Chapter 10: Antimicrobial Drugs Flashcards
How can antimicrobial agents be effective in the inhibition of metabolic pathways?
If there are differences between the metabolic processes of the pathogen and its host, antimicrobial agents may be effective
Examples: Quinolones interfere with the metabolism of malaria parasites
Atovaquone- interferes in ETC in protozoa and fungi
Heavy metals inactivate enzymes
Agents that disrupt tubulin polymerization and glucose uptake against many protozoa and parasitic worms
Drugs block activation of viruses
Metabolic antagonists- Sulfonamides, Trimethoprim
What is antibiotic action of Sulfonamides?
Competitive inhibitors in enzymes thatt convert PABA into dihydrofolic acid
PABA is needed to synthesize DNA and RNA PABA to dihydrofolic acid to tetrahydrofolic acid
Occurs in pathogens- Not in humans
What is the antibiotic agent of Trimethoprim?
Interferes with nucleic acid synthesis
Binds to enzyme that converts dihydrofolic acid into tetrahydrfolic acid
What are the effects of antiviral agents?
May target unique aspects of viral metabolism
Amantadine, rimantadine, and weak organic bases prevent viral uncoating
Protease inhibitors- interfere with the action of protease- HIV needs this enzyme near the end of its replication cycle
How can the Inhibition of nucleic acid synthesis occur?
Several drugs block DNA replication of mRNA transcription
Drugs often affect both eukaryotic and prokaryotic cells- DNA and RNA the same
Not normally used to treat infections
Used in research and perhaps to slow cancer cell replication
E.g. Actinomycin- binds to DNA and block replication and transcription in both pathogen and host
What are nucleotide analogs?
Interfere with the function of nucleic acids
Incorporated and distorts shape of nucleic acid molecules and prevent further replication, transcription, or translation
Most often used against viruses
Effective against rapidly dividing cancer cells Drugs include Acyclovir, Ribavarin
What is the antibiotic effect of quinolones, fluoroquinolones, ciprofloxacin, and nalidixic acid?
Active against prokaryotic DNA synthesis only, target DNA gyrase
Little effect on viruses and eukaryotes
What is the antibiotic effect of Rifampin?
Inhibit the action of RNA polymerases during transcription
Binds more readily to prokaryotic RNA polymerase than eukaryotic RNA polymerase (used in treatment of M.tuberculosis)
What is the antibiotic effect of Clofazimine?
Binds to DNA of M. leprae
Prevents normal replication and transcription
What are the antibiotic effects of Pentamidine and Propamidine?
Bind to protozoan DNA, inhibit reproduction and development
What are the effects of reverse transcriptase inhibitors?
Act against an enzyme HIV uses in replication cycle
Do not harm humans- we lack enzyme
What are the antibiotic effects of Metronidazole?
When the nitro group enters the cell, it is reduced in the cytoplasm and forms cytotoxic compounds thatt disrupt the bacterial or protozoan DNA
How is the attachment of a virus prevented?
Attachment antagonists block viral attachment or receptor proteins
Arildone, Pleconaril
New area of development
What are the characteristics of an ideal antimicrobial agent?
Inexpensive
Readily available
Chemically stable
Easily administered
Nontoxic and nonallergenic
Selectively toxic against wide range of pathogens
What is the spectrum of action?
Defined as the number of different pathogens a drug acts against
Narrow- effective against few organisms
Broad- effective against many organisms
Use of broad spectrum antibiotics may allow for secondary infection of superinfections to develop
Killing of normal flora reduces microbial antagonism
How is the efficacy of an antimicrobial agent determined?
Measured by: Diffusion susceptibility test (Kirby-Bauer test) Minimum inhibitory concentration test (MIC) Minimum bactericidal concentration test
What is the Kirby-Bauer Test?
Uniformly inoculate plate with a standardized amount of pathogen
Small disks containing standard amounts of antibiotics are placed on plate
Incubated, examined for zones of inhibition
Zones compared with chart to determine efficacy, susceptible, intermediate, or resistant
What is the Minimum Inhibitory Concentration Test (MIC)?
Quantitatively express potency of antimicrobial
Smallest amount of drug that will inhibit growth and reproduction
Broth dilution test- standardized amount of bacteria added to serial dilutions of antimicrobial
Etest- combines aspects of Kirby-Bauer and MIC tests, MIC may be measured by reading scale
What is the Minimum Bactericidal Concentration (MBC) Test? What is its difference from the MIC?
Determines the amount of drug required to kill a microbe, rather than just to inhibit its growth
Samples taken from clear MIC tubes transferred to plates containing a drug-free medium If cells appear- concentration of drug bacteriostatic If cells do not appear- concentration of drug bacteriocidic
What are the various routes of administration?
Topical application of drugs for external infections
Oral route- no needles, self-administered, lower concentrations
Intramuscular- delivers drug via needle into muscle, lower than IV
Intravenous- drug delivered to bloodstream, lowered quickly by filtering by kidneys Must known how antimicrobial agent will be distributed to infected to tissues
What are the safety and side effect concerns?
Toxicity:Causes of many adverse reactions that are poorly understood , May be toxic to kidneys, liver, or nerves
Must take considerations when prescribing to pregnant women
Allergies: Allergic reactions are rare but may be life threatening, anaphylactic shock
Disruption of Normal Microbiota: May result in secondary infections, overgrowth of normal flora causing superinfections, greatest concern for hospitalized patients
How is resistance to antimicrobial agents developed?
Some pathogens are naturally resistant
Resistance acquired in 2 ways:
New mutations of chromosomal genes
Acquisition of R plasmids via transformation, transduction, and conjugation
What are the mechanisms of resistance?
At least six mechanisms of microbial resistance:
Production of enzyme that destroys or deactivates drug (Beta-lactamase)
Slow or prevent entry of drug into cell
Changes in the structure or electrical charge of cytolplasmic membrane
Alter target of drug- binds less effectively
Alter metabolic chemistry
Pump antimicrobial drug out of cell
M. tuberculosis produces MfpA protein- binds DNA gyrase preventing binding of fluoroquinolone drugs
What is Multiple Resistance and Cross Resistance?
Pathogen can acquire resistance to more than one drug
Common when R plasmids are exchanged
Common in hospitals and nursing homes (constant use of drugs eliminates sensitive cells)
Super bugs- multiple drug resistant pathogens, resistant to 3 or more types of antimicrobial
Cross resistance- one antimicrobial agent may confer resistance to similar drugs
How do you slow resistance?
Maintain high concentration of drug in patient for sufficient time (Kills all sensitive cells and inhibits others so immune system can destroy them)
Use antimicrobial agents in combination (syngerism vs. antagonism)
Limit the use of antimicrobial agents
Search for new antibiotics, semi-synthetics, and synthetics (Bacteriocins, drugs complementary to shape of microbial proteins to inhibit them)
New variations of existing drugs
