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.
State the 3 adverse effects of penicillins.
ADVERSE EFFECTS OF PENICILLINS
GIT distress
Hypersensitivity
Cross allergic reactions with cephalosporins
Cephalosporins
Like penicillins, cephalosporins work by inhibiting the synthesis of the bacterial cell wall, specifically by binding to and inactivating enzymes called penicillin-binding proteins (PBPs). This interference with cell wall synthesis weakens the bacteria, leading to cell lysis.
Cephalosporins are classified into generations based on their antimicrobial properties and the range of bacteria they can target.
There are four generations of cephalosporins, with each generation having a broader spectrum of activity than the previous one.
Describe the 4 generations of cephalosporins and give examples of drugs under each generation.
First-generation cephalosporins:
*Effective against Gram-positive bacteria.
EXAMPLE: Cephalexin
Second-generation cephalosporins:
*Extended coverage against some Gram-negative bacteria.
EXAMPLE: Cefuroxime (crosses the BBB)
Third generation cephalosporins:
*Broader spectrum, including better coverage of Gram-negative bacteria.
EXAMPLE:
*Ceftazidime (Pseudomonas)
*Ceftriaxone (Gonococcus)
Fourth generation cephalosporins:
*Broader spectrum, including better coverage of Gram-negative bacteria, and some have better resistance to beta-lactamases.
EXAMPLE: Cefepime
Is there any of the 4 generations of cephalosporins active against MRSA?
None of the 4 generations of cephalosporins are active against MRSA.
State the 3 adverse effects of cephalosporins.
ADVERSE EFFECTS OF CEPHALOSPORINS
Hypersensitivity reactions (Cross-reactions with
penicillins)
Disulfiram-like reactions (Alcohol intolerance)
Nephrotoxicity concerns (except ceftriaxone)
Gram positive cocci (staph, strep)
Gram negative rods (Proteus, E Coli,
Klebsiella)
Name the drug.
What generation of cephalosporins is the drug from?
Cephalexin
1st Generation drug
Hemophilus Influenza, Enterobacter,
Neisseria
Name the drug.
What generation of cephalosporins is the drug from?
Cefuroxime (crosses the BBB)
2nd generation
Less gram positive.
Extended gram-negative coverage
(Citrobacter, Serratia, Providentia)
Name the drug.
What generation of cephalosporins is the drug from?
Ceftazidime (Pseudomonas)
Ceftriaxone (Gonococcus)
3rd Generation drug.
Pseudomonas and gram-positive cocci
Name the drug.
What generation of cephalosporins is the drug from?
Cefepime
4th Generation drug
State 2 examples of carbapenems.
Describe their characteristics.
Imipenem and meropenem
Resistant to beta-lactamases.
Cover most gram positive, gram negative and
anaerobic organisms.
None is active against MRSA.
Why is Imipenem used compounded with CILASTATIN?
What can high level of imipenem result in?
What is the MOA of cilastatin?
*Imipenem is compounded with CILASTATIN to protect it from metabolism by renal dehydropeptidase.
*High levels of imipenem may provoke seizures.
Cilastatin (Dehydropeptidase inhibitor)
Give an example of monobactam.
How are they administered?
Describe their other characteristics.
Aztreonam
Administered IV or IM
Active against most gram-negative bacteria but has no activity against gram positive organisms.
No cross allergenicity with other beta lactam drugs
Relatively non-toxic but can cause phlebitis and skin rash.
Vancomycin is a type of cell wall synthesis inhibitors.
Describe its MOA.
Inhibits peptidoglycan polymerization (d-alanyl-d-alanine portion of cell membrane).
Effective against most gram positives (including MRSA)
Intravenous vancomycin is commonly used to treat sepsis.
Oral vancomycin is used to treat gastrointestinal infections with C. difficulty.
Resistance due to modification of the D-Ala-D-Ala binding site of the peptidoglycan building block in which the terminal D-Ala is replaced by D-lactate.
State the side effects of vanomycin.
Infusion related adverse effects (phlebitis, flushing)
Dose related ototoxicity (ear damage) & nephrotoxicity (kidney damage)
Protein synthesis inhibitors are a group of antibiotics and drugs that interfere with the process of protein synthesis in bacterial or eukaryotic cells.
Describe their MOA.
Target translation
Act on the 30s or 50s ribosomes
Protein synthesis inhibitors are classified according to the process they act on in protein synthesis by the bacteria.
*P-Site
*A site
*Peptidyl transferase
*Bind irreversibly on the 50s subunit and inhibit translocation, Peptide exit tunnel
*P-Site (Aminoglycosides)
* A site (Tetracyclines)
*Peptidyl transferase (Chloramphenicol)
*Bind irreversibly on the 50s subunit and inhibit translocation, Peptide exit tunnel (Macrolides, Clindamycin)
Give examples of aminoglycosides.
Describe MOA of aminoglycosides.
Aminoglycosides (e.g., Streptomycin, Tobramycin,
Gentamycin, Amikacin):
Mechanism of Action:
-Aminoglycosides bind to the 30S subunit of bacterial ribosomes and cause misreading of the genetic code during translation.
-Block initiation complex formation, mRNA misreading, Breakup of polysomes (Bactericidal)
This results in the production of nonfunctional or toxic proteins, ultimately leading to bacterial cell death.
