Chapter 10 Videos Flashcards

1
Q

Define Chemotherapeutic agents.

A

Drugs that act against diseases

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2
Q

Define Antimicrobial agents.

A

Drugs that treat infections

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3
Q

Define Antibiotics

A

Antimicrobial agents produced naturally by organisms.

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4
Q

Define Semisynthetics.

A

Chemically altered antibiotics that are more effective, longer lasting, or easier to administer than naturally occurring ones

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5
Q

Define Synthetics.

A

Antimicrobials that are completely synthesized in a lab

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6
Q

What makes a successful chemotherapy?

A

Successful chemotherapy requires selective toxicity
* must be more toxic to a pathogen than to the pathogen’s host

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7
Q

Define selective toxicity.

A

must be more toxic to a pathogen than to the pathogen’s host

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8
Q

How can selective toxicity be achieved during the design of an antimicrobial drug?

A

Differences in structure or metabolism between the pathogen and its host

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9
Q

Antibacterial drugs constitute the largest number and diversity of antimicrobial agents. Why?

A

The differences between the host and the pathogen allow for more chances for selective toxicity.

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10
Q

Fewer drugs to treat eukaryotic infections. Why?

A

There are few differences between eukaryotic cells, making it more difficult for selective toxicity.

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11
Q

Antiviral drugs are limited. Why?

A

Viruses take everything from the host to replicate.

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12
Q

Define Spectrum of Action.

A

Number of different pathogens a drug acts against

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13
Q

Define Narrow-spectrum and Broad-spectrum

A
  • Narrow-spectrum: effective against few organisms
  • Broad-spectrum: effective against many organisms
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14
Q

Disadvantages of Broad- spectrum drugs.

A
  • May allow for secondary or superinfections to develop
  • Killing of normal flora reduces microbial antagonism
    (Causes competition between normal microbes and pathogens for nutrients and space.)
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15
Q

What microbial antagonism?

A

Competition between normal microbes and pathogens for nutrients and space.

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16
Q

How is antimicrobial effectiveness measured?

A
  • Efficacy of antimicrobials assessed by a variety of tests

A) Diffusion susceptibility test
Example: Kirby-Bauer test

B.) Minimum inhibitory concentration test (MIC)
* Attempt to quantify the smallest amount of a drug that will inhibit the growth and reproduction of the pathogen

Can be determined by:
* Broth dilution test
* Etest

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17
Q

What are three pathogen classifications?

A

Susceptible, intermediate, resistant.

18
Q

What are the routes of administration?

A

Topical application of drug for external infections
* Ex. Athlete’s foot

The oral route requires no needles and is self-administered

intramuscular administration delivers the drug via a needle into the muscle

Intravenous administration delivers the drug directly to the bloodstream

19
Q

Describe toxicity in drugs.

A

Toxicity
* Drugs may be toxic (to cause harmful effects) to kidneys, liver, or nerves

  • Example: Polymyxin- permanent damage to kidneys
  • Example: Flagyl- temporary damage
    “black hairy tongue”
20
Q

Describe allergy considerations when taking drugs.

A
  • Hypersensitivity of your immune response
  • Allergic reactions are rare but may be life-threatening
  • Anaphylactic shock-
  • swelling of the tongue and breathing tubes, low blood pressure, heart failure, and death
21
Q

What can happen when there is a Disruption of normal microbiota?

A
  • May result in secondary infections
  • Overgrowth of normal flora, causing superinfection
22
Q

What are the six mechanisms of antimicrobial action?

A
  • Inhibition of Cell Wall Synthesis
  • Inhibition of Protein Synthesis
  • Inhibition of Cytoplasmic Membrane
  • Inhibition of Metabolic Pathways
  • Inhibition of DNA or RNA Synthesis
  • Inhibition of Pathogen’s Attachment or Entry into Cell Host
23
Q

Inhibition of cell wall synthesis methods.

A
  1. Inhibition of synthesis of bacterial walls
    * Most common agents prevent cross-linkage of NAM
    subunits
    * Beta-lactams are most prominent in this group
    * Functional groups are beta-lactam rings
    * Cause: They act by preventing the cross-linkage of NAM subunits
    * Effect: Bacteria have weakened cell walls and eventually lyse

Lipoglycopeptides: Vancomycin and cycloserine
* Interfere with particular alanine-alanine bridges that link NAM subunits in many Gram-positive bacteria

Bacitracin
* Blocks transport of NAG and NAM from cytoplasm

Isoniazid and ethambutol
* Disrupt mycolic acid formation in mycobacterial species

24
Q

Inhibition of Protein Synthesis Methods.

