Podcast
Questions and Answers
What is a primary target for antibacterial medications?
What is a primary target for antibacterial medications?
Which antibiotic is designed for increased Gram-negative activity?
Which antibiotic is designed for increased Gram-negative activity?
What component of bacterial cells do beta-lactam antibiotics target?
What component of bacterial cells do beta-lactam antibiotics target?
What is a common mechanism of resistance that bacteria use against beta-lactam antibiotics?
What is a common mechanism of resistance that bacteria use against beta-lactam antibiotics?
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Which of the following statements about the half-life of a drug is accurate?
Which of the following statements about the half-life of a drug is accurate?
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Which type of bacteria are beta-lactam antibiotics more often effective against?
Which type of bacteria are beta-lactam antibiotics more often effective against?
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Which function is not associated with the liver in drug metabolism?
Which function is not associated with the liver in drug metabolism?
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What characteristic do all beta-lactam antibiotics share?
What characteristic do all beta-lactam antibiotics share?
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What is the primary mechanism of action of Vancomycin?
What is the primary mechanism of action of Vancomycin?
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Bacitracin is mainly used in topical applications due to its:
Bacitracin is mainly used in topical applications due to its:
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Which antibiotic is described as having a low therapeutic index?
Which antibiotic is described as having a low therapeutic index?
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What defines the action of Tetracyclines in bacteria?
What defines the action of Tetracyclines in bacteria?
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Fluoroquinolones specifically target which bacterial process?
Fluoroquinolones specifically target which bacterial process?
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What is a primary side effect associated with Chloramphenicol?
What is a primary side effect associated with Chloramphenicol?
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Which antibiotic is considered an antibiotic of last resort for resistant Gram-positive infections?
Which antibiotic is considered an antibiotic of last resort for resistant Gram-positive infections?
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Rifampin is one of the first-line drugs for which condition?
Rifampin is one of the first-line drugs for which condition?
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What is the significance of Alexander Fleming's lab technique?
What is the significance of Alexander Fleming's lab technique?
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What purpose do antimicrobial medications serve?
What purpose do antimicrobial medications serve?
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Why is the search for new anti-microbial effects ongoing?
Why is the search for new anti-microbial effects ongoing?
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What does the term 'differential poisons' refer to in the context of medical history?
What does the term 'differential poisons' refer to in the context of medical history?
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What role does economic investment play in drug development?
What role does economic investment play in drug development?
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What are the traditional remedies that have been historically tested on infectious agents?
What are the traditional remedies that have been historically tested on infectious agents?
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What was a significant outcome of the discovery of microorganisms in relation to disease?
What was a significant outcome of the discovery of microorganisms in relation to disease?
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What is a contemporary focus in the modification of existing antibiotics?
What is a contemporary focus in the modification of existing antibiotics?
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Which type of vaccine involves the purification of key proteins using recombinant technology?
Which type of vaccine involves the purification of key proteins using recombinant technology?
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What is a significant advantage of mRNA vaccines compared to traditional vaccines?
What is a significant advantage of mRNA vaccines compared to traditional vaccines?
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Which vaccine type purifies toxins and retains the epitopes while destroying the toxic part?
Which vaccine type purifies toxins and retains the epitopes while destroying the toxic part?
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What potential risk is associated with attenuated vaccines when used in immunocompromised hosts?
What potential risk is associated with attenuated vaccines when used in immunocompromised hosts?
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What describes conjugate vaccines and their benefit?
What describes conjugate vaccines and their benefit?
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What is the primary target for antiviral drugs aimed at inhibiting viral replication?
What is the primary target for antiviral drugs aimed at inhibiting viral replication?
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Which viral entry mechanism involves binding to a specific receptor on the surface of a target cell?
Which viral entry mechanism involves binding to a specific receptor on the surface of a target cell?
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What kind of inhibitors is primarily utilized against HIV?
What kind of inhibitors is primarily utilized against HIV?
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Why are nucleic acid analogs considered a potential universal antiviral treatment?
Why are nucleic acid analogs considered a potential universal antiviral treatment?
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What characteristic makes HIV antiviral treatment specific rather than universal?
What characteristic makes HIV antiviral treatment specific rather than universal?
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Which drug has developed resistance despite being designed to inhibit viral uncoating?
Which drug has developed resistance despite being designed to inhibit viral uncoating?
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What is the most effective approach for the immune system to reduce viral infection, compared to antiviral drugs?
What is the most effective approach for the immune system to reduce viral infection, compared to antiviral drugs?
