Principles of antimicrobial therapy Flashcards
Targets of drug action
Enzymes Receptors Ion channels Transporters targets in host cell to later function
Immunity
Body’s ability to recognise and remove non-self material
Action of anti-microbial drugs
Ability to recognise and destroy non-self cells
What is chemotherapy based on?
Selective toxicity
What is selective toxicity?
Causes greater harm to micro-organism than host
Anti-microbial drugs must have limited toxicity but good selectivity
To increase efficacy= increase dose but efficacy and toxicity must be balanced
Chemotherapeutic index formula
Toxic Dose (lowest)/Therapeutic dose
Chemotherapeutic index meaning
The ratio of the minimal effective dose of a chemotherapeutic agent to the maximal tolerated dose
4 types of anti-microbial drugs
Anti-bacterial
Anti-fungal
Anti-protozoan
Anti-helminthic
Class I pathways that antimicrobial drugs target
Reactions that use glucose/other carbon sources to make ATP/substrates needed for class II reactions
Class II pathways
Pathways that use ATP and class I substrates to make small molecules e.g amino acids, nucleotides
Class III pathways
Convert small class II molecules into macromolecules e.g proteins, nucleic acids, polysaccharides, peptidoglycan
Name of a class II antimicrobial drug
Sulfonamide
What the pro drug of sulfonamide that is metabolized in the body to produce sulfonamide?
Prontosil
Sulfonamide mechanism of action
Competitive inhibitor of dihydropteroate synthetase
This enzyme normally produces folic acid
Prevent bacterial DNA synthesis and replication
Why can bacteria synthesise folate but humans can’t?
Bacteria have the enzyme dihydropteroate synthetase enzyme but humans don’t
What does dihydrofolate reductase catalyse?
Formation of tetrahydrofolate from dihydrofolate
What antimicrobial drugs prevent action of dihydrofolate reductase?
Trimethoprim
Methotrexate
Pyrimethamine
Mechanism of action of trimethoprim, methotrexate and pyrimethamine
(for trimethoprim) Type= antifolate antibacterial agent
Interaction- dihydrofolate reductase
Reversible inhibitor of dihydrofolate reductase
Tetrahydrofolate cant be made which is essential in making thymidine, nucleic acids and proteins (methionine)
so inhibits bacterial DNA synthesis
Killing bacteria
Example of a class III antimicrobial drug
Penicillin
What class of drug is penicillin?
Beta-lactam
Is penicillin broad/narrow spectrum antibiotic?
Narrow spectrum
Examples of Beta-Lactam drugs
Penicillins
Monobactams
Carbapenems
Cephalosporins
Bacteria cell wall peptidoglycan synthesis
Penicillin binding protein in cell wall e.g transpeptidase enzyme normally catalyses cross linking of peptidoglycan chains by binding to D-ALA D-ALA by transpeptidation reaction
What does beta-lactam do?
Inhibits peptidoglycan cell wall synthesis