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Pharm Exam 4 > General Principles of Chemotherapy > Flashcards

General Principles of Chemotherapy Flashcards

1
Q

What defines the selective destruction of invading organisms?

A

Chemotherapy

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2
Q

What does the ideal therapeutic agent exploit?

A

Differences between host and invading pathogen

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3
Q

What is the ratio of toxic dose/effective dose?

A

Therapeutic Index; relates to everything medicine does to a patient.

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4
Q

What is the difference between selective toxicity and therapeutic index?

A

They are not the same: Drug can be selective, but have narrow therapeutic index because it is still toxic to host by other modes.

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5
Q

What is the ideal chemotherapeutic agent and why?

A

Penicillin: selective toxicity and high therapeutic index

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6
Q

What are the aspects of the Triad of Infection?

A

Interaction between host, pathogen and drug

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7
Q

What does the Triad describe specifically (4)?

A

Metabolism of drug by host/pathogen, toxicity of drug to host/pathogen, Pathogen impairs host function, and host responds to pathogen with immune system

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8
Q

What are Koch’s Postulates?

A
  1. Microbe found abundantly in all disease individuals but not found in healthy ones.
  2. Microbe isolated from diseased individuals and grown in pure culture.
  3. Cultured microbe should cause same disease when inoculated in healthy individual.
  4. Microbe can be reisolalted from inoculated individual and be ID’d identical to original pathogen.
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9
Q

Does chemotherapy relate to how drugs act on disease, how drug effects the host or both?

A

Just how drug acts on the disease

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10
Q

Can very selective drugs still fail to produce a cure and why or why not?

A

Yes, they have a low therapeutic index.

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11
Q

What are two ways the drugs affect with host and parasite?

A

Metabolism of drug by host/parasite

Toxicity of drugs to host/parasite

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12
Q

What three general factors for drug/pathogen interaction should be considered when treating?

A

Drug resistance of pathogen, and whether drug is bacteriostatic or bactericidal

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13
Q

How do the host and pathogen interact in the triad?

A

Via the host immune response

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14
Q

Six types of pathogens/disease treated by chemotherapy?

A

Bacterial, fungal, protozoal, helminthic, viral and cancer

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15
Q

Primary problem in treating bacterial?

A

Antibiotic resistance

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16
Q

Character of treating a fungal infection?

A

Stubborn with high recurrence (was more superficial until AIDS/organ transplantation allowed them to be more systemic)

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17
Q

What is the most effective treatment for viral?

A

Immunization

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18
Q

What type of infection is the most common world wide and what generally causes it?

A

Malaria; protozoa

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19
Q

General problem for cancer chemotherapy tx?

A

Difficult to tell the difference between tumor and host cells and cancer drugs have a very narrow therapeutic index

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20
Q

The concept that compounds derived from living things may kill another living thing?

A

Antibiotic chemotherapy

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21
Q

Chemical substances produced by various species of microorganisms (bacteria, fungi) that suppress the growth of other microorganisms or kill other microorganisms

A

Antibiotics

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22
Q

Antibiotics can be ___ or ____.

A

Bacteriocidal or bacteriostatic

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23
Q

What was the first antibiotic: penicillin or sulfanilamide?

A

Sulfanilamide (1936)

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24
Q

Most effective group of anti-infectives?

A

Penicillins

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25
Q

Two ways to classify therapeutics?

A

Mechanism of action or Bacteriocidal/Bacteriostatic

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26
Q

Five chemotherapeutic MOA?

A 
Inhibit cell wall synthesis
Act directly on cell membrane
Affect bacterial ribosome function
Affect nucleic acid synthesis
Block metabolic steps
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27
Q

What will happen to a bacterial cell wall if its bacterial cell wall synthesis is inhibited? Five drug examples?

A

Cell lyses; Cephalosporins/penicillins, vancomycin, bacitracing and cycloserine

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28
Q

Agents that act directly on the bacterial cell membrane will do what? Two drug examples?

A

Affect bacterial cell permeability causing leakage of intracellular constituents; antifungals (nystatin and amphotericin B)

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29
Q

If the bacterial ribosome function is affected by chemotherapy, what is inhibited in the bacteria? Four drug examples and classification?

A

Inhibit protein synthesis;
Bacteriostatic=chloramphenicol and tetracycline
Bacteriocidal: aminoglycosides (streptomycin)

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30
Q

Drug that limit growth of invading microorganisms allowing host defenses to catch up?

A

Bacteriostatic

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31
Q

Even with bacteriocidal agents, what is a key component is required for a cure?

A

Functional immune system

32
Q

An antibiotic that inhibits cell wall synthesis, protein synthesis, and nucleic acid synthesis is best used when in the microorganism’s cell cycle?

A

When organism is growing

33
Q

T/F. Sulfonamides can be bacteriocidal or bacteriostatic.

A

T. Environment may affect which type of drug it becomes (e.g. pus filled abscess neutralizes sulfonamide so it’s more bacteriostatic)

34
Q

An antibiotic that binds directly to a cell membrane to create holes is best used when in the microorganism’s cell cycle?

A

Anytime, effective irrespective of cell growth

35
Q

What is a concern with antibiotics who are effective by targeting bacterial metabolism?

A

Might be a lag period while endogenous compounds are used up and antibacterials can be taken up

36
Q

Three basis for selectivity of antibacterial therapy

A

Biochemical differences, structural differences and metabolic differences

37
Q

What is exploited in the biochemical differences for antibacterial therapy? Metabolic difference exploited?