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Which class of antiviral drugs is known for targeting both disassembly and assembly of viral proteins?
Which class of antiviral drugs is known for targeting both disassembly and assembly of viral proteins?
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What was the percentage decrease in cases for Haemophilus influenzae type b invasive disease after immunization?
What was the percentage decrease in cases for Haemophilus influenzae type b invasive disease after immunization?
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Which of the following diseases has seen a nearly 100% decrease in cases after immunization?
Which of the following diseases has seen a nearly 100% decrease in cases after immunization?
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What misconception may increase the risk for unvaccinated children during an outbreak?
What misconception may increase the risk for unvaccinated children during an outbreak?
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Which disease is claimed to be the only one eradicated globally?
Which disease is claimed to be the only one eradicated globally?
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Which group is recommended to receive vaccinations for Pertussis?
Which group is recommended to receive vaccinations for Pertussis?
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Study Notes
Today's Class
- The class will primarily review previously learned material.
- Previously answered class questions are in the distributed notes and removing them would result in too many slides.
- The initial summary slide for particular sections will be omitted.
- For those sections, review previous material before reading.
- A pre-quiz will cover the material and answers will be released the next day.
History of Medicine
- Remedies have existed as long as diseases have.
- Some remedies were/are effective even if their mechanism isn't fully understood.
- Placebos have shown therapeutic effects.
- Discoveries of microorganisms led to links between microorganisms and disease.
- Early scientific tools like microscopy helped identify microorganisms and differences between them.
- The search for 'silver bullets' (differential poisons) is still part of modern medicine.
Search for Differential Poisons (Anti-microbials)
- Historical approaches tested remedies against infectious agents (quinine, mercury).
- Testing of any poison, looking for a therapeutic effect, expanded the scope of discovery.
- Alexander Fleming's accidental discovery of antibiotics (microbial medications) revolutionized medicine.
- Penicillin was, and is, a notable example of an effective antimicrobial medication.
- Further research continues to identify effective antimicrobials from varied organisms in diverse environments.
Addition of Science
- Existing antibiotics continued to be improved or modified to address emerging resistance.
- Resistance to antimicrobial medications is an ongoing challenge that necessitates frequent updates and the creation of newer medications.
Role of Money
- Drug development requires significant investment.
- Pharmaceutical companies balance risks and potential rewards (market factors).
- Factors like disease prevalence and treatment duration influence profitability.
- Costs associated with research, development, and manufacturing must be balanced with patient costs and healthcare coverage.
Golden Ticket – Rational Drug Design
- Scientific understanding of organisms guides the design of new and specific treatments.
- Analyzing chemical structure databases identifies potential interactions and targets.
- Animal and human testing are necessary before widespread use.
Few Drugs are Curative on their own
- Bacteriostatic drugs inhibit bacterial growth.
- Giving the patient's immune system a chance to eliminate the threat or pathogen is essential for complete healing.
- Bactericidal drugs kill bacteria, but resistance can emerge in the host.
- Immune systems of patients with compromised immune systems (e.g., HIV/AIDS) need long-term, multi-drug regimens for recovery.
Broad-Spectrum vs Narrow-Spectrum
- Understanding the infective agent helps choose treatment approach.
- Broad-spectrum treatments have wider effects but more collateral damage (possible harm to the body).
- Narrow spectrum treatments target specific organisms.
- The approach usually starts broad-spectrum and shifts towards narrower-spectrum treatments as more is known.
Drug Interactions are an Increasing Issue
- Combinations of medications can have additive, antagonistic, or synergistic effects.
- Additive effects: both drugs work well independently; when taken together, both work as well as expected.
- Antagonistic effects: one drug interferes with or cancels the effects of another
- Synergistic effects: the combination of two drugs creates an effect greater than the sum of the two independent effects.
- The number of medications an individual consumes daily can make interactions difficult to manage.
Specificity
- Many chemicals can kill bacteria, fungi, protozoa, helminths, and viruses.
- Most effective antimicrobial treatments are specific to target a single agent and not have many side effects on humans.
- Categories of microorganisms are separately addressed for specificity considerations.
Targets for Antibacterial Medications
- Specific targets for antibacterial medications are cell wall synthesis, protein synthesis, nucleic acid synthesis, metabolic pathways and cell membranes.
- These targets are crucial for the proper functioning of microbial cells and not human cells
Cell Wall Synthesis
- Beta-Lactam antibiotics and derivatives, competitively inhibit the enzymes needed to create cross-links between polymers in cell walls, blocking the formation.
