BIOL2100 Ch 20 Antimicrobials Nester 10th (PDF)

**BIOL2100 Ch 20 Antimicrobials** **Nester 10th** **Questions** - Describe the accomplishments of Paul Ehrlich, Alexander Fleming and Selman Waksman. - Briefly describe the history of the development of penicillin for commercial use. - Define the terms **therapeutic index and ther...

**BIOL2100 Ch 20 Antimicrobials** **Nester 10th** **Questions** - Describe the accomplishments of Paul Ehrlich, Alexander Fleming and Selman Waksman. - Briefly describe the history of the development of penicillin for commercial use. - Define the terms **therapeutic index and therapeutic window and explain how those terms are used to describe the therapeutic value of a drug.** - **What is selective toxicity?** - **How does toxicity of the drug play into the preferred route of its administration?** - **Why could topical drugs have higher toxicity than systemic drugs?** - **Why do some drugs have to be injected?** - **Why would you have to monitor for toxicity in kidney or liver impaired patients?** - **List adverse effects of antibiotics and give examples.** - **Give examples of intrinsic drug resistance of bacteria.** - **How may bacteria acquire drug resistance?** - **How does combination drug treatment prevent resistance?** - **List the mechanisms of action of antibacterials.** - **What is the difference between a bacteriostatic and a bactericide?** - What type of organism produces penicillin naturally, and how does penicillin kill target bacteria? - What types of bacteria are most susceptible to penicillin? - Define natural antibiotics (drugs), vs. synthetic. - What defines a broad-spectrum drug? - What are the preferred uses of broad-spectrum vs. narrow-spectrum antibiotics? - What is a Healthcare Associated Infection? Give examples. - What commonly causes antibiotics associated diarrhea, and how is it treated with antibiotics? - Describe characteristics of *C. difficile*. - What does it mean that drugs interact antagonistically, synergistically or additively? - List the drug targets of bacteria. - What is the mechanism of action of beta-lactam antibiotics? - What is the function of Penicillin-Binding-Proteins, and where are they found? - What is beta-lactamase? What organisms make them and what is the consequence to their antibiotics sensitivity? - What is penicillinase? - Give examples of non beta-lactam antibiotics that interfere with cell wall synthesis and how they are used. - What is the mode of action of a glycopeptide antibiotics? Give an example. - Why is Vancomycin described as a drug "of last resort"? - Give examples of antibiotics that interfere with the bacterial cell membrane. - Give examples of antibiotics that inhibit protein synthesis. - What is the mechanism of action of tetracycline? - Why is tetracycline not given to children or pregnant women? - What is the mechanism of action of neomycin? - What is the mechanism of action of chloramphenicol? - What is a serious side effect of chloramphenicol? - Give examples of antibiotics that are nucleic acid synthesis inhibitors. - What is the mechanism of action of fluoroquinolones and rifamycins? - What is the mechanism of action of sulfonamides? - What is a folate inhibitor? - Why is a disruptor of folate synthesis not affecting animals? - What is PABA, and how does a sulfonamide relate to the structure of PABA? - How does sulfonamide work as a competitive inhibitor of the metabolic pathway of folate? - Discuss the problems with antibiotics treatment of T.B. - Why does the common treatment of T.B. include four drugs? - Describe the Kirby-Bauer disc diffusion test. - What is the "Zone of Inhibition" pertaining to the Kirby-Bauer disc diffusion test. - What does MIC stand for? - Describe the MIC method. - What does MBC stand for? - List and **describe** the mechanisms of antibiotics resistance. - List reasons for the increase in antibiotics resistant strains, give examples. - How can health care workers, patients and the population as a whole fight antibiotics resistance? - List the mechanisms of antibacterial drug resistance. - What is MDR-TB and XDR-TB? - What is MRSA? - List drug targets of antiviral drugs. - What type of virus is treated with Acyclovir? - What type of virus is targeted with Reverse Transcriptase Inhibitors? - What are the problems with