Chapter 20 & 19 Flashcards
(146 cards)
1
Q
Father of Chemotherapy
A
Paul Ehrlich
German, 1910
-drug treatment for syphillis
-Selective toxicity
2
Q
Chemotherapy
A
Use of chemicals to treat a disease
3
Q
selective toxicity
A
toxic to microbe, but not host cells
4
Q
Domagk
A
1935 - Sulfa drugs -first major class of drugs with widespread clinical use
5
Q
Antibiotics
A
antibacterial compounds produced naturally by a microorganism
6
Q
father of penicillin
A
Flemming 1928
in Penicillium mold
7
Q
father of streptomycin
A
Waksman - 1943
from soil bacteria Streptomyces griseus
8
Q
Antimicrobial chemotherapy
A
use of drugs to destroy or inhibit the growth of microbes that are causing disease
9
Q
Antimicrobic
A
a word that incorporates all types of antimicrobial drugs, regardless of origin
10
Q
Synthetic
A
antimicrobial chemical produced in the lab (sulfa drug)
11
Q
Semisynthetic
A
antibiotic that has been chemically altered
12
Q
Types of antimicrobial drugs (4)
A
Antimicrobic
Antibiotic
Synthetic
Semisynthetic
13
Q
Therapeutic Index (TI)
A
lowest dose toxic to patient divided by normal dose used for therapy
-OR toxic dose divided by therapeutic dose
14
Q
Minimum Inhibitory Concentration (MIC)
A
lowest dose that prevents growth of the microbe (=normal dose used for therapy)
- TI= lowest dose toxic to patient divided by MIC
15
Q
High TI
A
antimicrobics are usually less toxic to host.
- good ratio is 10:1
- usually because they are specific to non-host processes
16
Q
Low TI
A
antimicrobics are potentially toxic to heat
17
Q
Spectrum of Activity
A
Broad spectrum
Narrow spectrum
18
Q
broad spectrum
A
affects a wide range of bacteria
- use if microbe is unknown and infection is serious
- usually have a low TI
19
Q
Narrow spectrum
A
affects a limited range of bacteria
- used if bacteria pathogen has been identified
- Usually have a high TI
20
Q
Half-life
A
time it takes for a drug to decrease in body by 50% = describes the rate of elimination.
- Determines the amount of drug given and how often
21
Q
Tissue distribution
A
- Antibiotic characteristics determine which tissue can be entered and how drug id given
- Ex. to cross blood/brain barrier antibiotics are lipid soluble and smaller molecules
ex. Penicillin G given IV - not stable in low pH of stomach
22
Q
Resistance to antimicrobials
A
Intrinsic (innate) resistance
acquired resistance
23
Q
intrinsic (innate) resistance
A
natural resistance based on bacteria’s characteristics
ex. mycoplasma (no cell wall) is not affected by antibiotics specific to peptidoglycan
24
Q
acquired resistance
A
resistance gained through mutation or genetic exchange
25
allergies
some antibiotics cause hypersensitivity in patient, resulting in immune responses or allergies
- most common - penicillin, cephalosporins, sulfas
26
Toxic effects
some antibiotics can cause damage to host often when used at high concentrations
-ex. streptomycin at high levels can damage kidneys
27
Antagonistic
two drugs make each other less effective.
| - Ex. bacteriostatic drugs (prevent binary fission) interfere with Penicillin
28
Synergistic
drugs are more effective when taken together
| ex. action of penicillin allows streptomycin to enter cell more easily
29
Additive
no drug interaction, drug combinations are neither antagonistic nor synergistic
30
Which microbes are easiest to treat using antimicrobial medication?
