6.1 Antimicrobial agents (intro + antibiotics) Flashcards
(36 cards)
What are antimicrobial agents, give 3 with examples
1) Products to control microorganisms in commercial and
industrial applications
- chemicals in foods, air-conditioning cooling towers, textile and paper products, fuel tanks
2) Products designed to prevent growth of human pathogens in inanimate environments and on external body surfaces - sterilants, disinfectants, sanitizers, and antiseptics
3) Antimicrobial drugs - chemotherapy
Define the following definitions..
a) Antimicrobial agent
b) Antibiotic
c) chemotherapy
a) a chemical that kills or inhibits the growth of organisms
b) a chemical produced by a microorganism that kills or inhibits the growth of another microorganism
b) any chemical-based treatment for diseases caused by bacteria, other microorganisms, parasites and tumour cells
What is the relationship between antimicrobial agents and antibiotics
ALL antibiotics are antimicrobials but not all antimicrobials are antibiotics
Name six characteristics of an ideal antimicrobial drug
(PSS MR P whats so good about your drug?)
1) reasonably Priced
2) Selectively toxic to the microbe but nontoxic to host cells
3) relatively Soluble; functions even when highly diluted in body fluids
4) Microbicidal rather than Microbistatic
5) doesn’t lead to the development of antimicrobial Resistance
6) remains Potent long enough to act and isn’t broken down or excreted prematurely
Define selective toxicity
Define a selective poison
Selective toxicity: drugs that specifically target microbial processes and not the human host cellular processes
Selective poison: targets bacteria not host
What are antibiotics?
Name two bacteria and two moulds that produce them
Antibiots are naturally occuring antimicrobials
These are metabolic products produced by bacteria and fungi that usually aid them to reduce competition for nutrients and space
Bacteria: Bacillus, Streptomyces
Molds: Penicillium, Cephalosporin
Which part of penicillin’s chemical structure is the key to its function, describe this?
What mold produces penicillin
The Beta-lactam ring is key to penicillin’s function (targeted by B-lactam antibiotics)
Penicillin consists of a 4 membered nitrogen containing structure with the B-lactam ring at its core
Produced by the mold Penicillium chrysogenum
What are two modes of action of an antibacterial drug and compare them?
Give two examples of each
1) Bacteriostatic: halts growth of bacteria giving the immune system a chance to clear the infection
* E.g tetracyclines, sulfonamides
2) Bactericidal: kills the bacteria (no more active bacteria left)
- E.g penicillin’s, cephalosporins
- Bacteriolytic drugs also lyse dead bacteria
Bacteriostatic drugs tend to be slower and require a working immune system for effective elimination of the microorganism. Therefore not advisable for use in immunosuppressed conditions or for those suffering from life-threatening acute conditions
** some antibiotics can be both bacterostatic and bactericidal
How can you classify antibacterial agents?
What can be said about antibiotcs that share similar structures?
1) Their molecular structure
2) Their spectrum of activity (broad - killing a wide variety of organisms or narrow)
3) Function or mechanism of action (how it works)
*Antibiotics within a structural class usually show similar modes of action and spectrum of activity
What is meant by the antimicrobial spectrum of activity?
What is a narrow spectrum antibiotic? + example
What is a broad-spectrum antibiotic? + example
When prescribing when would you use each?
antimicrobial spectrum of activity: is the scope that a drug kills or suppresses the growth of microorganisms.
Narrow spectrum: drugs that only act on one kind or one strain of bacteria
- Isoniazid (TB)
Broad-spectrum: have a wide antimicrobial scope.
- Tetracyclin
*begin with a broad-spectrum when unsure of what the infection is and introduce narrow-spectrum later
What is the spectrum of activity for the following bacteria and what is their main target
- Tetracycline
- Cephalosporins
- Streptomycin
- Penicillans
- Isoniazid
Tetracycline: broad spectrum (all except mycobacteria-TB)
Cephalosporins: broad spectrum (1/2 gram + and 1/2 gram -)
Streptomycin: broad spectrum (mycobacteria and gram -)
Penicillans: narrow spectrum (mainly targets gram +)
Isoniazid: narrow spectrum (only targets mycobacteria)
Name the five main targets for antibacterials
1) Inhibition of cell wall synthesis
2) Inhibition of protein synthesis
3) Inhibition of nucleic acid synthesis
4) disruption of cell membrane function
5) Inhibition of metabolism (Antimetabolites)
Explain the mode of action of drugs that inhibit cell wall synthesis?
Give 2 chacteristics of this drug that makes it a good antibiotic
1) they target peptidoglycans in cell wall causing it to become weakened while the cell is growing.
