WEEK 3: ANTI-BACTERIAL DRUGS Flashcards
State 4 types of anti-microbial drugs.
Antibacterial
Antivirals
Antifungal
Antiprotozoal
State 4 types of ANTIBACTERIAL DRUGS.
Bactericidal drugs (Kill)
Bacteriostatic (Stops growth)
Additive effects (Summative)
Antagonistic effects (Opposing)
Severely ill and immunosuppressed patients with bacterial infections should be treated with what type of antibiotics?
Severely ill and immunosuppressed patients with bacterial infections should be treated with bactericidal antibiotics.
What is the effect of combining bacteriostatic drug with a bactericidal drug?
…inhibition of growth induced by a bacteriostatic drug result in an overall reduction of efficacy when the drug is combined with a bactericidal drug…
Efficacy is the capacity to produce a therapeutic effect by a drug.
State the 4 classes of anti-bacteria drugs.
Cell wall synthesis inhibitors
Protein synthesis inhibitors
Nucleic acid synthesis inhibitors
Miscellaneous
State characteristics of CELL WALL SYNTHESIS INHIBITORS.
CELL WALL SYNTHESIS INHIBITORS
Bactericidal
Cause a structurally deficient cell wall.
B-lactam drugs
Vancomycin
State the 4 classes of beta lactam drugs.
Penicillin’s
Cephalosporins
Carbapenems
Monobactams
Describe MOA of penicillins.
Inhibit DD-transpeptidase (penicillin binding proteins)
How do bacteria develop resistance against penicillins?
Resistance
* Penicillinases (Beta lactamases)
* Structural changes of PBPs or porin channels
Why are Gram positives more sensitive to penicillins than gram negative organisms?
The difference in sensitivity to penicillins between Gram-positive and Gram-negative bacteria can be attributed to the structural and compositional variations in their cell walls.
Penicillin, including penicillin antibiotics like amoxicillin and ampicillin, target a specific component of bacterial cell walls called peptidoglycan.
Peptidoglycan is a critical structural component that provides rigidity and strength to the bacterial cell wall. However, Gram-positive and Gram-negative bacteria have distinct cell wall structures, and these differences contribute to the varying sensitivity to penicillins:
- Thicker Peptidoglycan Layer in Gram-Positives:
Gram-positive bacteria have a thick layer of peptidoglycan in their cell walls. This layer is readily accessible to penicillin antibiotics.
When penicillins bind to specific proteins (penicillin-binding proteins or PBPs) within the peptidoglycan synthesis machinery, they interfere with cell wall construction, ultimately leading to cell wall weakening and cell lysis.
- Thinner Peptidoglycan Layer in Gram-Negatives:
Gram-negative bacteria have a thinner peptidoglycan layer, and it is sandwiched between an inner and outer membrane.
These additional membranes act as a barrier, making it more challenging for penicillins to access the peptidoglycan layer.
In Gram-negatives, penicillin molecules may struggle to penetrate the outer membrane, which acts as a permeability barrier.
Additionally, the presence of efflux pumps in the outer membrane can actively remove penicillins from the bacterial cell.
- Porins and Efflux Pumps in Gram-Negatives:
Gram-negative bacteria possess porins in their outer membrane, which allow the passage of certain molecules, including antibiotics. However, these porins are selective, and not all antibiotics can pass through easily.
Gram-negative bacteria may also have efflux pumps that actively pump out antibiotics, including penicillins, from within the bacterial cell.
State the 4 classes of penicillins.
- Natural penicillins
2.Anti-staphylococcal penicillins
3.Aminopenicillins
4.Anti-pseudomonal penicillins
Penicillin V (oral)
Penicillin G (parenteral)
Gram positive. Gram negative cocci. Anaerobes. Spirochetes.
Penicillinase sensitive
Treponema pallidum +++
What class of penicillins is this?
Natural penicillin
Methicillin, Nafcillin, Oxacillin
Narrow spectrum, Penicillinase resistant
DOC for staphylococci
Methicillin Resistant Staphylococcus Aureus (MRSA) is due to Modified PBPs
What class of penicillins is this?
Anti-staphylococcus penicillins
Give 2 examples of aminopenicillins.
Give characteristics of aminopenicillins.
Ampicillin, Amoxicillin
Extended spectrum, Penicillinase sensitive
Gram negatives (H Influenza, E Coli, Proteus, Salmonella, Shigella)
Give 2 examples of anti-pseudomonal penicillins.
Give characteristics of anti-pseudomonal penicillins.
Piperacillin, Ticarcillin
Extended spec, Penicillinase sensitive
Gram negative rods (Pseudomonas, Enterobacter, Klebsiella)
Penicillinase inhibitors, also known as beta-lactamase inhibitors or beta-lactamase-resistant antibiotics, are compounds used in combination with beta-lactam antibiotics to enhance their effectiveness against bacterial infections.
Describe the MOA of penicillinase inhibitors.
Beta-lactam antibiotics, which include penicillins, cephalosporins, and carbapenems, are widely used to treat a variety of bacterial infections.
However, some bacteria produce enzymes called beta-lactamases, which can break down and inactivate these antibiotics, rendering them ineffective.
Penicillin inhibitors help counteract the action of these enzymes and improve the antibiotic’s activity.
What penicillins are the following penicillinase inhibitors used in combination with?
- Clavulanic acid
- Sulbactam
- Tazobactam
- Avibactam
Here are some common penicillin inhibitors:
Clavulanic Acid: Clavulanic acid is often used in combination with amoxicillin to create the antibiotic combination known as amoxicillin-clavulanate (brand names Augmentin, Clavulin).
Clavulanic acid irreversibly binds to and inhibits beta-lactamases, preventing them from degrading amoxicillin and extending its antibacterial spectrum.
Sulbactam: Sulbactam is used in combination with ampicillin to create ampicillin-sulbactam (brand names Unasyn, Sultamicillin).
It acts as a beta-lactamase inhibitor, improving the activity of ampicillin against a broader range of bacteria.
Tazobactam: Tazobactam is often combined with piperacillin to create piperacillin-tazobactam (brand names Tazocin, Zosyn).
Tazobactam is a beta-lactamase inhibitor that enhances the spectrum of piperacillin.
Avibactam: Avibactam is a more recent beta-lactamase inhibitor used in combination with certain antibiotics, such as ceftazidime and aztreonam, to create effective treatments for Gram-negative bacterial infections.
The combination of ceftazidime-avibactam, for example, is used against some multidrug-resistant Gram-negative pathogens.
These inhibitors are essential in clinical practice to combat bacterial resistance. By combining a beta-lactam antibiotic with a beta-lactamase inhibitor, clinicians can effectively treat a broader spectrum of bacterial infections, including those caused by beta-lactamase-producing bacteria. This approach has become increasingly important as bacterial resistance mechanisms, such as the production of beta-lactamases, have become more widespread and complex.