Chapter 20 Learning Objectives PDF

**1. Terms Related to Chemotherapy:** - **Antimicrobial Drugs**: Substances that kill or inhibit the growth of microorganisms (bacteria, fungi, viruses, protozoa). - **Antibiotic**: A type of antimicrobial drug that is produced naturally by microorganisms, primarily bacteria and fungi,...

**1. Terms Related to Chemotherapy:** - **Antimicrobial Drugs**: Substances that kill or inhibit the growth of microorganisms (bacteria, fungi, viruses, protozoa). - **Antibiotic**: A type of antimicrobial drug that is produced naturally by microorganisms, primarily bacteria and fungi, to kill or inhibit other microbes (e.g., penicillin from mold). - **Bactericidal**: Antibiotics that **kill bacteria** directly (e.g., penicillin). - **Bacteriostatic**: Antibiotics that **inhibit bacterial growth** but do not kill them; they allow the immune system to eliminate the bacteria (e.g., tetracycline). - **Selective Toxicity**: The ability of an antimicrobial drug to target microorganisms without damaging host cells. This is achieved by targeting features unique to microbes, such as bacterial cell walls or specific enzymes. **2. Three Ways Microbes Damage Cells and Cause Disease:** 1. **Direct Damage**: Microbes can invade host cells and cause damage by replicating and destroying cells (e.g., viruses). 2. **Toxin Production**: Many bacteria produce toxins that damage host tissues and cells. - **Siderophores**: Molecules produced by bacteria to scavenge iron from the host, depriving host cells of this essential nutrient. - **Exotoxins**: Proteins secreted by bacteria (often Gram-positive) that have highly specific effects, such as neurotoxins or enterotoxins. Exotoxins are generally more potent and targeted. - **Endotoxins**: Part of the outer membrane of Gram-negative bacteria (specifically, **lipopolysaccharides** or LPS). Endotoxins are released when bacteria die and the cell walls break apart, leading to an inflammatory response. - **Difference between Exotoxins and Endotoxins**: Exotoxins are secreted, protein-based, and highly specific, while endotoxins are part of the bacterial structure (lipid-based) and cause more general inflammation. 3. **Immune Response**: Sometimes the body's immune response to an infection causes damage, such as inflammation and tissue destruction, in an attempt to eliminate the pathogen. - **How Viruses Damage Cells**: Viruses invade host cells, take over the cell's machinery to replicate themselves, and often lyse (burst) the cell to release new viral particles. This process directly destroys host cells and spreads infection. 4. **Antibiotics and Antimicrobial Drugs:** - **Antibiotic**: A substance produced by microbes (e.g., bacteria or fungi) to kill or inhibit other microorganisms. - **Types of Microbes that Produce Antibiotics**: Most antibiotics come from bacteria (e.g., *Streptomyces* species) or fungi (e.g., *Penicillium* species). - **Antimicrobial Drug**: A broader term that includes antibiotics and synthetic or semisynthetic drugs used to treat infections (e.g., sulfa drugs). - **Why Antibiotics Don't Harm Our Cells**: Antibiotics work by targeting structures or functions specific to bacteria (e.g., cell walls, 70S ribosomes) that are different from human cells (e.g., humans have no cell walls and have 80S ribosomes). 5. **Chemotherapy Challenges and Terms:** - **Problems of Chemotherapy for Infections**: - **Bacterial Infections**: Misuse or overuse of antibiotics can lead to resistance, like MRSA. - **Viral Infections**: Antiviral drugs have limited use since viruses use host cell machinery, making it hard to target them without damaging host cells. - **Fungal Infections**: Fungal cells are similar to human cells, making it harder to treat fungal infections without toxic side effects. **Key Terms**: - **Spectrum of Activity**: The range of microbes that an antimicrobial drug can target. - **Broad-Spectrum Antibiotic**: An antibiotic that targets a wide range of bacteria (both Gram-positive and Gram-negative) (e.g., tetracycline). - **Superinfection**: A secondary infection that occurs when antibiotics kill the normal flora, allowing resistant organisms or opportunistic pathogens to flourish (e.g., Candida overgrowth after antibiotic use). - **Importance of Understanding Mechanisms of Action**: Knowing how a drug works helps in selecting the right treatment and preventing resistance. For example, choosing a bactericidal drug for a life-threatening infection ensures the bacteria are killed rather than just inhibited. - **MRSA**: **Methicillin-Resistant Staphylococcus aureus** is a type of staph bacteria that has developed resistance to methicillin and many other antibiotics, making infections difficult to treat and a serious public health concern. 