Antifungal and Antiviral Drug Effects

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Questions and Answers

What is a common effect of antifungal drugs on fungal membranes?

They promote cell growth.

They increase cell constituent retention.

They disrupt membrane permeability. (correct)

They enhance membrane stability.

What can cause the development of superinfections?

The destruction of drug-sensitive strains by treatments. (correct)

The use of topical antifungals.

Regular consumption of probiotics.

Inadequate hydration during antibiotic use.

How can the emergence of drug resistance be prevented?

Giving only one drug at a time.

Only using drugs after resistance develops.

Using a single drug at lower doses.

Administering drugs in high concentrations when necessary. (correct)

Which of the following is not a class of antiviral drugs mentioned?

Beta-lactam antibiotics Signup and view all the answers

Why are relatively few antiviral drugs developed?

Viral replication is difficult to specifically target. Signup and view all the answers

Which enzyme is targeted by herpes virus inhibitors?

DNA polymerase Signup and view all the answers

What function do Fusion inhibitors serve in anti-HIV treatment?

They prevent HIV entry into cells. Signup and view all the answers

What is a strategy for making anti-HIV drugs more effective?

Employing drug cocktails. Signup and view all the answers

What is the therapeutic index in the context of antimicrobial drugs?

The ratio of toxic dose to therapeutic dose. Signup and view all the answers

Which of the following describes a broad-spectrum antibiotic?

Effective against a wide range of pathogens. Signup and view all the answers

What role does sulfonamide play in antimicrobial therapy?

Inhibits folic acid synthesis. Signup and view all the answers

What method is used to determine the minimal inhibitory concentration (MIC) of an antimicrobial agent?

Inoculating media with different drug concentrations. Signup and view all the answers

Which of the following is a notable discovery in the history of antibiotics?

Penicillin demonstrated effective by Florey and Chain. Signup and view all the answers

Which structural component is essential for the bioactivity of penicillins?

Beta-lactam ring. Signup and view all the answers

How can antimicrobial resistance originate?

Circumstances like plasmid transfer and mutations. Signup and view all the answers

What characteristic of a drug is most important for its therapeutic effectiveness?

Its concentration at the site of infection exceeding MIC. Signup and view all the answers

What mechanism does vancomycin use to combat bacterial infections?

Inhibits cell wall synthesis. Signup and view all the answers

What is a common side effect observed with excessive dosages of antimicrobial drugs?

Toxicity to the patient. Signup and view all the answers

Which of the following antibiotics is primarily ineffective against eukaryotic fungi?

Penicillin. Signup and view all the answers

In the Kirby-Bauer method, how is antimicrobial susceptibility assessed?

By examining the size of the zone of inhibition. Signup and view all the answers

Which of the following antibiotics is known for its activity against tuberculosis?

Streptomycin. Signup and view all the answers

Study Notes

Chemotherapeutic Agents

Chemical agents used to treat diseases
Destroy pathogenic microbes or inhibit their growth within a host
Most are antibiotics
Antimicrobial products or their derivatives kill susceptible microbes or inhibit their growth
The effect is potentially harmful

Development of Chemotherapy

Paul Ehrlich (1904) developed the concept of selective toxicity
Identified dyes that effectively treated African sleeping sickness
Sahachiro Hato (1910), working with Ehrlich, identified arsenic compounds that effectively treated syphilis
Gerhard Domagk, and Jacques and Therese Trefouel (1935) discovered sulfonamides and sulfa drugs (antibiotics)

Penicillin

First discovered by Ernest Duchesne (1896), but the discovery was lost
Accidentally discovered by Alexander Fleming (1928)
Observed penicillin activity on contaminated plates
Did not think it could be developed further
Effectiveness demonstrated by Florey, Chain, and Heatley (1939)

Later Discoveries

Streptomycin, an antibiotic active against tuberculosis, was discovered by Selman Waksman (1944)
Nobel Prize awarded to Waksman in 1952 for this discovery
By 1953, chloramphenicol, terramycin, neomycin, and tetracycline were isolated

General Characteristics of Antimicrobial Drugs

Selective Toxicity: Ability of a drug to kill or inhibit a pathogen while damaging the host as little as possible
Therapeutic Dose: The drug level required for clinical treatment
Toxic Dose: The drug level at which the drug becomes too toxic for a patient (produces side effects)
Therapeutic Index: The ratio of toxic dose to therapeutic dose. A higher therapeutic index suggests more selective toxicity

Antimicrobial Drug Properties

Cidal: Kills the microorganism
Static: Inhibits microorganism growth
Broad-spectrum: Attacks many different pathogens
Narrow-spectrum: Attacks only a few different pathogens
Lists examples of specific drugs, their primary effects, spectrum, and side effects

Microbial Sources of Antibiotics

Lists various microorganisms and the antibiotics derived from them

Determining the Level of Antimicrobial Activity

MIC (minimal inhibitory concentration): The lowest concentration of a drug that inhibits the growth of a pathogen
MLC (minimal lethal concentration): The lowest concentration of a drug that kills a pathogen
Techniques for testing MIC and MLC are also described.

