugs. What some common features of “good” drugs. What are some common concerns?
Ideal antimicrobial agent: Readily available, Inexpensive, chemically stable etc.
Common Concerns:
1. Routes of administration: Must know how antimicrobial agent will be distributed to infected tissues, Oral, intramuscular, or intravenous (IV)
- Spectrum of action: the number of different pathogens a drug acts against, Narrow vs broad spectrum
- Toxicity: Consideration for pregnant women, Cause of many adverse reactions poorly understood
- Allergies: Allergic reactions are rare but may be life threatening , Anaphylactic shock
Discuss the rise in drug resistance and how the medical community can reduce it. Discuss how drug resistance arises
Underdeveloped: don’t take correct dosage
Developed: don’t take it for the full course
Both are failure to complete dosage
Rise of antibiotic resistance:
Developing countries:
Insufficient use of antibiotics, too expensive
Feel better then save prescription for later (concentration of antibiotic increases but not enough to entirely kill, but then decreases rapidly because the dose was not finished → leads to bacteriostatic)
Failure to complete dose
Developed countries:
Overuse of antibiotics
Available virtually on demand
To reduce: Doctors should quit prescribing antibiotics before test results come back, and simply to make their patients happy by sending them home with medicine.
Describe common antibiotic susceptibility test
-
Diffusion susceptibility test: bacterial lawn interrupted by zone of inhibition caused by effective drug
- The larger the zone of inhibition around the disks, the more effective the antimicrobial
- The organism is classified as either susceptible, intermediate, or resistant to the antimicrobials tested - E-Tests: combine Bauer & MIC test
- Minimum inhibitory concentration (MIC) test: turbid vs. clear tubes–determines what concentration a drug is effective from clarity of liquid
- Minimum bactericidal concentration (MBC) test: Dilution of bacterial concentration until no colonies show up. The lowest concentration for which no bacterial growth occurs on the plate is the MBC
Provide the mechanism of action for common antibiotics (Penicillin, tetracycline, chloramphenicol, polymixin, polenes, quinolones)
Penicillin
inhibits cell wall synthesis
disrupting beta 1,4 linkage
Tetracycline
block docking site of tRNA
binds to amino acids so that they can’t form peptide bonds
inhibition of protein synthesis
Chloramphenicol
inhibition of protein synthesis
Polymixin
disrupts cytoplasmic membrane of Gram (-) bacteria
target LPS
toxic to human kidneys
Polyenes
target fungi
forms channels in membrane allowing cytoplasmic contents to leak out
disrupts cytoplasmic membrane
Quinolones
denatures & inhibits DNA gyrase and inhibits DNA replication, transcription
inhibition of NA synthesis
