Question

• Summarize the mode of action of major groups of antimicrobial and antiviral drugs.

• Summarize practices that have led to increased bacterial antibiotic resistance and strategize ways to limit this increased resistance.

• Describe factors to be taken into account when selecting antimicrobial and antiviral drugs;including drug effects on patients and teratogens.

Answer 1

Answer: Antimicrobial drugs acts to selectively kill or inhibit the growth of microbial pathogen, causing minimal or no harm to the host. There are several varieties of antimicrobial and antiviral drugs that act in different ways and their mode of acyion can be summarized as follows:

(i) Inhibition of cell wall biosynthesis: Several antimicrobial drugs, especially antibacterial drugs such as penicillin, cephalosporin, monobactams, etc belonging to a class known as $\beta$ -lactams act to inhibit cell wall biosynthesis. As $\beta$ -lactams are structural anlogs of peptidoglyca, the structural component of bacterial cell wall, it inhibits the activity of transpeptidase, the enzyme required for synthesis of peptidoglycan by interacting directly to penicillin-binding protein (PBPs) and blocks the cross-linking of peptide chains. The glycopeptides class of drugs like Vancomycin, a very large complex molecule that binds to peptide chains of peptidoglycan subunits blocking transglycosylation and transpeptidation. Another antimicrobial drug called bacitracin also act by blocking the specific cell-membtane molecule to transport the precursors of peptidoglycan synthesis, inducing cell lysis.

(ii) Inhibition of protein biosynthesis: There is a variety of broad spectrum antibiotics that act to inhibit protein biosynthesis by selectively targeting the prokaryotic 70S ribosomes. Some antimicrobial class of drugs such as aminoglycosides and tetracyclines bind to 30S subunit and induce false interaction between codon and anticodon leading to faulty proteins, blocks the tRNA with ribosomes whiile some other antimicrobial class of drugs binds to 50S subunits and blocks peptide formation between amino acids.

(iii) Inhibition of nucleic acid synthesis: The nucleic acid synthesis inhibitors is comprised of rifamycins and fluoroquinones. The former target RNA transcription by blocking the action of RNA polymerase whereas the latter inhibits DNA replication by blocking the activity of DNA gyrase enzyme.

(iv) Inhibition of Membrane functions: These class of drugs includes polymyxin and lipopeptide that acts to the outer membrane lipopolysacharide component, causing the disruption of the integrity of both the inner and outer membranes.

(v) Inhibition of metabolic pathways: There are some antimicrobial drugs that act to inhibit certain metabolic pathways and hence called antimetabolites. They act as competitive inhibitors against the bacterial enzymes, as for example, sulfonamides interfere in the bacterial folic acid synthesis while isoniazid inhibits the synthesis of mycolic acid in mycobacteria.

Answer: Antimicrobial resistance is the ability of a microbe to resist the effects of drugs that was once used to treat the microbe successfully. The different practices that led to increased bacterial antibiotic resistance are as follows:

(i) Over-prescription of antibiotics: The misuse of antibiotics is related to the over-prescription of antibiotics by majority of doctors that has a severe impact on antibacterial resistance.

(ii) Patients not finishing the entire antibiotic course: The self medication and the misuse of antibiotics for not completing the entire antibiotic course and leaving it in the middle stage can provoked the occurence of antibcaterial resistance in the body.

(iii) Overuse of antibiotics in livestock and and fish farming: The intoduction of antibiotics to the livestock and fish farming as a part of growth supplement and a preventive measure to infections, results in the transfer of resistant bacterial strains into the food that humans eat, causing fatal diseases.

(iv) Poor hygiene and sanitation: Poor hygiene and sanitation increase the risk of incidence of microbes attack and can persist in the body without any adverse symptoms and can become resistant in due course.

The preventive measures to limit the increased antibiotic resistance in bacteria can be summarized as follows:

The misuse of antibiotics should be stopped. Narrow spectrum antibiotics should be preferred over broad spectrum antibiotics as these are more effective and accurate and cause less harm or side effects to humans. People taking self medication at home need to be aware and have the proper education while taking any sort of medicines, and to prevent the practice of using antibiotics with minimal infections or when it is not required. The completion of the full antibiotic course should be done without any interruption or negligience. The spread of resistant infections can be prevented through proper hygiene and sanitation, including handwashing and disinfecting.

Answer: The factors that should be taken into account on selecting antimicrobials and antiviral drugs are as follows:

(i) Renal and hepatic function: As the liver and kidney are the main organs for the elimination and detoxification of drugs, it is important to determine the functioning of these primary organs with respect to antimicrobial drugs.

(ii) Age: Patients at both extremes of age react differently due to differences in body size and kidney function.

(iii) Pregnancy and lactation: When the fetus is in the mother's womb, then there is the highest possible chances of infections due to the presence of tertogens which can function either as animicrobials or toxic to fetus. Some class of drugs like sulfonamides are associated with several birth defects while other class of antibiotics such as tetracyclines or chloramphenicol is not associated with any neonatal defects. But in general, the use of antimicrobials or antiviral drugs is limited in pregnancy and lactation.

(iv) History of allergy or intolerance: Patients having a history of antibacterial allergy or intolerance cannot be provided with this drugs, otherwise it cam lead to a complex situation.