A
  • Prokaryotic ribosomes are 70S (30S and 50S)
  • Eukaryotic ribosomes are 80S (40S and 60S)
  • Mitochondria of animals and humans contain 70S
    ribosomes
  • Can be harmful to animals and humans, specially very active cells in the liver and bone marrow.
25
Disruption of Cytoplasmic Membranes methods
* Some drugs form channel through cytoplasmic membrane and damage its integrity * Polyenes (Amphotericin B) * attaches to ergosterol in fungal membranes * Disrupting the membrane and causing lysis
26
Inhibition of Metabolic Pathways Methods
* Antimetabolic agents can be effective when pathogen and host metabolic processes differ * Metabolic antagonists * Antimetabolic agents * Example: Sulfonomides (sulfa drugs) * They are structurally analog * As analog they compete for the active site of the enzyme for a specific pathway * Effect: termination of metabolism - cell death
27
Inhibition of Nucleic Acid Synthesis
* Several drugs block DNA replication or RNA transcription * Drugs often affect both eukaryotic and prokaryotic cells * Not normally used to treat infections * Used primarily in research and perhaps to slow cancer cell replication * Quinolones and fluoroquinolones * Act against prokaryotic DNA gyrase * Inhibitors of RNA polymerase * Reverse transcriptase inhibitors * Act against an enzyme HIV uses in its replication cycle * Do not harm people because humans lack reverse transcriptase * Examples: Nucleotide or nucleoside analogs * Interfere with function of nucleic acids * Distort shapes of nucleic acid molecules and prevent further replication, transcription, or translation * Most often used against viruses * Effective against rapidly dividing cancer cells
28
Prevention of Virus Attachment and Entry Methods
* Attachment is an essential step during the virus replication * Attachment of viruses can be blocked ther by interrupting the viral replication * Example: Attachment antagonists * Pleconaril (to treat some cold viruses)
29
What is drug resistance?
* Some pathogens are naturally resistant * In nature, microbes are constantly evolving in order to overcome the antimicrobial compounds produced by other microorganisms. * Human development of antimicrobial drugs and their widespread clinical use has simply provided another selective pressure that promotes further evolution.
30
What Drug Resistance Means?
* Antibiotic resistance does not mean that your body is becoming resistant to antibiotics; * it is that bacteria (microbes) have become resistant to the antibiotics designed to kill them. * Antibiotic resistant infection are: * Difficult, and sometimes impossible, to treat * Can require extended hospital stays * additional follow-up doctor visits * costly and toxic alternatives.
31
Bacteria acquire resistance in two ways
1. New chromosomal mutations * Can be transferred vertically to subsequent microbial generations 2. Acquisition of R plasmids * via horizontal gene transfer
32
How does antibiotic resistance happen?
1. Lots of germs. A few are drug-resistant. 2. Antibiotics kill bacteria that cause illness, and good bacteria protect the body from infection. 3. The drug-resistant bacteria are now allowed to grow and take over. 4. Some bacteria give their drug-resistance to other bacteria, causing more problems.
33
Drug modification or inactivation (resistance mechanism)
* Microbes change or destroy the antibiotics with enzymes, proteins that break down the drug. * Example: beta-lactamase or penicillinase Once the B-lactam bond is broken, the drug loses its antibacterial activity.
34
Block Penetration (resistance mechanism)
Slow or prevent entry of drug into the cell * Microbes restrict access by changing the entryways or limiting the number of entryways. * Microbes change the structure or electrical charge of cytoplasmic membrane proteins * Example: Porins
35
Target Modification (resistance mechanism)
Drug Binding Site Alter * Microbes change the antibiotic's target so the drug can no longer fit and do its job. * Preventing drug binding * Example: Genetic changes impacting the active site of penicillin-binding proteins (PBPs) can inhibit the binding of B-lactam drugs and provide resistance to multiple drugs within this class.
36
Alternate metabolic pathway (resistance mechanism)
* By increasing the concentration of targeted enzymes * overproduce the target enzyme such that there is a sufficient amount of antimicrobial-free enzyme to carry out the proper enzymatic reaction. * By developing new cell processes that avoid using the antibiotic's target. * By absorbing its product from the environment.
37
Drug Pumps (resistance mechanism)
Prevention of Cellular Uptake or Efflux * Microbes get rid of antibiotics using pumps in their cell walls to remove antibiotic drugs that enter the cell. * One single efflux pump can have the ability to translocate multiple types of antimicrobials. * Example: Efflux Pumps * actively transport an antimicrobial drug out of the cell and prevent the accumulation of drug to a level that would be antibacterial.
38
Biofilms (resistance mechanism)
* bacteria in biofilms can resist antimicrobials * Retard diffusion of the drugs * Slow metabolic rate reduces drug effectiveness
39
Target Mimicry (resistance mechanism)
* Microbes produces a protein (mimics the target) that binds to the target of an antimicrobial drug * Preventing the drugs from binding to their target. * Example: Mycobacterium tuberculosis produces MfpA protein, that binds DNA gyrase, preventing the binding of fluoroquinolone drugs
40
Describe Multiple Resistance and Cross Resistance.
Multiple resistance: * Pathogen can acquire resistance to more than one drug * Resistant to three or more different drugs Cross-resistance: * Pathogen can acquire resistance to similar drugs * This occurs when drugs are similar in structure.
41
Retarding Resistance: Solutions
* Synergism: * One drug enhance the effect of a second drug * Use antimicrobials only when necessary * limiting usage of antibiotics in health care, agriculture industry, animal husbandry * Develop new variations of existing drugs * Search for new antibiotics, semisynthetics, and synthetics