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Questions and Answers
Who is considered the father of chemotherapy?
Who is considered the father of chemotherapy?
What is the mechanism of action of Trimethoprim?
What is the mechanism of action of Trimethoprim?
Which scientist discovered Penicillin?
Which scientist discovered Penicillin?
Vancomycin is active against both gram-positive and gram-negative bacteria.
Vancomycin is active against both gram-positive and gram-negative bacteria.
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Nucleic Acid Inhibitors like Quinolones are highly selective, targeting only bacterial DNA.
Nucleic Acid Inhibitors like Quinolones are highly selective, targeting only bacterial DNA.
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What is the mechanism of action of Penicillin?
What is the mechanism of action of Penicillin?
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What are some side effects of ATP and GTP drugs?
What are some side effects of ATP and GTP drugs?
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Trimethoprim acts as a competitive inhibitor of ____________ reductase.
Trimethoprim acts as a competitive inhibitor of ____________ reductase.
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Match the scientist with their contribution:
Match the scientist with their contribution:
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What alteration occurs in aureus and Enterococcus bacteria that can lead to drug resistance?
What alteration occurs in aureus and Enterococcus bacteria that can lead to drug resistance?
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Which lipid molecules are blocked by Bacitracin, preventing the incorporation of peptidoglycan precursors into the cell wall?
Which lipid molecules are blocked by Bacitracin, preventing the incorporation of peptidoglycan precursors into the cell wall?
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Polymyxin is most active against gram-positive bacteria.
Polymyxin is most active against gram-positive bacteria.
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_________ are structurally distinct from 70S ribosomes found in bacterial cells.
_________ are structurally distinct from 70S ribosomes found in bacterial cells.
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Match the following antibiotics with their activities:
Match the following antibiotics with their activities:
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Study Notes
Antimicrobial Drugs
Sulpha Drugs
- Compete with PABA for active site of bacterial dihydropteroate synthase
- Inhibit folate synthesis, leading to inhibition of DNA replication and protein synthesis
- Selectively toxic to bacteria and protozoa
- Humans do not contain dihydropteroate synthase enzyme, must obtain folic acid from diet
- Resistance: bacteria develop sulphonamide-resistant dihydropteroate synthase enzyme
Trimethoprim
- Competitive inhibitor of dihydrofolate reductase
- Interferes with folic acid production
- Often combined with sulpha drugs to increase efficacy of treatment
- Resistance: permeability barrier, efflux pumps, naturally resistant dihydrofolate reductase, and acquired resistance
Quinolones/Fluoroquinolones
- Contain a 4-quinolone ring
- Broad spectrum, effective against E. coli, Klebsiella pneumoniae, Neisseria, P. aeruginosa, S. aureus, and Streptococcus pyogenes
- Act by inhibiting bacterial DNA gyrase and topoisomerase
- Inhibit DNA replication, repair, and chromosome separation, leading to bacterial death
- Resistance: DNA mutations in gyrase and topoisomerase coding genes, increased efflux, and plasmid-mediated resistance genes
Fundamentals
Bacteriostatic vs Bactericidal
- Bacteriostatic: reversible inhibition of growth, regrowth after elimination of the drug
- Bactericidal: death of target organism, non-reversible effect
- Choice of drug depends on type of infection and immune status
Spectrum of Activity
- Narrow Spectrum: targets subset of pathogens
- Broad Spectrum: targets a wider group of pathogens
- Used for empirical therapy, polymicrobic infections, and prophylactic prevention of infections
Dosage and Route of Administration
- Dosage: amount of medication given during a certain time interval
- Route of Administration: oral, intravenous, or intramuscular injection
- Depends on patient mass, metabolism, and elimination needs to be taken into account
Drug Interactions
- Synergetic interactions: better efficacy than individual drugs
- Antagonistic interactions: harmful effects, varied depending on drugs involved
- Examples: trimethoprim and sulfamethoxazole, antagonism between antimicrobials and non-antimicrobials
Cell Wall Synthesis Inhibitors
Penicillin
- Targets cell wall synthesis mediated by penicillin-binding proteins (PBPs)
