General Principles of Chemotherapy Flashcards
How did Ehrlich define chemotherapy?
Selective destruction of invading organisms without harming the host
What is the goal of chemotherapeutic agents?
To exploit differences between the host and the invading organism
Why might a highly selective compound fail as a chemotherapeutic agent?
Due to a low therapeutic index or side effects like immunosuppression
What is selective toxicity in chemotherapy?
Maximizing toxicity to disease-causing organisms while minimizing toxicity to host tissue
Why is penicillin considered close to an ideal chemotherapeutic agent?
It has high selective toxicity and a generally high therapeutic index
How does penicillin’s therapeutic index relate to its selective toxicity?
The therapeutic index parallels its selective toxicity
What are the three main factors in the triad of infection?
Metabolism of drug by host and parasite, toxicity of drug to host and parasite, and parasite impairing host function
How can a parasite impair host function?
Directly through its effects or indirectly by triggering host defenses like inflammation
What determines the outcome of infection treatment?
The interplay of drug metabolism, toxicity, and host-parasite interactions
What type of diseases are generally well controlled with chemotherapy?
Bacterial diseases
What is the primary challenge in bacterial infection treatment?
Drug resistance
Why are fungal infections difficult to treat?
They are stubborn and have a high incidence of recurrence
How successful is chemotherapy for protozoal infections?
Most types can be treated, but more progress is needed
Are helminthic (worm) infections generally treatable?
Yes
What is the most effective approach for treating viral infections?
Immunization
Why is chemotherapy for cancer particularly challenging?
Tumor cells and host cells are not clearly different, and cancer drugs have a narrow therapeutic index
What are some diseases preventable by vaccination?
Polio, measles, mumps, rubella, and cervical cancer
What is the concept behind antibiotic chemotherapy?
Substances from one living thing can kill or suppress the growth of other living things
What are antibiotics?
Chemical substances produced by microorganisms that suppress or kill other microorganisms
Why were systemic infections difficult to treat before sulfanilamide?
Available compounds were too toxic
Why is penicillin significant in antimicrobial chemotherapy?
It remains one of the most effective groups of anti-infective drugs
How have antibiotics impacted bacterial infections?
They have significantly reduced morbidity and mortality
What is the mechanism of action for penicillin and cephalosporins?
Inhibition of bacterial cell wall synthesis, leading to cell lysis
Name an antibiotic that inhibits bacterial cell wall synthesis besides penicillin and cephalosporins.
Vancomycin, bacitracin, or cycloserine
How do polyene antifungal agents like nystatin and amphotericin B work?
They bind to cell membrane sterols, affecting permeability and causing leakage of intracellular components
What is the target of antibiotics like chloramphenicol and tetracyclines?
Bacterial ribosomes, inhibiting protein synthesis (bacteriostatic)
Which antibiotics affect ribosomes and are bactericidal?
Aminoglycosides (streptomycin) and macrolides (erythromycin)
How do rifampin and fluoroquinolones like ciprofloxacin work?
They affect nucleic acid metabolism
What is the mechanism of nucleic acid analogs like acyclovir?
They bind to viral enzymes needed for DNA synthesis, limiting viral replication
What is the function of antimetabolites like sulfonamides and trimethoprim?
They block metabolic steps essential to microorganisms
Name two examples of bacteriostatic drugs.
Tetracyclines and chloramphenicol
Name four examples of bactericidal drugs.
Penicillin, cephalosporin, erythromycin, and streptomycin
How do sulfonamides function?
They can be bacteriostatic or bactericidal depending on the environment (e.g., in blood, pus, or urine)
Why is a functional immune system often needed even with bactericidal agents?
To fully eliminate the infection and effect a cure
Which antibiotics are effective only when the organism is growing?
Those that inhibit cell wall synthesis, protein synthesis, and nucleic acid synthesis
Name two antibiotics effective regardless of cell growth.
Amphotericin and nystatin
How do amphotericin and nystatin work?
They bind to sterols in fungal membranes, creating holes in the membrane
How do some antibiotics interfere with metabolism?
By inhibiting the synthesis of necessary compounds, requiring exhaustion of endogenous compounds before effects are seen
What biochemical difference helps make antibacterial therapy selective?
Ribosomes in bacteria differ from those in animal cells both physically and biochemically
How do structural differences between prokaryotes and animal cells aid selective antibacterial therapy?
Prokaryotes have a cell wall, allowing drugs like penicillins, cephalosporins, and bacitracin to target it
What metabolic differences help in selective antibacterial therapy?