Prokaryote cells
| because of selective toxicity, unique cellular targets different from host must be found
31
Targets of antimicrobial drugs
synthesis, structure, function of:
- cell wall
- cell membrane
- proteins
- nucleic acids
32
Cell Wall Synthesis
| Target
- formation of cell wall is inhibited
- if cell wall is not intact, osmotic pressure will cause bacteria to lyse
- high TI b/c we do not have cell walls
33
Cell Membrane: function
| target
- drugs bind to cell membrane and produce large holes
- causes "leaky" cells and cell death
- very low TI b/c we also have cell membranes
34
proteins: metabolic pathways
| target
- some drugs target unique metabolic pathways
| - high TI
35
proteins: synthesis/transcription
| target
Transcription (DNA to mRNA) is prevented by inhibition of RNA polymerase
- low TI b/c our RNA polymerase is similar to microbes so it could affect us as well
36
Proteins: synthesis/translation
| target
- protein synthesis is stopped by disrupting the ribosome
- drugs attach to bacteria 70S ribosomes
- Medium/high TI b/c ribosomes found in mitochondria are also 70S so they may be affected
37
Nucleic acids: DNA synthesis
| target
- inhibition of bacterial enzymes needed for DNA synthesis (DNA polymerase, gyrase)
- low TI b/c our cells also have those cells to go through DNA synthesis
38
Antibacterial drug families
- Sulfonamides
- B-lactams
- Glycopeptides
- Aminoglycosides
- Tetracyclines
- Macrolides
- Rifamycins
- Quinolones
39
Sulfonamides
-Synthetic
| Broad spectrum - both Gram - and +
40
Mode of Action for SULFONAMIDES
- competitive inhibitor in METABOLIC PATHWAY that synthesized folic acid
- human cells do not make folic acid
- Same pathway makes precursors to proteins and nucleic acids for bacteria
41
Toxicity of SULFONAMIDES
nearly harmless to humans
High TI
- Some allergic reactions
42
B- Lactams
- contain B-lactam ring
- antibiotics produced by fungi/molds
- many semi-synthetic versions (methicillin)
- used for first time in 1941, very important in WWII
43
Mode of action of B-LACTAMS
interferes with CELL WALL SYNTHESIS, causes bacteria cell to lyse
- inhibits enzymes that form peptide bridges between glycan chains
- only work on actively growing cells
44
Toxicity of B- LACTAMS
very little - high TI
- animal cells do not have cell walls or peptidoglycan
- sever allergies to penicillin possible
45
Current effectiveness of B-LACTAMS
- usually more effective against Gram+ bacteria
- difficult for B-lactams to penetrate Gram - outer membrane, but some can.
- Broad and narrow spectrum
- older and newer penicillins
46
Glycopeptides
- usually injected - is not absorbed well through intestines
| - can be taken orally for intestinal pathogens
47
Mode of Action of GLYCOPEPTIDES
- inhibits CELL WALL SYNTHESIS by binging to peptidoglycan
48
Toxicity of GLYCOPEPTIDES
low toxicity, high TI
| - serious side-effects can include nausea and hearing loss
49
Current effectiveness of GLYCOPEPTIDES
```
Narrow spectrum (Gram + only)
- usually little resistance, although some seen with S.A and intestinal pahtogens
```
50
Aminoglycosides
- from filamentous soil bacteria Streptomyces griseus
51
mode of action of AMINOGLYCOSIDES
- inhibit TRANSLATION by attaching to 30S subunit of bacterial ribosomes, mRNA is misread and proteins are synthesized incorrectly
52
Toxicity of AMINOGLYCOSIDES
- severe = low TI
- used in low doses
- severs side-effects include kidney and inner ear damage
53
Current effectiveness of AMINOGLYCOSIDES
- broad spectrum
- many bacteria are resistant, so not used much
- often used with other antibiotics (PENICILLIN)
54
Tetracyclines
from streptomyces species and semi-synthetic
| -drug of choice for un-diagnosed diseases
55
Mode of action of TETRACYCLINES
- inhibit TRANSLATION by attaching to 30S subunit of bacterial ribosomes, precents attachment of tRNA, protein synthesis completely blocked
56
Toxicity of TETRACYCLINES
- low = high TI, but not given to patients with liver and kidney damage or are pregnant
57
Current effectiveness of TETRACYCLINES
Very broad spectrum, resistance is common
58
Macrolides
-often used when patient is allergic to penicillin
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mode of action of MACROLIDES
- prevents TRANSLATION by binding to 50S subunit of ribosome
60
Toxicity of MACROLIDES
little = high TI
| - gastric distress, reversible liver damage
61
current effectiveness of MACROLIDES
```
narrow spectrum (gram + and mycoplasma)
- gram - are resistant b/c macrolides can't pass their cell wall (intrinsic resistance)
```
62
Rifamycins
-from streptomyces bacteria
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mode of action of RIFAMYCINS
prevents RNA polymerase from starting transcription
64
toxicity of RIFAMYCINS
low = high TI
| - specific to bacteria RNA polymerase
65
Current effectiveness of RIFAMYCINS
broad spectrum, Gram +, some Gram - , used for mycobacterium tuberculosis, resistance develops easily
66
Quinolones
Sythetic
67
Mode of action of QUINOLONES
- inhibits gyrase (DNA SYNTHESIS)
68
Toxicity of QUINOLONES
little = high TI
| eukaryotes have different enzyme
69
Current effectiveness of QUINOLONES
Broad spectrum
Gram + more resistant, overuse causing some resistance.
