Premed - Lecture 9. Antimicrobials

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Antimicrobials are;

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superbugs

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4 types of anti-microbials (for example) are:

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Anti-bacterial
Anti - fungal
Anti - Viral
Anti - Parasite

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Define: Antibiotic

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Substance produced by a microorganism in minute/small qualities, is able to inhibit other microorganisms.

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Define: Antimicrobial

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Is any compound – natural, semi synthetic or synthetic, that is clinically useful in the treatment of bacterial infection

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Define: Antimicrobial chemotherapy

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use of antibiotics/ antibacterial/ antifungal/ antiviral agents to treat infections.

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Define: Narrow-spectrum

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active against one or few types of pathogens

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Define: Broad spectrum

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active against a wide variety of pathogens

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Define: Cidal:

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Kills the pathogen

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Define: Static

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Inhibit the growth of the pathogen
Withdrawal of drug – growth of agent
Assists the host defense by limiting the populations size

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Who discovered penicilin

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Alex Fleming in 1928

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Why was Gram negative Resistant to early pencillin

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because it could not get in
Inhibit the synthesis of the cell wall

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* *
Antibacterial Agents:
What are the steps

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1. Inhibit cell wall synthesis
2. inhibit protein synthesis
3. Inhibit nucleic acid synthesis
4. Alteration of cell membrane function

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What are peptidoglycan synthesis inhibitors?

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Betalactams
(penicillins and cephalosporins)

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What are betalactans?

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inhibit peptiglocyan synthesis

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what is – Beta-lactamase?

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break the betalactam ring and inactivate the drug

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What are the 2 majour groups of beta - lactam?

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penicillins and the cephalosporins

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Various R groups can be selected for:

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broader spectrum activity
less toxicity
oral use

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bactericidal is needed for:

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for growing bacterial cells which need peptidoglycan in order to grow
but bacteriostatic for resting cells

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* *
Penicillins and cephalosporins bind to

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the transpeptidase (TP) enzyme and block the formation of the peptide cross-links

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Bacteria with beta lactamase enzymes (penicillinase) are resistant. Where is this enzyme seen?

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This enzyme is often seen in plasmids

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Properties of Penecillin G:

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Original Penecillin.
Effective against Gram positive.
Less effective against gram neative

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Penicillin G is sensative to:

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acid hyrdolysis

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Penecillin G is inactivated by

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beta-lactamaes

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How were deritives of Penicillin G made?

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By replacing R group by different compounds

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Cephaloporins: has different ___ Groups.

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R groups.

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Drugs that inhibit cell wall synthesis: List 3

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1. * * Vanocomycin: Glycoprotein
(binds to peptide chians. Bactericidial, narrow spectrum).
* * 2. Bacitracin
(inhibit cell wall synthesis by intefering with the transport of the cell wall subunits across the membrane) Is too toxic for systemic use (usedful for skin infections).
3. Isoniazid
(inhibits mycolic acid synthesis)

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List 5 protein synthesis inhibitors:

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Aminoglycoside
Tetracycline
Choramphenicol,
Macrolides
Clindamycin

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Aminoglycosides are composed of:

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amino sugars linked to glycosidic bonds to other sugar deritivies.
There are 2 R groups

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Sugar deritives for Aminoglycosides:
(do not need to know)

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Gentamicin
Streptomycin
kanamycin

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* Mode of action for Aminoglycosides

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Inhibit protein synthesis by interfering with the function of the 30S ribosome
miread mRNA

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Tetracyclines are produced by organisms of the:

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streptomyces species

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Characteristics of Tetracyclines:

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Structure consists of four joined cyclic rings.
Derivatives; A few varieties exist,
Have a broad spectrum and are bacteriostatic
Act to inhibit bacterial synthesis at tRNA level and inhibit elongation

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Chloramphenicol structure is:

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Nitrobenzene structure
with no derivatives

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Characteristics of Chloramphenicol :

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Bactericidal as well as bacteriostatic depending on the organism
active against Gram positives, negatives and anaerobes
Binds to 50S; Inhibits protein synthesis at peptidy transferase or elongation stage
highly toxic, may cause aplastic anemia

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Macrolides basic structure:

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Basic structure large lactone ring and two sugars

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Macrolides inhibit protein synthesis by binding to:

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50s ribosome
Prevents the release of tRNA after formation of peptide bond

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Characteristics of Macrolides:

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Less toxic; causes GIT disturbances due to suppression of the normal flora

Could be bacteriostatic or bactericidal


Broad spectrum, Gram positive and negative and mycoplasma

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2 Nucleic Acid Inhibitors are:

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1. Fluoroquinolones;(quinolones)
2. Rifampin (rifamycin

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* Define Rifampin:

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Binds to DNA dep-RNApoly and inhibits RNA synthesis
Useful in treating tuberculosis, Gram positive bacteria
Is bactericidal

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* Define Fluoroquinolones:

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Inhibit DNA gyrase, and related enzymes, topoisomerase IV needed for DNA replication and repair: Broad spectrum, example-ciprofloxacin, norfloxacin .

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Damage of bacterial membranes: Polymyxins define:

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Act as detergents to disrupt the cell
membrane of Gram negative bacteria

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2 Antimetabolites:

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Sulfonamides
Trimethoprim

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Inhibiting nucleic acid synthesis by inhibiting synthesis of:

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adenine, guanine and thymine.

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List Problems in Antimicrobial Use:

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=

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Mechanisms of resistance be either:

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Acquired or transferred.

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Mechanisms of resistance are either (2 things)

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Intrinisic or Aquired.

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Aquired are (2 thinsg) either

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mutation or transferred

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Transferred are (3 things)

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conjugation, transformation, transduction.

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What is the name of a diffusion test?

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Kirby-Bauer method

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Kirby-Bauer method: Describe it:

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place paper discs impregnated with known conc. Of antibiotics on a smear of culture on semisolid media, measure zone of inhibition in mm

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Describe the Dilution Test:

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Whether bacteria are killed or if they are inhibited

series of dilutions of the drug in broth media – inoculate same number of bacteria in every tube and determine the lowest concentration of drug that inhibits the growth of a particular bacteria,
minimum inhibitory concentration (MIC)
3.1 g/mL

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E-test: What is it?

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MIC determination on semisolid media (diffusion) with a strip of paper with decreasing conc. Of antibiotic

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What are the sites of Anti-Viral Drug Action?

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Oseltamivir
Indiavir
Enfuvirtide

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3 Classes of Antifungal Agents are:

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1. Polyenes (bind to fungal cell memebrane)
2. Griseofulvin (deposit keratin, inhibit dermatophytes)
3. Azoles, cytosine analogs.