BIO 220 Chapter 12: The Elements of Chemotherapy

What is the goal of antimicrobial chemotherapy?

To administer a drug that destroys the infecting agent without harming the host's cells.

Why is selective toxicity important in antimicrobial chemotherapy?

The drug should kill or inhibit microbial cells without simultaneously damaging host tissues.

What characteristics describe the ideal antimicrobial drug?

Selectively toxic, microbicidal, soluble, remains potent long enough to act, does not promote resistance, assists host defenses, remains active in tissues, reaches infection sites, reasonably priced, and causes minimal disruption to the host.

What genera of bacteria commonly produce antibiotics?

Streptomyces and Bacillus.

What genera of molds commonly produce antibiotics?

Penicillium and Cephalosporium.

Who accidentally discovered penicillin?

Alexander Fleming.

Why do microorganisms produce antibiotics?

To reduce competition for nutrients and space.

What is antimicrobial chemotherapy?

The use of chemotherapeutic drugs to control infection.

What are semisynthetic drugs?

Drugs chemically modified in the laboratory after being isolated from natural sources.

What are synthetic drugs?

Antimicrobial compounds synthesized entirely in the laboratory.

Why is complete selective toxicity difficult to achieve with some pathogens?

Because some pathogens are very similar to host cells, causing more side effects.

What are the five major targets of antimicrobial drugs?

Cell wall synthesis, cell membrane function, DNA/RNA function, protein synthesis, and metabolic pathways.

What is the sixth mode of antimicrobial action mentioned in the course objectives?

Block attachment to host cells.

What is a drug's spectrum?

The range of activity of a drug.

How are narrow-spectrum drugs used?

They target a small range of microbes and specific cellular components.

Give an example of a narrow-spectrum drug.

Bacitracin.

How are broad-spectrum drugs used?

They target components common to many pathogens.

Give an example of a medium-spectrum drug.

Ampicillin.

Give an example of a broad-spectrum drug.

Tetracycline.

What major component is found in most bacterial cell walls?

Peptidoglycan.

How do penicillins and cephalosporins affect bacterial cell walls?

They block peptidoglycan synthesis, causing cell lysis.

Why are cell-wall drugs most effective on young bacteria?

Because they are actively growing and synthesizing cell walls.

Why are some penicillins less effective against gram-negative bacteria?

They do not penetrate the outer membrane.

How do broad-spectrum penicillins and cephalosporins affect gram-negative bacteria?

They cross the cell wall, create weak spots, and leave cells osmotically vulnerable.

What classes of drugs inhibit bacterial cell wall synthesis?

Penicillins, cephalosporins, vancomycin, bacitracin, monobactams/carbapenems, fosfomycin, cycloserine, and isoniazid.

How does a damaged cell membrane kill a microbial cell?

It disrupts metabolism or causes cytolysis.

Why do membrane-targeting drugs show specificity?

Because microbial groups differ in membrane lipid composition.

How do polymyxins work?

They interact with phospholipids and cause membrane leakage.

Which bacteria are especially susceptible to polymyxins?

Gram-negative bacteria.

How do some antifungal membrane drugs work?

They form complexes in fungal membranes that cause leakage.

How do drugs affect nucleic acid synthesis?

They block nucleotide synthesis, inhibit replication, or stop transcription.

How does chloroquine affect nucleic acids?

It binds and cross-links the DNA double helix.

How do quinolones affect bacterial DNA?

They inhibit DNA helicases.

How do antiviral nucleic acid analogs work?

They mimic purines or pyrimidines and prevent viral replication.

Why are protein synthesis inhibitors selectively toxic?

Prokaryotic ribosomes differ from eukaryotic ribosomes.

What are the ribosome sizes of bacteria and eukaryotes?

Bacteria have 70S ribosomes; eukaryotes have 80S ribosomes.

How can protein synthesis inhibitors still harm host cells?

They may damage eukaryotic mitochondria.

How do aminoglycosides affect bacterial ribosomes?

They bind the 30S subunit and cause mRNA misreading.

Give examples of aminoglycosides.

Streptomycin and gentamicin.

How do tetracyclines inhibit protein synthesis?

They block attachment of tRNA at the A site.

How do some drugs acting on the 50S subunit inhibit protein synthesis?

