CELLULAR AND MOLECULAR MECHANISM OF ACTION AND RESISTANCE OF ANTIMICROBIAL AGENT

CELLULAR AND MOLECULAR MECHANISM OF ACTION AND RESISTANCE OF ANTIMICROBIAL AGENT

1. Presented By: SOURABH KUMAR Enrollment no. 2303920986013 M. Pharm 2 ND SEM ( PHARMACOLOGY ) ; CELLULAR AND MOLECULAR MECHANISM OF ACTION AND RESISTANCE OF ANTIMICROBIAL AGENT UNDER THE GUIDANCE OF- DR. O.P. Verma (Professor)

2. Introduction Classification of Antibiotics Cellular and molecular MOA Consequence of Resistance Mechanism of Resistance Summary Reference CONTENTS

3. Introduction An antimicrobial is an agent that kills or inhibit the growth of microorganism without harming the cells of the host. The antimicrobial agent may be chemical compound and physical agents. These agents interfere with the growth and reproduction of causative organism like bacteria, fungi, parasites, virus . Antibiotics- These are the substance produce by the microorganisms which selectively suppress the growth of bacteria

4. Broad spectrum: Effective to Gram +, Gram – bacteria, mycoplasmas, chlamydiae , rickettsiae, sometimes protozoa – chloramphenicol , tetracyclin . Narrow spectrum: effective to Gram + / Gram – bacteria only – penicillins , cephalosporins, erythromycin, polymyxins. 1 . Based on spectrum of action

5. Inhibit cell wall synthesis ex: β -lactams, vancomycin, cycloserine , bacitracin. Inhibit protein synthesis ex: Tetracyclin , chloramphenicol, aminoglycosides, Macrolides erythromycin, clindamycin. Inhibit metabolic pathway ex: Sulfonamides, sulfones, trimethoprine . Damage cell membrane ex-Amphotericin B, polymixines , nystatin D.N.A. function ex- Rifamicin , quinolones. D.N.A. gyrase ex: fluoroquinolones. 2. Based on mechanism of action

6. Mechanism of Action Penicillin

7. Kinetic of penicillin Acid Labile – orally not effective Route - IM or IV Distribution – widely distributed Urinary Excretion usually occurs by tubular secretion Use Syphilis Diptheria Tetanus

8. Mechanism of action Aminoglycosides

9. Kinetics of Aminoglycosides Poor oral absorption from intact GIT mucosa After im /iv inj. Peak concentration in 30-60 min Highly polar mainly extracellular Cleared by kidneys: Extraction directly purpotional to creatinine Clarence Normal Half life in Serum 2-3 hrs Can cross placenta Use Pneumonia Meningitis Topical adm. - cream, ointment, burns

10. Mechanism of action Macrolides Inhibits protein synthesis by reversibly binding to the 50S ribosomal subunit Suppression of RNA-
dependent protein synthesis by inhibition of translocation of mRNA.
Typically bacteriostatic activity
→Bactericidal at high concentrations against very susceptible organisms

11. Kinetic of erythromycin Erythromycin base is acid labile. To protect it from gastric acid, it is given as enteric coated tablets, from which absorption is incomplete and food delays absorption by retarding gastric emptying.
Its acid stable esters are better absorbed Erythromycin is widely distributed in the body, enters cells and into abscesses, crosses serous membranes and placenta, but not blood brain barrier.

12. Antimicrobial Drug Resistance Resistance is said to be developed when microbes are less treatable with one or more medication used to treat or prevention effect . Fig Ref- Difference between non-resistant bacteria and drug resistant bacteria.... | Download Scientific Diagram (researchgate.net)

13. Mechanism of Resistance Microbes can resist an antimicrobial agents by 1. Alteration in receptor of drug Ex. Β lactam resistance (alteration in receptors of penicillin 2. Decreasing the amount of drug that reaches the receptor by altering the entry / increasing removal of the drug. Ex: Tetracyclines resistance, aminoglycosides resistance. Mechanism of Resistance

14. Reference Padmaja uday kumar (2017), 4 th edition, jaypee brothes , page no 244.245. KD Tripathi, essemtial of medical pharmacology, 7 th edition, jaypee brothers, page no 688,689. https://www.researchgate.net/figure/Figure2-2-Difference-between-non-resistant-bacteria-and-drug-resistant-bacteria_fig2_340264874 . https://www.semanticscholar.org/paper/Molecular-mechanisms-of-bacterial-resistance-to-Kumar-Varela/29f0074aef87485de2f70f6e92da9c831e2925c9 . Slidedhare by gagan antimicrobial agent

15. Thanks