Chapter 7

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antimicrobial compounds

used to inhibit or kill microorganisms

what makes an appropriate microbial compound

easily administered
selective toxicity
needs to remain in the system long enough to be effective
must be broken down and secreted by the host

selective toxicity

kill or inhibit the microorganism without simultaneously damaging the host tissue

goal of selective toxicity

to target specific function or structure in the pathogen that is not present in the host
-cell wall (not present in humans)
70S ribosome (some toxicity to mitochondria)
harder to have selective toxicity with some pathogens (fungi, helminths, and viruses)

chemotherapeutic agent

chemical that is used in the treatment, relief, or prophylaxis of disease

prophylaxis

use of a drug to prevent imminent infection of a person at risk

antibiotic

compound produced by one microorganism that inhibits or kills another microorganism

synthetic drugs

drugs that are synthesized in a laboratory

semisynthetic

drugs that are naturally produced but chemically altered in the laboratory

narrow spectrum

chemotherapeutic agent that is effective against a narrow range of microorganisms

broad spectrum

chemotherapeutic agent that is effective against a wide variety of microorganisms

Paul Ehrlich

worked into antimicrobial compounds
-used an arsenic based drug that was toxic to cause syphilis

origins of antimicrobial drugs

antibiotics are common metabolic products of aerobic spore-forming bacteria and fungi

Targets of antimicrobial drugs

-inhibition of cell wall synthesis
-inhibition of nucleic acid synthesis, structure or function
-inhibition of protein synthesis
-disruption of cell membrane structure or function

Penicillin and cephalosporins

react with one or more nzymes that synthesize/complete the cell wall, causing the cell to lyse

Penicillin

blocks the peptidase enzymes that link the cross bridges between the glycans in peptidoglycan

Drugs that inhibit nucleic acid synthesis

may block synthesis of nucleotides, inhibit replication, or stop transcription

sulfonamides and trimethoprim

block enzymes required for tetrahydrofolate synthesis needed for DNA and RNA synthesis.
-these drugs are competitive inhibitors called metabolic analogs

synergistic effect

an additive effect, achieved by multiple drugs working together, requiring a lower dose of each

Aminoglycosides

streptomycin, gentamicin
insert on sites on the 30S subunit and cause misreading of mRNA

Tetracyclines

block attachment of tRNA to stop protein synthesis

Drugs that disrupt cell membrane function

-cell with a damaged membrane dies from disruption in metabolism or lysis
-these drugs have specificty for a particular microbial group, based on differences in types of lipids in their cell membranes

Penicillin consist of 3 parts

-thiazolidine ring
-beta-lactam ring
-variable sidechain dictates microbial activity

Penicillin is the drug of choice for

gram-positive cocci
and some gram-negative bacteria

Primary problems with penicillin

allergies and resistant strains of bacteria

cephalosporins

-account for majority of all antibitics administered
-beta-lactam ring that can be altered

1st generation of cephalosporins

most effective against gram-positive cocci

2nd generation of cephalosporins

more effective against gram-negative bacteria

3rd generation

broad-spectrum activity against enteric bacteria with beta-lactamase

chromobacterium violaceum

may be used by people allergic to penicillin

aminoglycosides

impair ribosome function
-comosed of 2 or more amino sugarsand an aminocyclitol (6C ring)

Aminoglycosides

broad spectrum
inhibit protein synthesis especially useful against gram-negtive rods and certain gram-positive bacteria

examples of aminoglycosides

steptomyocin
gentamicin

side effects of aminoglycosides

hearing loss
dizziness
loss of appetite
nausea, vomiting

tetracycline

blocks protein synthsis
-prevents the binding of aminoacyl tRNA to the ribosome

Tetracycline antibiotics

taken orally
needs to be taken 2 hours after eating to prevent binding with food
-also inactivated by antacids

side effects tetracycline antibiotics

-potential damage to developing bones of a fetus
-diarrhea
-discoloration of teeth in children
-sensitivity to light

chloamphenicol

blocks peptie bond formation
inhibits protein synthesis

chloramphenicol

typhoid fever
brain abscesses
rickettsial & chlamydial infections
reserved for serious infections

chloroamphenicol-mode of action

-irreversibly binds with 50s subunit
prevents the formation of peptide bond
-can interact with mitochondrial ribosomes

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