developing anti-fungal and anti-parasitic drugs? - What are the drug targets of anti-fungals? **Notes** **Paul Ehrlich:** Developed Salvarsan, the "magic bullet" for treating syphilis. **Alexander Fleming:** Identified penicillin, made by the *Penicillum* mold. Penicillin was developed commercially during WWII by the US -- Penicillin G. **Selman Waksman:** Purified streptomycin from *Streptomyces* bacteria. **Synthetic drugs** (antibiotics) are made in a pharmaceutical lab **Natural antibiotics** are made by microorganisms (bacteria, fungi) -- can be modified in labs into new drug variants **(semi-synthetics**). **Selective toxicity** Drug should have a **high therapeutic index / high therapeutic window**, i.e. a low dose is required to eliminate the pathogen and the drug is not toxic unless it is given in high amounts. **Bacteriostatic dru**g -- **inhibits** bacterial **growth** **Bactericidal drug** -- **kills** bacteria Topical /local administration of drug for external infection (on skin) Oral, intramuscular (IM) or intravenous (IV) administration of drug for internal infection Mode of administration depends on type and location of infection, and type of antibiotics. The **stomach acid** destroys acid sensitive drugs. Blood brain barrier -- difficult to penetrate (brain and spinal cord infections) Half-life of drug -- serum level at 50%. Short half-life = more frequent drug administration. Kidney and liver dysfunction can lead to poor elimination and metabolism -- toxicity more likely **Antimicrobial spectrum** **Broad spectrum** -- works against several taxonomic groups, Gram positive and negative **Narrow spectrum** -- works against few taxonomic groups **Drug combinations** can lead to **Antagonistic effect --** drugs counteract treatment **Synergistic effect** -- drug interactions enhance treatment **Additive effect --** no drug interaction, but resistance will be prevented **[Modes of Action of Antibiotics]** - Inhibit cell wall synthesis - Interfere with cell membrane - Target protein synthesis - Inhibit nucleic acid synthesis **[Inhibition of Cell Wall Synthesis]** The **Beta-Lactam Family** of Antibiotics: **Penicillin -- a natural antibiotics -** mainly active against **Gram positive** bacteria **Penicillin G** (I.M. and I.V.) was commercially developed during WWII (U.S.) **Drawbacks** Allergies **Other cell wall inhibitors that are not beta-lactam antibiotics** **[Inhibit Protein Synthesis:]** Interfere with the function of the bacterial 70S ribosome (smaller than eukaryotic ribosome) - Cause discoloration of teeth and skeleton (not prescribed for children and pregnancy) - May cause aplastic anemia **[Inhibitors of Nucleic Acid Synthesis]** **[Interfere with Metabolic Pathways:]** Folic acid (folate) is needed for nucleic acid synthesis, thus DNA replication is inhibited and thus bacterial growth. Folic acid is not produced in animals (we need to get it from our diet), so this is therefore a selective drug target. Target both Gram positive and Gram negative bacteria **[Evaluation of Antibiotics Effectiveness:]** **Diffusion Susceptibility Testing (Kirby-Bauer)** **Minimum Inhibitory Concentration (MIC) test** **Minimum Bactericidal Concentration (MBC) test** **[Antibiotics Resistance:]** **Spontaneous mutations** (less likely with combination drug treatment) and **Horizontal Gene Transfer (**R-plasmids via transformation or conjugation**)** **Mechanisms** - Antibiotics modification by the bacterium - Bacterium produces substance that can inactivate the drug (beta-lactamase) - Altered drug target - Structural changes prevent drug binding to bacterial target - Reduced permeability / active export - Preventing entrance by changes to **porins** - Increasing outward **pumping** of drug Antibiotics resistance may arise due to: **Antiviral medications:** - Interfere with attachment, entry, uncoating, synthesis, assembly, viral exit. - Virus relies on host mechanisms -- those cannot be targeted without toxicity to host. - Herpes virus uses virally encoded polymerase that is targeted by the drug Acyclovir. - HIV virus is targeted by Reverse Transcriptase Inhibitors. - Those are usually nucleotide analogs that are integrated and then terminate replication. **Anti-fungal medications:** Cell wall -- targets chitin Cell membrane -- targets ergosterol