Antimicrobial drugs lecture

Question 1

Antimicrobial drugs are chemicals that affect physiology in any manner
• Chemotherapeutic agents are?
• Antimicrobial agents are?

Answer 1

• Chemotherapeutic agents– Drugs that act against diseases

* Antimicrobial agents– Drugs that treat infections

Question 2

What is semisynthetics?

Answer 2

Chemically altered antibiotics that are more effective than naturally occurring ones

Question 3

What is synthetics?

Answer 3

Antimicrobials that are completely synthesized in a lab

Question 4

Mechanisms of Antimicrobial Action (4 points)

Answer 4

• Key is selective toxicity
• Antibacterial drugs constitute largest number
and diversity of antimicrobial agents
• Fewer drug y s to treat eukaryotic infections
• Even fewer antiviral drugs

Question 5

Describe the Inhibition of bacterial wall synthesis

Answer 5

– Most common agents prevent cross-linkage of NAM subunits
– Beta-lactams are most prominent in this group
* Functional groups are beta-lactam rings
* Beta-lactams bind to enzymes that cross-link
NAM subunits
– Bacteria have weakened cell walls and eventually lyse

Question 6

Describe the Inhibition of synthesis of bacterial walls

Answer 6

– Semisynthetic derivatives of beta-lactams
– More stable in acidic environments
– More readily absorbed
– Less susceptible to deactivation
– More active against more types of bacteria
– Simplest beta-lactams – effective only against
aerobic Gram-negatives

Question 7

During Inhibition of synthesis of bacterial walls describe the roles of:
– Vancomycin and cycloserine
– Bacitracin
– Isoniazid and ethambutol

Answer 7

– Vancomycin and cycloserine: Interfere with bridges that link NAM subunits in many Gram many Gram-positives
– Bacitracin: Blocks secretion of NAG and NAM from cytoplasm
– Isoniazid and ethambutol: Disrupt mycolic acid formation in mycobacterial species

Question 8

Inhibition of synthesis of bacterial walls prevents what?

Answer 8

– Prevent bacteria from increasing amount of peptidoglycan
– Have no effect on existing peptidoglycan layer
– Effective only for growing cells

Question 9

Inhibition of Protein Synthesis

Answer 9

– Prokaryotic ribosomes are 70S (30S and 50S)
– Eukaryotic ribosomes are 80S (40S and 60S)
– Drugs can selectively target translation
– Mitochondria of animals and humans contain 70S
ribosomes
– Can be harmful

Question 10

Disruption of Cytoplasmic Membranes

Answer 10

– Some drugs form channel through cytoplasmic
membrane and damage its integrity
– Amphotericin B attaches to ergosterol in fungal membranes
– Humans somewhat susceptible because cholesterol similar to ergosterol
– Bacteria lack sterols; not susceptible

Question 11

Disruption of Cytoplasmic Membranes

1) What inhibits ergosterol synthesis?
2) What disrupts cytoplasmic membranes of Gram-negatives?
3) Some parasitic drugs act against?

Answer 11

1) Azoles and allylamines inhibit ergosterol synthesis
2) Polymyxin disrupts cytoplasmic membranes of Gram-negatives– Toxic to human kidneys
3) cytoplasmic membranes

Question 12

1) Antimetabolic agents can be effective when?
2) Quinolones interfere with?
3) Inactivates enzymes
4) Agents that disrupt tubulin polymerization and
glucose uptake by?
5) Drugs block activation of?
6) Metabolic antagonists

Answer 12

1) Metabolic processes of pathogen and host differ
2) The metabolism of malaria parasites
3) Heavy metals
4) Many protozoa and parasitic
worms
5) Viruses
6) Inhibition of metabolic pathways

Question 13

Antiviral agents can target?

Answer 13

Unique aspects of viral metabolism

Question 14

Prevents viral uncoating

Answer 14

Amantadine, rimantadine, and weak organic bases

Question 15

Protease inhibitors interfere with?