- Their effectiveness is particularly strong against rapidly dividing cells.
- This class has a narrow therapeutic index.
- Penicillin G and the various semi-synthetic penicillin derivatives offer differing sensitivities versus Gram-negative bacteria.
Beta-Lactams cont
- Effectiveness differences exist between Gram-positive and Gram-negative organisms in response to beta-lactam agents.
- Resistance to β-lactam antibiotics is often due to bacterial enzymes that break down the drugs.
- This resistance occurs more often with gram-negative bacteria than gram-positive bacteria.
Different Mechanism Cell Wall: Glycopeptides
- Vancomycin is one of the major glycopeptide agents (used last when other drugs fail).
- It works by binding to the amino acid chain of peptidoglycan, blocking peptidoglycan synthesis.
- Vancomycin is primarily effective on Gram-positive bacteria. (it does not cross the cell membrane of Gram-negative ones)
Bacitracin
- Inhibits peptidoglycan precursor transport, across the cytoplasmic membrane.
- Toxic to human cells, suitable only for topical use.
Bacterial Protein Synthesis
- Ribosomes are the main target of protein synthesis inhibitors, such as chloramphenicol, macrolides, aminoglycosides, lincosamides, oxazolidinones, and streptogramins.
- Some of these antibiotics have significant toxicity as they affect the host's ribosomes.
Protein Synthesis
- Many compounds interact with large ribosomal subunit (50s), which can either be bacteriostatic.
- Interactions with small subunit (30s) are also possible, often leading to bacteriostatic effects.
- Erythromycin is an example of a drug that targets a large ribosomal subunit.
Nucleic Acid (both DNA & RNA) Synthesis
- Drugs acting on topoisomerases (DNA gyrase and topoisomerase IV) are often targeted to treat infections from bacteria.
- These compounds can have adverse effects, making them suitable for either topical or last resort usage.
- Rifamycins selectively target bacterial RNA polymerase initiation, often used to treat tuberculosis.
- Other drugs block DNA and RNA synthesis, often in a way that is specific to each organism.
Metabolic Pathways
- Many bacterial metabolic pathways are similar to those in eukaryotes.
- Targeting unique metabolic pathways in bacteria or those not present in mammals can increase the chance of successful treatment without excessive side effects.
- Sulfa drugs are competitive inhibitors, targeting the synthesis of folic acid, a crucial element for bacteria.
Membrane Integrity
- Bacterial and eukaryotic membranes share features.
- Targeting these components can yield severe side effects.
- Polymixins are an example of drugs targeting cell membranes, most often used as a topical medication.
Special Case: Mycobacterium
- Mycobacterium has waxy surfaces with mycolic acids that make it resilient to treatment and can spread easily through aerosols.
- Certain infections require extended therapy regimens.
- First-line drugs might include isoniazid (blocks mycolic acid synthesis), and ethambutol (blocks cell wall components), with rifampin (RNA polymerase inhibitor) from earlier stages.
Summary – Anti-bacterial Medications
- Treatment sufficient differences should be observed in order to develop effective treatment plans
- Agents should target cell walls, ribosomes, nucleic acids, and cell membranes as major targets.
Targets for Anti-Viral Drugs
- Viruses depend on host functions and need to be targeted in their unique phases of reproduction.
- Targeting viral components like nucleic acid synthesis offers a possible approach to treatment.
- The differences existing between viral and host machinery offer some unique opportunities to design treatments.
Viral entry
- The first step of viral infection is to attach to the surface receptor of the targeted cells and cause infection.
- Anti-viral drugs can target the virus by blocking the virus from attaching to the host cell, or blocking the viral cell from entry.
- Virus attachment is highly specific to the target cells, and so are the molecules needed to inhibit the connection.
Virus uncoating
- Viral uncoating is an important aspect of the viral life cycle to be targeted to treat viruses.
- Anti-influenza drugs (Amantadine, Rimantadine) and Lenacapavir treat multiple viral categories.
Number 1 Target → Nucleic Acid Synthesis
- Many viruses have their own specific nucleic acid polymerases.
- Targeting viral nucleic acid polymerases is a crucial strategy in antiviral therapy, as many RNA viruses code for this activity.
- Drug analogs can integrate into the DNA replication process, causing defects. This can be beneficial, as viruses require frequent replication, but the drugs have effects on the host cell.
