Drugs, Microbes, Host Microbio

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Doctrine of Signatures

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Original source of drug knowledge: characteristic appearance indicated function divinely preordained.

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Antibiotic Sources

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Derived from compounds found in bacteria and fungi. Natural: straight from producer w/o modification. Semisynthetic: modified after taken from producer. Synthetic: made in lab based on nature.

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Antibiotic

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A metabolic compound from one microorganism which intends to destroy or inhibit another microorganism.

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Mechanisms of Drug Action

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Disrupt cell walls, cell membranes, proteins, nucleic acids, or other.

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Cell Wall Disruptive Drugs

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Inhibit cell wall synthesis; target young cells actively building new cell walls, less effective with dormant/older cells.

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Ways Drugs Disrupt Cell Walls

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Inhibit transpeptidase from cross-linking (cephalosporin, penicillin), inhibit peptidoglycan subunit construction (cycloserine), inhibit elongation of peptidoglycan chains (vancomycin).

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Cell Membrane Disruptive Drugs

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Disrupt cell membrane integrity by disrupting phospholipid integrity (polymyxins), disrupting embedded molecules (amphitericin B & nystatin disrupt sterols), or prohibiting ergosterol production (azoles). Can harm human cells.

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Protein Disruptive Drugs

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Interfere with protein synthesis or function; human mitochondria have a bacterium-like ribosome and can be impacted.

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Ways Drugs Disrupt Proteins

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Inhibit protein synthesis initation (oxazolidones). Interfere w/ ribosome function. Inhibit tRNA docking (tetracycline). Interfere with associated enzymes (protease inhibitors). Interfere with proteins themselves.

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Ribosome Function Interference

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Bind to 30S subunit to result in misread mRNA (streptomycin) or disrupt proofreading/subunit sliding (aminoglycosides), bind to 50S subunit to prohibit peptide bonding between amino acids (chloramphenicol) or prevent protein detachment or mRNA translocation (erythromycin).

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Protease Inhibitors

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Inhibit the enzyme that cleaves polyproteins resulting in long, nonfunctional chains of proteins.

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Nucleic Acid Disruptive Drugs

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Interfere w/ nucleic acid itself by cross-linking the double-helix (chloroquine) or mimicking nucleotide (nucleotide analogues like AZT acyclovir, flucytosine); interfere with associated enzymes like gyrases (quinolones) or polymerases (rifamycins, non-nucleoside analogues).

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Other Mechanisms of Drug Action

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Interfere w/ virus entry (as Fuzeon blocks HIV), or entry and release both by disrupting H+ dynamics (amantadine) or neuraminidase activity.

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Antiviral Drug Activity

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Blocks adsorption (Amantidine, Fuzeon, Relenza, Tamiflu), blocks transcription/translation/replication (Acyclovir, AZT, nevirapine), prevent virion maturation (Saquinavir, Amantadine, Tamiflu).

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Interferon

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Produced by leukocytes and fibroblasts; alpha, beta, or gamma; antiviral and anticancer properties.

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Interferon Functions

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Reduce healing time and side effects of viral infection, reduce symptoms of acute and chronic viral infection, slow cancer progress.

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Interferon Activity

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Hijacked cell can warn surrounding cells by producing interferons, and all cells induce resistance. Early step used by immune system.

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Antibacterial Drugs 1

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Beta-lactam compounds, aminoglycosides, and tetracyclines.

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Beta-lactam Compounds

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Penicillin & cephalosporin groups.

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Aminoglycosides

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Gentamicin and streptomycin.

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Tetracyclines

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Aureomycin, tetracyline, doxcycline (both natural & synthetics).

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Antibacterial Drugs 2

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Chloramphenicol, -mycin, bacitracin and polymyxin; synthetics & derivatives of these include Sulfa drugs, sulfones, trimethoprim, & oxazolidones.

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Antifungal Drugs

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Often have side effects on humans. Macrolide polyenes (amphotericin B and nystatin), griseofulvin, azoles, flucytosine.

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Griseofulvin

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Interferes with mitosis by disrupting spindle fibers.

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Antiprotozoan / Antimetazoan Drugs

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Protozoan malaria ("quin") and amoebas. Eukaryotic piperazine and pyrantel paralyze muscles.

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Drug Resistance

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Intrinsic (resistant to own products) or acquired (mutations and recombination - a medical concern).

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R (resistance) Factors

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Plasmids transferred mainly thru conjugation; also transduction or transformation.

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Transposens

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"Jumping genes" between chromosomes and plasmids; sometimes replicate.

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Drug Resistance Evolution

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Broad spectrum drugs and crowded conditions invite microbes to adapt.

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Drug Resistance Mechanisms

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Inactivate drug, decrease drug permeability, inc. drug elimination, change drug receptor, change metabolic pattern.

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Drug Inactivation

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Allow drug in and an enzyme acts on it, rendering it dysfunctional (ex. beta lactamases). Inherent or acquired.

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Decreasing Drug Permeability

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Change transport mechanism that lets drug in (ex. blocking penicillin entry)

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Increasing Drug Elimination

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Allow drug in and spit it back out via efflux pump - works against multiple drugs (ex. tetracycline resistance).

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Changing Drug Receptor

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Modify or shield drug target; change ribosome structure, protein structure, or target composition.

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Changing Metabolic Pattern

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Choose a different metabolic option or stop metabolic activity completely.