Pharmacology – ANTIBIOTICS – DNA, RNA, FOLIC ACID, PROTEIN SYNTHESIS INHIBITORS (MADE EASY)

Summary

This lecture provides an in-depth overview of the pharmacology of antibiotics, focusing on nucleic acid synthesis inhibitors, protein synthesis inhibitors, and metabolic pathway inhibitors. It covers key antibiotics such as Metronidazole, Quinolones, Rifamycins, Aminoglycosides, Tetracyclines, and others, explaining their mechanisms of action, from inhibiting DNA or RNA synthesis to blocking protein synthesis at various stages. The lecture also highlights common side effects and potential risks associated with these antibiotics, emphasizing their selective toxicity for bacteria over human cells. The material is designed to deepen understanding of antibiotic functions and therapeutic uses in bacterial infections.

Takeaways

• 😀 Nucleic acid synthesis inhibitors target bacterial DNA or RNA to prevent replication and protein production, providing a mechanism for selective toxicity.
• 😀 Metronidazole, a prodrug, requires activation by anaerobic bacterial enzymes to form a radical that damages DNA and causes cell death.
• 😀 Quinolones inhibit DNA replication by blocking topoisomerases (DNA gyrase and topoisomerase IV), essential enzymes for DNA unwinding and separation.
• 😀 Rifamycins prevent bacterial transcription by binding to RNA polymerase, halting RNA synthesis and blocking protein production.
• 😀 Aminoglycosides bind to the 30S ribosomal subunit to misread genetic code, leading to nonfunctional proteins or premature termination of synthesis.
• 😀 Tetracyclines and Glycylcyclines block the entry of tRNA into the ribosome’s A-site, preventing the elongation of the protein chain.
• 😀 Amphenicols bind to the 50S ribosomal subunit, inhibiting peptide bond formation and leading to bacteriostatic effects.
• 😀 Macrolides and Ketolides target the 50S ribosomal subunit, preventing protein elongation by blocking the peptide exit tunnel.
• 😀 Lincosamides and Streptogramins act on the 50S subunit to inhibit protein synthesis, specifically affecting the translocation step.
• 😀 Metabolic pathway inhibitors like Sulfonamides and Trimethoprim disrupt folic acid synthesis in bacteria, interfering with DNA replication and cell growth.
• 😀 Sulfonamides mimic para-aminobenzoic acid (PABA) and inhibit dihydropteroate synthase, blocking folic acid synthesis in bacteria.
• 😀 Trimethoprim inhibits dihydrofolate reductase, further disrupting folic acid synthesis and bacterial growth.

Q & A

What is the primary target of nucleic acid synthesis inhibitors?

Nucleic acid synthesis inhibitors primarily target the bacterial processes involved in DNA and RNA synthesis, such as DNA replication, transcription, and RNA synthesis.

How does Metronidazole work as a nucleic acid synthesis inhibitor?

Metronidazole is a prodrug that gets activated in anaerobic bacteria by the enzyme pyruvate:ferredoxin oxidoreductase, forming a nitro radical anion. This radical attacks bacterial DNA, causing strand breaks and mutations that lead to cell death.

What is the mechanism of action of Quinolones in bacteria?

Quinolones inhibit the function of topoisomerases, specifically DNA gyrase and topoisomerase IV, which are responsible for unwinding and separating DNA strands during replication. This inhibition prevents DNA synthesis and bacterial cell growth.

How do Rifamycins interfere with bacterial cell function?

Rifamycins bind to RNA polymerase, preventing it from synthesizing RNA from DNA. This halts transcription and consequently protein synthesis, leading to bacterial cell death.

What are some common side effects of Metronidazole?

Common side effects of Metronidazole include headaches, nausea, metallic taste, and alcohol intolerance, which can cause symptoms like vomiting and tachycardia.

What differentiates protein synthesis inhibitors from nucleic acid synthesis inhibitors?

Protein synthesis inhibitors target the bacterial ribosome, blocking different steps in protein synthesis, while nucleic acid synthesis inhibitors target DNA or RNA processes, preventing replication or transcription.

How do Aminoglycosides interfere with bacterial protein synthesis?

Aminoglycosides bind to the 30S subunit of the bacterial ribosome, causing misreading of mRNA and premature termination of protein synthesis, resulting in nonfunctional proteins.

What are the potential side effects of Tetracyclines?

Tetracyclines can cause GI disturbances, photosensitivity, hepatotoxicity, and in children, they may lead to discoloration of teeth and inhibit bone growth due to their affinity for calcium.

How do Amphenicols, such as Chloramphenicol, affect bacterial protein synthesis?

Amphenicols bind to the 50S subunit of the ribosome, blocking peptide bond formation during protein synthesis. This results in bacteriostatic effects by inhibiting protein elongation.

What is the role of Sulfonamides in metabolic pathway inhibition in bacteria?

Sulfonamides inhibit the enzyme dihydropteroate synthase, which is involved in folic acid synthesis. Since bacteria rely on folic acid for DNA replication and growth, this inhibition stops bacterial growth.