6. **Groups of Antimicrobial Drugs and Modes of Action:** - **Three Groups of Antimicrobial Drugs**: 1. **Antibacterial Drugs**: Target bacteria (e.g., penicillin, tetracycline). 2. **Antiviral Drugs**: Target viruses (e.g., acyclovir). 3. **Antifungal Drugs**: Target fungi (e.g., amphotericin B). - **Five Modes of Action of Antibiotics**: 1. **Inhibition of Cell Wall Synthesis**: These antibiotics prevent bacteria from forming a functional cell wall, leading to cell death due to osmotic pressure. - **Example**: **Penicillin** blocks the enzyme transpeptidase, which is required for peptidoglycan cross-linking in bacterial cell walls. This is specific to bacteria, as human cells lack cell walls. 2. **Inhibition of Protein Synthesis**: These antibiotics bind to bacterial ribosomes (70S), preventing protein production. - **Example**: **Tetracycline** binds to the 30S ribosomal subunit, blocking tRNA attachment, which is specific to bacterial ribosomes (human cells have 80S ribosomes). 3. **Inhibition of Nucleic Acid Synthesis**: These drugs prevent the synthesis of bacterial DNA or RNA. - **Example**: **Ciprofloxacin** targets bacterial DNA gyrase, an enzyme crucial for DNA replication in bacteria (humans have a different topoisomerase). 4. **Injury to Plasma Membrane**: These drugs disrupt the bacterial cell membrane, causing leakage of essential contents. - **Example**: **Polymyxin B** binds to the phospholipids of bacterial membranes, increasing permeability. This is specific to bacterial membranes due to differences in lipid composition. 5. **Inhibition of Metabolic Pathways**: These antibiotics act as competitive inhibitors for enzymes involved in essential bacterial metabolic pathways. - **Example**: **Sulfonamides** inhibit folic acid synthesis, which is necessary for bacterial growth. Humans do not synthesize folic acid and obtain it through diet, so they are not affected. 7. **Anti-fungal Antibiotics:** - **Mode of Action**: Many anti-fungal antibiotics target the fungal cell membrane. A common target is **ergosterol**, a lipid found in fungal cell membranes but not in human cells. - **Example**: **Amphotericin B** binds to ergosterol, forming pores in the membrane, which leads to leakage of cell contents and fungal cell death. - **Challenges**: Fungi are eukaryotic, like human cells, so drugs that target fungal cells can also harm human cells, leading to toxic side effects. Additionally, fungal infections can be more difficult to treat due to slower growth rates compared to bacteria. 8. **Anti-viral Drugs and Penicillin:** - **Mode of Action of Anti-viral Drugs**: Antiviral drugs work by interfering with viral replication, targeting specific viral processes. - **Example**: **Acyclovir** for herpes viruses. Acyclovir is a nucleoside analog that inhibits viral DNA polymerase, preventing viral DNA replication. - **General Structure of Penicillin**: Penicillin contains a **beta-lactam ring**, which is essential for its antibacterial action. It inhibits bacterial cell wall synthesis by blocking the enzyme **transpeptidase**, which is necessary for cross-linking peptidoglycan chains, weakening the bacterial cell wall and causing cell lysis. - **Difference between Natural and Synthetic Penicillin**: - **Natural penicillin** (e.g., Penicillin G) are derived directly from mold and have a limited spectrum of action. - **Synthetic penicillin** (e.g., amoxicillin, methicillin) are chemically modified to increase effectiveness, broaden their spectrum, or resist degradation by bacterial enzymes. - **Penicillinase**: Also called **beta-lactamase**, it is an enzyme produced by certain bacteria that breaks the beta-lactam ring of penicillin, rendering it inactive. - **Penicillin Sensitive to Penicillinase**: Natural penicillin, like Penicillin G, are sensitive to penicillinase because they lack structural modifications to protect their beta-lactam ring. Some synthetic penicillin, like methicillin, are resistant to penicillinase. 