Nucleic Acid Synthesis (and integration)
- Polymerase inhibitors target viral polymerase enzymes, crucial for viral replication.
- Reverse transcriptase inhibitors target RNA retroviruses like HIV.
- Integrase inhibitors also target HIV.
Protease inhibitors (cont.)
- Proteases are essential for viral replication - inhibiting these enzymes effectively targets viral replication.
- HIV protease inhibitors are a type of anti-viral medication.
- COVID-19 drugs like PAXLOVID are a combination of Ritonavir and Nirmatrelvir
Why do we keep seeing HIV drugs?
- HIV medications slow or control, but do not eliminate, the virus. They allow the immune system to do more and the time of infection can be lessened.
- The high risk of drug resistance in HIV necessitates repeated drug changes.
- HIV-infected patients frequently require long-term treatments to balance both the high cost and risk versus the high benefit.
- The chronic nature of HIV infection necessitates long-term medications.
Speaking of Immune systems
- Antibodies are frequently used for treating many viral illnesses, and they have historically been used for many infections like snake bites.
- Producing monoclonal antibodies in the lab creates highly specific antibodies targeted at particular agents that cause disease. - This approach is beneficial for infectious illnesses that might not yield a recovery if not treated early.
There is a better way...Vaccines
- Vaccines train the immune system to recognize antigens, eliminating the need for treatment afterward.
- Inactivated vaccines use killed or inactivated pathogens to elicit an immune response.
- Attenuated vaccines use a weakened version of a pathogen.
- The weakened version of the pathogen does not harm the host, but elicits a powerful antigenic response that prevents disease.
- Different types of vaccines target various aspects of the viral or bacterial life cycle
Other "inactivated" Vaccines
- Conjugate vaccines link polysaccharides to proteins.
- Nucleic acid-based vaccines (like mRNA vaccines) use mRNA to trigger an immune response.
- Both approaches are designed to create a tailored immune response against a target.
Attenuated Vaccines
- Weakened pathogens trigger an immune response.
- The attenuated pathogen elicits an immunological reaction.
- The pathogen can be transmitted to other organisms and elicit a wider community immune response.
Effectiveness for Bacteria and Viruses
- Many bacterial and viral illnesses were dramatically reduced with the advent and widespread adoption of vaccinations.
- Diseases like smallpox are now almost entirely eradicated, while others like polio have very low incidence.
- People often forget the drastic differences in disease status before immunization and how they have been altered.
CEC Vaccinations recommended for Bacterial Diseases
- This slide lists the CEC's recommended vaccinations for bacterial diseases
- The list includes different types of microorganisms and targeted vaccinations for effective immunity
CDC Recommended Vaccinations for Viral Diseases
- This slide highlights CDC's recommended vaccinations for viral illnesses.
- Different types of viruses are listed along with the recommended vaccinations to combat these diseases more effectively
Non-routine Vaccines (for special cases)
- Vaccines for diseases like adenovirus, anthrax, cholera, Ebola, Japanese encephalitis, rabies, tuberculosis, typhoid fever, and yellow fever.
Anti-Fungal Medications
- Fungi (eukaryotic) share some metabolic pathways with humans, making treatment more challenging.
- Fungi are frequently targeted by cell division inhibitors, cell wall synthesis inhibitors, nucleic acid synthesis inhibitors and protein synthesis inhibitors.
Ergosterol vs Cholesterol
- Ergosterol is the primary sterol in fungal cell membranes.
- Ergosterol and cholesterol are very similar and both perform the same basic functions
- Most antifungals target ergosterol synthesis, causing membrane damage
Cell Wall synthesis
- In fungal cells, this is a unique target.
- Targeting the unique bet-1,3 glucan linkage in fungal cells helps manage drug resistance against fungal infections
Other
- Cell division inhibitors like Griseofulvin affect fungal cells.
- Flucytosine interferes with fungal nucleic acid synthesis; it's often considered a last-resort treatment.
Parasitic Protozoa
- Some specialized metabolic pathways or structures allow for repurposing of drugs
- Some commonly used anti-bacterial drugs are effective against some types of protozoa.
Parasitic Helminths
- Neurological inhibitors are used to manage parasitic helminths
- Different medical solutions are frequently studied and tested for treating different types of parasitic illnesses with varying effectiveness
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Description
Test your knowledge on various antibacterial medications and their mechanisms of action. This quiz covers beta-lactam antibiotics, resistance strategies, and specific drug classifications. Perfect for students of pharmacology or microbiology.
