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Controlling Microbial Growth in the Body Part 1
- 1. 1 CONTROLLING MICROBIAL GROWTH IN THE BODY: ANTIMICROBIAL DRUGS
- 2. THE HISTORY OF ANTIMICROBIAL AGENTS • Drugs- Chemicals that affect physiology • Chemotherapeutic agents- against diseases • Antimicrobial agents or antimicrobials- infections 2
- 3. THE HISTORY OF ANTIMICROBIAL AGENTS • Antibiotics- biologically produced agents • Semisynthetic antimicrobials-chemically modified antibiotics • Synthetic drugs- completely synthesized in a • lab 3
- 4. THE HISTORY OF ANTIMICROBIAL AGENTS 1902 • The thick “pseudomembrane” of diphtheria • bacteria, mucus, blood-clotting factors, and white blood cells • Removal: rip open the underlying mucous membrane 4
- 5. CORYNEBACTERIUM DIPHTHERIAE 5 False layer- pseudo; membrane
- 6. THE HISTORY OF ANTIMICROBIAL AGENTS 20TH CENTURY • Focus: Diagnosing and disease course • 1/3 children born in the early 1900s died from infectious diseases before 5yo • Paul Ehrlich-chemotherapy • “magic bullets” Bind to receptors on germs killing without harm to host • Arsenic compounds- syphillis 6
- 7. THE HISTORY OF ANTIMICROBIAL AGENTS 20TH CENTURY • Alexander Fleming • Penicillin released from Penicillium mold, which creates a zone where bacteria don’t grow 7
- 8. THE HISTORY OF ANTIMICROBIAL AGENTS • Sulfanilamide • 1932 Gerhard Domagk • first practical antimicrobial for many bacterial infections 8
- 9. 9
- 10. MECHANISMS OF ANTIMICROBIAL ACTION • Selective toxicity • Effective antimicrobial agent: more toxic to a pathogen than host • More antibacterial than anti: fungals, helmithic and protozoan • Eukaryotes vs prokaryotes 10
- 11. 11
- 12. ANTIVIRAL • Arildone- polio related death; herpes • Pleconaril- rhinoviruses • Enfuvirtide- antiretroviral combination tx hiv-1 12
- 13. INHIBITION OF SYNTHESIS OF BACTERIAL WALLS • Peptidoglycan layer/ other way to disrupt cell wall formation • Beta-lactams: penicillins, cephalosporins, and carbapenems), • Lipoglycopeptides • Vancomycin • Isoniazid- TB • mycolic acid/ waxy lipids- complex • Treated for months to years 13
- 14. 14
- 15. INHIBITION OF SYNTHESIS OF FUNGAL WALLS • Polysaccharides not in mammalian cell • Echinocandins • Caspofungin-inhibit the enzyme that synthesizes glucan • Fungicidal Candida spp. and fungistatic against Aspergillus (aspergillosis- respi mold) 15
- 16. INHIBITION OF PROTEIN SYNTHESIS • Interference with Prokaryotic Ribosomes • Prokaryotic vs eukaryotic ribosomes • Side effects- 70s ribosomes (mitochondria) • 30S aminoglycosides (Streptomycin & Gentamicin) and tetracyclines 16
- 17. INHIBITION OF PROTEIN SYNTHESIS • Interference with Charging of Transfer RNA Molecules • Mupirocin as an essential medicine for bacterial skin infections (WHO)- selectively toxic because it does not bind to any eukaryotic tRNA molecules 17
- 18. W 18
- 19. DISRUPTION OF CYTOPLASMIC MEMBRANES • Gramticidin- damages the cytoplasmic membrane • Polyenes (antifungal)- fungicidal • Azoles- antifungal /protozoal • Ergosterol – harmless to humans 19
- 20. DISRUPTION OF CYTOPLASMIC MEMBRANES • Polymyxin-Gram-negative bacteria • Eg. Pseudomonas • Nephrotoxic • Pyrazinamide-most effective against intracellular, nonreplicating bacterial cells • Praziquantel (antihelmithic)- permeability of CM 20
- 21. INHIBITION OF METABOLIC PATHWAYS • Kinds: • • Atovaquone-electron transport in protozoa and fungi • • Heavy metals (such as arsenic, mercury) inactivate enzymes • •• Drugs that block the activation of viruses • • Metabolic antagonists: sulfanilamide 21
- 22. INHIBITION OF METABOLIC PATHWAYS • Antiviral-Amantadine, rimantadine • Prevent viral uncoating • Protease inhibitors- HIV replication cycle • Used with other drugs as cocktail 22
- 23. INHIBITION OF NUCLEIC ACID SYNTHESIS • Nucleic acids- DNA and RNA • SEVERAL DRUGS- Block DNA replication or RNA transcription • Actinomycin- chemo drug • Quinolones/ flouroquinolones (levofloxacin, moxifloxacin) 23
- 24. PREVENTION OF VIRUS ATTACHMENT, ENTRY, OR UNCOATING • Attachment of viruses-blocked by peptide and sugar analogs of either attachment or receptor proteins • Uncoating- necessary to release DNA • Arildone –antiviral 24
Editor's Notes
- Lipoglycopeptides – antibiotics for MRSA ; semisynthetic Antisense therapy is a form of treatment for genetic disorders or infections; turning off some gene Nucleotide analogs- antiviral; hiv or cancer Actinomycin D- chemotherapy medication
- Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium that causes infections in different parts of the body ** usually skin - boils
- Glucan- cell wall component No cell wall=osmotic rupture
- Prokaryotic ribosomes are 70S : 30S and 50S subunits Eukaryotic ribosomes : 80S with 60S and 40S subunits Eukaryotic mitochondria, which also contain 70S ribosomes- se
- Cytoplasmic membrane- protection; semi-permeable ergosterol, a lipid component of fungal membranes Polyyenes: Nystatin and amphotericin B Zoles- fulconazole
- Metabolism can be defined simply as the sum of all chemical reactions Sulfonamides don’t affect human metabolism
- Uncoating of virus- releases genetic material Protease- enzyme needed by hiv to complete replication cycle Cocktail- combination
- Peptide- amino acids