A

Ribosomes in bacteria differ physically and biochemically from ribosomes in animal cells; metabolic needs differ between host and bacteria

38
Q

What is the structural difference between prokaryotes and eukaryotes that is the basis for selectivity in some antibiotics?

A

Prokaryotes have a cell wall

39
Q

2 bacteriostatic agents used together are additive, antagonistic, or synergistic? Two bacteriocidal? One bacteriocidal and one bacteriostatic?

A

Additive; synergistic; generally antagonistic

40
Q

How would a bacteriostatic antagonize a bacteriocidal?

A

Bacteriostatic stops cell growth which blocks bacteriocidal target

41
Q

What are the dangers of drug combinations (2)?

A

Increase host toxicity and antagonism

42
Q

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…

A

Resistant

43
Q

2 types of antibiotic resistance

A

Acquired and denovo

44
Q

3 ways to get acquire resistance

A

Transduction, transformation and conjugation

45
Q

Plasmid DNA in a phage virus transfering resistance Is called

A

Transduction

46
Q

Naked DNA picked up by other cells and transferring resistance is called

A

Transformation

47
Q

Direct cell to cell contact that transfers resistance is called

A

Conjugation

48
Q

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?

A

De Novo/Intrinsic

49
Q

Type of resistance when pathogen is exposed and eventually no longer responds?

A

Acquired (may occur prolonged period or can occur quickly)

50
Q

If have a patient, give them penicillin, kills the infection. Then two months later, have similar infection give penicillin but it no longer works. Is this intrinsic or acquired?

A

No, not sure if it’s one bacteria that intrinsically had resistance or if resistance was acquired over time

51
Q

6 mechanisms of drug resistance

A 
Absence of target
Altered Target
Low concentration of drug at target 
Lack of metabolic activation
Inactivation
Escape from drug effects
52
Q

What mechanism of resistance: 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?

A

Absence of target

53
Q

What mechanism of resistance: If a bacteria is able to alter its enzymes so they have less affinity for a drug or alters their drug binding characteristics?

A

Alteration of target

54
Q

What mechanism of resistance: 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?

A

Low concentration of drug at target

55
Q

What mechanism of resistance: A bacteria starts to producing β-lactamases which will inactivated penicillin?

A

Inactivation

56
Q

What mechanism of resistance: If a bacteria can alter its metabolic pathway so as to avoid the step that is blocked by the antibiotic?

A

Escape from drug effect

57
Q

2 requirements for prescribing antibiotics?

A

Drug is selective for most likely infecting organism Drug has least chance of allergic reaction or host
toxicity

58
Q

Is antibiotic prophylaxis to prevent postoperative infections supported by controlled studies?

A

No

59
Q

What mechanism of resistance: bacteria over expresses target so there is not enough drug to block the receptor?

A

Alteration of target

60
Q

8 factorsto consider in antibiotic treatment and pt response?

A

Age, Distribution, Excretion, Genetic factors, Pregnancy, Drug allergies, Underlying conditions, Immune status

61
Q

What do we take into consideration with newborns or elderly when considering chemotherapy?

A

Renal excretion and hepatic elimination is poorly developed or functioning. Newborns also have bilirubin that is replaced in certain drugs.

62
Q

Drug distribution is related to the development of which body system

A

Cardiovascular

63
Q

Example of Genetic Factor that would contraindicate treatment with sulfonamides and chloramphenicol? What can this cause?

A

Glucose-6-phosphate dehydrogenase deficiency in African or Mediterranean descent, leads to hemolysis of red blood cells if prescribed sulfonamides or chloramphenicol

64
Q

Can you prescribe Sulfonamides to newborns? Why or why not?

A

No, they can’t excrete or eliminate it.

65
Q

Can you prescribe Streptomycin to newborns? Why or why not?

A

No, produces hearing loss

66
Q

What are alternatives for newborns to avoid the hearing loss caused by Streptomycin?

A

Penicillin or erythromycin

67
Q

Five ways pregnancy and nursing can interact with drugs?

A 
Alter drug pharmacokinetics
Increased fluid retention
Pass drugs across placenta 
Deposit drugs in fetal organs
Can be passed to child while nursing
68
Q

What is a superinfection?

A

Antibiotic kills normal flora allowing an opportunistic infection by normal bacteria (e.g. C.diff)

69
Q

New way to treat superinfection?

A

Fecal transplant. Puts normal intestinal flora back into wiped out patient.

70
Q

6 potential problems with antibiotics?

A

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)

71
Q

2 causes of superinfection?

A

Broad spectrum antibiotic therapy and prolonged antibiotic treatment

72
Q

Explain the concept of Log Cell Kill

A

Drug kills a constant fraction/percentage of the bacteria with each dose, not a constant number

73
Q

A drug that eliminates 90% of bacterial population has a Log Cell kill of …

A

1 (90% killed = 10% remain = 1/10= 0.1, neg log 0.1 = 1)

74
Q

A drug that eliminates 99% of bacterial population has Log Cell Kill of

A

2 (99% killed = 1% remain = 1/100=0.01, neg log 0.01 = 2)

75
Q

What is the Log Cell Kill required to cure microbial infections?

A

2 (10^6 –>10^4) the immune system should eliminate the remaining bacteria

Pharm Exam 4 (4 decks)

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