Drugs
Chemicals that affect physiology in any manner
Chemotherapeutic Agents
Drugs that act against diseases
Paul Ehrlich
“Magic Bullet” used trepamine (arsenic)
Alexander Flemming
Found penicillin in fungus. First Antibiotic
Gerhard Domagk
Sulfa (synthetic penicillin)
Cell wall synthesis inhibitors
Penicillin. Interferes with the linking enzymes between NAG and NAM. Cell continues making NAG/NAM but osmotic forces will cause cell to lyse without adhesive enzyme.
Inhibition of Cell wall synthesis
Act by preventing cross-linkage of NAM subunits by binding to enzymes. Beta-lactams and beta lactam rings.
Semisynthetic beta-lactams
More stable in acidic environments, more readily absorbed, less susceptible to deactivation, more active against more types of bacteria.
Vancomycin/cycloserine
Interfere with alanine-alanine bridges that link NAM subunits in many gram-positives.
Bacitracin
Blocks secretion of NAM and NAM from cytoplasm
Isoniazid/Ethambutol
Disrupt formation of arabinogalactan-mycolic acid (mycobacterium) ex. tuberculosis .
Protein Synthesis Inhibitors
Prokaryotic ribosomes are 70S versuses Eukaryotic ribosomes which are 80S which allows selective drugs that target a specific ribosome. May be harmful to humans due to mitochondrial DNA.
Disruption of cytoplasmic membranes
Some drugs become incorporated into cytoplasmic membrane and damage integrity.
Amphotericin B (Polyene)
Attaches to ergosterol found in fungal membranes.
Azoles and Allyamines
Inhibit ergosterol synthesis
Polymyxin
Disrupts cytoplasmic membranes of Gram negative, but can be toxic to human kidneys
Quinolones
Inhibition of metabolic pathways. Interfere with the metabolism of malaria parasites
Heavy Metals
can inactivate enzymes in some of these pathways.
Sulfonamide
Inhibition of Metabolic Pathways
Analogs of PABA prevent folic acid production so cell dies.
Trimethoprim
Inhibition of metabolic pathways
Specifically binds to enzyme involved in conversion of dihydrofolic acid to THF
Amantadine/rimantadine
Neurtralize acidity of phagolysosome and prevent viral uncoating. If virus is unable to uncoat it CANNOT replicate
Quinolones/fluoroquinolones
act against prokaryotic DNA gyrase; little effect on eukaryotes or viruses since we dont use gyrase.
Rifampin
Bind to and inhibit action of RNA polymerase during transcription
Efficacy
Dosages required to be effective routes of administration and overall safety. Ascertained by diffusion susceptibility/ Kirby bauer method; Minimum inhibitory concentration test, Minimum bactericidal concentration test.