Answer 15

An enzyme HIV needs in its replication cycle

Question 16

Inhibition of Nucleic Acid Synthesis

Answer 16

– Several drugs block DNA replication or mRNA transcription
– Drugs often affect both eukaryotic and prokaryotic cells
– Not normally used to treat infections
– Used in research and perhaps to slow cancer cell replication

Question 17

Inhibition of Nucleic Acid Synthesis: Nucleotide or nucleoside analogs

Answer 17

– Interfere with function of nucleic acids
– Distort shapes of nucleic acid molecules and prevents further replication, transcription, or translation
– Most often used against viruses
– Effective against rapidly dividing cancer cells

Question 18

Inhibition of Nucleic Acid Synthesis:

1) Quinolones and fluoroquinolones act against?
2) Inhibitors of RNA polymerase during?
3) Reverse transcriptase inhibitors do what?

Answer 18

1) Prokaryotic DNA gyrase
2) Transcription
3) Act against an enzyme HIV uses in its replication
cycle
– Do not harm people because humans lack
reverse transcriptase

Question 19

Prevention of Virus Attachment

Answer 19

– Attachment antagonists block viral attachment or receptor proteins
– New area of antimicrobial drug development

Question 20

An Ideal Antimicrobial Agent should be 6 main things

Answer 20

– Readily available
– Inexpensive
– Chemically stable
– Easily administered
– Nontoxic and nonallergenic
– Selectively toxic against wide range of pathogens

Question 21

What is the spectrum of Action for drugs?

Answer 21

– Number of different pathogens a drug acts against
– Narrow-spectrum effective against few organisms
– Broad-spectrum effective against many organisms
* May allow for secondary or superinfections to
develop
* Killing of normal flora reduces microbial antagonism

Question 22

Efficacy of drugs is Ascertained by?

Answer 22

– Diffusion susceptibility test
– Minimum inhibitory concentration test
– Minimum bactericidal concentration test

Question 23

Routes of Administration for drugs

Answer 23

– Topical application of drug for external infections
– Oral route requires no needles and is self-administered
– Intramuscular administration delivers drug via needle into muscle
– Intravenous administration delivers drug directly to
bloodstream

Question 24

Safety and Side Effects of drugs

Answer 24

1) Toxicity
– Cause of many adverse reactions poorly understood
– Drugs may be toxic to kidneys liver or nerves
– Consideration needed when prescribing drugs to
pregnant women
2) Allergies
– Allergic reactions are rare but may be life threatening
– Anaphylactic shock

Question 25

Safety and Side Effects: Disruption of normal microbiota

Answer 25

– May result in secondary infections
– Overgrowth of normal flora causes superinfections
– Of greatest concern for hospitalized patients

Question 26

The Development of Resistance in Populations

Answer 26

– Some pathogens are naturally resistant
– Resistance by bacteria acquired in two ways
1) New mutations of chromosomal genes
2) Acquisition of R-plasmids via transformation, transduction, and conjugation

Question 27

At least seven mechanisms of microbial resistance

Answer 27

– Produce enzyme that destroys or deactivates drug
– Slow or prevent entry of drug into the cell
– Alter target of drug so it binds less effectively
– Alter their metabolic chemistry
– Pump antimicrobial drug out of the cell before it can act
– Biofilms retard drug diffusion and slow metabolic rate
– Mycobacterium tuberculosis produces MfpA protein

Question 28

Multiple Resistance and Cross Resistance

Answer 28

– Pathogen can acquire resistance to more than one drug
– Common when R-plasmids exchanged
– Develop in hospitals and nursing homes Develop in hospitals and nursing homes
– Constant use of drugs eliminates sensitive cells
– Superbugs
– Cross resistance

Question 29

Retarding Resistance is?

Answer 29

– Maintain high concentration of drug in patient for sufficient time
– Kills all sensitive cells and inhibits others so immune system can destroy
– Use antimicrobial agents in combination
– Synergism vs. antagonism

Question 30

Retarding Resistance

Answer 30

Retarding Resistance
– Use antimicrobials only when necessary
– Develop new variations of existing drugs
* Second-generation drugs
* Third-generation drugs
– Search for new antibiotics, semisynthetics, and
synthetics
* Bacteriocins
* Design drugs complementary to the shape of
microbial proteins to inhibit them