Sulfonamides and trimethoprim exploit different metabolic needs of host and bacterial cells
What is the effect of combining two bacteriostatic agents?
Generally produces an additive effect
What is the effect of combining two bactericidal agents?
It usually results in a synergistic effect, such as with trimethoprim and sulfamethoxazole
What is the goal of chemotherapy in antimicrobial treatment?
To weaken the microorganism enough for host defenses to be effective without harming the host
What happens when a bactericidal and a bacteriostatic agent are combined?
Generally results in antagonism, as bactericidal drugs often require active cell division
What can be a danger of using drug combinations?
Increased host toxicity and antagonism
When is a microorganism considered resistant to an antimicrobial agent?
When the drug concentration required to weaken or kill it is higher than what the host can tolerate
Why is the ratio of toxic to therapeutic concentrations critical in antimicrobial therapy?
It determines whether the drug can be used effectively without harming the host
Do physicians typically culture infections before prescribing antibiotics?
No, they usually use broad-spectrum antibiotics
What is acquired resistance?
Resistance that develops over time, either gradually or rapidly
What is de novo (intrinsic) resistance?
Resistance that exists without selective pressure
How does selective pressure lead to resistance?
Killing off sensitive bacteria allows resistant strains to survive and grow
How can mutation contribute to antibiotic resistance?
Stable genetic changes may randomly occur and persist even without the drug present
How can inappropriate antibiotic use contribute to resistance?
It can promote resistant strains, such as in cattle feed leading to resistant Salmonella and tuberculosis bacilli
What is transduction in bacterial resistance?
Transfer of resistance genes via plasmid DNA in a phage virus
What is conjugation in bacterial resistance?
Direct transfer of DNA between bacteria through cell-to-cell contact
What is transformation in bacterial resistance?
Uptake of naked DNA from the environment
Why are bacteria resistant to polyene antibiotics like amphotericin B and nystatin?
Bacterial membranes lack ergosterol, the target of these drugs
How can bacteria alter drug targets to develop resistance?
By modifying penicillin-binding proteins or increasing the amount of the target enzyme
How do gram-negative bacteria limit penicillin’s effectiveness?
They have an additional outer membrane that restricts access to penicillin-binding proteins
Name two antibiotics that can be inactivated by bacterial enzymes.
Aminoglycosides and chloramphenicol
How does lack of metabolic activation contribute to resistance?
Some drugs, like antifungal flucytosine, require activation, which may not occur in resistant organisms
How can bacteria escape the effects of sulfonamides?
By utilizing purines, thymidine, methionine, and serine from pus or developing an alternative metabolic pathway
How do bacteria inactivate drugs?
By producing enzymes like penicillinases that degrade antibiotics
How should an antibiotic be selected?
Choose one that is selectively active against the likely infecting organism and has minimal risk of allergic reactions or toxicity
How long should antibiotic treatment continue?
Until evidence of infection is absent for several days
What should be done in cases where relapse is likely?
Take smears and cultures, ensuring they are negative on 2–3 successive days
When is antibiotic prophylaxis indicated for oral surgery?
In patients with a history of rheumatic endocarditis or conditions like heart murmur, hip replacement, or kidney dialysis, due to risk of streptococcal infection
Why are newborns and elderly patients more susceptible to drug toxicity?
They have underdeveloped or impaired renal and hepatic elimination
Why should tetracyclines be avoided in young children?
They bind to developing teeth and bones, causing discoloration
How can certain drugs cause brain damage in newborns?
They compete with bilirubin for protein binding sites
Why is chloramphenicol dangerous for newborns?
It is detoxified slowly, leading to severe toxicity
How does impaired renal function affect drug excretion?
It slows elimination of drugs like aminoglycosides and penicillins
How does impaired hepatic function affect drug metabolism?
It reduces the body’s ability to metabolize drugs like erythromycin and chloramphenicol
Why are patients with glucose-6-phosphate dehydrogenase deficiency at risk with sulfonamides or chloramphenicol?
These drugs can cause hemolysis of red blood cells due to high oxidative stress
Why should streptomycin be avoided during pregnancy?
It can cause hearing loss in the newborn
What are safer antibiotic options during pregnancy?
Penicillin and erythromycin
How does pregnancy affect drug pharmacokinetics?
Increased fluid retention, drug passage across the placenta, and deposition in fetal organs
How can antibiotics trigger hypersensitivity reactions?
They may cause rashes, anaphylactic shock, or seizures (e.g., Penicillin G)
How does diabetes affect drug response?
It may alter the body’s reaction to medications
