Antibiotics Pharmacology Free Course

This course explains the pharmacology of the different classes of antibiotics

The theory explained here will satisfy your boards and clinical practice

Idea behind antibiotics

There is differences between bacterial cell and animal cell that the antibiotics exploit to harm the bacterial cell without harming the human cell
Bacterial cells genome not enclosed fully with nuclear membrane , no nuclear membrane (prokaryotes) While in animal cells have real nuclear membrane (eukaryotes); so we can give antibiotic that target the DNA of the bacteria and not the animal cell because it has nuclear membrane
Another difference is that the bacteria have cell wall and the animal cell doesn’t have that so we can target the cell wall with antibiotic
We also can target the plasma membrane and ribosomes and the metabolic pathways because bacteria have different types of these parts
We call it antibiotic chemotherapy because killing bacteria

There was a scientist called gram who did experiments on the bacteria with crystal violet stain and find out that some bacteria would be stained while others would not according to the thickness of the cell wall (peptidoglycan)
After research he discovered that the bacteria with thick peptidoglycan layer get stained with that stain
Gram positive in bacteria with thick peptidoglycan which will be stained by the gram stain when applied while if narrow cell wall then would not be stained and called gram negative
Gram positive => well developed cell wall; gram negative => defective cell wall
In gram negative bacteria mostly have outer membrane that have pores that control transportation and it is highly selective so it would be hard for the antibiotics to go throw it
So treating gram negative bacteria is harder than gram positive by antibiotics that the bacteria can’t identify so it go throw its outer membrane

Classified according to the source
1. Natural antibiotic like aminoglycosides, penicillin/ cephalosporins
2. Synthetic like quinolones and sulfonamides
3. Semi synthetic like ampicillin, amoxicillin
Classified according to mode of action
1. Bactericidal => kill bacteria
2. Bacteriostatic => arrest growth
Classified according to mechanism of action
1. Cell wall inhibitors => like penicillin, cephalosporins, vancomycin and mostly gram positive bacteria because it has thick cell wall => bactericidal
2. Cell membrane => isoniazid (TB); azoles, nystatin => mostly work on fungi => bactericidal
3. Inhibitors of DNA function or synthesis => bactericidal; quinolones, rifampin
4. Ribosome => prevent protein synthesis (30s and 50s subunits); may be bactericidal or bacteriostatic; examples: tetracyclines, aminoglycosides
5. Metabolic pathways => sulfa => bacteria can’t synthesize folic acid => stop metabolic in bacteria => bacteriostatic

Resistance is bacterial resistance to antibiotic in presence of max level of antibiotic conc tolerated by host
Bacterial resistance is genetic to bacteria and it is on two types:
1. Innate: resistant by default (e.g., most gram negative bacteria resistant to vancomycin; mycobacterial TB which have thick cell wall)
2. Acquired: horizontal transmission or modification of normal function
  1. Horizontal transmission: resistance genes transferred between different bacteria
  2. Vertical transmission: gene passed to daughter bacteria
  3. Modification of normal function: examples include
    1. Secretion of beta lactamase that breaks penicillin (enzymatic inactivation)
    2. Decreased permeability of outer membrane to prevent antibiotic entry
    3. Alternative metabolic pathways if the antibiotic blocks one
    4. Mutations in ribosome binding site prevent antibiotic action

Combination is using more than one antibiotic at a time
Combination used when:
1. Mixed infection (e.g., diabetic foot, peritonitis) => need multiple antibiotics to cover gram positive, gram negative, anaerobes
2. Severe infection (e.g., meningitis)
3. Highly resistant bacteria (e.g., TB with 4 antibiotics, Pseudomonas)
4. Synergism: combined antibiotics produce greater effect than individually
  1. Example: sulfonamide + trimethoprim
  2. Example: penicillin (cidal) + aminoglycosides (cidal)
Result of combination:
1. Bactericidal + bactericidal = synergism
2. Bacteriostatic + bacteriostatic = additive
3. Bactericidal + bacteriostatic = may be ineffective (e.g., penicillin + tetracycline)
4. Exception: meningitis penicillin (cidal) + sulfadiazine (static) => both reach high concentration in CSF

Narrow spectrum antibiotics: active on single or limited microorganisms (e.g., isoniazid active against Mycobacterium tuberculosis only)
Extended spectrum antibiotics: active against gram positive and some gram negative (e.g., ampicillin)
Broad spectrum antibiotics: active against wide variety of microorganisms (e.g., tetracyclines, fluoroquinolones, carbapenems)

Classified into general adverse effects that happen with all antibiotics, and special ones
General adverse effects:
1. Allergic reaction (skin rash, edema)
2. Hypo vitamin B and K (broad spectrum antibiotics kill vitamin-producing gut bacteria => petechiae)
3. Superinfection with broad spectrum antibiotics:
  1. Clostridium difficile, pseudomonas, candida overgrow and cause infection
  2. Toxins damage GIT mucosa => antibiotic-associated diarrhea, pseudomembranous colitis
  3. Treatment: stop antibiotic; use metronidazole or vancomycin; candida treated with nystatin or fluconazole for pharyngitis