Antibodies Flashcards
Selective Toxicity
More harm to microbes compared to humans
Theraputic Index
- Lowest dose to the patient / the theraputic dose
- Increased toxicity lead to topical usage!
Theraputic Window
Range between Theraputic Dose and Toxic dose
Toxic Action
Bacteriostatic
- Decreased Growth of bacteria
- still requires immune system to kill
- Example = Sulfa Drugs
Bactericidal
- Kill or Inhibit Bacteria
How is drug –> body spread measured?
- Design
- Half-Life
- Appropriate Dosage
- Examples:- Pencilin V = 4/day vs Azitromycin = 1/day
- Kidney/ liver dysfunction if not used properly
Spectrum of Activity
Broad-spectrum
- wide range of effectiveness
- Positive: can stop acute lif-threatening diseases
- Negative: causes dysbiosis
Spectrum of activity
Narrow Spectrum
- ID and Susceptibility of pathogen
- Positive: less affect on microbiome
Advenrse Side Effects
Types??
- Allergic Reactions
- Toxic Effects
- Dysbiosis
Adverse Side Effects
Toxic Effects
- Resulting from lower TI drugs –> monitoring
- deadly side effects
Adverse Side Effects
Dysbiosis
- Can result in C. diff growth
Resistance by microbes to antibiotics
Types
- Intrinisic/ Innate Resistance
- Acquired
Resistance by microbes to antibiotics
How is Acquired acquired? 🤣
- Mutations
- Horizontal Gene Transfer
What antibiotics inhibit cell wal synthesis
- Bacitracin
- B-lactam antibiotics
- glycopeptide antibiotics
Beta-lactam Antibiotics
What makes it up/ defines it structurally?
- Beta-lactam ring
- High TI
Beta-lactam Antibiotics
Examples
- Carbapenems
- Penicillin
- Cephalosporins
4.Monobactems
Beta-lactam Antibiotics
How do they inhibit(esp Penicillin)
- Penicillin-Binding Peptides(PBPs) or transpeptidases
- form peptide bridges between adjacent glycanstrands –> less cell wall synthesis
- Only In ACTIVELY GROWING cells!!!
Beta-lactam Antibiotics
what weakens/ breaks down these antibiotics
- B-lactamase = Penicillinase –> Breaking B-lactam ring
- More powerful version = Extended Spectrum B-lactamases
- CREATED MAINLY BY GRAM (-)!!!
Beta-lactam Antibiotics
Penicillin
- Extended Spectrum penicillins
- Reduce Gram (+)
- However, can kill Enterobacteriaceae and Pseudomonas
- Affected by B-lactamases
Augmentin = If combined with Beta- lactamase inhibitor, it can counter B-lactamases
Beta-lactam Antibiotics
Penicillin G
- first natural antibiotic
- Has a high TI
Beta-lactam Antibiotics
Cephalosporins
- Has a lower PBP affinity with gram(+)
- Has structure which isn’t as affected by B-lactamase
If combined with Beta- lactamase inhibitor, then same logic as penicillin- Later generations(5th) = Effective against MRSA
Glycopeptide Antibiotics
How does it work and what does it affect?
- Binds to NAM amino acid chain –> No peptidoglycan formation
- Affects Gram(+) bacteria
- Problem: VERY TOXIC
Glycopeptide Antibiotics
What are some examples?
- Tetracyclines
- Glycylcyclines
Both are cell membrane disrupting
- Vancomycin
A last resort after Beta-lactam because so toxic and require an IV drip
- Macrolides
Bacitracin
What are they are how are they used?
- Highly Toxic –> Topical Applications
- Peptidoglycan precursor will not transport across the membrane
What Antibiotics Inhibit protein synthesis and how do they work?
- Bacteriostatic
- Aminoglycosides are the only bactericidal ones
- Exploit difference between prokaryotic and eukaryotic ribosomes: 70s vs 80s
Aminoglycosides
How do they work?
- Bind to 30s
- They are unable to start translation making it bactericidal
- Cannot be used for anaerobes, enterococci, and streptococci
If penicillin is included, then aminoglycosides can be used against these things
Aminoglycosides
Types/ Examples!
- Neomycin = Topical usage
- Streptomycin
- Gentamicin
- Amikavicin
- Tobramycin = Inhaled and can treat Psuedomonas in lungs in Cystic Fibrosis
Tetracyclines and Glycylcylines
What do both do?
- Reversibly bind to 30s –> bacteriostatic
- No fRNA attachment –> No translation allowed
- Equal Gram (+) and Gram (-) atk
Tetracyclines and Glycylcylines
What are their differences?