-Used for UTI and anthrax
70
Triple Antibiotic Lotions
Neomycin - aminoglycoside - affects translation
Polymyxin - affects cell membrane
Bacitracin - affects cell wall
Topical because of low TI
71
Antifungal drugs
- most are very toxic and have low TI
- Usually given topically
- ex. Polyenes, Flucytosine
72
Polyenes
made by streptomyces species, disrupt fungal CELL MEMBRANE and cause leakage, amphoterican B used systemically (IV drop) only for life-threatening infections, nystatin used topically
73
Flucytosine
inhibits NUCLEIC ACID SYNTHESIS, synthetic version of cytosine, effective against yeast cells only and used for severs/systemic yeast infections, taken orally.
74
Drugs that treat Anthrax
tetracyclines
| quinolones
75
Drugs that treat E.coli
no antibiotics used unless very severe b/c of resistance
76
Drugs for HIV/AIDS
antiviral cocktail
77
Drugs for Staph
vancomycin, resistant to penicillin & B-lactams
78
Example of B-Lactams
Penicillin, Cephalosporin
79
Example of Glycopeptides
Vancomycin
80
Example of Aminoglycosides
Streptomycin, Gentamicin
81
Example of tetracyclines
tetracycline, doxycycline, oxytetracycline
82
Example of macrolides
erythromycin, azithromycin
83
example of rifamycins
rifampin
84
example of quinolones
ciprofloxacin
85
Types of Antiviral Drugs
Nucleotide analogs
Amantadine and Rimantadine
Reverse transcriptase inhibitors
others
86
Nucleotide analogs
AZT, ddl, acyclovir
- Have similar structure to nucleotides
- halts DNA SYNTHESIS
- low TI
- exception acyclovir: few side effects bc only activated by viral coded enzymes
87
Amantadine and Rimantadine
- prevent uncoating of influenza virus
- helps alleviate symptoms
- must be given in early stages of infection
88
Revers transcriptase inhibitors
- prevents DNA synthesis in HIV virus
89
Others (antiviral)
-prevent transcription and translation or prevent maturation of viruses
90
Properties of Antiviral Drugs
- Do not give a cure - only slow progression of disease
- "Drug cocktails" use 3-4 different antiviral compounds for AIDS patients, lowers the number of replicating viruses, can greatly improve life for patient, but if treatment is stopped viruses return
91
Bacterial resistance types
Intrinsic (innate) resistance
| Acquired resistance
92
Acquired resistance
resistance from mutation or genetic exchange (conjugation/ R plasmid)
93
Mechanisms of Acquired resistance
- Alteration of target molecule
- alteration of drug
- decreased uptake of drug
- prevention of competitive inhibitors
94
Alteration of target molecule
can prevent drug from binding to target
ex. tetracycline binds to 30S subunit of ribosome, a change in the ribosome molecular structure could prevent tetracycline from binding
95
Alteration of drug
bacteria produces enzymes that alter, destroy or attach to drug
Ex. penicillinase produced by bacteria can destroy penicllin
96
Decreased uptake of drug
alteration of permeability of bacteria membrane
-especially true of Gram - bacteria
Ex. these changes can prevent streptomycin from entering bacteria cells
97
Prevention of Competitive inhibitors
if bacteria produces a large amount of affected enzyme the metabolic pathways is not inhibited
-ex Sulfa drugs need to be in a very high concentration to inhibit large amounts of PABA enzyme
98
Consequences of overuse of antibiotics
Hypersensitivites (allergies)
- toxicity
- Secondary infections
- production of resistant strains
99
Immunity
stimulating the body's natural ability to combat infection (infection can provide immunity)
100
Immunization
producing immunity by providing exposure to altered organisms that do not cause disease
101
Vaccine
preparation of a pathogen or its products to provide immunity
102
Cowpox and Smallpox in milkmaids
Edward Jenner 1796
103
Anthrax and rabies vaccination
Pasteur 1881,1184
104
Attenuated vaccine
weakened form of pathogen that is unable to cause the disease
105
Inactivated vaccine
unable to replicate but can still trigger immunity response - killed bacteria, inactive toxins, pieces of pathogen
106
Which drugs affect Protein metabolic pathways
Sulfa drugs
107
Which drugs affect Cell wall synthesis
B-Lactams
| Glycopeptides
108
Which drugs affect Translation
Aminoglycosides
Macrolides
Tetracyclines
109
Which drugs affect Transcription
Rifamycin
110
Which drugs affect DNA synthesis
Quinolones
111
Epidemiology
The study of the cause, frequency and distribution of disease in a population
112
What does an epidemiologist do?
