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52 Cards in this Set
- Front
- Back
Are all chemotherapeutic agents toxic?
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1. Yes
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What is the ideal Chemotherapy?
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Drug is toxic to pathogen, little toxicity to patient
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What 3 things is Selective Toxicity a consequence of?
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1. uniqueness of the target
2. specificity of the drug for that target 3. Dose of active drug delivered |
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By what 3 ways is Selective Toxicity achieved?
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1. unique target present in pathogen, absent in host (cell wall)
2. target is structurally different in the pathogen than in the host (70S vs. 80S) 3. Target is more essential in the pathogen than in the host |
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Give an example of when the target is more essential in the pathogen than in the host
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In anti-cancer therapies
- drugs affect DNA synthesis and replication |
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4 things that a drug must have/be to be effective
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1. must be able to get where its needed
2. must be in an active form 3. must be in sufficient quantity 4. must be available for a sufficient time |
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Sites of drug exclusion (6)
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1. CNS/CSF
2. Ocular fluid 3. Synovial fluid 4. Pleural fluid 5. Cysts 6. Necrotic tissue |
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Sites where drugs may concentrate (8)
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1. Urine
2. Bile 3. Liver 4. Kidney 5. Bone 6. Fat 7. RBC's 8. Skin |
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With what drugs is host metabolism not that important? Why?
With what drugs is host metabolism required? |
1. Anti-microbials b/c metabolism by the pathogen may be a key determinant of activity
2. Anti-tumor drugs |
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This is a critical factor for Selective Toxicity and may be a key part of distribution
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Excretion = if drugs are not excreted their concentrations will increase and may bind to receptors of low affinity and cause toxicity
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What are the 5 key features of Pharmacodynamics for Chemotherapeutic drugs
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1. Mechanism of action
2. Spectrum of activity (how many things it is active against) 3. Static vs. Cidal 4. Development/Incidence of resistance 5. Role of host defenses |
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When are Narrow Spectrum drugs employed?
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-When the pathogen and its sensitivity to the drug are documented
-When the SPECIFICITY for the pathogen is present |
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When are Broad Spectrum drugs employed?
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-For "mixed" infection
- When pathogen identity and sensitivities are not known |
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Why do we not always give Broad Spectrum drugs?
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Because we don't want to kill off our natural flora (commensal organisms)
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What do Static drugs do?
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inhibit growth and proliferation
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What do "-cidal" drugs do?
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kill pathogens
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T or F: High doses of bacteriostatic agents sometimes are bactericidal
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True
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T or F: Combinations of bacteriostatic drugs can have a bactericidal effect
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True
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Which are preferred in IC'ed patients: Bactericidal or Bacteriostatic?
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BacteriCIDAL
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Explain "Concentration-dependent cell killing"
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When the PEAK SERUM CONCENTRATION relates to the extent of killing = killing continues to increase above MBC = Cmax
*Concentration of the drug is important, not time *higher peak values results in increased efficacy and decrease development of resistance |
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Give 2 examples of Concentration-dependent drugs
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Aminoglycosides
Quinolones |
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In Concentration-dependent killing, what do higher peak values result in? (2)
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1. Increased Efficacy = how well a drug produces a response
2. Decreased development of resistance |
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Describe "Time-dependent cell killing"
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The time above the MBC relates to the drug's efficacy
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Give 3 examples of Time-dependent killing drugs
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1. Penicillins
2. Cephalosporins 3. Vancomycin *why you take Penicillin for 10-14 days |
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What is "Post-Antibiotic Effect"?
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the persistent suppression of pathogen growth after removal of the drug
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What pathogens is Post-Antibiotic Effect more common in?
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Gram +
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Why does the Post-antibiotic effect occur?
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1. pathogens have to release and washout the drug
2. pathogens have to synthesize new enzymes |
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Why is time to re-entry into Log growth in bacteria longer in vivo than in vitro?
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Because bacteria are more susceptible to Neutrophil attack during recovery IN VIVO
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Explain the concept of Resistance to Chemotherapeutic Drugs
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EVERY TIME a chemotherapeutic drug is used, it will SELECT for RESISTANT strains of the pathogen
-they will have a selective advantage because the competition has been wiped out |
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What are 6 general mechanisms for Resistance?
