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

Gram +/- bacterial cells

• -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

Classification of antibiotics

• -Classified according to the source (natural, synthetic, semi synthetic)
  • -Natural antibiotic like aminoglycosides, penicillin/ cephalosporins
  • -Synthetic like quinolones and sulfonamides
  • -Semi synthetic like ampicillin, amoxicillin
• Also classified According mode of action (bactericidal, bacteriostatic)
  • -Bactericidal => kill bacteria
  • -Bacteriostatic => arrest growth
• Also classified According mechanism of action (5 types of MOA only) (cell wall inhibitors (in gram positive bacteria) ; cell membrane, dna, ribosome , metabolic pathways)
  • -Cell wall inhibitors => like penicillin and cephalosporins and vancomycin and mostly gram positive bacteria because it has thick cell wall => bactericidal
  • -Cell membrane;; isoniazid=> TB;;;  => azoles, nystatin => mostly work on fungi => bactericidal
  • -Inhibitors of Dna function or synthesis => bactericidal ;; quinolones, rifampin
  • -Ribosome => prevent protein synthesis we have 30s subunit and 50s subunit => might be bactericidal or bacteriostatic according to the protein inhibited ;;; examples are tetracyclines, aminoglycosides
  • -Metabolic pathways => sulfa => bacteria can’t synthesize folic acid => stop metabolic in bacteria => bacteria can’t do functions => bacteriostatic

Bacterial Resistance

• -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: innate (resistant by default) like most gram negative bacteria are resistant to vancomycin;; mycobacterial TB which have a thick cell wall that protect it
• -and also there is acquired resistance that is acquired by horizontal transmission or by modification of normal function
• -There is bacteria that has resistance gene that can be transmitted to another bacteria that don’t have the gene in what is called Horizontal transmission by moving the resistance to another bacteria while and this bacteria is going to move the gene into the daughter bacteria by vertical transmission
• -Horizontal transmission transferring resistant genes between different types of bacteria while vertical transmission in the same type
• -By modification of normal function; some bacteria when treated with antibiotics at the beginning it is very susceptible to the antibiotic but with time it develops some resistant patterns like some bacteria secreting beta lactamase that break the penicillin (enzymatic inactivation); and when the antibiotic is going through the pores of the outer membrane, this bacteria will stop the antibiotic from going through (decreased permeability); if the drug is working on metabolic pathway the bacteria will develop an alternative pathway from the pathway inhibited ; and when some bacteria inhibiting the ribosomes , some bacteria would have mutations to the binding site of the antibiotic to the ribosome and that lead to antibiotic not working

Antibiotic combination

• -Combination is using more than one antibiotic at time
• -Combination used when
  • -1- there is mixed infection like diabetic foot or peritonitis => infection with multiple organism gram positive and negative and anaerobe => you need multiple antibiotics to cover all of that because there is antibiotics that is good with gram positive and some good with gram negative and with anaerobes
  • -2- sever infection like meningitis
  • -3- when the bacteria is highly resistant like TB treated with 4 antibiotics and pseudomonas
  • -4- synergism: some antibiotic when given together there would be greater effect; the sum of effect of combined drugs is greater than their individual effect like sulphonamide / trimethoprim , sulfa works on specific metabolic pathway and the trimetho works on the next step of that pathway; penicillin and aminoglycosides both are bactericidal, penicillin better with gram positive, aminoglycosides better with gram negative, penicillin destruct the cell wall and make it easy for the aminoglycoside to enter the cell
• -Result of combination is good when we combinate bactericidal with bacetericidal we get synergisim;; if we combine bacteriostatic with bacteriostatic we get addition like combinating tetracycline and erythromycin ;;; if we combinate bacteriocidal with bacteriostatic the result will be not guarentted because if we add pencillin with tetracycline => pencillin need bacteria to be rapidly multiplying to destruct cell wall of it, while if we give drug that arrest growth (bacteria slow to divide) like tetracyclines , we end up with penicillin not effective;; but in case of meningitis if we combine penicillin (cidal) with sulfadiazine (static) we get both high concentration in CSF

Antibiotics chemotherapeutic spectrum

• -Narrow spectrum antibiotics: antibiotics acting only on single or limited group of microorganisms like => isoniazid active against mycobacterium tuberculosis only
• -Extended spectrum antibiotics: active against gram positive organisms and some of the gram negative organisms ;; ampicillin
• -Broad spectrum antibiotics: active against wide variety of microorganisms;; tetracyclines, fluoroquinolones, carbapenems

General side effects of antibiotics

• -Classified into general adverse effects that happen with all of the antibiotics, and special ones
• -General adverse effects:
• -allergic reaction (skin rash, edema),
• -hypo vitamin B and K (because it kills that bacteria that produce these vitamins in the GIT with broad spectrum antibiotics => lead to petechiae (bleeding under skin) that happen with every broad spectrum antibiotic ;;;
• -super infection happen when broad spectrum antibiotic used and kill most of the bacteria in GIT except for highly resistant ones like Clostridium difficile, pseudomonas, candida (fungi) => clostridium infection, pseudomonas will become more dominant and cause infection and they secrete toxins lead superficial necrosis to the GIT tract that lead to abdominal pain and diarrhea => when toxins kill mucosa like that the mucosa undergoes shedding => this condition named antibiotic associated diarrhea, pseudomembranous colitis (superficial necrosis looks white), clostridium difficile colitis => when patient have diarrhea associated with antibiotic , this antibiotic should be stopped and we give metronidazole which works on anaerobes like difficile , vancomycin also works ;;; candida also cause that and treated with nystatin which is antifungal , if patient have candida pharyngitis then you should consider fluconazole (powerful antifungal drug)

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