Chapter 10: Antimicrobial Drugs

Question 1

How can antimicrobial agents be effective in the inhibition of metabolic pathways?

Answer 1

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

Question 2

What is antibiotic action of Sulfonamides?

Answer 2

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

Question 3

What is the antibiotic agent of Trimethoprim?

Answer 3

Interferes with nucleic acid synthesis

Binds to enzyme that converts dihydrofolic acid into tetrahydrfolic acid

Question 4

What are the effects of antiviral agents?

Answer 4

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

Question 5

How can the Inhibition of nucleic acid synthesis occur?

Answer 5

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

Question 6

What are nucleotide analogs?

Answer 6

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

Question 7

What is the antibiotic effect of quinolones, fluoroquinolones, ciprofloxacin, and nalidixic acid?

Answer 7

Active against prokaryotic DNA synthesis only, target DNA gyrase

Little effect on viruses and eukaryotes

Question 8

What is the antibiotic effect of Rifampin?

Answer 8

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)

Question 9

What is the antibiotic effect of Clofazimine?

Answer 9

Binds to DNA of M. leprae

Prevents normal replication and transcription

Question 10

What are the antibiotic effects of Pentamidine and Propamidine?

Answer 10

Bind to protozoan DNA, inhibit reproduction and development

Question 11

What are the effects of reverse transcriptase inhibitors?

Answer 11

Act against an enzyme HIV uses in replication cycle

Do not harm humans- we lack enzyme

Question 12

What are the antibiotic effects of Metronidazole?

Answer 12

When the nitro group enters the cell, it is reduced in the cytoplasm and forms cytotoxic compounds thatt disrupt the bacterial or protozoan DNA

Question 13

How is the attachment of a virus prevented?

Answer 13

Attachment antagonists block viral attachment or receptor proteins

Arildone, Pleconaril

New area of development

Question 14

What are the characteristics of an ideal antimicrobial agent?

Answer 14

Inexpensive

Readily available

Chemically stable

Easily administered

Nontoxic and nonallergenic

Selectively toxic against wide range of pathogens

Question 15

What is the spectrum of action?

Answer 15

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

Question 16

How is the efficacy of an antimicrobial agent determined?

Answer 16

Measured by: Diffusion susceptibility test (Kirby-Bauer test) Minimum inhibitory concentration test (MIC) Minimum bactericidal concentration test

Question 17

What is the Kirby-Bauer Test?

Answer 17

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

Question 18

What is the Minimum Inhibitory Concentration Test (MIC)?

Answer 18

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

Question 19

What is the Minimum Bactericidal Concentration (MBC) Test? What is its difference from the MIC?

Answer 19

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

Question 20

What are the various routes of administration?

Answer 20

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

Question 21

What are the safety and side effect concerns?

Answer 21

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

Question 22

How is resistance to antimicrobial agents developed?

Answer 22

Some pathogens are naturally resistant

Resistance acquired in 2 ways:

New mutations of chromosomal genes

Acquisition of R plasmids via transformation, transduction, and conjugation

Question 23

What are the mechanisms of resistance?

Answer 23

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

Question 24

What is Multiple Resistance and Cross Resistance?

Answer 24

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

Question 25

How do you slow resistance?

Answer 25

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