They prevent peptide bond formation.

What drug blocks initiation and assembly of bacterial ribosomes?

Linezolid.

What is a metabolic analog?

A drug that resembles a normal substrate but cannot function properly in metabolism.

How do metabolic analogs inhibit microbial growth?

They block production of needed metabolic products.

What classes of drugs affect metabolic pathways?

Sulfonamides and trimethoprim.

How do sulfonamides and trimethoprim affect folic acid synthesis?

They block enzymes needed to produce compounds required for DNA and RNA synthesis.

Why are sulfonamides selectively toxic?

Mammals obtain folic acid from the diet, but microbes synthesize it.

What is a synergistic effect?

The combined effect of two drugs is greater than the sum of their individual effects.

Why are sulfonamides and trimethoprim often combined?

To maximize synergistic effects.

What infections can sulfonamide-trimethoprim combinations treat?

UTIs, protozoan infections, and Pneumocystis pneumonia.

Why are fungal infections difficult to treat?

Fungal cells are eukaryotic and more similar to human cells.

How do some antifungal drugs work?

They target fungal cell membranes and cause leakage.

What are antiprotozoal drugs?

Drugs used to treat infections caused by protozoan parasites.

What are antihelminthic drugs?

Drugs used to treat infections caused by parasitic worms.

Why are parasite infections difficult to treat?

Parasites are eukaryotic and resemble host cells.

Why are antiviral drugs difficult to develop?

Viruses use host-cell machinery for replication.

What is a major challenge of antiviral therapy?

Avoiding damage to host cells while inhibiting viral replication.

How do antiviral nucleoside analogs work?

They interfere with viral nucleic acid replication.

What are the three major coronaviruses?

SARS-CoV, MERS-CoV, and SARS-CoV-2.

What is the overall result of severe COVID-19 infection?

Severe respiratory disease that can progress to respiratory failure.

What was one major treatment approach for severe COVID-19?

Supportive care and management of inflammation and respiratory failure.

What is drug resistance?

An adaptive response in which microorganisms tolerate a drug that would normally inhibit them.

What is the major problem facing antimicrobial chemotherapy?

Acquisition of microbial drug resistance.

How can drug resistance be intrinsic?

The microorganism naturally possesses resistance traits.

How can drug resistance be acquired?

Through mutations or genetic exchange.

How does drug resistance develop?

Through spontaneous mutations, acquisition of new genes, R-factor plasmids, or transposons.

What are R factors?

Resistance plasmids that carry drug-resistance genes.

How do transposons contribute to resistance?

They move resistance genes between plasmids and chromosomes.

What are the major mechanisms of microbial drug resistance?

Drug inactivation, altered drug targets, decreased permeability, efflux pumps, and bypass pathways.

How does drug resistance spread through populations?

Through genetic transfer and natural selection.

What is the long-term effect of widespread drug resistance?

Reduced effectiveness of antimicrobial therapy.

What is the first major strategy for limiting drug resistance?

Limit drug use through accurate diagnosis and proper prescribing.

What is the second major strategy for limiting drug resistance?

Use drugs properly and complete full-dose therapy.

What is the third major strategy for limiting drug resistance?

Use narrow-spectrum drugs whenever possible.

How can multiple-drug therapy reduce resistance?

The drugs work synergistically and resistance is less likely to develop.

What long-term strategies can help reduce drug resistance?

Research, antibiotic stewardship, reduced agricultural use, increased access to therapy, and vaccination.

T or F: About 5% of people taking antimicrobials experience serious adverse reactions.

True.

What are the major side effects of antimicrobial drugs?

Toxic tissue damage, allergic reactions, and disruption of normal flora.

How can antimicrobial drugs lead to superinfections?

By destroying beneficial resident species and disrupting the balance of normal flora.

What three important factors should be considered in drug therapy?

The pathogen, the host, and the drug.

What is the minimum inhibitory concentration (MIC)?

The lowest concentration of a drug that inhibits visible microbial growth.

How is MIC used in drug selection?

It helps determine the effectiveness of a drug against a pathogen.

How is the therapeutic index used in drug selection?

To help estimate drug safety.

T of F: A lower therapeutic index is preferred.

False.

How is final drug selection influenced by the therapeutic index?

Higher safety margins are generally preferred when the drug is effective.