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1. pathogen does not ABSORB drug
2. pathogen PUMPS drug out 3. pathogen METABOLISM inactivates drug 4. MODIFIED TARGET in pathogen is not affected by drug 5. INCREASED PRODUCTION of target molecule 6. Development of altered metabolic pathways to bypass the target |
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How does non-genetic (temporary) resistance arise?
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pathogen may be metabolically inactive or dormant
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Name two genetic (permanent) ways resistance arises
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1. Chromosomal
-mutation in gene coding for target -lose effect of drug but maintain normal fxn -pass on to progeny 2. Extrachromosomal -addition of plasmid to pathogen |
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What are 2 important properties of Plasmids in drug resistance
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1. may carry multiple genes providing multiple drug resistances
2. may be passed on to other cells WITHOUT proliferation |
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List ways to minimize the emergence of resistance
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1. only use drugs when they are clearly indicated
2. use narrow-spectrum drug known to be effective against the pathogen, which is present 3. use an effective dose of the drug 4. ensure that the duration of therapy is adequate 5. use older drugs when possible 6. use multiple drugs in combo therapy when the pathogen is noted to develop resistance to an individual drug rapidly |
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Describe Superinfections
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Is the appearance of a new, often more severe, infection as a result of primary chemotherapy
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What is the mechanism of Superinfection?
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The normal flora is alterd of the GI, GU, or respiratory tract and there is an overgrowth of other microbes
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How do you distinguish between a drug irritation of the GI or a Superinfection?
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- if GI problem started as soon as taking drug = irritant
- if GI problems start 3 days later = Superinfection |
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List the 3 major classes of GI Superinfection
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1. Intestinal Candidiasis
2. Staphylococcal Enterocolitis (life-threatening) 3. Pseudomembranous Colitis (life-threatening) |
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What is the most common type of Superinfection?
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Intestinal Candidiasis
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What is the treatment for Intestinal Candidiasis?
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continue antibacterial but add antifungal drug
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What is the treatment for Staphylococcal Enterocolitis?
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1. DISCONTINUE anti-bacterial
2. Administer anti-staph penicillin or vancomycin |
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What is the pathogen of Pseudomembranous Colitis?
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C. difficile
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What is the treatment for Pseudomembranous Colitis?
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1. DISCONTINUE antibacterial
2. Administer Metronidazole |
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What provides the final "cure" in infections?
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Host immune fxn
*chemotherapy seldom produces a cure directly |
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What are the 3 general adverse effects of chemotherapy?
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1. Toxicity to host
2. Hypersensitivity 3. Idiosyncratic responses |
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Toxicity to host:
-__1__-related -may result from altered __2__ -often related to __3__ for the drug |
1. dose
2. Pharmacokinetics (ADME) 3. mechanism of action |
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What is "Combination Chemotherapy?
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The use of multiple drugs against the same pathogen
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What are the 5 indications for using Combination Chemotherapy?
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1. for enhanced therapeutic effect (synergism)
2. To allow the use of lower doses of individual drugs to minimize toxicity to the patient 3. to delay the development of resistance 4. For the treatment of "mixed" infections 5. To initiate therapy in life-theatening situations when the pathogen is not known |
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What are 4 circumstances in which Chemoprophylaxis is indicated?
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1. to protect healthy individuals following expousure to specific pathogens
2. to minimize active, symptomatic episodes of chronic infections (herpes, TB) 3. to prevent post-surgical infections 4. to prevent bacterial endocarditis in susceptible individuals |
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What are 2 ways in which surgery can cause infection?
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1. Abdomenal surgery where commensal flora are release from GI
2. Betadine scrub can still leave pathogens on the skin -> incision |
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What is an example of why chemoprophylaxis is used to prevent Bacterial endocarditis?
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A person with Prosthetic heart valves are susceptible to infection after a dental procedure
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What are the 5 guidelines for successful Surgical Chemoprophylaxis?
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1. the specific pathogens and their sensitivity should be known
2. Short duration 3. Pathogen should be slow to develop resistance to the drug chosen 4. Doses should be equal to those used in chemotherapy 5. Efficacy should be established |