Antimicrobial drugs lecture Flashcards
Antimicrobial drugs are chemicals that affect physiology in any manner
• Chemotherapeutic agents are?
• Antimicrobial agents are?
- Chemotherapeutic agents– Drugs that act against diseases
* Antimicrobial agents– Drugs that treat infections
What is semisynthetics?
Chemically altered antibiotics that are more effective than naturally occurring ones
What is synthetics?
Antimicrobials that are completely synthesized in a lab
Mechanisms of Antimicrobial Action (4 points)
• 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
Describe the Inhibition of bacterial wall synthesis
– 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
Describe the Inhibition of synthesis of bacterial walls
– 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
During Inhibition of synthesis of bacterial walls describe the roles of:
– Vancomycin and cycloserine
– Bacitracin
– Isoniazid and ethambutol
– 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
Inhibition of synthesis of bacterial walls prevents what?
– Prevent bacteria from increasing amount of peptidoglycan
– Have no effect on existing peptidoglycan layer
– Effective only for growing cells
Inhibition of Protein Synthesis
– 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
Disruption of Cytoplasmic Membranes
– 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
Disruption of Cytoplasmic Membranes
1) What inhibits ergosterol synthesis?
2) What disrupts cytoplasmic membranes of Gram-negatives?
3) Some parasitic drugs act against?
1) Azoles and allylamines inhibit ergosterol synthesis
2) Polymyxin disrupts cytoplasmic membranes of Gram-negatives– Toxic to human kidneys
3) cytoplasmic membranes
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
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
Antiviral agents can target?
Unique aspects of viral metabolism
Prevents viral uncoating
Amantadine, rimantadine, and weak organic bases
Protease inhibitors interfere with?
An enzyme HIV needs in its replication cycle
Inhibition of Nucleic Acid Synthesis
– 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
Inhibition of Nucleic Acid Synthesis: Nucleotide or nucleoside analogs
– 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
Inhibition of Nucleic Acid Synthesis:
1) Quinolones and fluoroquinolones act against?
2) Inhibitors of RNA polymerase during?
3) Reverse transcriptase inhibitors do what?
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
Prevention of Virus Attachment
– Attachment antagonists block viral attachment or receptor proteins
– New area of antimicrobial drug development
An Ideal Antimicrobial Agent should be 6 main things
– Readily available – Inexpensive – Chemically stable – Easily administered – Nontoxic and nonallergenic – Selectively toxic against wide range of pathogens
What is the spectrum of Action for drugs?
– 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
Efficacy of drugs is Ascertained by?
– Diffusion susceptibility test
– Minimum inhibitory concentration test
– Minimum bactericidal concentration test
Routes of Administration for drugs
– 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
Safety and Side Effects of drugs
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
Safety and Side Effects: Disruption of normal microbiota
– May result in secondary infections
– Overgrowth of normal flora causes superinfections
– Of greatest concern for hospitalized patients
The Development of Resistance in Populations
– 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
At least seven mechanisms of microbial resistance
– 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
Multiple Resistance and Cross Resistance
– 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
Retarding Resistance is?
– 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
Retarding Resistance
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