Dilution Susceptibility Tests

Involves inoculating media containing different drug concentrations
Broth or agar with lowest concentration showing no growth is the MIC
If broth is used, tubes showing no growth can be subcultured into a drug-free medium
Broth from which the microbe can't be recovered is the MLC

Disk Diffusion Tests

Disks impregnated with specific drugs are placed on inoculated agar plates.
Drug diffuses into the agar, creating a concentration gradient.
Clear zones (no growth) around the disks are observed

Kirby-Bauer Method

Standardized method for carrying out disk diffusion tests
Sensitivity and resistance are determined using tables correlating zone diameter to microbial resistance.
Table values are plotted and used to determine if drug concentrations in the body will be effective

Measuring Antimicrobial Sensitivity

Detailed description of testing procedures

Measuring Drug Concentrations in the Blood

Drug concentration at infection site must be higher than the MIC for effectiveness
Microbiological, chemical, immunological, enzymatic, or chromatographic assays can be used to determine drug concentration in the blood

Mechanism of Action of Antimicrobial Agents

Drugs target functions needed for pathogen reproduction or survival
Highly specific targeting to pathogen leads to higher therapeutic index

Mechanisms of Antibacterial Drug Action

Details the mechanisms of action of various antibacterial drugs, categorizing them by their target in the bacterial cell

Modes of Antimicrobial Action

Diagram illustrating the major modes of antimicrobial action, targeting various bacterial processes

Competitive Inhibitors

Sulfonamides (sulfa drugs): Inhibit folic acid synthesis.
Broad spectrum

Factors Influencing the Effectiveness of Antimicrobial Drugs

Ability of the drug to reach the site of infection
Susceptibility of the pathogen to the drug
Ability of the drug to reach concentrations in the body that exceed the pathogen's MIC

Ability of Drug to Reach Site of Infection

Depends on the mode of administration
Examples: oral (destroyed by stomach acid), topical (skin surface), and parenteral (injection) routes

Inhibitors of Cell Wall Synthesis

Penicillins:
- 6-aminopenicillanic acid derivatives
- Differ in side chains attached to amino group
- Crucial feature is the β-lactam ring, essential for bioactivity
- Many penicillin-resistant organisms produce β-lactamase (penicillinase) breaking a bond in this ring

Mode of Action of Penicillins

Blocks the enzyme that catalyzes transpeptidation (cross-link formation in peptidoglycan)
Prevents the synthesis of complete cell walls, leading to lysis of growing bacteria that are synthesizing new peptidoglycan

Cephalosporins

Structurally and functionally similar to penicillins
Broad-spectrum antibiotics
Useful for patients allergic to penicillin
Four categories based on their spectrum of activity

Vancomycin and Teicoplanin

Glycopeptide antibiotics
Inhibit cell wall synthesis
Important for treatment of antibiotic-resistant staphylococcal and enterococcal infections
Previously considered a "drug of last resort".

Protein Synthesis Inhibitors

Many antibiotics bind to bacterial ribosomes.
Binding can be to either the 30S or 50S ribosomal subunit.
Other antibiotics interfere with steps in protein synthesis, including aminoacyl-tRNA binding, peptide bond formation, mRNA reading, and translocation.

Nucleic Acid Synthesis Inhibitors

Inhibit DNA replication, transcription, or RNA polymerase activity.
Drugs (e.g., Rifampin) are less selective for bacteria compared to other antibiotics because the mechanisms for nucleic acid synthesis are similar.

Antifungal Agents

Nystatin (mycostatin): Yeasts
Griseofulvin (Grisactin): Dermatophyte fungi
Amphotercin B (Fungizone): Systemic fungi.

Antifungal Characteristics

Many antifungal drugs are quite toxic to humans.
Most fungi have a detoxification system that likely modifies many antibiotics by hydroxylation.
Fungal infections are typically subdivided into superficial mycoses and systemic mycoses.
Most antifungal drugs interfere with sterols in fungal membranes, causing disruption of membrane permeability and cell leakage.

Superinfection

Development and spread of drug-resistant pathogens, often caused by the original drug treatment that destroys the sensitive strains.
Examples such as pseudomembranous enterocolitis due to Clostridium difficile

Preventing Emergence of Drug Resistance

Use high drug concentrations when necessary
Administer multiple drugs at the same time, if needed
Use drugs only when medically necessary
Development of new drugs
Use of bacteriophages to target bacterial diseases

Antiviral Drugs

Relatively few because of difficulty targeting viral replication.

Antiviral Examples

Amantadine: Prevents influenza infections by blocking viral penetration and uncoating
Drugs inhibiting herpes virus enzymes involved in DNA or RNA synthesis & function (e.g., acyclovir, adenine arabinoside, foscarnet)
Broad-spectrum anti-DNA virus drugs (e.g., cidofovir) inhibit viral DNA polymerase

Anti-HIV Drugs

Reverse transcriptase (RT) inhibitors (nucleoside and non-nucleoside).
Protease inhibitors mimic peptide bonds attacked by HIV protease.
Fusion inhibitors prevent HIV entry into cells.
Most successful strategies combine drug cocktails to combat resistance.

Mechanisms of Drug Resistance

Exclusion of drug (drug can't bind or penetrate).
Drug efflux (pumping the drug out).
Drug inactivation (chemical modification by pathogen).
Alteration of target (enzyme/organelle).
Use of alternative pathways or increase in target metabolite production.

Origin of Resistance Genes

Resistance genes can be chromosomal or on plasmids.
Plasmids are small DNA molecules existing separately or integrated into the chromosome.

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Description

This quiz explores key concepts related to antifungal and antiviral drugs, including their effects on membranes, factors contributing to superinfections, and drug resistance. It also covers specific drug classes and strategies for improving antiviral effectiveness, particularly in HIV treatment.