Principles of Chemotherapy Flashcards
LIst Koch’s postulates
- microbe found abundantly in all diseased organisms, but not found in healthy individuals
- microbe isolated from diseased individuals and grown in pure culture
- cultured microbe should cause same disease when inoculated into healthy individual
- must reisolate microbe from inoculated individual and be identified as identical to original pathogen
Is Koch’s first postulate hard and fast
No. You can have the microbe but be healthy(e.g. cholera, typhoid fever)
Is Koch’s third postulate a “must” or a “should”
“Should” because exposure does not mean you will get the infection
What is the term for selective destruction of invading organisms? (Selective means it does not harm the host)
Chemotherapy
Chemotherapeutic design exploits what?
The difference between host and invader.
Does chemotherapy relate how the drug acts on just the disease or how it effects the disease and the host
Just how the drug relates to the disease
What is the goal of selective toxicity?
Administer a substance to produce maximal toxicity to disease-causing organisms, but with minimal toxicity to host.
This is the ratio of the toxic dose/effective dose. This relates everything the medicine does to the patient
Therapeutic Index (TI)
Is selective toxicity the same as therapeutic index?
No. Drug can be selective but have narrow therapeutic index because it is still toxic to host by other modes.
Can very selective compounds fail to produce a cure and why?
Yes. Because they have low therapeutic index.
What are the three parts of the triad of infection?
Host, Drug and Pathogen
What are the ways a drug reacts with host and pathogen in the triad of infection?
Metabolism of drug by host and parasite.
Toxicity of drug to host and parasite.
What 3 general factors for drug-pathogen interaction should be considered when treating?
- Drug resistance of pathogen
- Drug is bacteriostatic
- Drug is bacteriocidal
How do the host and pathogen interact in the triad of infection?
Via the host immune response.
What is the overall goal of the triad of infection?
to illustrate that the interplay of the Host, Drug, and Pathogen determines the outcome
List 6 types of diseases treated by chemotherapy
- Bacterial
- Fungal
- Protozoal
- Helminthic
- Viral
- Cancer
What is the primary problem in treating bacterial infection?
Antibacterial resistance
What characteristic of a fungal infection is important to remember when treating it?
Fungal infections are stubborn and have high recurrence.
What is the more effective treatment for viral infections?
Immunization
Generally speaking, what is the main problem with using chemotherapy to treat cancer?
The difference between tumor and host cells unclear and the cancer drugs have narrow therapeutic index.
What is the concept that substances derived from one living thing may serve to kill other living things?
Antibiotic chemotherapy
What are chemical substances produced by various species of microorganisms (bacteria, fungi) that suppress the growth of other microorganisms or kill other microorganisms?
Antibiotics
Antibiotics can have what two types of effect on bacteria?
- bacteriostatic
2. bacteriocidal
What was first antibiotic: Penicillin or Sulfanilamide?
Sulfanilamide (1936)
What is the most effective group of anti-infectives?
Penicillins
What are the 2 ways to classify chemotherapeutics?
- Mechanism of Action
2. Bacteriostatic vs Bacteriocidal
What are 5 mechanisms of action for chemotherapeutics?
- Inhibit cell wall synthesis
- Act directly on cell membrane
- Affect bacterial ribosome function
- Affect nucleic acid synthesis
- Block metabolic steps
What will happen to a bacterial cell wall if its bacterial cell wall synthesis is inhibited?
Cell lysis
Agents that act directly on the bacterial cell membrane will do what?
Affect bacterial cell permeability causing leakage of intracellular constituents.
If the bacterial ribosome function is affected by chemotherapy, what is inhibited in the bacteria?
protein synthesis
What type of drug limits growth of invading microorganisms allowing host defenses to catch up?
Bacteriostatic drug
What type of drug kills the invading microorganisms?
Bacteriocidal
Even with bacteriocidal agents, what is a key component required for a cure?
A functional immune system
An antibiotic that inhibits cell wall synthesis, protein synthesis, and nucleic acid synthesis is best used when in the microorganism’s cell cycle?
When the organism is growing.
An antibiotic that binds directly to a cell membrane to create holes is best used when in the mircroorganism’s cell cycle?
Anytime. It is effective irrespective of cell growth cycle.
What is a concern with antibiotics who are effective by targeting bacterial metabolism?
There might be a lag period while endogenous compounds are used up and antibacterials can be taken up
What are 3 basis for selectivity of antibacterial therapy
- Biochemical differences
- Structural differences
- Metabolic differences
What is exploited in the biochemical differences for antibacterial therapy?
Ribosomes in bacteria differ physically and biochemically from ribosomes in animal cells
What is the structural difference between prokaryotes and eukaryotes that is the basis for selectivity in some antibiotics?
Prokaryotes have a cell wall.
Are 2 bacteriostatic agents used together called additive, antagonistic, or synergistic?
Additive
When one bacteriocidal and one bacteriostatic agents used together are additive, antagonistic, or synergistic?
Usually antagonistic
How would a bacteriostatic drug antagonize a bacteriocidal one?