Clinical Use: Aminoglycosides are used to treat serious Gram-negative bacterial infections, including certain types of pneumonia and sepsis.
Streptomycin, Tobramycin, Gentamycin, Amikacin
Block initiation complex formation, mRNA misreading, Breakup of polysomes (Bactericidal)
Gram negative rods, gram positive cocci, mycoplasma (No effect on anaerobes)
Nephrotoxicity and Ototoxicity (Prolonged intake, Elderly, renal insufficiency, Overdose)
Inhibit calcium uptake resulting in neuromuscular paralysis (Respiratory paralysis, Myasthenia gravis)
Resistance (Ribosome alteration, Efflux pumps, Drug modifying enzymes)
What type of protein synthesis inhibitors is this?
AMINOGLYCOSIDES
Give examples of tetracyclines.
Describe their MOA.
Tetracyclines (e.g., doxycycline, tetracycline):
Mechanism of Action:
Tetracyclines inhibit protein synthesis by binding to the 30S ribosomal subunit and preventing the attachment of tRNA to the ribosome.
*Prevent the (aminoacyl) tRNA from entering the acceptor site.
Clinical Use: Tetracyclines are used to treat a wide range of bacterial infections, including respiratory tract infections, urinary tract infections, and certain sexually transmitted diseases.
Prevent the (aminoacyl) tRNA from entering the acceptor site.
Gram Negative Rods
Gram Positive Cocci, Gram
Positive Bacilli,
Anaerobes, Mycoplasma
Rickettsia, Spirochetes & Chlamydia
Doxycycline has a better oral bioavailability, longer duration of action and eliminated to a
lesser extend in urine than tetracycline.
Gastric discomfort
Bind to calcium and deposited in bones and teeth.
What type of protein synthesis inhibitors is this?
TETRACYCLINS
Give examples of macrolides.
Describe MOA of macrolides.
Macrolides (e.g., erythromycin, azithromycin):
Mechanism of Action:
*Macrolides bind to the 50S ribosomal subunit, preventing the elongation of the polypeptide chain during translation.
Block translocation
Clinical Use: Macrolides are effective against a variety of Gram-positive and some Gram-negative bacteria. They are often used to treat respiratory tract infections and skin infections.
Block translocation
Erythromycin’s active against susceptible strains of gram-positive organisms, especially pneumococci, streptococci, staphylococci and
corynebacteria.
Clarithromycin more active against haemophiles influenza, helicobacter pylori and intracellular organisms (chlamydia)
Azithromycin less active against gram positives. More active against Hemophilus influenza and
chlamydia spp.
+++ Gastric Upset
All except azithromycin (CP450 inhibitors)
Clindamycin (MRSA)
Linezolid (MRSA, VRSA)
What type of protein synthesis inhibitors is this?
MACROLIDES
NUCLEIC ACID SYNTHESIS INHIBITORS
Nucleic acid synthesis inhibitors are a group of drugs and antibiotics that interfere with the replication and transcription of nucleic acids, such as DNA and RNA, in bacterial or eukaryotic cells.
By disrupting the processes of DNA replication or RNA transcription, these inhibitors can inhibit the growth and reproduction of microorganisms, including bacteria, and are commonly used in the treatment of various infections.
State the 3 classes of nucleic acid synthesis inhibitors.
DNA synthesis inhibitors (Quinolones)
RNA synthesis inhibitors (Rifamycin’s)
Folic acid synthesis inhibitors (Trimethoprim and
sulfonamides)
State 2 examples of quinolones
Describe the MOA of quinolones.
Quinolones (e.g., nalidixic acid):
Mechanism of Action:
Inhibit DNA gyrase and topoisomerase IV, which are essential for DNA replication and repair.
Topoisomerase II (DNA Supercoiling)
Topoisomerase IV (Separation of newly
replicated DNA)
State the 4 generations of quinolones.
1) Nalidixic acid (nonfluorinated quinolone, gram negative
organisms, UTIs).
2) Ciprofloxacin (Aerobic gram-negative. Moderate activity against
gram positive bacteria)
3) Levofloxacin (…increased activity against gram-positive bacteria)
4)Moxifloxacin (…activity against anaerobic
Outline the adverse effects of quinolones.
TOXICITY
Common adverse effects are nausea, vomiting and diarrhea.
Articular cartilage erosion (Avoid in children)
Ingestion of fluroquinolones with dietary supplements containing iron or zinc can reduce their absorption.
Give examples of rifamycins.
Describe their MOA.
Rifamycin’s (e.g., rifampin, rifabutin):
Mechanism of Action:
Rifamycin’s interfere with RNA synthesis in bacteria by binding to the bacterial RNA polymerase enzyme and preventing transcription.
Clinical Use: Rifamycins are used primarily to treat tuberculosis (TB) and are also used in combination with other antibiotics for other mycobacterial infections.
TRIMETHOPRIM AND SULFAMETHOXAZOLE
Cotrimoxazole is a bactericidal and broad spectrum.
Bacteria (MRSA, Nocardia, E coli…)
Fungi (Pneumocystis jiroveci)
Protozoa (Toxoplasma Gondi)
Folic acid deficiency (megaloblastic) anemia
Cotrimoxazole= Trimethoprim + Sulfamethoxazole
