Pharmacology

Learning Objectives

  • Know:

    • Specific drug names.

    • Main features: Mechanism of action, Resistance, Spectrum of action, ADME (Absorption, Distribution, Metabolism, Excretion), Main side effects.

  • Comprehend:

    • How these features affect the clinical aspects of using antibiotics.

Different Types of Protein Synthesis Inhibitors

  • Inhibitors of Ribosomal 30S Subunit:

    • Aminoglycosides

    • Tetracyclines

  • Inhibitors of Ribosomal 50S Subunit:

    • Macrolides

    • Lincosamides

    • Phenicols

    • Pleuromutilins

    • Streptogramins

Tetracyclines

  • Sections Include:I. IntroductionII. ChemistryIII. Mechanism of Action and Development of ResistanceIV. PharmacokineticsV. Side EffectsVI. Therapeutic UsesVII. Pharmaceutical Preparations

Examples of Tetracyclines

  • Tetracyclines:

    • Tetracycline (CLSI Group A/B)

    • Oxytetracycline (Group A/B)

    • Chlortetracycline (Group A/B)

    • Doxycycline

    • Minocycline

Overview of Tetracyclines

  • General Information:

    • Tetracyclines are one of the most commonly used antibiotics in veterinary medicine.

    • Properties:

      • Bacteriostatic and time-dependent.

      • Wide spectrum of activity against Gram+ and Gram-, aerobes and anaerobes, mycoplasma, and various intracellular bacteria.

      • Effective against resistant microorganisms (e.g., Rickettsiae, Spirochetes like Lyme disease, Mycoplasma, Chlamydia, and protozoan parasites including Giardia and Plasmodium).

Chemistry of Tetracyclines

  • Characteristics:

    • Amphoteric and hygroscopic compounds in aqueous solutions.

    • Form salts, most commonly marketed as hydrochloride salt.

    • Form insoluble chelates with cations (Ca, Mg, Fe, Al).

Spectrum of Action

  • Coverage:

    • Tetracyclines cover all four quadrants:

      • Gram + Aerobic

      • Gram - Aerobic

      • Gram + Anaerobic

      • Gram - Anaerobic

Mechanism of Action and Resistance Development

  1. Transport into Bacteria:

    • Cross outer membrane by diffusion (Gram-) or energy-dependent process (Gram+).

  2. Binding:

    • Bind to the 30S ribosomal subunit, inhibiting protein synthesis by preventing the attachment of aminoacyl-tRNA to the mRNA ribosomal complex.

  3. Resistance Mechanisms:

    • Increased efflux, decreased influx, enzymatic hydroxylation, ribosomal RNA mutations, and ribosomal protection by plasmid-generated proteins.

Pharmacokinetics

  1. Absorption:

    • Oral administration preferred; also available IV and IM.

    • Oral bioavailability: 35-60%; doxycycline: ~95%.

    • Absorption inhibited by certain foodstuffs and medications.

  2. Distribution:

    • Good tissue distribution; poor CNS penetration except for minocycline and doxycycline.

  3. Metabolism and Elimination:

    • Some tetracyclines are not well metabolized and are excreted via urine or feces. Doxycycline/minocycline are excreted as inactive compounds.

Toxicity

  • General Safety:

    • Relatively safe at recommended doses; toxicity more common with renal impairment.

  • Common Side Effects:

    • GI tract disturbances (e.g., nausea, vomiting, especially in cats).

    • Allergic reactions are rare; photosensitization can occur.

  • Severe Effects:

    • Hypersensitivity and gastrointestinal distress; potential for nephrotoxicosis with high doses.

    • Teeth discoloration effects in pregnant or young animals.

Therapeutic Uses

  • Broad-Spectrum Agents:

    • Effective against a variety of bacteria, protozoa, and intracellular organisms.

    • Used in various species: dogs, cats, ferrets, cattle, and more.

    • Commonly used for growth promotion in food animals and for treating infections in veterinary medicine.

Summary of Tetracyclines

  • Key Features:

    • Bacteriostatic, time-dependent with wide activity spectrum.

    • Good oral absorption (modest for chlorotetracycline).

    • Contraindicated in ruminants and with caution in horses.

    • Doxycycline and Minocycline are particularly useful for certain infections (e.g., CNS).

    • Special care regarding side effects, especially in cats.

Antimicrobial Testing and Reporting

  • Objectives:

    • Methods of susceptibility testing with pros and cons.

    • Understanding MIC Testing and CLSI breakpoints.

  • Mic Testing:

    • Determine susceptibility. Specific approaches like Kirby Bauer and MIC broth dilution methods.

Research and Resources

  • References:

    • TARGET, Feedlot Pharmaceutical Documentation, CLSI Vet 08 standards.

Questions

  1. Most common antibiotic with rifampin?

  2. Penicillins metabolism and excretion?

  3. Tetracyclines contraindications?