ANTIBIOTICS AND ANTIMICROBIAL DRUGS

 

Antibiotics: Antimicrobial substances produced by __microorganisms__.

Major Genera

1) Penicillium (fungi)

2) Cephalosporium (fungi)

3) Streptomyces (Actinomycetes)

4) Micromonospora (Actinomycetes)

5) Bacillus (Gram + Bacteria)

 

Bacteriostatic_: Inhibit the growth of bacteria.

Bactericidal: Kills bacteria.

 

_Narrow-spectrum: Affect only a select group of microbes.

Broad-spectrum: Affect large numbers of bacteria (Gm+ and Gm-)

Superinfection: Overgrowth by a resistant organism.

 

Modes of Action

1) Inhibition of Cell Wall Synthesis

2) Inhibition of Protein Synthesis

3) Injury to the Plasma Membrane

4) Inhibition of Nucleic Acid Synthesis

5) Inhibition of the Synthesis of Essential Metabolites

 

Inhibitors of Cell Wall Synthesis
Penicillin (6 natural Penicillins: G and V most often used) Limitations of Natural Penicillins

· Narrow spectrum of activity

· Susceptibility to Penicillinases/_Beta lactamases

· Pen G destroyed by gastric fluids

 

Advantage: Low toxicity to human tissue. (Except allergic people ~1-5% of adults)

 

Semisynthetic Penicillins

Part mold made and part man made.

Side chains are attached to the natural penicillin molecule.

Advantages:

1) Broad spectrum

2) More stable in gastric fluid

3) Resistant to Penicillinase

4) Longer shelf life

 

Cephalosporium

Cephalosporins: Molecule similar to Penicillin ( b-lactam ring)

Broad spectrum of activity. eg. Cephalothin

 

 

Polypeptide antibiotics

Bacillus subtilis: Produces Bacitracin. Topical application against gram-positives.

 

Streptomyces derived: Vancomycin Glycopeptide

Important "last line" against antibiotic resistant S. aureus

 

Antimycobacterium antibiotics

Isoniazid (INH)

Inhibits mycolic acid synthesis.

Ethambutol

Inhibits incorporation of mycolic acid.

 

 

 

 

 

 

Inhibitors of Protein Synthesis

Aminoglycosides: Broad spectrum activity.

May have serious side effects: damage to auditory nerve and kidneys.

e.g. Streptomycin, Neomycin, Gentamicin

 

Streptomyces spp.:
Streptomycin: Changes shape of 30S portion of the ribosome causes misreading of mRNA.

 

Tetracycline: Interferes with attachment of tRNA.

 

Chloramphenicol: Binds to 50S portion and inhibits peptide bond formation.

 

Erythromycin: Macrolide (Large molecule)

Binds to 50S portion and prevents translocation (movement) of the ribosome along the mRNA.

 

Streptogramins: Gram-positives. Binds 50S subunit, inhibits translation

 

Synercid: Gram-positives. Binds 50S subunit, inhibits translation

 

Oxazolidinones: Linezolid Gram-positives. Binds 50S subunit, prevents formation of 70S ribosome.

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Injury to the Plasma Membrane

Bacillus polymyxa: Produces Polymyxin B.

Used topically.

Effective against Pseudomonas.

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Inhibitors of Nucleic Acid Synthesis

 

Rifampin: Inhibits synthesis of mRNA.

Can penetrate tissues and reach therapeutic levels in cerebrospinal fluid.

Used to treat tuberculosis.

 

Quinolones and Fluorquinolones: Synthetic drug (Nilidixic acid)

Inhibits DNA gyrase needed for DNA replication.

Quinolones: Limited use (UTIs).

Fluorquinolones: Norfloxacin and Ciprofloxacin: Broad spectrum, penetrate tissues well.

May adversely affect the development of cartilage.

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Competitive Inhibitors of the Synthesis of Essential Metabolites

 

Sulfonamides/Sulfa drugs: Derived from coal tar.

Structure similar to PABA

 

Prevents synthesis of folic acid (precursors of proteins, DNA and RNA)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Mechanisms of Resistance
1) Ability to destroy the antimicrobial

2) Prevent penetration of the antimicrobial

3) Alteration of target structure

 

4) Active transport (efflux pumps)

 

 

Control of Resistance

1) Administer effective dose and finish the complete dosage.

2) Avoid using outdated, weakened antibiotics

3) Eliminate indiscriminate use.

 

4) Combination therapy: Two or more antibiotics given simultaneously.

 

Synergistic e.g. Penicillin and Streptomycin.

Avoid antagonistic: e.g. Penicillin and Tetracycline.

Combine an antibiotic with a b-lactamase inhibitor:

 

Augmentin (Amoxicillin combined with Potassium clavulanate).

 

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Antiviral Drugs
Nucleoside and Nucleotide Analogs

 

Antiviral Drugs
Protease inhibitors: Indinavir: HIV

Neuraninidase Inhibitors: Zanamivir: Influenza Prevents release/budding of virus

 

Inhibit uncoating: Amantadine: Influenza

 

nterferons: Viral hepatitis

 

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Antiprotozoan Drugs

Chloroquine: Inhibits DNA synthesis: Malaria

Metronidazole: Interferes with anaerobic metabolism.: Entamoeba, Trichomonas, Giardia

 

Antihelminthic Drugs

Niclosamide: Prevents ATP generation: Tapeworms

Pyantel pamoate: Neuromuscular block: Intestinal roundworms

Mebendazole Inhibits nutrient absorption: Intestinal roundworms

Ivermectin: Paralyzes worm: Intestinal roundworms