- Inhibits transglycosylation and transpeptidation, leading to osmotic lysis
- Bacteria producing β-lactamases hydrolyse the C-N bond in the β-lactam ring
- Semi-synthetic penicillins have a broader spectrum of activity
Cephalosporins
- Resemble penicillin in structure, containing a β-lactam ring
- Bind to PBPs, inhibiting transpeptidation and causing osmotic lysis
- Chemical difference provides increased resistance to enzymatic inactivation of β-lactamases
- Used as an alternative to penicillin
Carbapenems and Monobactams
- Inhibit transpeptidase activity of PBPs
- Carbapenem family includes semi-synthetic drugs with a broad spectrum of activity
- Monobactam aztreonam is a narrow spectrum antibacterial, active against gram-negative bacteria
Vancomycin
- Glycopeptide that binds to the D-alanyl-D-alanine end of the pentapeptide
- Prevents cell wall synthesis, leading to osmotic lysis
- Active against gram-positive bacteria, including Staphylococcus aureus
- Last resort for Staphylococcus aureus### Antibiotics and Protein Synthesis Inhibitors
Bacitracin
- A group of structurally similar peptide antibiotics
- Blocks the dephosphorylation of C55-isoprenyl pyrophosphate and bactoprenol pyrophosphate
- Prevents incorporation of peptidoglycan precursors into the cell wall
- Broad spectrum, including gram-positive organisms on the skin
- Nephrotoxic (damaging to kidneys)
Polymyxin
- Cyclic polypeptides that insert into the cell membrane
- Makes a pore in the cell membrane, increasing permeability leading to cell death
- Most active against gram-negative rods
- Valuable against Pseudomonas aeruginosa and other gram-negative bacilli
Protein Synthesis Inhibitors
Ribosome Structure
- Ribosomes made of rRNA and proteins
- Prokaryotes have 23S, 16S, and 5S rRNA
- 23S and 5S are part of the large ribosomal subunit
- 16S is part of the small ribosomal subunit
- mRNA binds to the 16S ribosomal subunit
Translation
- The small and large subunit form a structure that allows mRNA to move through the ribosome
- Amino acids are joined according to sequence on mRNA by tRNA
- tRNA is at P-site (peptidization site)
- Anticodon on tRNA is complementary to the sequence on mRNA
- 23S RNA forms peptide bonds between adjacent amino acids
Overview
- 80S cytoplasmic ribosomes in animal cells are structurally distinct from those found in bacterial cells
- Makes protein synthesis a good selective target for antibacterial drugs
- Therapeutic index is fairly high, but not as high as that of cell wall inhibitors
Aminoglycosides
- Contain cyclohexane ring and amino sugars
- Effective against gram-negative bacteria and Mycobacterium
- Toxic in high doses, causing deafness, renal damage, loss of balance, nausea, and allergic reactions
- Attaches irreversibly to the 30S subunit of bacterial ribosomes
- Blocks the reading of the genetic code on mRNA
- Impairs proofreading ability of the ribosomal complex
Tetracyclines
- Family of antibiotics with a common 4-ring benzene structure
- Bacteriostatic and broad spectrum
- Side effects limit their use, including phototoxicity, permanent discoloration of developing teeth, and liver toxicity
- Binds to the 30S subunit
- Inhibits aminoacyl-tRNA (tRNA with bound amino acid) to the A-site of the ribosome
Macrolides
- Has a lactone ring structure containing 12-22 carbons
- Broad spectrum and bacteriostatic
- Effective against gram-negative and few gram-positive bacteria
- Binds to the 23S rRNA of the 50S ribosomal subunit
- Inhibits peptide chain elongation
Chloramphenicol
- Broad spectrum activity
- Very toxic, reducing bone marrow function and leading to aplastic anaemia
- Binds to the 23S rRNA of the 50S ribosomal subunit
- Inhibits peptidyl transferase activity of the large ribosome
Lincosamines
- Broad spectrum activity against anaerobic bacteria
- Limited activity against aerobes
- Reversibly binds to the 50S ribosomal subunit
- Inhibits translocation of mRNA
- Prevents protein synthesis
Metabolic Antagonists
Introduction
- Antimetabolites block proper functioning of metabolic pathways
- Structurally similar to key enzyme substrate
- Compete with the authentic substrate for binding site on enzyme
- Different enough to prevent or block enzyme activity
- Broad spectrum and bacteriostatic
Sulpha drugs
- Structurally related to sulphanilamide (p-aminobenzoic acid/PABA)
- PABA is needed for folic acid synthesis and is an enzyme co-factor
- Folic acid is a precursor of purines and pyrimidines
- Bases used for DNA and RNA synthesis and other cellular constituents
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Description
This quiz explores the historical use of antimicrobials in various cultures and civilizations, from ancient Egypt to modern times. Learn how different societies have utilized mouldy substances to treat infections. Test your knowledge of the fascinating history of antimicrobials!