- Glycylcylines: wider activity and is good for tetracycline resistant bacteria
Tetracyclines and Glycylcylines
How has there been higher resistance in these?
- Lower Uptake
- Higher Excretion
Which antibiotics disrupt cell membrane integrity, and what do they generally do?
- Daptomycin
- Polymyxins
Macrolides
Examples
- Erythromycin
- Azithromycin
Macrolides
What does it do?
- It is used instead of penicilin
- Reversibly bind to 50s
- No translation continued
- Bacteriostatic to Gram (+)
–> atypical pneumonia - Blocked by Enterobacteriaceae
Macrolides
How is resistance built?
- Modification of ribosomal RNA Target
- Enzymes causing a chemical modification
- Decreased uptake
What inhibit Nucleic Acid synthesis?
- Fluoroquinolones
- Rifamycin’s
Chloramphenicol
Actions
- 50s –> No translation
- Wider range
Chloromphenicol
Problem!!
Aplastic Anemia
Fluoroquinolones
What does it do?
- Stops topoisomeraces which stops supercoiling of DNA
- Bactericidal
- wider range
- Break DNA gyrase
Fluoroquinolones
How is resistance against built?
Change in DNA gyrase
Rifamycin’s
What does it do?
Stops prokaryon RNA polymerase –> No transcription start
- Kills Gram (+), some Gram (-), Mycobacterium
Sulfonamides
What do they do?
- AKA Sulfa Drugs
- Similar to Para-aminobenzoic acid(PABA)
- Chemically bind to enzyme which leads to competitive inhibition
- Work for Gram (+) and (-)
Trimethoprim
What does it do?
- Inhibit enzyme in later step
How do Sulfonamides and Trimethoprim work together?
co-trimoxazole
Daptomycin
What does it do?
- inserts into cytoplasmic membrane
- Used against Gram (+) that are resistant to other antibiotics
Daptomycin
What is resistant to it?
No Gram (-) because they cannot penetrate the outermembrane
Polymyxins
What does it do or work with?
- topical usage
- binds to eukaryotic ells
works with Daptomycin to bind to Gram (-) membrane
What is Mycobacterium tuberculosis?
- It has a waxy coat
- has less antimicrobial effectiveness
Mycobacterium tuberculosis
What works against it?
- Target cell wall
1. Isoniazid = No mycolic acid synthesis
2. Ethambutol = No enzymes –> No synthesis of other cell components
3. Pyrazinamide = No protein synthesis
Mycobacterium tuberculosis - Fight!!
What are 1st line drugs
- Have high effectiveness and low toxicity
With combination therapy --> resistance can be staved off!
Mycobacterium tuberculosis - Fight!!
2nd Line
- Used if there is resistance to 1st line drugs
- They are less effective
- They are more toxic
Susceptibility testing
Kirby-Bauer Disc Diffusion Test
- concentration gradient of antibiotic dics to test their power in agar plate with microbe
Susceptibility testing
Zone of Inhibition
Where the antibiotic clears microbe
Susceptibility testing
Minimum Inhibitory Concetraion(MIC)
- Lowest antibiotic concetraion that stops in vitro growth
- Serial dilution
Susceptibility testing
Intermediate
A Microbe with MIC that is between resistant and susceptible
Susceptibility testing
Minimal Bacteria Concentration(MBC)
- Lowest concentration of antibiotic that kills 99.9% of in vitro bacteria killed
- plate count
Susceptibility testing
How is resistance built?
- Misuse of antibiotics
- Cause Increased costs and complications
- Worsens outcomes
Resistance Building
Mechanisms
- Antibiotic inactivating Enzymes
- Alterations in target molecule
- reduced uptake of medicines
- Increased elimination
Resistance Mechanisms
What are the Antibiotic Inactivating Enzymes
- Penicillinase
- Chloramphenicol acetyltransferase
- Produced Enzymes which interfere with drug
Resistance Mechanisms
What is altering of target molecule?
- decreased binding of PBPs and ribosomal RNA antibiotics
- Structure changes in molecule –> no binding
Resistance Mechanisms
What is increased elimination defined by?
-
Efflux pumps
- Remove components of cell by changing pumps
- resistance to range
Resistance Acquisition
(How to stop) Spontaneous Mutation
Can be reduced with more binding sites or combination therapy
Resistance Acquisition
Gene transfer
- can spread resistance to differnt strains, species, and genera
can be combined with Spontaneous mutation when R plasmids are transferred
Preventing Resistance
how is it done?
- Patient Responsibility
- Follow instructions and dosage taking
- Educating the Public
- Antibiotics are not used for viruses
- Misuse can lead to problems listed above
Preventing Resistance
How has it become a worldwide problem
- Animal feed
- No need for prescripton
- Overuse
