Lecture 2 Chemotherapy

Lecture Overview

• Course: AAP 2214: GENERAL PHARMACOLOGY & PHARMACOGNOSY

• Topic: Chemotherapy

• Speaker: Dr. Jakait J.A (BVM, Ph.D)

Objectives of the Lecture

• Define chemotherapy.

• Understand principles of chemotherapy.

• Identify factors influencing selection of antimicrobial agents.

• Explain complications of antimicrobial therapy.

• Discuss antimicrobial resistance including its types, mechanisms, causes, and prevention.

Definition of Chemotherapy

• Chemotherapy refers to the treatment of infectious diseases and malignancies using specific chemicals (chemotherapeutic agents) that selectively inhibit or destroy pathogens or cancer cells while minimally affecting normal host cells.

• Examples of Chemotherapeutic Agents:

  • Antibiotics

  • Antifungals

  • Antineoplastics

  • Antivirals

  • Antiparasitic (antihelminthics, antiprotozoals)

Key Principles of Chemotherapy

• Selective Toxicity:

  • The drug must selectively target the pathogen or cancerous cells without harming host cells.

• Rational Use:

  • Treatment should be based on clinical or microbiological diagnosis.

• Pathogen Characterization:

  • Understanding the pathogen's characteristics and its sensitivity to antimicrobial agents is crucial.

• Drug Selection:

  • Must consider pathogen type, patient factors, and drug properties.

• Proper Administration:

  • Administration route, dosage, and duration must be optimized to ensure effective concentrations at infection sites.

• Supportive Therapy:

  • Specific supportive measures should accompany the therapy.

Factors Influencing Selection of Antimicrobial Agents (AMAs)

Microorganism-Related Factors

• Diagnosis and Sensitivity Testing:

  • Diagnosis should guide AMA choice based on clinical signs and microbiological culture sensitivity tests.

• Minimum Inhibitory Concentration (MIC):

  • Determining the MIC is vital for effective AMA selection.

Animal-Related Factors

• Age:

  • Affects pharmacokinetics and drug metabolism.

  • Caution with oxytetracyclines in young animals.

• Organ Function:

  • Attention to kidney and liver function is necessary to avoid toxicity.

• Pregnancy and Lactation:

  • Certain AMAs are contraindicated during pregnancy due to teratogenic effects.

• Host Defense Status:

  • Choice of bacteriostatic versus bactericidal agents depends on the animal's immune status.

• History of Drug Allergy:

  • Ensure no previous allergic reactions to specific AMAs.

Complications of Antimicrobial Therapy

Toxicity

• Common AMAs may cause adverse effects:

  • Aminoglycosides: Ototoxicity and nephrotoxicity.

  • Tetracyclines: Hepatotoxicity.

  • Chloramphenicol: Bone marrow depression.

Allergic Reactions

• Risk of hypersensitivity and dermatitis is associated with many AMAs, particularly penicillins and sulfonamides.

Superinfection

• Development of new infections post-AMA therapy, particularly with broad-spectrum agents.

Microbial Drug Resistance

• Insensitivity of pathogens resulting from overuse or misuse of antibiotics can lead to treatment failures.

Antimicrobial Resistance (AMR)

Types of Resistance

• Natural Resistance:

  • Some organisms are inherently resistant (e.g., E. coli to benzyl penicillin).

• Acquired Resistance:

  • Previously sensitive bacteria become resistant through genetic mutations or gene transfer.

Mechanisms of Resistance

• Bacteria may:

  1. Produce enzymes that inactivate drugs.

  2. Modify target sites of drugs.

  3. Alter membrane permeability to drugs.

  4. Utilize alternative metabolic pathways.

Causes of Resistance

• Misuse of antibiotics, poor infection control, and lack of regulatory enforcement.

Prevention Measures

• Use antibiotics only when necessary, opt for narrow-spectrum drugs initially, maintain stringent hygiene measures, and invest in new drug development.

Conclusion

• Understanding the principles and complexities of chemotherapy and addressing microbial resistance is crucial in veterinary pharmacology.