Shirin Abadi, B.Sc.(Pharm.), ACPR, Pharm.D. Clinical Pharmacy Specialist & Pharmacy Education Coordinator, BC Cancer Agency Clinical Associate

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1 Shirin Abadi, B.Sc.(Pharm.), ACPR, Pharm.D. Clinical Pharmacy Specialist & Pharmacy Education Coordinator, BC Cancer Agency Clinical Associate Professor of Pharmacy & Associate Member of Medicine, UBC September 16 th, 2014

2 1. Define the term microorganism. 2. Differentiate between gram positive, gram negative & anaerobic bacteria. 3. Identify the factors that contribute to antimicrobial efficacy. 4. Describe the mechanisms of action of betalactams, macrolides, aminoglycosides, tetracyclines, quinolones, glycopeptides & oxazolidinones. 5. List the common side effects associated with antibiotics. 6. Explain the most common mechanisms of antibiotic resistance.

3 Organisms of microscopic size Consist of a single cell or cluster of cells Examples: Bacteria Viruses Fungi Protozoa Algae Good or bad?

4 Microscopic Single-celled Prokaryotic Fission/Spores Ubiquitous

5 Spherical (Cocci) Example: Staphylococcus, Streptococcus, Rod-shape (Bacilli) Example: E. coli, Klebsiella, Spiral Example: Spirochaeta,

6 Differentiate bacteria into two large groups: Gram Positive thick cell wall (peptidoglycan layer) violet or purple Gram Negative thin cell wall (peptidoglycan layer) red or pink

7 Examples: Staphylococcus Streptococcus Enterococcus Corynebacterium Listeria

8 Examples: E. coli Klebsiella H. influenzae N. meningitidis Pseudomonas

9 Examples: Bacteroides Clostridium Actinomyces

10 Large group Diverse structures Different mechanisms of actions Different types: Bacteria Antibacterials Viruses Antivirals Fungi Antifungals Parasites Antiparasitic agents

11 Inhibit: Cell wall synthesis Cell membrane synthesis 30s and 50s ribosomal subunits synthesis Nucleic acid metabolism Topoisomerases function Viral proteases Viral integrases Viral envelope fusion proteins Folate synthesis Chemical detoxification processes (e.g., in parasites)

12 Bug sensitive to drug Penetrate site of infection: Physical barriers for drug to traverse (e.g., epithelial & endothelial cells & type of junction between cells) Chemical properties of drug (e.g., hydrophilic or hydrophobic) Presence of multidrug transporters (e.g., P- glycoprotein) Achieve concentration above MIC (minimum inhibitory concentration) during dosing interval

13 Examples: Penicillins Cephalosporins Carbapenems Mechanism of Action: Inhibit synthesis of bacterial peptidoglycan cell wall

14 Products of actinomycetes (soil bacteria) Examples: Erythromycin Azithromycin Clarithromycin Mechanism of Action: Inhibit bacterial protein synthesis by binding to 50S subunit of bacterial ribosomes

15 Examples: Gentamicin Tobramycin Amikacin Mechanism of Action: Inhibit bacterial protein synthesis by binding to 30S subunit of bacterial ribosomes

16 Examples: Tetracycline Doxycycline Minocycline Mechanism of Action: Inhibit bacterial protein synthesis by binding to 30S subunit of bacterial ribosomes

17 Examples: Levofloxacin Ciprofloxacin Moxifloxacin Mechanism of Action: Inhibit DNA gyrase/topoisomerase inhibit bacterial DNA replication

18 Example: Vancomycin Mechanism of Action: Inhibits cell wall synthesis in Gram Positive bacteria, by binding to the D-alanyl-D-alanine terminus of cell wall precursor units

19 Example: Linezolid Mechanism of Action: Inhibits protein synthesis by binding at the P site of the 50S ribosomal subunits

20 Rash Diarrhea Abdominal pain Nausea/vomiting Drug fever Hypersensitivity (allergic) reactions Photosensitivity Headache Dizziness Taste alterations

21 entry of antibiotic into pathogen export of antibiotic by efflux pumps Release of microbial enzymes that destroy antibiotic Alteration of microbial proteins that transform pro-drugs to effective moieties Alteration of target proteins Development of alternative pathways to those inhibited by antibiotic Goodman & Gilman, The Pharmacological Basis of Therapeutics, 12 th Ed, 2011

22 Diverse & large number of microorganisms Bacteria: Gram Positive Gram Negative Anaerobes Antimicrobials: Different types Different mechanisms of action Efficacy depends on sensitivities, penetration, and concentration at site of infection Prone to resistance, side effects, & drug interactions

23

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