Collect and interpret data to control, prevent or predict diseases
113
Hantavirus
1993 southwestern US
- Acute respiratory failure caused by unknown type of hantavirus- severe pneumonia
- virus carried by mice
- increased food sources led to increased population of mice
- transmitted through air in dust of urine and feces
- search led to similar cases as far back as 1959
114
Communicable disease
an infectious disease caused by a pathogen that can be transmitted from one host to another = contagious
115
Non-communicable diseases
does not spread from one host to another
116
Example of Non-communicable microbes
botulism, tetanus, Toxic Shock Syndrome
117
Rate of Disease
the proportion (percentage) of a population who have the disease.
118
Attack rate of disease
percentage of population that develop the disease after they have been directly exposed to the pathogen
119
Morbitity
rate of new cases of a disease in a specific time period in a certain population
120
which diseases have high morbitity rate?
contagious diseases
121
Mortality
overall death rate in a population
122
Endemic
diseases that are constantly present in a population
| ex. cold and flu
123
Epidemic
disease in unusually high frequencies in a population
| ex. ebola in certain African countries
124
Pandemic
epidemic that has spread world-wide (AIDS)
125
Transmission of Disease (chain of infection)
- Reservoir
- Portal of exit
- Mode of transmission
- portal of entry
126
Reservoir
- environment where pathogen can live, grow and spread to other hosts
127
Types of Reservoir
1. Human reservoir - most common
2. Other animal (zoonotic diseases)
3. Environmental - microbes in soil, water, etc
128
Anthrax is what kind of reservoir
environment and zoonotic
129
Portal of Exit
Ex. Digestive system - anus or mouth
Urinary system - urethra
Respiratory system - mouth, nose
etc
130
Mode of Transmission
feces, vomit
urine
mucous, droplets
131
Portal of entry
similar routes of exit, not necessarily same route in as out.
132
Mode of Transmission
- Direct contact
- Indirect contact
- Non-contact sources
133
Direct contact
any physical contact
| -ex. Fecal-oral transmission
134
Indirect contact
-From a non-human source
| Vector, Fomite, or Droplet transmission
135
Vector
living organism that carries disease-causing microbes
136
Fomite
inanimate object that could carry the microbe
137
Non-contact sources
air transmission, food and water contamination
138
Incubation period
length of time between exposure to the pathogen and onset of disease symptoms
139
Symptomatic
host shows symptoms
140
Asymptomatic
host does not show symptoms, but can possibly transmit the disease
141
Dosage
the number of pathogens the host is originally exposed to
142
Large dosage
more likely to cause disease, will shorten incubation time
143
Small dosage
less likely to cause disease or will lengthen incubation time
144
Immunity to Pathogen
immunity through previous exposure or immunization decreases the possible reservoirs
145
Herd immunity
susceptible (non-immune) hosts are protected because disease cannot spread in a population where the majority of individuals are immune
146
What certain characteristics of the population can increase susceptibility to a disease?
- malnutrition
- crowding
- fatigue
- stress
- age
- gender
- genetics
