Antimicrobial Agents - Mechanism of Action | Medical Science Optional Notes for UPSC PDF Download

Introduction

1. Inhibit cell wall synthesis:

   • Penicillins
   • Cephalosporins
   • Cycloserine
   • Vancomycin
   • Bacitracin

2. Cause leakage from cell membranes:

   • Polypeptides
   • Polymyxins
   • Colistin
   • Bacitracin
   • Polyenes (Amphotericin B, Nystatin, Hamycin)

3. Inhibit protein synthesis:

   • Tetracyclines
   • Chloramphenicol
   • Erythromycin
   • Clindamycin
   • Linezolid

4. Cause misreading of mRNA code and affect permeability:

   • Aminoglycosides
   • Streptomycin
   • Gentamicin

5. Inhibit DNA gyrase:

   • Fluoroquinolones (Ciprofloxacin)

6. Interfere with DNA function:

   • Rifampin

7. Interfere with DNA synthesis:

   • Acyclovir
   • Zidovudine

8. Interfere with intermediary metabolism:

   • Sulfonamides
   • Sulfones
   • PAS (Para-Aminosalicylic Acid)
   • Trimethoprim
   • Pyrimethamine
   • Metronidazole

Antimicrobial Agents - Adverse Effects

Antimicrobial Agents - Mechanisms of Resistance 

Three fundamental mechanisms include:

1. Modifying or bypassing targets that experience diminished drug binding,
2. Changing the drug's access to its target through decreased uptake or heightened active efflux,
3. Modifying the drug itself to diminish its activity.

Beta Lactam Antibiotics

MRSA Management

Methicillin resistance signifies resistance to all semisynthetic penicillinase-resistant penicillins (SPRPs), including oxacillin or nafcillin, as well as resistance to all cephalosporins (except ceftaroline). The emergence of methicillin resistance is attributed to the production of a novel penicillin-binding protein (PBP2a) synthesized by the mecA gene. It is hypothesized that this genetic material was acquired through horizontal transfer from a related staphylococcal species, such as Staphylococcus sciuri.
Vancomycin and daptomycin are currently recommended as the drugs of choice for treating Methicillin-Resistant Staphylococcus aureus (MRSA).

Vancomycin:

• A glycopeptide antibiotic that inhibits bacterial cell wall synthesis.
• It binds to the terminal dipeptidic 'D-ala-D-ala' sequence of peptidoglycan units, preventing their release from the bactoprenol lipid carrier. This action inhibits the assembly of units at the cell membrane and their cross-linking to form the cell wall.
• Systemic use is restricted to serious MRSA infections, with recommended doses of 500 mg every 6 hours or 1 g every 12 hours infused intravenously over 1 hour.
• Vancomycin has the potential to release histamine, causing adverse reactions such as chills, fever, urticaria, and intense flushing known as 'Red man syndrome.'

Daptomycin:

• A lipopeptide antibiotic that disrupts multiple aspects of bacterial cell membrane.
• The recommended dosage is 4-6 mg/kg intravenously once daily.
• It binds avidly to pulmonary surfactant, rendering it ineffective in respiratory infections.
• Common adverse reactions include rash, hypersensitivity, alterations in blood pressure, swelling, insomnia, and eosinophilia.

Antimicrobial Agents

Antimicrobial Agents - Mechanism of Action

Antimycobacterial Agents

Inhibitors of Protein Synthesis

Antibacterial Agents - Repeats

• Explore the primary anti-mycobacterial drugs, focusing on their mechanism of action, side effects, and the development of resistance. (2013)
• Outline the general mechanism of action of antimicrobial drugs and delve into the specific mechanism of action and adverse reactions of penicillins. (2014)
• Examine the pharmacotherapy for methicillin-resistant Staphylococcus aureus infection. (2016)
• Elaborate on the mechanism of action of sulfonamides and elucidate the methods bacteria employ to develop resistance to them. (2017)
• Clarify the reasons behind using Imipenem, a beta-lactam antibiotic, in combination with cilastatin. (2018)
• Review the adverse effects associated with the utilization of antimicrobial agents. (2018)