9. **Resistance of Mycobacteria to Antibiotics:** - **Why Mycobacteria Are Resistant**: Mycobacteria, such as **Mycobacterium tuberculosis**, have a complex, waxy cell wall rich in **mycolic acids** that makes them impermeable to many antibiotics. Their slow growth rate and ability to survive in a dormant state also contribute to their resistance. - **Example of an Antibiotic**: **Isoniazid** works by inhibiting the synthesis of mycolic acids, which are essential components of the mycobacterial cell wall. 10. **Antibiotic Sensitivity Tests:** - **Disk-Diffusion Test (Kirby-Bauer Test)**: Antibiotic-impregnated paper disks are placed on an agar plate inoculated with bacteria. The antibiotic diffuses into the agar, creating a zone of inhibition where bacteria can't grow. The size of this zone is measured to determine sensitivity. - **E-test**: A strip with a gradient of antibiotic concentration is placed on a bacterial lawn. The point where bacterial growth stops along the strip indicates the **minimum inhibitory concentration (MIC)**, the lowest concentration that inhibits bacterial growth. - **Broth-Dilution Test**: Bacteria are grown in a series of broths with increasing concentrations of an antibiotic. The lowest concentration that inhibits visible growth is the **MIC**, and the concentration that kills the bacteria is the **minimum bactericidal concentration (MBC)**. 11. **Synergism vs. Antagonism and Antibiotic Resistance:** - **Synergism**: Two antibiotics work together to produce a greater effect than either alone (e.g., penicillin and aminoglycosides). - **Antagonism**: One antibiotic reduces the effectiveness of another (e.g., bacteriostatic drugs can inhibit the action of bactericidal drugs). - **Antibiotic Resistance**: This occurs when bacteria develop the ability to survive exposure to antibiotics that would normally kill them. It's a major problem because it makes infections harder to treat. - **MRSA (Methicillin-Resistant Staphylococcus aureus)**: A type of bacteria resistant to many antibiotics, including methicillin, making infections difficult to treat. **Three Ways Bacteria Obtain Resistance Genes**: 1. **Transformation**: Bacteria take up free DNA from the environment. 2. **Conjugation**: Transfer of DNA between bacteria through direct cell-to-cell contact, often via plasmids. 3. **Transduction**: Transfer of bacterial DNA by bacteriophages (viruses that infect bacteria). - **Spread of Resistance**: Resistance genes can be shared between bacteria through **horizontal gene transfer**, such as conjugation, transformation, or transduction. These genes can then spread through a bacterial colony. 12. **Bacterial Resistance Mechanisms:** **Five Modes of Action for Bacterial Resistance**: 1. **Enzymatic Destruction**: Bacteria produce enzymes (e.g., beta-lactamase) that destroy the antibiotic. 2. **Altered Targets**: Mutations change the antibiotic's target, preventing it from binding (e.g., changes in ribosomes or enzymes). 3. **Efflux Pumps**: Bacteria use pumps to remove the antibiotic from the cell before it can cause harm. 4. **Reduced Permeability**: Bacteria modify their cell wall or membrane to block antibiotic entry. 5. **Bypass Mechanisms**: Bacteria develop alternate pathways to bypass the step that the antibiotic blocks. - **Worsening Antibiotic Resistance**: Overuse and misuse of antibiotics (in humans, animals, and agriculture) accelerate the development of resistance. - **Consequences**: If antibiotics stop working, simple infections could become deadly, and medical procedures such as surgeries and cancer treatments would carry higher risks. - **Solutions**: Developing new antibiotics, promoting the correct use of antibiotics, and improving infection control measures. 13. **Modes of Action for Antiviral Drugs:** **Four Modes of Action**: 1. **Inhibition of Viral Entry**: Prevents the virus from entering host cells (e.g., fusion inhibitors for HIV). 2. **Inhibition of Nucleic Acid Synthesis**: Stops viral replication by interfering with the synthesis of viral DNA or RNA (e.g., **Acyclovir** for herpes). 3. **Inhibition of Viral Protein Synthesis**: Blocks the production of viral proteins (e.g., **protease inhibitors** for HIV). 4. **Inhibition of Viral Release**: Prevents the release of new viral particles from the host cell (e.g., **neuraminidase inhibitors** like Oseltamivir for flu).