2) the weakening of the cell wall increases permeability
3) the difference in osmotic gradients causes water to enter the cell
4) results in lysis of the cell (bactericidal)
Chacteristics: bactericidal and low toxisity to humans (because we do not have a cell wall)
Give 4 drugs that target cell wall synthesis and specifically explain how
1) Penicillin – binds and blocks peptidases involved in cross-linking the glycan molecules
2) Cephalosporins – same as penicillin
3) Vancomycin – hinders peptidoglycan elongation
4) Cycloserine – inhibits the formation of the basic peptidoglycan subunits
Cell walls of Gram + and + bacteria contain peptidoglycan layers (thick= + or thin = -), describe the structure of the peptidoglycan layer
Which 2 antibiotics target these structures?
Peptidoglycan contains sugar (glycan) chains, which are cross-linked by short peptide bridges.
The glycan chains consist of alternating units of NAG and NAM joined by glycosidic linkages
- NAG: N-acetylglucosamine (GlcNAc)
- NAM: N-acetylmuramic acid (MurNAc)
Penicillan and Cephalosporin bind and block theses peptides involved in cross-linking the glycan molecules
How do B-lactam antibiotics work (eg penicillin)?
They target the PBPs (penicillin binding proteins) which are a group of enzymes that are found anchored to the cell memebrane involved in the cross-linking of the cell wall
The B-lactam ring portion of penicillin binds to these PBPs rendering them unable to perform their role in cell wall synthesis
This leads to death of the cell by osmotic instability or autolysis
How may some bacteria aquire resistance to penicillin?
Some bacteria may evolve to produce a beta-lactamase gene which encodes beta-lactamase/penicillinase
These are enzymes that destroy the beta-lactam ring of the antibiotic, making the penicillin ineffective
Compare Natural penicillins to Semisynthetic penicillins
Give 2 types of semisynthetic penicillins that can be used to overcome resistance + examples
Both share a common core structure (beta-lactam ring) but the chemical modification on the side chain of the ring changes.
Natural penicillins: have a narrow range of activity
Semisynthetic penicillins: overcome disadvantages
1) Penicilinase-resistant penicillins
* Eg. Methicillin (there is reduced use due to MRSA)
2) Penicillins + β-lactamase inhibitors
- Eg. co-amoxiclav (Augmentin)
- combines amoxicillin with clavulanic acid which inhibits penicillinase
What mold produces Cephalosporin?
Compare the molecular structures and spectrum range of penicillin and cephalosporin
How are semi-synthetic verisons of cephalosporin grouped and what can be said about this?
Produced by the mold Acremonium Cephalosporium
Both have a beta-lactam ring, but penicillin is attached to a 5C ring whereas cephalosporin has a 6C ring
Cephalosporin is a broader spectrum drug
Semi-synthetic versions are grouped as generations (new generations are less susceptible to β -lactamases)
What spectrum of activity do drugs inhibiting protein synthesis have?
What is their mechanism of action and which mode of action do they tend to be?
What common problem can occur with these types of drugs and why?
These are broad-spectrum
1) they target prokaryotic ribosomes (not eukaryotic) hence display selective toxicity.
2) many bind to either the 30S or 50S subunits of the intracellular ribosomes causing disruption of the bacteria’s normal metabolism
3) leads to death of the organism or inhibition of its growth and multiplication.
** They tend to be bacteriostatic
Common problem is toxicity problems
Give 4 antibiotics that target protein synthesis and explain specifically how
1) Aminoglycosides: Streptomycin, neomycin, gentamycin
binds to the 30s ribosomal subunit chaning its shape causing misreading of mRNA
2) Tetracyclines
binds to the 30s ribosomal subunit, preventing attachment of the tRNA to the RNA ribosome complex, preventing additon of amino acids to the elongating peptide chain
3) Macrolides: Erythromycin
binds to the 50s ribosomal subunit preventing movement of ribosome along the mRNA, inhibiting translocation
4) Chloramphenicol:
binds to the 50s ribosomal subunit and inhibits the formation of peptide bonds
What was streptomycin formerly used to treat?
The plague caused by the Yersinia pestis bacteria
Give the two major drug targets for inhibitors of nucleic acid synthesis and state how they do this
State whether these are broad or narrow spectrum and give an example of each including what treatment they are used for
1) β-subunit of bacterial RNA polymerase
- Inhibits RNA synthesis
- Narrow spectrum: (mycobacteria-anti TB and gram +)
- eg. Rifamycins
- Used in treatment of TB
2) DNA gyrase/topoisomerase
- Interferes with separation/reannealing of dsDNA
- Broad spectrum -> bactericidal
- eg. Quinolones and fluoroquinolones
- Used in urinary and respiratory tract infections
What are Rifamycins used to treat?
Are they broad of narrow spectrum
What is their mechanism of action?
Rifamycins are used in the treatment of TB
They are narrow spectrum: (mycobacteria-anti TB and gram +)
They inhibit nucleic acid synthesis by targeting the B-subunit of RNA polymerase which inhibits RNA synthesis
