Antibiotics that inhibit cell wall synthesis Flashcards
What is the most common mechanism of antibiotic activity?
Inhibition of Cell Wall synthesis
What are the classifications of cell wall active antibiotics?
Beta Lactam, Glycopeptides, Lipopeptides, Polypeptides, and Antimycobacterial agents (Isoniazid, Ethionamide, Ethambutol, and Cycloserine).
What are the Beta Lactam Antibiotics? Further, what are their targets? Lastly, how is resistance to Beta Lactams acquired?
Beta Lactam Antibiotics are Penecillins, Cephalosporins and Cephamycins, and Carbapenems and Monobactams. All share common Beta Lactam Ring Structure.
Their targets are the serine protease enzymes that build the peptidoglycan layer. These enzymes are known as Penecillin Binding Proteins since they are targets of Beta Lactams. Beta Ls bind to specific PBPs in Bacterial cell wall and inhibit assembly of peptidoglycan chain. This activates autolysins that degrade cell wall leading to bacterial death.
Resistance to Beta Lactams aquired by:
1) prevention of the interaction between antibiotc and target PBP (e.g. Gram -)
2) Modification of the binidng of the antibiotic to the PBP (e.g overproduction of PBP, aquisition of a new PBP, and modification of an existing PBP through recombination or point mutation
3) hydrolysis of antibiotic by bacterial enzymes: Beta Lactamases
Where do Penicillins act? Are they generally considered broad spectrum? Which type of bacteria do they target? (ie Gram +/Gram -) What is their Beta Lactamase?
(Beta Lactam)
Penicillins act on PBPs. They are considered broad spectrum. They target Gram +, but can target some Gram -. Penicinillinase is their Beta Lactamase.
Note: Resistance to Penicillin is rising. Some penicllins are combined with Beta Lactamase inhibitors to increase effectiveness.
Also, have low toxicity. Come from Mold Penicllium Chrysogenum.
Cephalosporins and Cephamycins
Where do these antibiotics act? Are they generally considered broad spectrum? Which type of bacteria do they target? (ie Gram +/Gram -)
(Beta Lactam)
Lactamases: cephalosporinases, carbapenemases (metallo Beta Lactamases)
Same mechanism of action as Penicillin. Have wider spectrum than Penicillins. Resistant to many Beta Lactamases. Have Improved Pharmokinetics (longer half life).
Target Gram +, but also have increased activity against Gram - compared to Penicillin.
Have a broader spectrum of action as the antiobiotic increases in generation.
Many Gram - have rapidly developed resistance to most cephalosporins and cephamycins.
Carbapenems and Monobactams
Do Carbapenems have a broad or narrow spectrum?
Do Monobactams have a broad or narrow spectrum?
(Both Beta Lactams)
Carbapenems are widely prescribed that are active against many group of organims.
Monobactams are narrow spectrum that are active ONLY against aerobic/gram - bacteria
Note: narrow spectrum antibiotics can treat susceptive organisims without disruption of patient’s normal, flora bacteria
What is the name of the glycopeptide antibiotic? What is its mechanim of action?
When is it used?
Can it be used against Gram - Bactria?
Its name is Vancomycin. It disrupts the synthesis of peptidoglycan layer of Gram + bacteria by reacting with the D-Alanine D-Alanine termini of the pentapeptide side chains which prevents the formation of the bridges between the peptidoglycan chains.
Some bacteria have intrinsic resistance due to D-Alanine-D Lactate or D-Alanine -DSerine termini
Used in management of infections caused by gram + bacteria resistant to Beta Lactams
INACTIVE AGAINST GRAM - Bacteria
What is the name of the Lipopeptide antibiotic? What is its mechanim of action?
Which type of Bacteria is it used against? (ie Gram +/Gram -)
Deptomycin.
Binds irreversably to cytoplasmic membrane: resulting in membrane depolarization, leading to disruption of ionic gradiants and cell death.
Potent to Gram +. DOES NOT WORK ON GRAM -
What are the names of the polypeptide antiobiotics?
Bacitracin and Polymyxins
What is its mechanism of action of Bacitracin? What kind of Bacteria does it effect?
(Polypeptide Antibiotic)
It is topically applied and treats skin infections caused by staphylococcus and group A streptococcus.
Gram - bacteria are resistant
Inhibits cell wall synthesis by interfering with dephosphoryalation and the recycling of the lipid carrier responsible for the moving of peptidoglycan precursors through the cytoplasmic membrane to the cell wall.
Also may damage the bacterial cytoplasmic membrane and inhibit RNA transcription.
What types of Polymyxins are there?
What is their mechanism of action?
Are they active agains Gram + Bacteria?
Type B and E (colistin)
They insert into membranes like detergents. This increases cell permiability, leading to cell death.
They can cause serious nephrotoxicity; however, some organisims are only susceptible to colistin, and is used in systemic treatment.
Most active against gram - rods because gram + don’t have an outer membrane.
What are the names of the anti mycobacterial drugs that disrupt the cell wall?
- Isonaizid and Ethionamide (inhibits mycolic acid synthesis)
- Ethambutol (inhibits arabinogalactan synthesis)
- Cycloserine (inhibits cross linkage of peptidoglycan layers)
Resistance to these four results primarily from reduced drug uptake into the bacterial cell or alteration of the target sites