The bacteriostatic drug stops cell growth which would block the bacteriocidal drug’s target
What are the dangers of drug combinations?
Antagonism and/or toxicity
If the concentration of drug required to weaken or kill the microorganism is greater than can be tolerated by the host the microorganism is said to be.
Resistant
What are 2 types of antibiotic resistance?
Acquired and de novo.
What are three ways to acquire resistance?
- Transduction
- Transformation
- Conjugation
Plasmid DNA in a phage virus transfering resistance Is called what?
Transduction
Naked DNA picked up by other cells and transferring resistance is called what?
Transformation
Direct cell to cell contact that transfers resistance is called what?
Conjugation
The capacity of a pathogen to not respond to a drug, e.g. a fungal cell resisting penicillin because the fungus does not have the cell wall target for the penicillin is an example of what type of resistance?
Denovo/Intrinsic
What are 6 mechanisms of drug resistance?
- Absence of target
- Altered Target
- Low concentration of drug at target
- Lack of metabolic activation
- Inactivation
- Escape from drug effects
A fungus not being affected by penicillin because it lacks the cell wall target or a bacteria not responding to antifungal drug because the bacteria lack the ergosterol target is called De Novo/ Intrinsic Resistance, and is what mechanism of resistance?
Absence of Target
If a bacteria is able to alter its enzymes so they have less affinity for a drug or alters their drug binding characteristics, this is an example of what mechanism of resistance?
Alteration of target
A gram-negative bacteria has an outer-membrane that reduces the amount of penicillin that can get to its cell wall to bind to the penicillin binding protein, this is an example of what mechanism of resistance?
Low concentration of drug at target
A bacteria starts to producing β-lactamases which will inactivated penicillin, this is an example of what mechanism of resistance?
Inactivation
If a bacteria can alter its metabolic pathway so as to avoid the step that is blocked by the antibiotic, that is an example of what mechanism of resistance?
Escape from drug effect
What are 2 requirements for prescribing antibiotics?
1 Drug is selective for most likely infecting organism
2. Drug has least chance of allergic reaction or host toxicity
Is antibiotic prophylaxis to prevent postoperative infections supported by controlled studies?
No
Antibiotic prophylaxis is indicated for oral surgery patients who have rheumatic endocarditis, artificial joints, some heart conditions, kidney dialysis. What bacteria are they subject to infection by?
Streptococcus
What are 8 factorsto consider in antibiotic treatment and patient response?
- Age
- Distribution
- Excretion
- Genetic factors
- Pregnancy
- Drug allergies
- Underlying conditions
- Immune status
What must you consider when When considering drug treatment in newborns as well as the elderly?
Renal excretion and hepatic elimination poorly developed or functioning
Drug distribution is related to the development of which body system?
Cardiovascular
What is an example of a genetic factor that would contraindicate treatment with sulfonamides and chloramphenicol?
Glucose-6-phosphate dehydrogenase deficiency in African or Mediterranean descent, leads to hemolysis of red blood cells if prescribed sulfonamides or chloramphenicol
Can you prescribe Sulfonamides to newborns?
No because they cannot excrete or eliminate it.
Can you prescribe Streptomycin to newborns?
No because it may produce a hearing loss.
What are alternatives for newborns to avoid the hearing loss caused by Streptomycin?
Penicillin or erythromycin
Ways pregnancy and nursing can interact with drugs?
Alter drug pharmacokinetics Increased fluid retention Pass drugs across placenta Deposit drugs in fetal organs Can be passed to child while nursing
What is a superinfection?
Antibiotic kills normal flora allowing an opportunistic infection by normal bacteria (e.g. C.diff)
What is a new way to treat superinfection?
Fecal transplant. Puts normal flora back into wiped out patient.
What are 6 potential problems with antibiotics?
- Incorrect diagnosis (e.g. Antibiotic for a virus)
- Admin via wrong route (e.g. acid labile penicillin via mouth)
- Inadequate dose
- Inappropriate treatment regimen (too long or too short)
- Abscesses (their pH decreases drug effect)
- Adverse drug effects (allergy, GI, superinfection)
What are 2 causes of superinfection?
- Broad spectrum antibiotic therapy
2. Prolonged antibiotic treatment
Explain the concept of Log Cell Kill
The drug kills a constant fraction/percentage of the bacteria with each dose, not a constant number.
What is the Cell Log Kill for bacteriostatic drugs?
0 (Zero)
Do you want a high or low Log Cell Kill for cancer drugs and why?
High Log Cell Kill because even one remaining cell can restart the tumor
A drug that eliminates 90% of bacterial population has a Log Cell kill of what?
1 (90% killed = 10% remain = 1/10= 0.1, neg log 0.1 = 1)
A drug that eliminates 99% of bacterial population has Log Cell Kill of what?
2 (99% killed = 1% remain = 1/100=0.01, neg log 0.01 = 2)
What is the Log Cell Kill required to cure microbial infections?
2 (106 104) the immune system should eliminate the remaining bacteria.
