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Transcript
Chapter 10
Antimicrobial Medications
• Chemotherapy
• Antibiotic
• Synthetic drugs
• Semi-synthetic drugs
• In 1910, Paul Ehrlich discovered Salvarsan
– Arsenic derivative used to treat syphilis
• In 1935, Gerhard Domagk discovered a red dye
that inhibited G+ bacteria
– Prontosil
• In 1936, Ernest Fourneau discovered it was the
sulfur portion of the dye that was active
– stimulated the development of sulfa drugs
• In 1928, Alexander Flemming -1st true antibiotic
– Penicillium mold secretes compound that
inhibits bacterial growth
• Selman Waksman isolated streptomycin from
the soil bacteria Streptomyces
• In 1940s, Howard Florey and Ernst Chain
performed first clinical trials of penicillin
– Developed a method for mass production
– Penicillin G
• More than ½ of antibiotics in use come from bacteria
– Primarily species of Streptomyces
– Some are isolated from species of Bacillus
• Some are isolated from various molds
– Penicillium and Cephalosporium
• Most antibiotic producers are spore formers
• Selective Toxicity
• Magic bullet
– causes damage to the microorganism without
causing significant harm to the host
– Easier with prokaryotic pathogens
– Why?
• Chemotherapeutic index
– maximum tolerable dose (per kg body weight) /
minimum effective dose (per kg body weight)
– Higher the index the safer for host
• Spectrum of activity
– range of different microorganisms against which
the drug is effective
– Narrow-spectrum
• Example – anti-mycobacterials
– Broad-spectrum
• May disturb normal microbiota
• May lead to superinfection
• Synergism
– increased effect of two drugs when used together
– clavulanic acid and amoxicillin
• Antagonism
– reduction of a drug’s desirable effect when
administered with another
• penicillin and tetracycline
• Adverse effects of antimicrobials
– Allergic reactions
– Toxic effects
– Suppression of normal flora
Primary Modes of Action
Inhibition of Cell Wall Synthesis
– Bacterial cell walls are composed of the
polysaccharide peptidoglycan
• Some antibiotics prevent the synthesis of
intact peptidoglycan
• Human cells are unaffected
Disruption of Cell Membrane
• changes permeability of the plasma
membrane
– Results in the loss of important metabolites
– May target specific membrane components
– Ex. particular sterols in fungi cell membranes
Inhibition of Protein Synthesis
•
Common feature of all cells
–
May target the ribosomes
•
•
•
•
–
Change ribosome shape
Block binding sites for tRNA/rRNA
Inhibit peptide bond formation
Prevent shift of reading frame
Use is limited
Inhibition of Nucleic Acid Synthesis
•
Interfere with DNA or RNA synthesis
– May act as nucleoside/nucleotide analogs
– Some have an extremely limited usefulness
– Others are widely used because they are more
selectively toxic
• May act only on bacterial or viral enzymes
Metabolic Antagonists
•
Inhibition of the synthesis of essential metabolites
– enzymatic activity of microbes can be inhibited
by a substance that closely resembles the
normal substrate for the enzyme
– Competitive inhibition
Inhibition of Host Recognition or
Attachment
• Depends on chemical reaction between
pathogen and host
– Pathogen proteins and specific host receptors
– Modification of either attachment or receptor
proteins can inhibit attachment and entry
Mechanisms for Administration of
Drugs
•
•
•
•
Topical
Orally
Intramuscularly (IM)
Intravenously (IV)
Tests to Guide Chemotherapy
• Disk-diffusion method (Kirby-Bauer test)
• Minimum Inhibitory Concentration tests
(MIC)
• E-test
• Minimum Bactericidal Concentration tests
(MBC)
Kirby-Bauer Test
MIC Test
E Test
MBC Test